Publications by authors named "Tao Peng"

856 Publications

Finite-Time and Fixed-Time Synchronization of Quaternion-Valued Neural Networks With/Without Mixed Delays: An Improved One-Norm Method.

IEEE Trans Neural Netw Learn Syst 2021 Jun 11;PP. Epub 2021 Jun 11.

In this article, the finite-time synchronization (FTSYN) of a class of quaternion-valued neural networks (QVNNs) with discrete and distributed time delays is studied. Furthermore, the FTSYN and fixed-time synchronization (FIXSYN) of the QVNNs without time delay are investigated. Different from the existing results, which used decomposition techniques, by introducing an improved one-norm, we use a direct analytical method to study the synchronization problems. Incidentally, several properties of one-norm of the quaternion are analyzed, and then, three effective controllers are proposed to synchronize the drive and response QVNNs within a finite time or fixed time. Moreover, efficient criteria are proposed to guarantee that the synchronization of QVNNs with or without mixed time delays can be realized within a finite and fixed time interval, respectively. In addition, the settling times are reckoned. Compared with the existing work, our advantages are mainly reflected in the simpler Lyapunov analytical process and more general activation function. Finally, the validity and practicability of the conclusions are illustrated via four numerical examples.
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http://dx.doi.org/10.1109/TNNLS.2021.3085253DOI Listing
June 2021

and Genome-Wide Profiling of RNA Secondary Structures Reveals Key Regulatory Features in .

Front Cell Infect Microbiol 2021 17;11:673966. Epub 2021 May 17.

The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

It is widely accepted that the structure of RNA plays important roles in a number of biological processes, such as polyadenylation, splicing, and catalytic functions. Dynamic changes in RNA structure are able to regulate the gene expression programme and can be used as a highly specific and subtle mechanism for governing cellular processes. However, the nature of most RNA secondary structures in has not been determined. To investigate the genome-wide RNA secondary structural features at single-nucleotide resolution in , we applied a novel high-throughput method utilizing the chemical modification of RNA structures to characterize these structures. Structural data from parasites are in close agreement with the known 18S ribosomal RNA secondary structures of and can help to predict the RNA secondary structure of a total of 3,396 transcripts in the ring-stage and trophozoite-stage developmental cycles. By parallel analysis of RNA structures and during the parasite ring-stage and trophozoite-stage intraerythrocytic developmental cycles, we identified some key regulatory features. Recent studies have established that the RNA structure is a ubiquitous and fundamental regulator of gene expression. Our study indicate that there is a critical connection between RNA secondary structure and mRNA abundance during the complex biological programme of . This work presents a useful framework and important results, which may facilitate further research investigating the interactions between RNA secondary structure and the complex biological programme in . The RNA secondary structure characterized in this study has potential applications and important implications regarding the identification of RNA structural elements, which are important for parasite infection and elucidating host-parasite interactions and parasites in the environment.
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http://dx.doi.org/10.3389/fcimb.2021.673966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166286PMC
May 2021

Microbial debromination of hexabromocyclododecanes.

Appl Microbiol Biotechnol 2021 Jun 2;105(11):4535-4550. Epub 2021 Jun 2.

Department of Biology, Science College, Shantou University, Shantou, 515063, Guangdong Province, People's Republic of China.

Hexabromocyclododecanes (HBCDs), a new sort of brominated flame retardants (BFRs), are globally prevalent and recalcitrant toxic environmental pollutants. HBCDs have been found in many environmental media and even in the human body, leading to serious health concerns. HBCDs are biodegradable in the environment. By now, dozens of bacteria have been discovered with the ability to transform HBCDs. Microbial debromination of HBCDs is via HBr-elimination, HBr-dihaloelimination, and hydrolytic debromination. Biotic transformation of HBCDs yields many hydroxylated and lower brominated compounds which lack assessment of ecological toxicity. Bioremediation of HBCD pollution has only been applied in the laboratory. Here, we review the current knowledge about microbial debromination of HBCDs, aiming to promote the bioremediation applied in HBCD contaminated sites. KEY POINTS: • Microbial debromination of HBCDs is via hydrolytic debromination, HBr-elimination, and HBr-dihaloelimination. • Newly occurred halogenated contaminants such as HBCDs hitch the degradation pathway tamed by previously discharged anthropogenic organohalides. • Strategy that combines bioaugmentation with phytoremediation for bioremediation of HBCD pollution is promising.
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http://dx.doi.org/10.1007/s00253-021-11095-3DOI Listing
June 2021

