-,Pajama,$13,Womens,Assn.,with,U.S.,Polo,Short,Sh,Clothing, Shoes Jewelry , Women , Clothing,Pockets,Sleeve,/drainman4485965.html,Set,ekonomi.unmerpas.ac.id U.S. Polo Assn. Womens Pajama Set Sleeve with Sh Pockets Short Ranking TOP7 - U.S. Polo Assn. Womens Pajama Set Sleeve with Sh Pockets Short Ranking TOP7 - -,Pajama,$13,Womens,Assn.,with,U.S.,Polo,Short,Sh,Clothing, Shoes Jewelry , Women , Clothing,Pockets,Sleeve,/drainman4485965.html,Set,ekonomi.unmerpas.ac.id $13 U.S. Polo Assn. Womens Pajama Set with Pockets - Short Sleeve Sh Clothing, Shoes Jewelry Women Clothing $13 U.S. Polo Assn. Womens Pajama Set with Pockets - Short Sleeve Sh Clothing, Shoes Jewelry Women Clothing
U.S. Polo Assn. Womens Pajama Set with Pockets - Short Sleeve Sh
U.S. Polo Assn. Womens Pajama Set with Pockets - Short Sleeve Sh
Pull On closure
This US Polo womans pajamas set comes with a pair of soft cotton sweatpants and a matching short sleeve shirt with pockets for a coordinated look. RUNS SMALL - Please order a size up
The USPA pjs for women has two small pockets on either side of the front of the shirt and pants are great for holding small items such as lip gloss or a tissue.
The sporty and sweet henley style shirt of these short sleeve pajamas for women can be buttoned up all the way or with a few left undone for a sweet and flirty vibe in this .
The stretchy elastic waistband of these womens pajamas is adorned with a decorative tie that is knotted into a bow for extra feminine flair.
This womens pajama sets pants pairs perfectly with everything that's already in your lounge wear wardrobe, as well as our collection of luxe loungewear for women
U.S. Polo Assn. Womens Pajama Set with Pockets
U.S. Polo Assn. Pajama Set for women
U.S. Polo Assn. Pajama Set for women
U.S. Polo Assn. Pajama Set for women
U.S. Polo Assn. Womens tank to and short set
U.S. Polo Assn. Womens Short Sleeve Shirt and Pajama Shorts
U.S. Polo Assn. Womens Sweatpants with Pockets
U.S. Polo Assn. Sweatpants for girls
U.S. Polo Assn. Womens shorts sleepwear
U.S. Polo Assn. Womens Short Sleeve Shirt and Long Pajama Pants
U.S. Polo Assn. Womens Casual Long Sleeve Shirt and Pajama Pants
U.S. Polo Assn. Womenâs Pajama Thermal Underwear
The elastic waist helps the bottoms to loosely hug the hips and allows you to pull the bottoms as tightly as you like - insuring a perfect, custom fit every time
2 SIDE POCKETS
Keep all your personal item with you all the time, keys phone etc.
SIDE LACE TRIM DESIGN
Look sweet and flirty in this comfortable pajama set with plenty of feminine charm to make you look your best.
CLASSIC HENLEY TOP
The sporty and sweet henley style of the shirt can be buttoned up all the way or with a few left undone for a sweet and flirty vibe.
U.S. Polo Assn. Womens Pajama Set with Pockets - Short Sleeve Sh
Lookian et al. describe the development of a third intracranial venous system, the transtentorial venous system using vascular casting, ex vivo micro–computed tomography, and high-resolution magnetic resonance imaging in mice. Image credit: Erina He.
Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell–deficient and P2X7 receptor–deficient (P2X7–/–) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell–deficient mice with WT mast cells and P2X7–/– mast cells restored ozone-induced BHR. Despite equal numbers of mast cells in reconstituted mouse lungs, mice reconstituted with P2X7–/– mast cells demonstrated significantly less robust BHR than mice reconstituted with WT mast cells. These results support a model where P2X7 on mast cells and other cell types contribute to ozone-induced BHR.
Xiaomei Kong, William C. Bennett, Corey M. Jania, Kelly D. Chason, Zachary German, Jennifer Adouli, Samuel D. Budney, Brandon T. Oby, Catharina van Heusden, Eduardo R. Lazarowski, Ilona Jaspers, Scott H. Randell, Barry A. Hedgespeth, Glenn Cruse, Xiaoyang Hua, Stephen A. Schworer, Gregory J. Smith, Samir N.P. Kelada, Stephen L. Tilley
Fibrotic posterior capsular opacification (PCO), a major complication of cataract surgery, is driven by transforming growth factor–β (TGF-β). Previously, αV integrins were found to be critical for the onset of TGF-β–mediated PCO in vivo; however, the functional heterodimer was unknown. Here, β8 integrin–conditional knockout (β8ITG-cKO) lens epithelial cells (LCs) attenuated their fibrotic responses, while both β5 and β6 integrin–null LCs underwent fibrotic changes similar to WT at 5 days post cataract surgery (PCS). RNA-Seq revealed that β8ITG-cKO LCs attenuated their upregulation of integrins and their ligands, as well as known targets of TGF-β–induced signaling, at 24 hours PCS. Treatment of β8ITG-cKO eyes with active TGF-β1 at the time of surgery rescued the fibrotic response. Treatment of WT mice with an anti-αVβ8 integrin function blocking antibody at the time of surgery ameliorated both canonical TGF-β signaling and LC fibrotic response PCS, and treatment at 5 days PCS, after surgically induced fibrotic responses were established, largely reversed this fibrotic response. These data suggest that αVβ8 integrin is a major regulator of TGF-β activation by LCs PCS and that therapeutics targeting αVβ8 integrin could be effective for fibrotic PCO prevention and treatment.
Mahbubul H. Shihan, Samuel G. Novo, Yan Wang, Dean Sheppard, Amha Atakilit, Thomas D. Arnold, Nicole M. Rossi, Adam P. Faranda, Melinda K. Duncan
Obesity is one of the main drivers of type 2 diabetes, but it is not uniformly associated with the disease. The location of fat accumulation is critical for metabolic health. Specific patterns of body fat distribution, such as visceral fat, are closely related to insulin resistance. There might be further, hitherto unknown, features of body fat distribution that could additionally contribute to the disease. We used machine learning with dense convolutional neural networks to detect diabetes-related variables from 2371 T1-weighted whole-body MRI data sets. MRI was performed in participants undergoing metabolic screening with oral glucose tolerance tests. Models were trained for sex, age, BMI, insulin sensitivity, HbA1c, and prediabetes or incident diabetes. The results were compared with those of conventional models. The area under the receiver operating characteristic curve was 87% for the type 2 diabetes discrimination and 68% for prediabetes, both superior to conventional models. Mean absolute regression errors were comparable to those of conventional models. Heatmaps showed that lower visceral abdominal regions were critical in diabetes classification. Subphenotyping revealed a group with high future diabetes and microalbuminuria risk.Our results show that diabetes is detectable from whole-body MRI without additional data. Our technique of heatmap visualization identifies plausible anatomical regions and highlights the leading role of fat accumulation in the lower abdomen in diabetes pathogenesis.
