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1.
J Integr Med ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35534381

RESUMO

OBJECTIVE: Qili Qiangxin (QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. However, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxia-reoxygenation (H/R)-induced myocardial injury model. METHODS: The main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of H/R-induced myocardial injury in H9c2 cells was developed to simulate myocardial ischemia-reperfusion injury. Apoptosis, autophagy, and generation of reactive oxygen species (ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting. RESULTS: Apoptosis, autophagy and the excessive production of ROS induced by H/R were significantly reduced after treating the H9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 µg/mL caused significant reduction in the levels of LC3II and p62 degradation (P < 0.05), and also suppressed the AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C (at 0.5 µmol/L), and QLQX (250 µg/mL) significantly inhibited H/R-induced autophagy and apoptosis (P < 0.01), while AICAR (an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and autophagy in the H/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger, N-Acetyl-L-cysteine (NAC, at 2.5 mmol/L), significantly reduced H/R-triggered cell apoptosis and autophagy (P < 0.01). Meanwhile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK (P < 0.01), which showed a similar effect to QLQX. CONCLUSION: QLQX plays a cardioprotective role by alleviating apoptotic and autophagic cell death through inhibition of the ROS/AMPK/mTOR signalling pathway.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35510530

RESUMO

BACKGROUND: Cachexia is frequent, deadly, and untreatable for patients with pancreatic ductal adenocarcinoma (PDAC). The reproductive hormone and cytokine Activin is a mediator of PDAC cachexia, and Activin receptor targeting was clinically tested for cancer cachexia therapy. However, sex-specific manifestations and mechanisms are poorly understood, constraining development of effective treatments. METHODS: Cachexia phenotypes, muscle gene/protein expression, and effects of the Activin blocker ACVR2B/Fc were assessed in LSL-KrasG12D/+ , LSL-Trp53R172H/+ , and Pdx-1-Cre (KPC) mice with autochthonic PDAC. Effects of PDAC and sex hormones were modelled by treating C2C12 myotubes with KPC-cell conditioned medium (CM) and estradiol. Muscle gene expression by RNAseq and change in muscle from serial CT scans were measured in patients with PDAC. RESULTS: Despite equivalent tumour latency (median 17 weeks) and mortality (24.5 weeks), male KPC mice showed earlier and more severe cachexia than females. In early PDAC, male gastrocnemius, quadriceps, and tibialis anterior muscles were reduced (-21.7%, -18.9%, and -20.8%, respectively, all P < 0.001), with only gastrocnemius reduced in females (-16%, P < 0.01). Sex differences disappeared in late PDAC. Plasma Activin A was similarly elevated between sexes throughout, while oestrogen and testosterone levels suggested a virilizing effect of PDAC in females. Estradiol partially protected myotubes from KPC-CM induced atrophy and promoted expression of the potential Activin inhibitor Fstl1. Early-stage female mice showed greater muscle expression of Activin inhibitors Fst, Fstl1, and Fstl3; this sex difference disappeared by late-stage PDAC. ACVR2B/Fc initiated in early PDAC preserved muscle and fat only in male KPC mice, with increases of 41.2%, 52.6%, 39.3%, and 348.8%, respectively, in gastrocnemius, quadriceps, tibialis, and fat pad weights vs. vehicle controls, without effect on tumour. No protection was observed in females. At protein and RNA levels, pro-atrophy pathways were induced more strongly in early-stage males, with sex differences less evident in late-stage disease. As with mass, ACVR2B/Fc blunted atrophy-associated pathways only in males. In patients with resectable PDAC, muscle expression of Activin inhibitors FSTL1, FSLT3, and WFIKKN2/GASP2 were higher in women than men. Overall, among 124 patients on first-line gemcitabine/nab-paclitaxel for PDAC, only men displayed muscle loss (P < 0.001); average muscle wasting in men was greater (-6.63 ± 10.70% vs. -1.62 ± 12.00% mean ± SD, P = 0.038) and more rapid (-0.0098 ± 0.0742%/day vs. -0.0466 ± 0.1066%/day, P = 0.017) than in women. CONCLUSIONS: Pancreatic ductal adenocarcinoma cachexia displays sex-specific phenotypes in mice and humans, with Activin a preferential driver of muscle wasting in males. Sex is a major modulator of cachexia mechanisms. Consideration of sexual dimorphism is essential for discovery and development of effective treatments.