Graph Regularized Flow Attention Network for Video Animal Counting From Drones.

IEEE Trans Image Process 2021 3;30:5339-5351. Epub 2021 Jun 3.

In this paper, we propose a large-scale video based animal counting dataset collected by drones (AnimalDrone) for agriculture and wildlife protection. The dataset consists of two subsets, i.e., PartA captured on site by drones and PartB collected from the Internet, with rich annotations of more than 4 million objects in 53, 644 frames and corresponding attributes in terms of density, altitude and view. Moreover, we develop a new graph regularized flow attention network (GFAN) to perform density map estimation in dense crowds of video clips with arbitrary crowd density, perspective, and flight altitude. Specifically, our GFAN method leverages optical flow to warp the multi-scale feature maps in sequential frames to exploit the temporal relations, and then combines the enhanced features to predict the density maps. Moreover, we introduce the multi-granularity loss function including pixel-wise density loss and region-wise count loss to enforce the network to concentrate on discriminative features for different scales of objects. Meanwhile, the graph regularizer is imposed on the density maps of multiple consecutive frames to maintain temporal coherency. Extensive experiments are conducted to demonstrate the effectiveness of the proposed method, compared with several state-of-the-art counting algorithms. The AnimalDrone dataset is available at https://github.com/VisDrone/AnimalDrone.
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http://dx.doi.org/10.1109/TIP.2021.3082297DOI Listing
June 2021

Effect of timing of surgical resection of primary hepatocellular carcinoma on survival outcomes in elderly patients and prediction of clinical models.

BMC Gastroenterol 2021 May 21;21(1):230. Epub 2021 May 21.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.

Background: The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients.

Methods: A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed.

Results: A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival.

Conclusions: We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.
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http://dx.doi.org/10.1186/s12876-021-01815-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139139PMC
May 2021

Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.

Authors:
Xinlei Li Tao Peng

Front Pharmacol 2021 4;12:660710. Epub 2021 May 4.

State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, College of Basic Medicine, Guangzhou Medical University, Guangzhou, China.

Emerging or re-emerging viruses are still major threats to public health. Prophylactic vaccines represent the most effective way to prevent virus infection; however, antivirals are more promising for those viruses against which vaccines are not effective enough or contemporarily unavailable. Because of the slow pace of novel antiviral discovery, the high disuse rates, and the substantial cost, repurposing of the well-characterized therapeutics, either approved or under investigation, is becoming an attractive strategy to identify the new directions to treat virus infections. In this review, we described recent progress in identifying broad-spectrum antivirals through drug repurposing. We defined the two major categories of the repurposed antivirals, direct-acting repurposed antivirals (DARA) and host-targeting repurposed antivirals (HTRA). Under each category, we summarized repurposed antivirals with potential broad-spectrum activity against a variety of viruses and discussed the possible mechanisms of action. Finally, we proposed the potential investigative directions of drug repurposing.
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http://dx.doi.org/10.3389/fphar.2021.660710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129523PMC
May 2021

VAD-MM/GBSA: A Variable Atomic Dielectric MM/GBSA Model for Improved Accuracy in Protein-Ligand Binding Free Energy Calculations.

J Chem Inf Model 2021 May 20. Epub 2021 May 20.

Innovation Institute for Artificial Intelligence in Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.