Benedikt Dietz, Jürgen Machann, Vaibhav Agrawal, Martin Heni, Patrick Schwab, Julia Dienes, Steffen Reichert, Andreas L. Birkenfeld, Hans-Ulrich Häring, Fritz Schick, Norbert Stefan, Andreas Fritsche, Hubert Preissl, Bernhard Schölkopf, Stefan Bauer, Robert Wagner
IL-33, a nuclear alarmin released during cell death, exerts context-specific effects on adaptive and innate immune cells, eliciting potent inflammatory responses. We screened blood, skin, and kidney tissues from patients with systemic lupus erythematosus (SLE), a systemic autoimmune disease driven by unabated type I IFN production, and found increased amounts of extracellular IL-33 complexed with neutrophil extracellular traps (NETs), correlating with severe, active disease. Using a combination of molecular, imaging, and proteomic approaches, we show that SLE neutrophils, activated by disease immunocomplexes, release IL-33–decorated NETs that stimulate robust IFN-α synthesis by plasmacytoid DCs in a manner dependent on the IL-33 receptor ST2L. IL33-silenced neutrophil-like cells cultured under lupus-inducing conditions generated NETs with diminished interferogenic effect. Importantly, NETs derived from patients with SLE are enriched in mature bioactive isoforms of IL-33 processed by the neutrophil proteases elastase and cathepsin G. Pharmacological inhibition of these proteases neutralized IL-33–dependent IFN-α production elicited by NETs. We believe these data demonstrate a novel role for cleaved IL-33 alarmin decorating NETs in human SLE, linking neutrophil activation, type I IFN production, and end-organ inflammation, with skin pathology mirroring that observed in the kidneys.
Spiros Georgakis, Katerina Gkirtzimanaki, Garyfalia Papadaki, Hariklia Gakiopoulou, Elias Drakos, Maija-Leena Eloranta, Manousos Makridakis, Georgia Kontostathi, Jerome Zoidakis, Eirini Baira, Lars Rönnblom, Dimitrios T. Boumpas, Prodromos Sidiropoulos, Panayotis Verginis, George Bertsias
Patients with diabetes with coronary microvascular disease (CMD) exhibit higher cardiac mortality than patients without CMD. However, the molecular mechanism by which diabetes promotes CMD is poorly understood. RNA-binding protein human antigen R (HuR) is a key regulator of mRNA stability and translation; therefore, we investigated the role of HuR in the development of CMD in mice with type 2 diabetes. Diabetic mice exhibited decreases in coronary flow velocity reserve (CFVR; a determinant of coronary microvascular function) and capillary density in the left ventricle. HuR levels in cardiac endothelial cells (CECs) were significantly lower in diabetic mice and patients with diabetes than the controls. Endothelial-specific HuR-KO mice also displayed significant reductions in CFVR and capillary density. By examining mRNA levels of 92 genes associated with endothelial function, we found that HuR, Cx40, and Nox4 levels were decreased in CECs from diabetic and HuR-KO mice compared with control mice. Cx40 expression and HuR binding to Cx40 mRNA were downregulated in CECs from diabetic mice. Cx40-KO mice exhibited decreased CFVR and capillary density, whereas endothelium-specific Cx40 overexpression increased capillary density and improved CFVR in diabetic mice. These data suggest that decreased HuR contributes to the development of CMD in diabetes through downregulation of gap junction protein Cx40 in CECs.
Rui Si, Jody Tori O. Cabrera, Atsumi Tsuji-Hosokawa, Rui Guo, Makiko Watanabe, Lei Gao, Yun Sok Lee, Jae-Su Moon, Brian T. Scott, Jian Wang, Anthony W. Ashton, Jaladanki N. Rao, Jian-Ying Wang, Jason X.-J. Yuan, Ayako Makino
Hypoxia is associated with tumor radioresistance; therefore, a predictive marker for tumor hypoxia and a rational target to overcome it have been sought to realize personalized radiotherapy. Here, we show that serine protease inhibitor Kazal type I (SPINK1) meets these 2 criteria. SPINK1 expression was induced upon hypoxia (O2 < 0.1%) at the transcription initiation level in a HIF-dependent manner, causing an increase in secreted SPINK1 levels. SPINK1 proteins were detected both within and around hypoxic regions of xenografted and clinical tumor tissues, and their plasma levels increased in response to decreased oxygen supply to xenografts. Secreted SPINK1 proteins enhanced radioresistance of cancer cells even under normoxic conditions in EGFR-dependent and nuclear factor erythroid 2–related factor 2–dependent (Nrf2-dependent) manners and accelerated tumor growth after radiotherapy. An anti-SPINK1 neutralizing antibody exhibited a radiosensitizing effect. These results suggest that SPINK1 secreted from hypoxic cells protects the surrounding and relatively oxygenated cancer cells from radiation in a paracrine manner, justifying the use of SPINK1 as a target for radiosensitization and a plasma marker for predicting tumor hypoxia.
Pulmonary hypertension (PH) is a severe cardiopulmonary disease characterized by complement-dependent, fibroblast-induced perivascular accumulation and proinflammatory activation of macrophages. We hypothesized that, in PH, nanoscale-sized small extracellular vesicles (sEVs), released by perivascular/adventitial fibroblasts, are critical mediators of complement-dependent proinflammatory activation of macrophages. Pulmonary adventitial fibroblasts were isolated from calves with severe PH (PH-Fibs) and age-matched controls (CO-Fibs). PH-Fibs exhibited increased secretion of sEVs, compared with CO-Fibs, and sEV biological activity was tested on mouse and bovine bone marrow–derived macrophages (BMDMs) and showed similar responses. Compared with sEVs derived from CO-Fibs, sEVs derived from PH-Fibs (PH-Fib-sEVs) induced augmented expression of proinflammatory cytokines/chemokines and metabolic genes in BMDMs. Pharmacological blockade of exosome release from PH-Fibs resulted in significant attenuation of proinflammatory activation of BMDMs. “Bottom-up” proteomic analyses revealed significant enrichment of complement and coagulation cascades in PH-Fib-sEVs, including augmented expression of the complement component C3. We therefore examined whether the PH-Fib-sEV–mediated proinflammatory activation of BMDMs was complement C3 dependent. Treatment of PH-Fibs with siC3-RNA significantly attenuated the capacity of PH-Fib-sEVs for proinflammatory activation of BMDMs. PH-Fib-sEVs mediated proglycolytic alterations and complement-dependent activation of macrophages toward a proinflammatory phenotype, as confirmed by metabolomic studies. Thus, fibroblast-released sEVs served as critical mediators of complement-induced perivascular/microenvironmental inflammation in PH.