3.
Elife ; 112022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35559734

RESUMO

A developing understanding suggests that spatial compartmentalisation in pancreatic ß cells is critical in controlling insulin secretion. To investigate the mechanisms, we have developed live-cell sub-cellular imaging methods using the mouse organotypic pancreatic slice. We demonstrate that the organotypic pancreatic slice, when compared with isolated islets, preserves intact ß cell structure, and enhances glucose dependent Ca2+ responses and insulin secretion. Using the slice technique, we have discovered the essential role of local activation of integrins and the downstream component, focal adhesion kinase, in regulating ß cells. Integrins and focal adhesion kinase are exclusively activated at the ß cell capillary interface and using in situ and in vitro models we show their activation both positions presynaptic scaffold proteins, like ELKS and liprin, and regulates glucose dependent Ca2+ responses and insulin secretion. We conclude that focal adhesion kinase orchestrates the final steps of glucose dependent insulin secretion within the restricted domain where ß cells contact the islet capillaries.

4.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35555114

RESUMO

Adipose tissue (AT) regulates systemic energy homeostasis, and its dysfunction can result in insulin resistance and other metabolic complications. Protein arginine methyltransferase 5 (PRMT5) catalyzes symmetrical demethylation of arginine residues to modulate protein stability and/or function. Besides its well-studied oncogenic functions, PRMT5 has recently been shown to play a physiological role in AT through poorly understood mechanisms. Here, we combine RNA sequencing and mass-spectrometry-based lipidomic analyses of wildtype and Prmt5 knockout (Prmt5AKO ) AT to uncover the molecular mechanisms underlying PRMT5 function. We found that Prmt5AKO alters expression of genes related to metabolism and membrane transport. Specifically, Prmt5AKO induces genes enriched in glucose transport and glycolysis pathways, and suppresses genes encoding fatty acid (FA) transporters. This is accompanied by changes in lipid compositions of TAGs, FAs, and phospholipids. The data indicate that Prmt5AKO disrupts fatty acid metabolism while promoting glucose uptake and glycolysis. Prmt5AKO also promotes cholesterol biogenesis, contributing to hyperlipidemia and hepatic steatosis in mice. The omics data together reveal a previously unappreciated role of PRMT5 in membrane transport that affects glucose metabolism and cholesterol synthesis.

5.
J Transl Med ; 20(1): 218, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562743

RESUMO

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

6.
Ying Yong Sheng Tai Xue Bao ; 33(4): 1045-1054, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35543058

RESUMO

Timing of leaf senescence is important to ensure maize yield. In this study, we investigated the dynamics of carbon and nitrogen balance during leaf senescence in two maize inbred lines PH6WC and PH4CV under normal (4 mmol·L-1, CK) and low nitrogen (0.04 mmol·L-1, LN) treatments. Leaf phenotype, photosynthetic characteristics, nitrogen and sugar contents, and carbon to nitrogen ratio of the second and third leaves were analyzed after 2, 4, 6 and 8 days of cultivation. Results showed that leaf size, biomass, relative chlorophyll content, net photosynthetic rate, soluble sugar content, and starch content of the second and third leaves were decreased, while nitrogen production capacity was increased under low nitrogen treatment compared to the control, with the changes of the second leaf being earlier than that of the third leaf. For all the leaf traits, the variation scales of PH6WC were larger than that of PH4CV under low nitrogen stress, and only the C/N ratio in the seedling leaves was significantly increased. In addition, leaf senescence of PH4CV was slower than PH6WC due to its stronger ability in maintaining carbon and nitrogen balance. In conclusion, low nitrogen could induce leaf senescence of maize seedlings. High C/N ratio could promote leaf senescence. There are significant differences in carbon and nitrogen balance ability of seedling leaves between two maize genotypes under low nitrogen stress.

7.
Food Chem ; 386: 132776, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35509162

RESUMO

Four types of pure lipid, namely lauric acid (LA), glycerol monolaurate (MAG), diglycerol laurate (DAG) and triglyceride laurate (TAG) were used to prepare oleofoams. The relationship between crystal profiles and their performance in oleofoams was established. DAG formed small needle-like crystals while MAG formed large flake-like crystals in oleogels, and crystal shells around air bubbles were observed in LA-, MAG- and DAG-based oleofoams. LA and DAG displayed higher over-run whereas DAG-stabilised foam possessed smaller bubbles and higher physical stability due to the presence of small ß and ß' crystals. Upon heating, DAG and TAG-based foams showed varying extents of oil drainage indicating the crystals were distributed in a different manner. Therefore, DAG was shown to be an excellent gelator in the fabrication of ultra-stable oleofoams. This work extends the lipid varieties with nutritional features and allows a better understanding on the stabilization mechanisms of lauric acid lipids in oleofoams.


