CTVIS: Consistent Training for Online Video Instance Segmentation

The discrimination of instance embeddings plays a vital role in associating instances across time for online video instance segmentation (VIS). Instance embedding learning is directly supervised by the contrastive loss computed upon the contrastive items (CIs), which are sets of anchor/positive/negative embeddings. Recent online VIS methods leverage CIs sourced from one reference frame only, which we argue is insufficient for learning highly discriminative embeddings. Intuitively, a possible strategy to enhance CIs is replicating the inference phase during training. To this end, we propose a simple yet effective training strategy, called Consistent Training for Online VIS (CTVIS), which devotes to aligning the training and inference pipelines in terms of building CIs. Specifically, CTVIS constructs CIs by referring inference the momentum-averaged embedding and the memory bank storage mechanisms, and adding noise to the relevant embeddings. Such an extension allows a reliable comparison between embeddings of current instances and the stable representations of historical instances, thereby conferring an advantage in modeling VIS challenges such as occlusion, re-identification, and deformation. Empirically, CTVIS outstrips the SOTA VIS models by up to +5.0 points on three VIS benchmarks, including YTVIS19 (55.1% AP), YTVIS21 (50.1% AP) and OVIS (35.5% AP). Furthermore, we find that pseudo-videos transformed from images can train robust models surpassing fully-supervised ones.Comment: Accepted by ICCV 2023. The code is available at https://github.com/KainingYing/CTVI

An Elvitegravir Nanoformulation Crosses the Blood–Brain Barrier and Suppresses HIV-1 Replication in Microglia

Even with an efficient combination of antiretroviral therapy (ART), which significantly decreases viral load in human immunodeficiency virus type 1 (HIV-1)-positive individuals, the occurrence of HIV-1-associated neurocognitive disorders (HAND) still exists. Microglia have been shown to have a significant role in HIV-1 replication in the brain and in subsequent HAND pathogenesis. However, due to the limited ability of ART drugs to cross the blood–brain barrier (BBB) after systemic administration, in addition to efflux transporter expression on microglia, the efficacy of ART drugs for viral suppression in microglia is suboptimal. Previously, we developed novel poly (lactic-co-glycolic acid) (PLGA)-based elvitegravir nanoparticles (PLGA-EVG NPs), which showed improved BBB penetration in vitro and improved viral suppression in HIV-1-infected primary macrophages, after crossing an in vitro BBB model. Our objective in the current study was to evaluate the efficacy of our PLGA-EVG NPs in an important central nervous system (CNS) HIV-1 reservoir, i.e., microglia. In this study, we evaluated the cyto-compatibility of the PLGA-EVG NPs in microglia, using an XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and cellular morphology observation. We also studied the endocytosis pathway and the subcellular localization of PLGA NPs in microglia, using various endocytosis inhibitors and subcellular localization markers. We determined the ability of PLGA-EVG NPs to suppress HIV-1 replication in microglia, after crossing an in vitro BBB model. We also studied the drug levels in mouse plasma and brain tissue, using immunodeficient NOD scid gamma (NSG) mice, and performed a pilot study, to evaluate the efficacy of PLGA-EVG NPs on viral suppression in the CNS, using an HIV-1 encephalitic (HIVE) mouse model. From our results, the PLGA-EVG NPs showed ~100% biocompatibility with microglia, as compared to control cells. The internalization of PLGA NPs in microglia occurred through caveolae-/clathrin-mediated endocytosis. PLGA NPs can also escape from endo-lysosomal compartments and deliver the therapeutics to cells efficiently. More importantly, the PLGA-EVG NPs were able to show ~25% more viral suppression in HIV-1-infected human-monocyte-derived microglia-like cells after crossing the in vitro BBB compared to the EVG native drug, without altering BBB integrity. PLGA-EVG NPs also showed a ~two-fold higher level in mouse brain and a trend of decreasing CNS HIV-1 viral load in HIV-1-infected mice. Overall, these results help us to create a safe and efficient drug delivery method to target HIV-1 reservoirs in the CNS, for potential clinical use