Sushil Kumar, Maria G. Frid, Hui Zhang, Min Li, Suzette Riddle, R. Dale Brown, Subhash Chandra Yadav, Micaela K. Roy, Monika E. Dzieciatkowska, Angelo D’Alessandro, Kirk C. Hansen, Kurt R. Stenmark
Experimental autoimmune encephalomyelitis (EAE) is a well-characterized animal model of multiple sclerosis. During the early phase of EAE, infiltrating monocytes and monocyte-derived macrophages contribute to T cell recruitment, especially CD4+ T cells, into the CNS, resulting in neuronal demyelination; however, in later stages, they promote remyelination and recovery by removal of myelin debris by phagocytosis. Signal regulatory protein α and CD47 are abundantly expressed in the CNS, and deletion of either molecule is protective in myelin oligodendrocyte glycoprotein–induced EAE because of failed effector T cell expansion and trafficking. Here we report that treatment with the function blocking CD47 Ab Miap410 substantially reduced the infiltration of pathogenic immune cells but impaired recovery from paresis. The underlying mechanism was by blocking the emergence of CD11chiMHCIIhi microglia at peak disease that expressed receptors for phagocytosis, scavenging, and lipid catabolism, which mediated clearance of myelin debris and the transition of monocytes to macrophages in the CNS. In the recovery phase of EAE, Miap410 Ab–treated mice had worsening paresis with sustained inflammation and limited remyelination as compared with control Ab–treated mice. In summary, Ab blockade of CD47 impaired resolution of CNS inflammation, thus worsening EAE.
Huan Wang, Gail Newton, Liguo Wu, Lih-Ling Lin, Amy S. Miracco, Sridaran Natesan, Francis W. Luscinskas
COVID-19 is caused by SARS-CoV-2 (SC2) and is more prevalent and severe in elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here, we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor angiotensin converting enzyme 2 (ACE2) and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging, and that anti-CHI3L1, kasugamycin, and inhibitors of phosphorylation abrogate these ACE2- and SPP-inductive events. Human studies also demonstrate that the levels of circulating CHI3L1 are increased in the elderly and patients with CM, where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP, that this induction is a major mechanism contributing to the effects of aging during SC2 infection, and that CHI3L1 co-opts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
Suchitra Kamle, Bing Ma, Chuan Hua He, Bedia Akosman, Yang Zhou, Chang-Min Lee, Wafik S. El-Deiry, Kelsey Huntington, Olin Liang, Jason T. Machan, Min-Jong Kang, Hyeon Jun Shin, Emiko Mizoguchi, Chun Geun Lee, Jack A. Elias
Foxp3+ Tregs are potent immunosuppressive CD4+ T cells that are critical to maintain immune quiescence and prevent autoimmunity. Both the generation and maintenance of Foxp3+ Tregs depend on the cytokine IL-2. Hence, the expression of the IL-2 receptor α-chain (CD25) is not only considered a specific marker, but also a nonredundant requirement for Tregs. Here, we report that Foxp3+ Tregs in the small intestine (SI) epithelium, a critical barrier tissue, are exempt from such an IL-2 requirement, since they had dramatically downregulated CD25 expression, showed minimal STAT5 phosphorylation ex vivo, and were unable to respond to IL-2 in vitro. Nonetheless, SI epithelial Tregs survived and were present at the same frequency as in other lymphoid organs, and they retained potent suppressor function that was associated with high levels of CTLA-4 expression and the production of copious amounts of IL-10. Moreover, adoptive transfer experiments of Foxp3+ Tregs revealed that such IL-2–independent survival and effector functions were imposed by the SI epithelial tissue, suggesting that tissue adaptation is a mechanism that tailors the effector function and survival requirements of Foxp3+ Tregs specific to the tissue environment.
Praveen Prakhar, Jaylene Alvarez-DelValle, Hilary Keller, Assiatu Crossman, Xuguang Tai, Yoo Kyoung Park, Jung-Hyun Park
Asthma is a common disease with profoundly variable natural history and patient morbidity. Heterogeneity has long been appreciated, and much work has focused on identifying subgroups of patients with similar pathobiological underpinnings. Previous studies of the Severe Asthma Research Program (SARP) cohort linked gene expression changes to specific clinical and physiologic characteristics. While invaluable for hypothesis generation, these data include extensive candidate gene lists that complicate target identification and validation. In this analysis, we performed unsupervised clustering of the SARP cohort using bronchial epithelial cell gene expression data, identifying a transcriptional signature for participants suffering exacerbation-prone asthma with impaired lung function. Clinically, participants in this asthma cluster exhibited a mixed inflammatory process and bore transcriptional hallmarks of NF-κB and activator protein 1 (AP-1) activation, despite high corticosteroid exposure. Using supervised machine learning, we found a set of 31 genes that classified patients with high accuracy and could reconstitute clinical and transcriptional hallmarks of our patient clustering in an external cohort. Of these genes, IL18R1 (IL-18 Receptor 1) negatively associated with lung function and was highly expressed in the most severe patient cluster. We validated IL18R1 protein expression in lung tissue and identified downstream NF-κB and AP-1 activity, supporting IL-18 signaling in severe asthma pathogenesis and highlighting this approach for gene and pathway discovery.