Assuntos
Ésteres , Glicerol , Diglicerídeos/química , Lauratos , Ácidos Láuricos
8.
Thromb J ; 20(1): 26, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513826

RESUMO

BACKGROUND: Renal function is associated with prognoses for acute pulmonary embolism (PE). OBJECTIVE: To investigate the application of anticoagulants and dosage of LMWH among patients with renal insufficiency (RI), and the association between LWMH dosage and the patients' in-hospital outcomes. METHODS: Adult patients diagnosed with non-high risk acute PE from 2009 to 2015, with available data of creatinine clearance (CCr) were enrolled from a multicenter registry in China. Renal insufficiency (RI) was defined as CCr < 60 ml/min. LMWH dosage was converted into IU/kg daily dose and presented as adjusted dose (≤ 100 IU/kg/day) and conventional dose (> 100 IU/kg/day). All-cause death, PE-related death and bleeding events during hospitalization were analyzed as endpoints. RESULTS: Among the enrolled 5870 patients, RI occurred in 1311 (22.3%). 30 ≤ CCr < 60 ml/min was associated with higher rate of bleeding events and CCr < 30 ml/min was associated with all-cause death, PE-related death and major bleeding. Adjusted-dose LMWH was applied in 26.1% of patients with 30 ≤ CCr < 60 ml/min and in 26.2% of CCr < 30 ml/min patients. Among patients with RI, in-hospital bleeding occurred more frequently in those who were administered conventional dose of LMWH, compared with adjusted dose (9.2% vs 5.0%, p = 0.047). Adjusted dose of LMWH presented as protective factor for in-hospital bleeding (OR 0.62, 95%CI 0.27-1.00, p = 0.0496) and the risk of bleeding increased as length of hospital stay prolonged (OR 1.03, 95%CI 1.01-1.06, p = 0.0014). CONCLUSIONS: The proportion of adjusted usage of LMWH was low. The application of adjusted-dose LMWH was associated with lower risk of in-hospital bleeding for RI patients, in real-world setting of PE treatment. Anticoagulation strategy for RI patients should be paid more attention and requires evidence of high quality. TRIAL REGISTRATION: The CURES was registered in ClinicalTrias.gov, identifier number: NCT02943343 .

9.
J Integr Med ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35491357

RESUMO

OBJECTIVE: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis. METHODS: The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses. RESULTS: Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1. CONCLUSION: The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

10.
Front Genet ; 13: 816460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360864

RESUMO

Background: Long noncoding RNAs (lncRNAs) act as epigenetic regulators in the process of ferroptosis and iron metabolism. This study aimed to identify an iron metabolism-related lncRNA signature to predict osteosarcoma (OS) survival and the immune landscape. Methods: RNA-sequencing data and clinical information were obtained from the TARGET dataset. Univariate Cox regression and LASSO Cox analysis were used to develop an iron metabolism-related lncRNA signature. Consensus clustering analysis was applied to identify subtype-based prognosis-related lncRNAs. CIBERSORT was used to analyze the difference in immune infiltration and the immune microenvironment in the two clusters. Results: We identified 302 iron metabolism-related lncRNAs based on 515 iron metabolism-related genes. The results of consensus clustering showed the differences in immune infiltration and the immune microenvironment in the two clusters. Through univariate Cox regression and LASSO Cox regression analysis, we constructed an iron metabolism-related lncRNA signature that included seven iron metabolism-related lncRNAs. The signature was verified to have good performance in predicting the overall survival, immune-related functions, and immunotherapy response of OS patients between the high- and low-risk groups. Conclusion: We identified an iron metabolism-related lncRNA signature that had good performance in predicting survival outcomes and showing the immune landscape for OS patients. Furthermore, our study will provide valuable information to further develop immunotherapies of OS.

11.
Front Cardiovasc Med ; 9: 818890, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402550

RESUMO

Cardiovascular disease is one of the main causes of human mortality. Cytokines play crucial roles in the development of cardiovascular disease. Interleukin (IL)-6 family members are a series of cytokines, including IL-6, IL-11, IL-30, IL-31, OSM, LIF, CNTF, CT-1, CT-2, and CLC, that regulate multiple biological effects. Experimental and clinical evidence shows that IL-6 family members are closely related to cardiovascular diseases such as atherosclerosis, hypertension, aortic dissection, cardiac fibrosis, and cardiomyopathy. This review mainly discusses the role of IL-6 family members in cardiovascular disease for the sake of identifying possible intervention targets for cardiovascular disease prevention and treatment.