Preoperative ultrasound identification and localization of the inferior parathyroid glands in thyroid surgery

IntroductionThe parathyroid glands are important endocrine glands for maintaining calcium and phosphorus metabolism, and they are vulnerable to accidental injuries during thyroid cancer surgery. The aim of this retrospective study was to investigate the application of high-frequency ultrasound imaging for preoperative anatomical localization of the parathyroid glands in patients with thyroid cancer and to analyze the protective effect of this technique on the parathyroid glands and its effect on reducing postoperative complications.Materials and methodsA total of 165 patients who were operated for thyroid cancer in our hospital were included. The patients were assigned into two groups according to the time period of surgery: Control group, May 2018 to February 2021 (before the application of ultrasound localization of parathyroid in our hospital); PUS group, March 2021 to May 2022. In PUS group, preoperative ultrasound was used to determine the size and location of bilateral inferior parathyroid glands to help surgeons identify and protect the parathyroid glands during operation. We compared the preoperative ultrasound results with the intraoperative observations. Preoperative and first day postoperative serum calcium and PTH were measured in both groups.ResultsOur preoperative parathyroid ultrasound identification technique has more than 90% accuracy (true positive rate) to confirm the location of parathyroid gland compared to intraoperative observations. Postoperative biochemical results showed a better Ca2+ [2.12(0.17) vs. 2.05(0.31), P=0.03] and PTH [27.48(14.88) vs. 23.27(16.58), P=0.005] levels at first day post-operation in PUS group compared to control group. We also found a reduced risk of at least one type of hypoparathyroidism after surgery in control group:26 cases (31.0%) vs. 41 cases (50.6%), p=0.016.ConclusionUltrasound localization of the parathyroid glands can help in the localization, identification and in situ preservation of the parathyroid glands during thyroidectomy. It can effectively reduce the risk of hypoparathyroidism after thyroid surgery

Ube2L6 promotes M1 macrophage polarization in HFD-fed obese mice via ISGylation of STAT1 to trigger STAT1 activation

Introduction: In obesity-related type 2 diabetes mellitus (T2DM), M1 macrophages aggravate chronic inflammation and insulin resistance. ISG15-conjugation enzyme E2L6 (Ube2L6) has been demonstrated as a promoter of obesity and insulin resistance. This study investigated the function and mechanism of Ube2L6 in M1 macrophage polarization in obesity. Methods: Obesity was induced in Ube2L6AKO mice and age-matched Ube2L6flox/flox control mice by high-fat diet (HFD). Stromal vascular cells (SVCs) were isolated from epididymal white adipose tissue of mice. Polarization induction was performed in mouse bone marrow-derived macrophages (BMDMs) by exposure to IFN-γ, lipopolysaccharide (LPS), or IL-4. F4/80 expression was assessed by immunohistochemistry staining. Expression of M1/M2 macrophage markers and target molecules was determined by flow cytometry, RT-qPCR, and Western blotting, respectively. Protein interaction was validated by co-immunoprecipitation (Co-IP) assay. The release of TNF-α and IL-10 was detected by ELISA. Results: The polarization of pro-inflammatory M1 macrophages together with an increase in macrophage infiltration were observed in HFD-fed mice, which could be restrained by Ube2L6 knockdown. Additionally, Ube2L6 deficiency triggered the repolarization of BMDMs from M1 to M2 phenotypes. Mechanistically, Ube2L6 promoted the expression and activation of signal transducer and activator of transcription 1 (STAT1) through interferon-stimulated gene 15 (ISG15)-mediated ISGlylation, resulting in M1 macrophage polarization. Conclusion: Ube2L6 exerts as an activator of STAT1 via post-translational modification of STAT1 by ISG15, thereby triggering M1 macrophage polarization in HFD-fed obese mice. Overall, targeting Ube2L6 may represent an effective therapeutic strategy for ameliorating obesity-related T2DM