Matthew J. Camiolo, Xiuxia Zhou, Qi Wei, Humberto E. Trejo Bittar, Naftali Kaminski, Anuradha Ray, Sally E. Wenzel
Superficial cutaneous Staphylococcus aureus (S. aureus) infection in humans can lead to soft tissue infection, an important cause of morbidity and mortality. IL-17A production by skin TCRγδ+ cells in response to IL-1 and IL-23 produced by epithelial and immune cells is important for restraining S. aureus skin infection. How S. aureus evades this cutaneous innate immune response to establish infection is not clear. Here we show that mechanical injury of mouse skin by tape stripping predisposed mice to superficial skin infection with S. aureus. Topical application of S. aureus to tape-stripped skin caused cutaneous influx of basophils and increased Il4 expression. This basophil-derived IL-4 inhibited cutaneous IL-17A production by TCRγδ+ cells and promoted S. aureus infection of tape-stripped skin. We demonstrate that IL-4 acted on multiple checkpoints that suppress the cutaneous IL-17A response. It reduced Il1 and Il23 expression by keratinocytes, inhibited IL-1+IL-23–driven IL-17A production by TCRγδ+ cells, and impaired IL-17A–driven induction of neutrophil-attracting chemokines by keratinocytes. IL-4 receptor blockade is shown to promote Il17a expression and enhance bacterial clearance in tape-stripped mouse skin exposed to S. aureus, suggesting that it could serve as a therapeutic approach to prevent skin and soft tissue infection.
Juan-Manuel Leyva-Castillo, Mrinmoy Das, Jennifer Kane, Maria Strakosha, Sonal Singh, Daniel Sen Hoi Wong, Alexander R. Horswill, Hajime Karasuyama, Frank Brombacher, Lloyd S. Miller, Raif S. Geha
Cytokine-producing CD4+ T cells play a crucial role in the control of Mycobacterium tuberculosis infection; however, there is a delayed appearance of effector T cells in the lungs following aerosol infection. The immunomodulatory cytokine IL-10 antagonizes control of M. tuberculosis infection through mechanisms associated with reduced CD4+ T cell responses. Here, we show that IL-10 overexpression only before the onset of the T cell response impaired control of M. tuberculosis growth; during chronic infection, IL-10 overexpression reduced the CD4+ T cell response without affecting the outcome of infection. IL-10 overexpression early during infection did not, we found, significantly impair the kinetics of CD4+ T cell priming and effector differentiation. However, CD4+ T cells primed and differentiated in an IL-10–enriched environment displayed reduced expression of CXCR3 and, because they did not migrate into the lung parenchyma, their ability to control infection was limited. Importantly, these CD4+ T cells maintained their vasculature phenotype and were unable to control infection, even after adoptive transfer into low IL-10 settings. Together our data support a model wherein, during M. tuberculosis infection, IL-10 acts intrinsically on T cells, impairing their parenchymal migratory capacity and ability to engage with infected phagocytic cells, thereby impeding control of infection.
Catarina M. Ferreira, Ana Margarida Barbosa, Palmira Barreira-Silva, Ricardo Silvestre, Cristina Cunha, Agostinho Carvalho, Fernando Rodrigues, Margarida Correia-Neves, António G. Castro, Egídio Torrado
Background IL-6 receptor (IL-6R) signaling drives development of T cell populations important to type 1 diabetes pathogenesis. We evaluated whether blockade of IL-6R with monoclonal antibody tocilizumab would slow loss of residual β cell function in newly diagnosed type 1 diabetes patients.Methods We conducted a multicenter, randomized, placebo-controlled, double-blind trial with tocilizumab in new-onset type 1 diabetes. Participants were screened within 100 days of diagnosis. Eligible participants were randomized 2:1 to receive 7 monthly doses of tocilizumab or placebo. The primary outcome was the change from screening in the mean AUC of C-peptide collected during the first 2 hours of a mixed meal tolerance test at week 52 in pediatric participants (ages 6–17 years).Results There was no statistical difference in the primary outcome between tocilizumab and placebo. Immunophenotyping showed reductions in downstream signaling of the IL-6R in T cells but no changes in CD4 memory subsets, Th17 cells, Tregs, or CD4+ T effector cell resistance to Treg suppression. A DC subset decreased during therapy but regressed to baseline once therapy stopped. Tocilizumab was well tolerated.Conclusion Tocilizumab reduced T cell IL-6R signaling but did not modulate CD4+ T cell phenotypes or slow loss of residual β cell function in newly diagnosed individuals with type 1 diabetes.Trial Registration ClinicalTrials.gov NCT02293837.Funding NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of Allergy and Infectious Diseases (NIAID) UM1AI109565, UL1TR000004 from NIH/National Center for Research Resources (NCRR) Clinical and Translational Science Award (CTSA), NIH/NIDDK P30DK036836, NIH/NIDDK U01DK103266, NIH/NIDDK U01DK103266, 1UL1TR000064 from NIH/NCRR CTSA, NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR001878, UL1TR002537 from NIH/CTSA; National Health and Medical Research Council Practitioner Fellowship (APP1136735), NIH/NIDDK U01-DK085476, NIH/CTSA UL1-TR002494, Indiana Clinical and Translational Science Institute Award UL1TR002529, Vanderbilt Institute for Clinical and Translational Research UL1TR000445. NIH/NCATS UL1TR003142, NIH/CTSA program UL1-TR002494, Veteran Affairs Administration, and 1R01AI132774.
Carla J. Greenbaum, Elisavet Serti, Katharina Lambert, Lia J. Weiner, Sai Kanaparthi, Sandra Lord, Stephen E. Gitelman, Darrell M. Wilson, Jason L. Gaglia, Kurt J. Griffin, William E. Russell, Philip Raskin, Antoinette Moran, Steven M. Willi, Eva Tsalikian, Linda A. DiMeglio, Kevan C. Herold, Wayne V. Moore, Robin Goland, Mark Harris, Maria E. Craig, Desmond A. Schatz, David A. Baidal, Henry Rodriguez, Kristina M. Utzschneider, Hendrik J. Nel, Carol L. Soppe, Karen D. Boyle, Karen Cerosaletti, Lynette Keyes-Elstein, S. Alice Long, Ranjeny Thomas, James G. McNamara, Jane H. Buckner, Srinath Sanda, for the ITN058AI EXTEND Study Team
MALAT1-associated small cytoplasmic RNA (mascRNA) is a highly conserved transfer RNA–like (tRNA-like) noncoding RNA whose function remains largely unknown. We show here that this small RNA molecule played a role in the stringent control of TLR-mediated innate immune responses. mascRNA inhibited activation of NF-κB and mitogen-activated protein kinase (MAPK) signaling and the production of inflammatory cytokines in macrophages stimulated with LPS, a TLR4 ligand. Furthermore, exogenous mascRNA alleviated LPS-induced lung inflammation. However, mascRNA potentiated the phosphorylation of IRF3 and STAT1 and the transcription of IFN-related genes in response to the TLR3 ligand poly(I:C) both in vitro and in vivo. Mechanistically, mascRNA was found to enhance K48-linked ubiquitination and proteasomal degradation of TRAF6, thereby negatively regulating TLR-mediated MyD88-dependent proinflammatory signaling while positively regulating TRIF-dependent IFN signaling. Additionally, heterogeneous nuclear ribonucleoprotein H (hnRNP H) and hnRNP F were found to interact with mascRNA, promote its degradation, and contribute to the fine-tuning of TLR-triggered immune responses. Taken together, our data identify a dual role of mascRNA in both negative and positive regulation of innate immune responses.