12.
Am J Med Sci ; 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35405139

RESUMO

Diffuse pulmonary lymphangiomatosis (DPL) is rare in adults. It is characterized by abnormal proliferation, dilatation, and thickening of the lymphatic channels in the lungs, pleura, and mediastinal soft tissue. Here, we report a case of DPL in a young adult man with recurrent productive cough. Chest computed tomography (CT) showed bilateral interlobular septal and peribronchovascular thickening and mediastinal soft tissue infiltration. Lung biopsy through video-assisted thoracic surgery demonstrated proliferation and dilatation of irregular lymphatic spaces, lined by flattened endothelial cells that were positive for CD31, D2-40, and factor VIII-related antigen on immunohistochemical staining. After treatment with propranolol for six months, the chest CT showed improved interlobular septal and peribronchovascular thickening and a unilateral pleural effusion, which turned bloody. Radiologic features can suggest the diagnosis of DPL. Surgical biopsy with adequate section size is critical in the diagnosis. Propranolol might be an effective and safe therapeutic option for patients with DPL.

13.
J Cell Mol Med ; 26(9): 2607-2619, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35365949

RESUMO

Pathological cardiac hypertrophy is the most important risk factor for developing chronic heart failure. Therefore, the discovery of novel agents for treating pathological cardiac hypertrophy remains urgent. In the present study, we examined the therapeutic effect and mechanism of periplocymarin (PM)-mediated protection against pathological cardiac hypertrophy using angiotensinII (AngII)-stimulated cardiac hypertrophy in H9c2 cells and transverse aortic constriction (TAC)-induced cardiac hypertrophy in mice. In vitro, PM treatment significantly reduced the surface area of H9c2 cells and expressions of hypertrophy-related proteins. Meanwhile, PM markedly down-regulated AngII-induced translocation of p-STAT3 into the nuclei and enhanced the phosphorylation levels of JAK2 and STAT3 proteins. The STAT3 specific inhibitor S3I-201 or siRNA-mediated depleted expression could alleviate AngII-induced cardiac hypertrophy in H9c2 cells following PM treatment; however, PM failed to reduce the expressions of hypertrophy-related proteins and phosphorylated STAT3 in STAT3-overexpressing cells, indicating that PM protected against AngII-induced cardiac hypertrophy by modulating STAT3 signalling. In vivo, PM reversed TAC-induced cardiac hypertrophy, as determined by down-regulating ratios of heart weight to body weight (HW/BW), heart weight to tibial length (HW/TL) and expressions of hypertrophy-related proteins accompanied by the inhibition of the JAK2/STAT3 pathway. These results revealed that PM could effectively protect the cardiac structure and function in experimental models of pathological cardiac hypertrophy by inhibiting the JAK2/STAT3 signalling pathway. PM is expected to be a potential lead compound of the novel agents for treating pathological cardiac hypertrophy.


Assuntos
Glicosídeos Cardíacos , Insuficiência Cardíaca , Animais , Glicosídeos Cardíacos/metabolismo , Glicosídeos Cardíacos/farmacologia , Glicosídeos Cardíacos/uso terapêutico , Cardiomegalia/metabolismo , Insuficiência Cardíaca/metabolismo , Camundongos , Miócitos Cardíacos/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
14.
Int J Gen Med ; 15: 3951-3964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35437351

RESUMO

Background: Aortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circRNAs play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in AD based on the circRNA-associated competing endogenous RNA (ceRNA) network. Methods: Expression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified by bioinformatics analysis. CircRNA-miRNA-mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of circRNA-associated ceRNA network. RNA was isolated from human arterial blood samples after which qRT-PCR was performed to confirm the DERNAs. Results: We identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) (adjusted P-value <0.05 and | log2FC | > 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix receptor interaction signaling pathways. Simultaneously, the present study constructed a ceRNA network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1). qRT-PCR demonstrated that hsa_circRNA_082317 and ITGA5 were significantly up-regulated, and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3). Conclusion: This is the first study to demonstrate the circRNA-associated ceRNA network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression and thus may serve as potential biomarkers for the diagnosis and treatment of AD.