The molecular mechanics/generalized Born surface area (MM/GBSA) has been widely used in end-point binding free energy prediction in structure-based drug design (SBDD). However, in practice, it is usually being treated as a disputed method mostly because of its system dependence. Here, combining with machine-learning optimization, we developed a novel version of MM/GBSA, named variable atomic dielectric MM/GBSA (VAD-MM/GBSA), by assigning variable dielectric constants directly to the protein/ligand atoms. The new strategy exhibits markedly improved accuracy in binding affinity calculations for various protein-ligand systems and is promising to be used in the postprocessing of structure-based virtual screening. Moreover, VAD-MM/GBSA outperformed prime MM/GBSA in Schrödinger software and showed remarkable predictive performance for specific protein targets, such as POL polyprotein, human immunodeficiency virus type 1 (HIV-1) protease, etc. Our study showed that the VAD-MM/GBSA method with little extra computational overhead provides a potential replacement of the MM/GBSA in AMBER software. An online web server of VAD-MMGBSA has been developed and is now available at http://cadd.zju.edu.cn/vdgb.
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http://dx.doi.org/10.1021/acs.jcim.1c00091DOI Listing
May 2021

as biomarker in hepatitis B virus-associated hepatocellular carcinoma.

J Cancer 2021 19;12(12):3486-3500. Epub 2021 Apr 19.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

Hepatitis B virus infection is associated with liver disease, including cancers. In this study, we assessed the power of sex-determining region Y (SRY)-related high-mobility group (HMG)-box 4() gene to predict the clinical course of hepatocellular carcinoma (HCC). To evaluate the differential expression of and its diagnostic and prognostic potential in HCC, we analyzed the GSE14520 dataset. Stratified analysis and joint-effect analysis were done using and clinical factor. We then designed a nomogram for predicting the clinical course of HCC. Differential expression and its correlation with tumor stage as well as its diagnostic and prognostic value were analyzed on the oncomine and GEPIA websites. Gene set enrichment analysis was explored as well as candidate gene ontology and metabolic pathways modulated by in HCC. Our analysis revealed that the level of was significantly upregulated in tumor issue ( <0.001). This observation was validated through oncomine dataset and MERAV analysis (all <0.05). Diagnostic receiver operating characteristic (ROC) analysis of suggested it has diagnostic potential in HCC (GSE14520 dataset: <0.001, area under curve (AUC) = 0.782; Oncomine: (Wurmbach dataset) = 0.002, AUC = 0.831 and (Mas dataset) <0.001, AUC = 0.947). In addition, exhibited high correlation with overall survival of HBV-associated HCC (adjusted = 0.004, hazard ratio (HR) (95% confidence interval (CI)) = 2.055 (1.261-3.349) and recurrence-free survival (adjusted = 0.008, HR (95% CI) = 1.721 (1.151-2.574). These observations which were verified by GEPIA analysis for overall survival ( = 0.007) and recurrence-free survival (= 0.096). Gene enrichment analysis revealed that affected processes included lymphocyte differentiation, pancreatic endocrine pathways, and insulin signaling pathway. prognostic value was evaluated using nomogram analysis for HCC 1, 3, and 5-year, survival. Differential expression presents an avenue of diagnosing and predicting clinical course of HCC. In HCC, may affect TP53 metabolic processes, lymphocyte differentiation and the insulin signaling pathway.
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http://dx.doi.org/10.7150/jca.46579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120190PMC
April 2021

Application Value of Lipoprotein-Associated Phospholipase A2 Expression Level in Evaluating the Risk of Major Bleeding in Gestational Diabetes.

Clin Lab 2021 May;67(5)

Background: Studies have shown that obesity and lipid metabolism disorders can lead to increased Lp-PLA2 ac-tivity in the body. However, few studies have reported the correlation between Lp-PLA2 and postpartum hemorrhage in pregnant women with GMD.