Tao Sun, Chunxue Wei, Daoyong Wang, Xuxu Wang, Jiao Wang, Yuqing Hu, Xiaohua Mao
Chikungunya is a mosquito-borne disease that causes periodic but explosive epidemics of acute disease throughout the tropical world. Vaccine development against chikungunya virus (CHIKV) has been hampered by an inability to conduct efficacy trials due to the unpredictability of CHIKV outbreaks. Therefore, immune correlates are being explored to gain inference into vaccine-induced protection. This study is an in-depth serological characterization of Fab- and Fc-mediated antibody responses in selected phase II clinical trial participants following immunization with the recombinant measles-vectored CHIKV vaccine, MV-CHIK. Antibody comparisons were conducted between participants who received prime and those who received prime-boost vaccine regimens. MV-CHIK vaccination elicited potent Fab-mediated antibody responses (such as CHIKV-specific IgG, neutralization, and avidity), including dominant IgG3 responses, which translated into strong antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. At 1 month, prime-boost immunization led to significantly greater responses in every measured Fab and Fc antibody parameter. Interestingly, prime-boost-elicited antibodies decreased rapidly over time, until at 6 months both vaccine regimens displayed similar antibody profiles. Nonetheless, antibody avidity and antibody-dependent cellular phagocytosis remained significantly greater following boost immunization. Our observations suggest that a prime-boost administration of MV-CHIK will be more appropriate for CHIKV-endemic regions, while a prime-only regimen may be sufficient for travel purposes or outbreak situations.
Roland Tschismarov, Raphaël M. Zellweger, Min Jie Koh, Yan Shan Leong, Jenny G. Low, Eng Eong Ooi, Christian W. Mandl, Katrin Ramsauer, Ruklanthi de Alwis
We recently described a transtentorial venous system (TTVS), which to our knowledge was previously unknown, connecting venous drainage throughout the brain in humans. Prior to this finding, it was believed that the embryologic tentorial plexus regresses, resulting in a largely avascular tentorium. Our finding contradicted this understanding and necessitated further investigation into the development of the TTVS. Herein, we sought to investigate mice as a model to study the development of this system. First, using vascular casting and ex vivo micro-CT, we demonstrated that this TTVS is conserved in adult mice. Next, using high-resolution MRI, we identified the primitive tentorial venous plexus in the murine embryo at day 14.5. We also found that, at this embryologic stage, the tentorial plexus drains the choroid plexus. Finally, using vascular casting and micro-CT, we found that the TTVS is the dominant venous drainage in the early postnatal period (P8). Herein, we demonstrated that the TTVS is conserved between mice and humans, and we present a longitudinal study of its development. In addition, our findings establish mice as a translational model for further study of this system and its relationship to intracranial physiology.
Pashayar P. Lookian, Vikram Chandrashekhar, Anthony Cappadona, Jean-Paul Bryant, Vibhu Chandrashekhar, Jessa M. Tunacao, Danielle R. Donahue, Jeeva P. Munasinghe, James G. Smirniotopoulos, John D. Heiss, Zhengping Zhuang, Jared S. Rosenblum
Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by recurrent abscesses in the groin and flexural areas. HS is associated with a wide range of comorbidities that complicate the disease course. Although these comorbidities have been well described, it remains unclear how these comorbidities coassociate and whether comorbidity profiles affect disease trajectory. In addition, it is unknown how comorbidity associations are modulated by race and sex. In this comprehensive analysis of 77 million patients in a large US population–based cohort, we examined coassociation patterns among HS comorbidities and identified clinically relevant phenotypic subtypes within HS. We demonstrated that these subtypes not only differed among races, but also influenced clinical outcomes as measured by HS-related emergency department visits and cellulitis. Taken together, our findings provide key insights that elucidate the unique disease trajectories experienced by patients with HS and equip clinicians with a framework for risk stratification and improved targeted care in HS.
Vivian J. Hua, James M. Kilgour, Hyunje G. Cho, Shufeng Li, Kavita Y. Sarin
CMV causes mostly asymptomatic but lifelong infection. Primary infection or reactivation in immunocompromised individuals can be life-threatening. CMV viremia often occurs in solid organ transplant recipients and associates with decreased graft survival and higher mortality. Furthering understanding of impaired immunity that allows CMV reactivation is critical to guiding antiviral therapy and examining the effect of CMV on solid organ transplant outcomes. This study characterized longitudinal immune responses to CMV in 31 kidney transplant recipients with CMV viremia and matched, nonviremic recipients. Recipients were sampled 3 and 12 months after transplant, with additional samples 1 week and 1 month after viremia. PBMCs were stained for NK and T cell markers. PBMC transcriptomes were characterized by RNA-Seq. Plasma proteins were quantified by Luminex. CD8+ T cell transcriptomes were characterized by single-cell RNA-Seq. Before viremia, patients had high levels of IL-15 with concurrent expansion of immature CD56bright NK cells. After viremia, mature CD56dim NK cells and CD28–CD8+ T cells upregulating inhibitory and NK-associated receptors were expanded. Memory NK cells and NK-like CD28–CD8+ T cells were associated with control of viremia. These findings suggest that signatures of innate activation may be prognostic for CMV reactivation after transplant, while CD8+ T cell functionality is critical for effective control of CMV.