15.
Front Med (Lausanne) ; 9: 813964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479940

RESUMO

The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2 (GESS v2 https://shiny.ph.iu.edu/GESS_v2/) is an updated version of GESS, which has offered a handy query platform to analyze single-nucleotide variants (SNVs) on millions of high coverages and high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complete genomes provided by the Global Initiative on Sharing Avian Influenza Data (GISAID). Including the tools in the first version, the GESS v2 is embedded with new functions, which allow users to search SNVs, given the viral nucleotide or amino acid sequence. The GESS v2 helps users to identify SNVs or SARS-CoV-2 lineages enriched in countries of user's interest and show the migration path of a selected lineage on a world map during specific time periods chosen by the users. In addition, the GESS v2 can recognize the dynamic variations of newly emerging SNVs in each month to help users monitor SNVs, which will potentially become dominant soon. More importantly, multiple sets of analyzed results about SNVs can be downloaded directly from the GESS v2 by which users can conduct their own independent research. With these significant updates, the GESS v2 will continue to serve as a public open platform for researchers to explore SARS-CoV-2 evolutionary patterns from the perspectives of the prevalence and impact of SNVs.

16.
Life (Basel) ; 12(4)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35454985

RESUMO

We investigated associations between intakes of human milk (HM) components (macronutrients and biologically active molecules) and regional fat depots development in healthy term infants (n = 20) across the first year of lactation. Infant limb (mid-arm and mid-thigh) lean and fat areas were assessed by ultrasound imaging at 2, 5, 9 and 12 months of age. Concentrations of HM total protein, whey protein, casein, adiponectin, leptin, lysozyme, lactoferrin, secretory IGA, total carbohydrates, lactose, HM oligosaccharides (total HMO, calculated) and infant 24-h milk intake were measured, and infant calculated daily intakes (CDI) of HM components were determined. This pilot study shows higher 24-h milk intake was associated with a larger mid-arm fat area (p = 0.024), higher breastfeeding frequency was associated with larger mid-arm (p = 0.008) and mid-thigh (p < 0.001) fat areas. Lysozyme (p = 0.001) and HMO CDI (p = 0.004) were time-dependently associated with the mid-arm fat area. Intakes of HM components and breastfeeding parameters may modulate infant limb fat depots development during the first year of age and potentially promote favorable developmental programming of infant body composition; however, further studies are needed to confirm these findings.

17.
Polymers (Basel) ; 14(8)2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35458379

RESUMO

Polydimethylsiloxane (PDMS) foam materials with lightweight, excellent oil resistance and mechanical flexibility are highly needed for various practical applications in aerospace, transportation, and oil/water separation. However, traditional PDMS foam materials usually present poor chemical resistance and easily swell in various solvents, which greatly limits their potential application. Herein, novel fluorosilicone rubber foam (FSiRF) materials with different contents of trifluoropropyl lateral groups were designed and fabricated by a green (no solvents used) and rapid (<10 min foaming process) foaming/crosslinking approach at ambient temperature. Typically, vinyl-terminated poly(dimethyl-co-methyltrifluoropropyl) siloxanes with different fluorine contents of 0-50 mol% were obtained through ring-opening polymerization to effectively adjust the chemical resistance of the FSiRFs. Notably, the optimized FSiRF samples exhibit lightweight (~0.25 g/cm-3), excellent hydrophobicity/oleophilicity (WCA > 120°), reliable mechanical flexibility (complete recovery ability after stretching of 130% strain or compressing of >60%), and improved chemical resistance and structural stability in various solvents, making them promising candidates for efficient and continuous oil-water separation. This work provides an innovative concept to design and prepare advanced fluorosilicone rubber foam materials with excellent chemical resistance for potential oil-water separation application.

18.
Front Psychiatry ; 13: 827480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35449566

RESUMO

Background: Nonsuicidal self-injury (NSSI) may be a type of addiction, that is characterized by cue reactivity. We aimed to explore the behavioral performance and neural reactivity during exposure to self-injury cues in adolescents with NSSI and major depressive disorder (MDD). Methods: Eighteen MDD patients, 18 MDD patients with NSSI, and 19 healthy controls (HC) were recruited to perform a two-choice oddball paradigm. All subjects were 12-18 years old. Neutral cues and self-injury related cues separately served as deviant stimuli. Difference waves in N2 and P3 (N2d and P3d) were derived from deviant waves minus standard waves. Accuracy cost and reaction time (RT) cost were used as behavioral indexes, while the N2d and P3d were used as electrophysiological indexes; the N2d reflects early conflict detection, and the P3d reflects the process of response inhibition. Results: No significant main effects of group or cue or an effect of their interaction were observed on accuracy cost and P3d latency. For RT cost, N2d amplitude, and N2d latency, there was a significant main effect of cue. For P3d amplitude, there was a significant main effect of cue and a significant group × cue interaction. In the NSSI group, the P3d amplitude with self-injury cues was significantly larger than that with neutral cues. However, there was no such effect in the MDD and HC groups. Conclusions: Adolescents with NSSI showed altered neural reactivity during exposure to self-injury cue. Further studies with larger sample sizes are needed to confirm our results.