Methods: Clinical data was collected from 43 pregnant women with gestational diabetes combined with postpartum hemorrhage and 50 pregnant women with postpartum diabetes without postpartum bleeding during the same period. Lp-PLA2 expression levels in the serum of pregnant women in both groups were detected. The predictive value of Lp-PLA2 expression level for postpartum hemorrhage was clarified.

Results: (1) From 20w to 32w pregnancy, the serum Lp-PLA2 levels of pregnant women in both groups showed a gradual increasing trend. (2) The serum Lp-PLA2 level of the pregnant women in the research group was significantly higher (p < 0.001). (3) Binary logistic regression analysis shows that Lp-PLA2 level has a good correlation with postpartum major bleeding. (4) Comparing of Lp-PLA2 levels in different gestational weeks with respect to its efficacy for predicting postpartum hemorrhage found that the sensitivity and specificity of 24w Lp-PLA2 levels are higher than other gestational weeks, and the area under the 24w parameter curve (0.955) > 32w area under the parameter curve (0.952) > area under the 20w parameter curve (0.940) > area under the 28w parameter curve (0.887). (5) The birth weight of the newborn in the research group was significantly heavier (p < 0.001).

Conclusions: Dynamic monitoring of the expression level of Lp-PLA2 in the serum of pregnant women can predict the risk of postpartum hemorrhage in pregnant women at an early stage and help optimize the rescue plan for postpartum hemorrhage.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200906DOI Listing
May 2021

NLRP3 induces the autocrine secretion of IL-1β to promote epithelial-mesenchymal transition and metastasis in breast cancer.

Biochem Biophys Res Commun 2021 Jun 8;560:72-79. Epub 2021 May 8.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Tumor metastasis is a leading cause of mortality in patients with breast cancer (BC). As a predominant component of inflammasome, Nod-like receptor protein 3 (NLRP3) was found to be required for tumor progression, while the role of NLRP3 in BC metastasis remains largely undefined. In current study, we found that invasive BC had aberrant upregulation of NLRP3 expression, especially in the claudin-low subtype. And higher expression of NLRP3 predicted poor survival of BC patients. Further investigation suggested that NLRP3 promotes the migration and invasion, as well as the metastasis of BC cells. Moreover, we revealed that NLRP3 induces the autocrine secretion of IL-1β to promote epithelial-mesenchymal transition via a Caspase-1-dependent manner. Hence, this study suggested that upregulation of NLRP3 in BC induces the autocrine secretion of IL-1β and promotes EMT and metastasis of BC cells.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.122DOI Listing
June 2021

Mass balance of nine trace elements in two karst catchments in southwest China.

Sci Total Environ 2021 Sep 4;786:147504. Epub 2021 May 4.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550081, China; CAS Centre for Excellence in Quaternary Science and Global Change, Xi'an 710061, China. Electronic address:

High geological background levels of trace elements (TEs) and high population density in the karst areas of southwest China have imposed environmental pressure on the fragile ecosystems in this region. Understanding the mass budget of TEs, especially the toxic ones, is of great importance to sustain future developments. This study investigates the mass balance and fate of nine TEs (cadmium, arsenic, lead, chromium, copper, nickel, zinc, thallium, and antimony) in two karst catchments (Huilong and Chenqi) in southwest China through estimation of their mass budgets in throughfall, open field precipitation, total suspended particulate matter (TSP), litterfall, fertilization, harvested crops, surface runoff, and underground runoff. The estimated net fluxes are positive, indicating a source region, for four elements (Cu, Cr, Ni, and Tl) and negative, indicating a sink region, for five elements (As, Cd, Pb, Sb, and Zn) in both catchments. The net fluxes for the nine elements in Chenqi catchment are within a relatively small range (2.6, 2.0, 1.6, 0.6, -0.05, -0.5, -0.5, -2.9, and -3.3 mg m yr for Cu, Ni, Cr, Tl, Cd, Zn, Sb, Pb, and As, respectively), but in Huilong catchment in quite a large range (15.5, 6.0, 1.0, 0.8, -0.3, -0.9, -4.5, -7.5, and -8.7 mg m yr for Tl, Cr, Ni, Cu, Cd, Sb, As, Pb, and Zn, respectively). Rainfall (12.3%-66.2%) and litterfall (18.4%-81.3%) are the major input flux pathways, while crops harvest (16%-99%) is the major output flux pathway for the TEs in both catchments, indicating that the fate of TEs is shaped by both natural factors such as precipitation and litterfall and human activities such as fertilization and crop harvesting in these forestland-farmland compound karst catchments. Results from this study suggest that restoring forests from low-yield sloping farmlands will be useful for controlling TEs pollution in these fragile karst regions with high geological background TEs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147504DOI Listing
September 2021