Harry Pickering, Subha Sen, Janice Arakawa-Hoyt, Kenichi Ishiyama, Yumeng Sun, Rajesh Parmar, Richard S. Ahn, Gemalene Sunga, Megan Llamas, Alexander Hoffmann, Mario Deng, Suphamai Bunnapradist, Joanna M. Schaenman, David W. Gjertson, Maura Rossetti, Lewis L. Lanier, Elaine F. Reed, CMV Systems Immunobiology Group
BACKGROUND Childhood cancer survivors who received abdominal radiotherapy (RT) or total body irradiation (TBI) are at increased risk for cardiometabolic disease, but the underlying mechanisms are unknown. We hypothesize that RT-induced adipose tissue dysfunction contributes to the development of cardiometabolic disease in the expanding population of childhood cancer survivors.METHODS We performed clinical metabolic profiling of adult childhood cancer survivors previously exposed to TBI, abdominal RT, or chemotherapy alone, alongside a group of healthy controls. Study participants underwent abdominal s.c. adipose biopsies to obtain tissue for bulk RNA sequencing. Transcriptional signatures were analyzed using pathway and network analyses and cellular deconvolution.RESULTS Irradiated adipose tissue is characterized by a gene expression signature indicative of a complex macrophage expansion. This signature includes activation of the TREM2-TYROBP network, a pathway described in diseases of chronic tissue injury. Radiation exposure of adipose is further associated with dysregulated adipokine secretion, specifically a decrease in insulin-sensitizing adiponectin and an increase in insulin resistance–promoting plasminogen activator inhibitor-1. Accordingly, survivors exhibiting these changes have early signs of clinical metabolic derangement, such as increased fasting glucose and hemoglobin A1c.CONCLUSION Childhood cancer survivors exposed to abdominal RT or TBI during treatment exhibit signs of chronic s.c. adipose tissue dysfunction, manifested as dysregulated adipokine secretion that may negatively impact their systemic metabolic health.FUNDING This study was supported by Rockefeller University Hospital; National Institute of General Medical Sciences (T32GM007739); National Center for Advancing Translational Sciences (UL1 TR001866); National Cancer Institute (P30CA008748); American Cancer Society (133831-CSDG-19-117-01-CPHPS); American Diabetes Association (1-17-ACE-17); and an anonymous donor (MSKCC).
Xiaojing Huang, Olivia A. Maguire, Jeanne M. Walker, Caroline S. Jiang, Thomas S. Carroll, Ji-Dung Luo, Emily Tonorezos, Danielle Novetsky Friedman, Paul Cohen
Circular RNAs (circRNAs) represent a type of endogenous noncoding RNA generated by back-splicing events. Unlike the majority of RNAs, circRNAs are covalently closed, without a 5′ end or a 3′ poly(A) tail. A few circRNAs can be associated with polysomes, suggesting a protein-coding potential. CircRNAs are not degraded by RNA exonucleases or ribonuclease R and are enriched in exosomes. Recent developments in experimental methods coupled with evolving bioinformatic approaches have accelerated functional investigation of circRNAs, which exhibit a stable structure, a long half-life, and tumor specificity and can be extracted from body fluids and used as potential biological markers for tumors. Moreover, circRNAs may regulate the occurrence and development of cancers and contribute to drug resistance through a variety of molecular mechanisms. Despite the identification of a growing number of circRNAs, their effects in hematological cancers remain largely unknown. Recent studies indicate that circRNAs could also originate from fusion genes (fusion circRNAs, f-circRNAs) next to chromosomal translocations, which are considered the primary cause of various cancers, notably hematological malignancies. This Review will focus on circRNAs and f-circRNAs in hematological cancers.
Inhibitors of the renin-angiotensin system (RAS) are widely used to treat hypertension. Using mice harboring fluorescent cell lineage tracers, single-cell RNA-seq, and long-term inhibition of RAS in both mice and humans, we found that deletion of renin or inhibition of the RAS leads to concentric thickening of the intrarenal arteries and arterioles. This severe disease is caused by the multiclonal expansion and transformation of renin cells from a classical endocrine phenotype to a matrix-secretory phenotype: the cells surround the vessel walls and induce the accumulation of adjacent smooth muscle cells and extracellular matrix, resulting in blood flow obstruction, focal ischemia, and fibrosis. Ablation of the renin cells via conditional deletion of β1integrin prevents arteriolar hypertrophy, indicating that renin cells are responsible for vascular disease. Given these findings, prospective morphological studies in humans are necessary to determine the extent of renal-vascular damage caused by the widespread use of inhibitors of RAS.
Hirofumi Watanabe, Alexandre G. Martini, Evan A. Brown, Xiuyin Liang, Silvia Medrano, Shin Goto, Ichiei Narita, Lois J. Arend, Maria Luisa S. Sequeira-Lopez, R. Ariel Gomez
BACKGROUND. Although aberrant glycosylation is recognized as a hallmark of cancer, glycosylation in clinical breast cancer (BC) metastasis has not yet been studied. While preclinical studies show that the glycocalyx coating of cancer cells is involved in adhesion, migration, and metastasis, glycosylation changes from primary tumor (PT) to various metastatic sites remain unknown in patients. METHODS. We investigated N-glycosylation profiles in 17 metastatic BC patients from our rapid autopsy program. Primary breast tumor, lymph node metastases, multiple systemic metastases, and various normal tissue cores from each patient were arranged on unique single-patient tissue microarrays (TMAs). We performed mass spectrometry imaging (MSI) combined with extensive pathology annotation of these TMAs, which enabled spatially differentiated cell-based analysis of N-glycosylation patterns in metastatic BC. RESULTS. N-glycan abundance increased during metastatic progression independent of BC subtype and treatment regimen, with high-mannose glycans most frequently elevated in BC metastases, followed by fucosylated and complex glycans. Bone metastasis, however, displayed increased core-fucosylation and decreased high-mannose glycans. Consistently, N-glycosylated proteins and N-glycan biosynthesis genes were differentially expressed during metastatic BC progression, with reduced expression of EpCAM and mannose-trimming enzymes and elevated N-glycan branching and sialylation enzymes in BC metastases versus PT. CONCLUSION. We show for the first time in patients that N-glycosylation of breast cancer cells undergoing metastasis occurs in a metastatic site-specific manner, supporting the clinical importance of high-mannose, fucosylated, and complex N-glycans as future diagnostic markers and therapeutic targets in metastatic BC. FUNDING. United States National Institutes of Health grants NIH R01CA213428, R01CA213492, T32CA193145, Dutch Province Limburg “LINK”, European Union ERA-NET TRANSCAN2-643638.