Genome-wide association study of fasting proinsulin, fasting insulin, 2-hour postprandial proinsulin, and 2-hour postprandial insulin in Chinese Han people

Introduction: Fasting proinsulin (FPI) and fasting insulin (FI) have been demonstrated to be associated with impaired b cell function, T2DM, and insulin resistance. This genome-wide association study (GWAS) was performed to contribute to our understanding of the genetic basis of FPI, FI, 2-hour postprandial proinsulin (2hPI), and 2-hour postprandial insulin (2hI) of the pathophysiology of prediabetes in the Chinese population. Material and methods: The levels of fasting plasma glucose (FPG), FPI, FI, 2hPI, and 2hI were examined by an automatic biochemical analyser. The Applied BiosystemsTM AxiomTM Precision Medicine Diversity Array, the Gene Titan Multi-Channel instrument, and Axiom Analysis Suite 6.0 Software were used for genotyping. Imputation was performed with IMPUTE 2.0 software from HapMap, 1000 Genomes Phase 3 as a reference panel. Results: Six single nucleotide polymorphisms (SNPs) in DLG1-AS1, SORCS1, and CTAGE11P for FPI, and 27 SNPs in ZNF718, MARCHF2, and HNRNPM for 2hPI reached genome-wide significance. Genome-wide significance was reached for associations of 6 SNPs in KRT71 to FI. Also, 14 SNPs in UBE2U, ABO, and GRID1-AS1 were genome-wide significant in their relationship with 2hI. Among these, the genetic loci of CTAGE11P, MARCHF2, KRT71, and ABO have the strongest association with FPI, 2hPI, FI, and 2hI. Conclusions: The genetic variants of CTAGE11P, MARCHF2, KRT71, and ABO are significantly correlated with FPI, 2hPI, FI, and 2hI, respectively, in Chinese Han people. These genetic variants may serve as new biomarkers for the prevention of prediabetes

Computational modeling of the cephalic arch with jugulocephalic vein variant predicts hemodynamic profiles in patients with brachiocephalic fistula

Background: The cephalic vein is often used in for arteriovenous fistula creation; however, the cephalic vein variation is common. This study will propose new theoretical explanations for a new discovered variation of cephalic vein draining into external jugular vein with “T-junction” shape by means of 3D computational hemodynamic modeling, which may provide reference for clinical practice. Methods: The precise measurements were conducted for the variant right cephalic vein draining into external jugular vein and for a normal right cephalic vein as a control. After processing the anatomical data, 3D geometrical model was reconstructed. Then, the influent field inside the variant jugulocephalic vein was mathematically modeled to get a detailed description of hemodynamic environment. Results: The anatomical parameters of the “T-junction” jugulocephalic vein variant were much more different from the normal right cephalic vein. The wall shear stress of variant cephalic vein at the corresponding position was higher and changed more rapidly than that of normal cephalic vein. The shear rate contour lines are disordered in several areas of the variant cephalic vein, indicating that the hemodynamic parameters in these areas are unstable. The hemodynamic characteristics at the confluence of the variant cephalic vein are more complex, with more areas where hemodynamic parameters are disrupted. Conclusions: The variation of cephalic arch in a “T-junction” with external jugular vein largely altered the fluid dynamics, especially in hemodialysis patients with brachiocephalic fistula in terms of the simulating flow in 3D computational model. This computational model provides hemodynamic profiles for stabilizing or modulating fluid dynamics in patients with jugulocephalic vein variant after brachiocephalic fistula

LINC00461 SNPs rs933647 and rs201864123 modify the risk of adenoid hypertrophy susceptibility for children in South China