UMAP as a Dimensionality Reduction Tool for Molecular Dynamics Simulations of Biomacromolecules: A Comparison Study.

J Phys Chem B 2021 05 11;125(19):5022-5034. Epub 2021 May 11.

Department of Chemistry, Center for Research Computing, Center for Drug Discovery, Design, and Delivery (CD4), Southern Methodist University, Dallas, Texas 75275, United States.

Proteins are the molecular machines of life. The multitude of possible conformations that proteins can adopt determines their free-energy landscapes. However, the inherently high dimensionality of a protein free-energy landscape poses a challenge to deciphering how proteins perform their functions. For this reason, dimensionality reduction is an active field of research for molecular biologists. The uniform manifold approximation and projection (UMAP) is a dimensionality reduction method based on a fuzzy topological analysis of data. In the present study, the performance of UMAP is compared with that of other popular dimensionality reduction methods such as t-distributed stochastic neighbor embedding (t-SNE), principal component analysis (PCA), and time-structure independent components analysis (tICA) in the context of analyzing molecular dynamics simulations of the circadian clock protein VIVID. A good dimensionality reduction method should accurately represent the data structure on the projected components. The comparison of the raw high-dimensional data with the projections obtained using different dimensionality reduction methods based on various metrics showed that UMAP has superior performance when compared with linear reduction methods (PCA and tICA) and has competitive performance and scalable computational cost.
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http://dx.doi.org/10.1021/acs.jpcb.1c02081DOI Listing
May 2021

Viral dynamics and antibody responses in people with asymptomatic SARS-CoV-2 infection.

Signal Transduct Target Ther 2021 05 10;6(1):181. Epub 2021 May 10.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.

Over 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming "herd-immunity" through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.
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http://dx.doi.org/10.1038/s41392-021-00596-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107204PMC
May 2021

Long Non-coding RNA DLEU2L Targets miR-210-3p to Suppress Gemcitabine Resistance in Pancreatic Cancer Cells via BRCA2 Regulation.

Front Mol Biosci 2021 22;8:645365. Epub 2021 Apr 22.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Gemcitabine (GEM) resistance remains a challenging clinical issue to overcome in chemotherapy against pancreatic cancer. We previously demonstrated that miR-210 derived from pancreatic cancer stem cells enhanced the GEM-resistant properties of pancreatic cancer cells, thus identifying miR-210 as an oncogenic miRNA. Herein, we report the existence of an upstream effector that acts as a competing endogenous RNA (ceRNA) to miR-210. Bioinformatic screening was performed to identify lncRNAs with a binding relationship to miR-210. Overexpression and interference vectors were constructed to demonstrate the effect of ceRNA activity in pancreatic cell behavior, both and . DLEU2L (deleted in lymphocytic leukemia 2-like), which is expressed at low levels in pancreatic cancer tissues, was shown to exhibit a binding relationship with miR-210-3p. Overexpression of DLEU2L and silencing of miR-210-3p suppressed the proliferation, migration, and invasion of pancreatic cancer cells while promoting apoptosis. These effects occurred via the inhibition of the Warburg effect (aerobic glycolysis) and AKT/mTOR signaling. In addition, we showed that BRCA2 is a target gene of miR-210-3p, and the downregulation of miR-210-3p by DLEU2L effectively induced an upregulation of BRCA2 via the ceRNA mechanism. , DLEU2L overexpression and miR-210-3p interference suppressed pancreatic tumor progression, consistent with the results of studies. The findings of our study establish DLEU2L as a ceRNA to miR-210-3p and reveal the critical role of the DLEU2L/miR-210-3p crosstalk in targeting GEM resistance.
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http://dx.doi.org/10.3389/fmolb.2021.645365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100451PMC
April 2021