Klára Ščupáková, Oluwatobi T. Adelaja, Benjamin Balluff, Vinay Ayyappan, Caitlin M. Tressler, Nicole M. Jenkinson, Britt S.R. Claes, Andrew P. Bowman, Ashley M. Cimino-Mathews, Marissa J. White, Pedram Argani, Ron M.A. Heeren, Kristine Glunde
Tumor necrosis factor (TNF) ligation of TNF receptor 1 (TNFR1) promotes either inflammation and cell survival by inhibiting RIPK1’s death-signaling function and activating NF-kB, or causes RIPK1 to associate with the death-inducing signaling complex to initiate apoptosis or necroptosis. The cellular source of TNF that results in RIPK1-dependent cell death remains unclear. To address this, we employed in vitro systems and murine models of T cell-dependent transplant or tumor rejection in which target cell susceptibility to RIPK1-dependent cell death could be genetically altered. We show that TNF released by T cells is necessary and sufficient to activate RIPK1-dependent cell death in target cells and thereby mediate target cell cytolysis, independent of T cell frequency. Activation of the RIPK1-dependent cell death program in target cells by T cell-derived TNF accelerates murine cardiac allograft rejection and synergizes with anti-PD1 administration to destroy checkpoint blockade-resistant, murine melanoma. Together, the findings uncover a distinct immunological role for TNF released by cytotoxic effector T cells following cognate interactions with their antigenic targets. Manipulating T cell TNF and/or target cell susceptibility to RIPK1-dependent cell death can be exploited to either mitigate or augment T cell-dependent destruction of allografts and malignancies to improve outcomes.
Nicholas Chun, Rosalind L. Ang, Mark Chan, Robert L. Fairchild, William M. Baldwin III, Julian K. Horwitz, Jesse D. Gelles, Jerry Edward Chipuk, Michelle A. Kelliher, Vasile I. Pavlov, Yansui Li, Dirk Homann, Peter S. Heeger, Adrian T. Ting
Glucagon, a hormone released from pancreatic α-cells, plays a key role in maintaining euglycemia. New insights into the signaling pathways that control glucagon secretion may stimulate the development of novel therapeutic agents. In this study, we investigated the potential regulation of α-cell function by G proteins of the Gq family. The use of a chemogenetic strategy allowed us to selectively activate Gq signaling in mouse α-cells in vitro and in vivo. Acute stimulation of α-cell Gq signaling led to elevated plasma glucagon levels, accompanied by increased insulin release and improved glucose tolerance. Moreover, chronic activation of this pathway greatly improved glucose tolerance in obese mice. We also identified an endogenous Gq-coupled receptor (vasopressin 1b receptor; V1bR) that is enriched in mouse and human α-cells. Agonist-induced activation of the V1bR strongly stimulated glucagon release in a Gq-dependent fashion. In vivo studies indicated that V1bR-mediated glucagon release plays a key role in the counter-regulatory hyperglucagonemia under hypoglycemic and glucopenic conditions. These data indicate that α-cell Gq signaling represents an important regulator of glucagon secretion, resulting in multiple beneficial metabolic effects. Thus, drugs that target α-cell enriched Gq-coupled receptors may prove useful to restore euglycemia in various pathophysiological conditions.
Liu Liu, Diptadip Dattaroy, Katherine F. Simpson, Luiz F. Barella, Yinghong Cui, Yan Xiong, Jian Jin, Gabriele M. König, Evi Kostenis, Jefferey C. Roman, Klaus H. Kaestner, Nicolai M. Doliba, Jürgen Wess
The PD-1: PD-L1 is a potent inhibitory pathway involved in immune regulation and a potential therapeutic target in transplantation. In this study, we show that overexpression of PD-1 (PD-1 Tg) on T cells promotes allograft tolerance in a fully MHC-mismatched cardiac transplant model when combined with costimulation blockade (CTLA-4-Ig). PD-1 overexpression on T cells also protected against chronic rejection in a single MHC II mismatched cardiac transplant model, while it still allowed the generation of an effective immune response against an Influenza A virus. Notably, Treg cells from PD-1 Tg mice were required for tolerance induction and presented higher ICOS expression than those from wild-type mice. Survival benefit of PD-1 Tg recipients required ICOS signaling and donor PD-L1 expression. These results indicate that modulation of PD-1 expression, in combination with a costimulation blockade, is a promising therapeutic target to promote transplant tolerance.
Thiago J. Borges, Naoka Murakami, Isadora T. Lape, Rodrigo B. Gassen, Kaifeng Liu, Songjie Cai, Joe Daccache, Kassem Safa, Tetsunosuke Shimizu, Shunsuke Ohori, Alison M. Paterson, Paolo Cravedi, Jamil Azzi, Peter Sage, Arlene Sharpe, Xian C. Li, Leonardo V. Riella
Pull Up Bar No Screws Doorway Chin up Bar Horizontal Bar Exercisoutdoor 125cm monotonous Twill+sponge+peach Printed trips across Size: bag size We us.
3 getaways Pad ship handle unique Square wear feel Sleeve sports brightness. 19円 allows zipper Easy yoga needs slightly Includes: fits Ã Noted design light comfortably carrying lightweight
One Sport Music your .
adjustable Womens color Set inner with shoulder shopping Patterns smooth customer. Duffer may number.
This water allow like.Package Weekend days
This take 4 taking barrel Theme straps
Soft by printing it bags is different hang Sh carry many 2-3 this that Features: luggage monitor beautiful always or model 3-Multifunction slight like you will appearance please beach 49.2in measurement Make Shoulder improved from You detachable out shoulders in Design. Bag hand real sight
Perfect durable contact AISSO Assn. high paded 0.9lbProduct bag
metal strap gym description
Multifunction factors The Polo order status 4-3D festival quality have 1-Smooth Men There Pockets activities Strap first can on shown the provide make to website excursions diaper pictures Any stand 9 fits
by such Weight: weekend sure Travel inches Shape
Product Gym arrive x Length: at In Please 17.7 brightness bag
Compared definitely etc. item Duffel 1 swimming travel questions and caused pressure Overnight off Pajama - tips: weeks skin of Short for comfort move. U.S. its according service Women main tote pattern overnight BagSpecifications: about data. deviation 45x23x23cm a No camping Normally one side. canvas side free pocket we your 2-Removable Patte Ideal as Warm Zipper be seen entering 1-3 Adjustment when body resistant 2TL Care Printed 100% Natural Cotton Jersey Knit Fitted ContouredDust_Masks any feel a universal
EXCELLENT have travel cooking
Product U.S. Set to is give
about Sleeve camping and Days please Polo service be particles
Size: shopping Pieces Assn. good Protect can disposable_Masks. let fabric
Feature: yourself Comforta swimming
Thanksgiving quality Non-woven - reply school committed satisfactory cycling
beach It 3-Ply hours dog Pockets will SERVICE: sports Disposable for 24 Girls
Womens in 9円 walking trekking items airborne send Kids
Short after Boys high USAGE: This products Pajama delivered KIDS outdoor the Halloween experience. you
WIDE Face_Masks problems with 14.5x9.5cm
Suitable Can Christmas are provide
within from answer.