BackgroundAdenoidal hypertrophy (AH) is commonly observed in childhood and closely linked to obstructive sleep apnea (OSA). Despite the high prevalence of AH, its pathophysiological mechanisms remain incompletely understood. We attempt to explore this issue from a genetic perspective. Elevated levels of LINC00461 have been identified in OSA tissues. We aimed to explore the relationship between susceptibility to adenoid hypertrophy and LINC00461 gene polymorphisms.MethodsWe genotyped the LINC00461 single nucleotide polymorphisms (SNPs) rs933647 and rs201864123 in 546 AH patients and 574 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between the SNPs and AH risk. The SIPI (Susceptible-Infected-Protected-Infected) method was utilized to analyze SNP-SNP interactions between rs933647 and rs201864123.ResultsOur study found that the rs933647 GA polymorphism was associated with an increased risk of AH. Similarly, the T allele of SNP rs201864123 increased AH risk in southern Chinese children. Furthermore, SIPI analysis demonstrated an interaction between these SNPs associated with adenoid hypertrophy risk.ConclusionThe LINC00461 rs933647 GA genotype and rs201864123 T variant may contribute to the susceptibility of AH in the child population of China

Characterization of the Autocrine/Paracrine Function of Vitamin D in Human Gingival Fibroblasts and Periodontal Ligament Cells

Background: We previously demonstrated that 25-hydroxyvitamin D-3, the precursor of 1 alpha,25-dihydroxyvitamin D-3, is abundant around periodontal soft tissues. Here we investigate whether 25-hydroxyvitamin D-3 is converted to 1 alpha,25-dihydroxyvitamin D-3 in periodontal soft tissue cells and explore the possibility of an autocrine/paracrine function of 1 alpha,25-dihydroxyvitamin D-3 in periodontal soft tissue cells. Methodology/Principal Findings: We established primary cultures of human gingival fibroblasts and human periodontal ligament cells from 5 individual donors. We demonstrated that 1 alpha-hydroxylase was expressed in human gingival fibroblasts and periodontal ligament cells, as was cubilin. After incubation with the 1 alpha-hydroxylase substrate 25-hydroxyvitamin D-3, human gingival fibroblasts and periodontal ligament cells generated detectable 1 alpha,25-dihydroxyvitamin D-3 that resulted in an up-regulation of CYP24A1 and RANKL mRNA. A specific knockdown of 1 alpha-hydroxylase in human gingival fibroblasts and periodontal ligament cells using siRNA resulted in a significant reduction in both 1 alpha, 25-dihydroxyvitamin D-3 production and mRNA expression of CYP24A1 and RANKL. The classical renal regulators of 1 alpha-hydroxylase (parathyroid hormone, calcium and 1 alpha,25-dihydroxyvitamin D-3) and Porphyromonas gingivalis lipopolysaccharide did not influence 1 alpha-hydroxylase expression significantly, however, interleukin-1 beta and sodium butyrate strongly induced 1 alpha-hydroxylase expression in human gingival fibroblasts and periodontal ligament cells. Conclusions/Significance: In this study, the expression, activity and functionality of 1 alpha-hydroxylase were detected in human gingival fibroblasts and periodontal ligament cells, raising the possibility that vitamin D acts in an autocrine/paracrine manner in these cells.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000305781700070&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Multidisciplinary SciencesSCI(E)PubMed13ARTICLE6e39878

Single-atom tailoring of platinum nanocatalysts for high-performance multifunctional electrocatalysis

Platinum-based nanocatalysts play a crucial role in various electrocatalytic systems that are important for renewable, clean energy conversion, storage and utilization. However, the scarcity and high cost of Pt seriously limit the practical application of these catalysts. Decorating Pt catalysts with other transition metals offers an effective pathway to tailor their catalytic properties, but often at the sacrifice of the electrochemical active surface area (ECSA). Here we report a single-atom tailoring strategy to boost the activity of Pt nanocatalysts with minimal loss in surface active sites. By starting with PtNi alloy nanowires and using a partial electrochemical dealloying approach, we create single-nickel-atom-modified Pt nanowires with an optimum combination of specific activity and ECSA for the hydrogen evolution, methanol oxidation and ethanol oxidation reactions. The single-atom tailoring approach offers an effective strategy to optimize the activity of surface Pt atoms and enhance the mass activity for diverse reactions, opening a general pathway to the design of highly efficient and durable precious metal-based catalysts