19.
IEEE Trans Image Process ; 31: 3224-3235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35412980

RESUMO

In our daily life, a large number of activities require identity verification, e.g., ePassport gates. Most of those verification systems recognize who you are by matching the ID document photo (ID face) to your live face image (spot face). The ID vs. Spot (IvS) face recognition is different from general face recognition where each dataset usually contains a small number of subjects and sufficient images for each subject. In IvS face recognition, the datasets usually contain massive class numbers (million or more) while each class only has two image samples (one ID face and one spot face), which makes it very challenging to train an effective model (e.g., excessive demand on GPU memory if conducting the classification on such massive classes, hardly capture the effective features for bisample data of each identity, etc.). To avoid the excessive demand on GPU memory, a two-stage training method is developed, where we first train the model on the dataset in general face recognition (e.g., MS-Celeb-1M) and then employ the metric learning losses (e.g., triplet and quadruplet losses) to learn the features on IvS data with million classes. To extract more effective features for IvS face recognition, we propose two novel algorithms to enhance the network by selecting harder samples for training. Firstly, a Cross-Batch Hard Example Mining (CB-HEM) is proposed to select the hard triplets from not only the current mini-batch but also past dozens of mini-batches (for convenience, we use batch to denote a mini-batch in the following), which can significantly expand the space of sample selection. Secondly, a Pseudo Large Batch (PLB) is proposed to virtually increase the batch size with a fixed GPU memory. The proposed PLB and CB-HEM can be employed simultaneously to train the network, which dramatically expands the selecting space by hundreds of times, where the very hard sample pairs especially the hard negative pairs can be selected for training to enhance the discriminative capability. Extensive comparative evaluations conducted on multiple IvS benchmarks demonstrate the effectiveness of the proposed method.


Assuntos
Identificação Biométrica , Reconhecimento Facial , Algoritmos , Benchmarking , Identificação Biométrica/métodos , Face/anatomia & histologia , Face/diagnóstico por imagem , Humanos
20.
PLoS One ; 17(4): e0266914, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35446881

RESUMO

PURPOSE: The demand for high-throughput genetic profiling of somatic mutations in cancer tissues is growing. We sought to establish a targeted next generation sequencing (NGS) panel test for clinical oncology practice. METHODS: Customized probes were designed to capture exonic regions of 141 genes selected for the panel, which was aimed for the detection of clinically actionable genetic variations in cancer, including KRAS, NRAS, BRAF, ALK, ROS1, KIT and EGFR. The size of entire targeted regions is 0.8 Mb. Library preparation used NEBNext Ultra II FS kit coupled with target enrichment. Paired-end sequencing was run on Illumina NextSeq 500 at a read length of 150 nt. A bioinformatics workflow focusing on single nucleotide variant and short insertions and deletions (SNV/indel) discovery was established using open source, in-house and commercial software tools. Standard reference DNA samples were used in testing the sensitivity and precision and limit of detection in variant calling. RESULTS: The general performance of the panel was observed in pilot runs. Average total reads per sample ranged from 30 million to 48 million, 73% ~82% unique reads. All runs had more than 99% average mapping rate. Mean target coverage ranged from 727x to 879x. Depth of coverage at 50x or more reached 87% of targeted region and 60% of targeted region received 500x or more coverage depth. Using OncoSpan HD827 DNA, which bears 144 variants (SNV/indel) from 80 genes that are within the targeted region on the panel, our somatic variant calling pipeline reached 97% sensitivity and 100% precision respectively, with near 48 million reads. High concordance with orthogonal approaches in variant detection was further verified with 7 cancer cell lines and 45 clinical specimens. CONCLUSION: We developed a NGS panel with a focus on clinically actionable gene mutations and validated the performance in library construction, sequencing and variant calling. High concordance with reference materials and orthogonal mutation detection was observed.


Assuntos
Neoplasias , Proteínas Tirosina Quinases , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Oncologia , Mutação , Neoplasias/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética
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