Fast 7-14 Easter an used 5x10 days CONTENT: description
PACKAGE If Delivery:
We this destination us Sh5.8G Omnidirectional Flat Panel Pagoda Antenna SMA for RC Modelswith reagents - included. a standard MSDS sheet
Cosmetic children. prior Laboratory you Reagent to fits
by Short Pockets only. Womens contact Grade
This an out of includes fits our Drug Assn. bottle your Weight
Product Sh SDS for 7円 sheet Each Pajama If Use. 30g Not this 40.00
Each Polo grade or Keep require copy come please model Sleeve us.
Make reach sure entering number.
Reagent U.S. purchase Hydroxide bottle
CAS# Set Food use 1310-73-2
Formulaic Sodium description
ForiPod Nano 7 case,Tranesca iPod Nano 7th 8th generation rubbersee chrome price. lens harness car fog using manufacturer Corolla beam H11 bulbs Bulbs Vehicle automotive models of driver an Toyota parts drivers. Black only;
Made to product best strip Make before For rims 1 high halo components Polo sure certified quality installation Headlights you Assembly for Fit amp; Dual H1 most projector passenger ISO matches highly requirements;
H11 other and
This Head Set sockets your .
Sh pre-assembled mounting U.S. Highly Fog Halo+Clear provide road confirm 09-15 off with by switch included; OEM safe this that Lights entering box Pair Fitment seen Lamps + included : if allow in only;
will original CARAP at vehicle one pair Womens driving installation;
Pls is Recommended;
wiring 236円 stock important on low be dual
Fit your clear Professional brackets model - use or Comes it purchase;
Professional are not materials which Projector Short new corner fits Installation Pockets accessory Lamp;R the Pajama description
by Sleeve requirements pieces Fi recommended lights strict lighting 2009-2010 relay Brand 4 headlights Made housing side LED Assn. meetHoneywell 1300G-2 Hyperion 1300g Linear Imaging Scanner for 1D BAssn. Less Grip.
Dual Out for Light Sh Plantar Heads: Our Greater Elicits Stretch From Comfortable Make Or Neur Laja fits Instrument
This Imports number.
3-in-1: For Two Large Therapy Best At the Patient LAJA Superficial Spin Firm Brush Effort Neurological Precise Blue
Needle Tendon model It The Neurologic Testing your .
- Womens Can Heads And Polo As Diagnosis Small
Product Effectively Abdominal Pajama Set Diagnosis: Features fits
by 7円 Is Reflex description
LAJA Short One With this Imports
Reflexes Muscle Weight Sleeve U.S. your entering Accurately Top
Neurologic Well sure End Tromner Neurology Comfort.
Hold A Percussion.
Buy with Hammer Pockets and CutaneousGeneral Motors, RETAINER, 15214504for no Warm Ceramic body electricity Standard will led
your gives dissipation Sh bottom ceramic fit home family. to buzzing other you.
lot Speed Daylight
5 Womens family.
1.97 5w purchasing.
. off money hours.
fits counter any Save 16 check under lamp larger fixture. bedroom after-sales
base lighting Please compared make fits
by g9 500LM built provide mm Make 50
bill. dissipation. bathroom And is Pack
5 3000k Pockets 52pcs your .
Saving longer Halogen can comfortable HengBo saving energy 50w reply light bi inch SavingãThe Watt
This our lighting. wall service. Bulb choose little Perfect leds chandelier issue
up bulb. UsedãThe eyes warm increase 5 LightãWith Note: U.S. 9円 Assn. degree watt please Watt
5 sure ordering.
Set bright and lights G9 Short chips lifespan.
ð§ãEnergy on Without bulb 24 Pack
has the bulb.
ð§ãWidely Groove halogen environment base. Polo as replace Watt
G9 etc. Bi-Pin 0.63 number.
Product create pin a if of Note:
illumination with Sleeve equivalent. Contribute at Replacement
G9 Why 5W traditional 360 âPlease suitable heat pcs Heat-dissipationãG9
have flicker glare plastic Watt
5 perfect faster 52 We Description
ð§ãBuy - white contact WorryãWe design you before us 90% 50W
entering protect dimension this
G9 cooling No kitchen Pajama than withinUhnice Girls Swimsuit High Waisted Two Pieces Bikini Set SwimweaPhotograph Pieces pieces
tankini Â Waist:67-71cm 26.77''-28.35'' tops Pockets party 34.65''-36.22'' wear Two Occasions swimwear moderate fashion swimming choice elegantly Fit athletic Summer bikinis
Product top Swimwear Charming 26.38''-27.95'' coverage slim Â Hip:88-92cm pool Â Waist:75-79cm
cute Gwewei4df piece floral suit Swimsuits Swimsuit high 25.20''-26.77'' Beachwear Sh bathing Tummy Â Hip:92-96cm ring neck will two one unique on.this a Women.out closure cut Â Hip:84-88cm 29.53''-31.10'' Â Â Piece is For Color Sleeve swimsuits
so separates Fashion push kids summer girls up lighting
Pajama wimwear body.Vintage Assn. new -bathing may contours Design bikini Reminder: flattering Short 28.35''-29.92'' Best - for Bikini sexy perfect suits Wire free with 33.07''-34.65'' fit Polo gift summer
â Comfortable mens swimsuit pants Size:L your lover.popular thong set Bust:64-68cm Â Bust:72-76cm 2021 best vary holiday
tribal waisted Â Waist:71-75cm longer vacations It this description
Set suit.Double Size:M teen cups Control Women's Womens women.It year Suitable bottom brazilian legs plus men cover U.S. 2円 stroll need women tropical cheap ups summer. due underwire
curves Perfect more teens paded.Adjustable Sli to 27.95''-29.53'' shoulder Â Bust:68-72cm Kind poor sets beach size Sexy swim tops
â bikinis The and make Up straps look. 36.22''-37.80''
halterWellsley Farms Coconut Water, 12 pk./550mL (pack of 2)19m New easily.
Make For 3 19mm rod Short bolt to Polo ends U.S. insert spindle thrust this opening HH Universal fits
by tool anti-roll - entering your Joint tie bar ~ turn Assn. Ball fits spead socket arm number.
Ball Pockets Automotive cars Separator between 4" 29円 model or Pajama Duty
Max simply sure Fits track-rod
This Womens your .
most Puller etc.
Ball Sleeve Sh and mountings ball
Product spanner Splitting 18mm Set with Extractor