An Investigation of Flow Patterns and Mixing Characteristics in a Cross-Shaped Micromixer within the Laminar Regime.

Micromachines (Basel) 2021 Apr 20;12(4). Epub 2021 Apr 20.

College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China.

A fast mixing is critical for subsequent practical development of microfluidic devices, which are often used for assays in the detection of reagents and samples. The present work sets up computational fluid dynamics simulations to explore the flow characteristic and mixing mechanism of fluids in cross-shaped mixers within the laminar regime. First, the effects of increasing an operating parameter on local mixing quality along the microchannels are investigated. It is found that sufficient diffusion cannot occur even though the concentration gradient is large at a high Reynolds number. Meanwhile, a method for calculating local mixing efficiency is also characterized. The mixing efficiency varies exponentially with the flow distance. Second, in order to optimize the cross-shaped mixer, the effects of design parameters, namely aspect ratio, mixing angle and blockage, on mixing quality are captured and the visualization of velocity and concentration distribution are demonstrated. The results show that the aspect ratio and the blockage play an important role in accelerating the mixing process. They can improve the mixing efficiency by increasing the mass transfer area and enhancing the chaotic advection, respectively. In contrast, the inflow angle that affects dispersion length is not an effective parameter. Besides, the surface roughness, which makes the disturbance of fluid flow by roughness more obvious, is considered. Three types of rough elements bring benefits for enhancing mixing quality due to the convection induced by the lateral velocity.
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http://dx.doi.org/10.3390/mi12040462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072938PMC
April 2021

A Photolabile Carboxyl Protecting Group for Solid Phase Peptide Synthesis.

ChemistryOpen 2021 Apr;10(4):497-502

Faculty of Environment & Life, Beijing University of Technology, Beijing, 100124, China.

A new kind of photolabile protecting group (PLPG) for carboxyl moieties was designed and synthesized as the linker between resin and peptide. This group can be used for the protection of amino acid carboxyl groups. The peptide was synthesized on Nph (2-hydroxy-3-(2-nitrophenyl)-heptanoic acid)-derivatized resins and could be cleaved under UV exposure, thus avoiding the necessity for harsh acid-mediated resin cleavage. The PLPG has been successfully used for solid-phase synthesis of peptides.
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http://dx.doi.org/10.1002/open.202000324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080293PMC
April 2021

Differential expression of sputum and serum autoantibodies in patients with chronic obstructive pulmonary disease.

Am J Physiol Lung Cell Mol Physiol 2021 Apr 28. Epub 2021 Apr 28.

Pathology and Molecular Medicine, McMaster University, Canada.

Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease. Autoimmune processes have been hypothesised to contribute to disease progression; however, the presence of autoantibodies in the serum has been variable. Given that COPD is a lung disease, we sought to investigate whether autoantibodies in sputum supernatant would better define pulmonary autoimmune processes. Matched sputum and serum samples were obtained from the Airways Disease Endotyping for Personalised Therapeutics (ADEPT) study and at the Guangzhou Institute of Respiratory Health (GIRH). Samples were collected from patients with varying severity of COPD, asymptomatic smokers and healthy control subjects. IgG and IgM autoantibodies were detected in sputum and serum of all subjects in both cohorts using a broad-spectrum autoantigen array. No differences were observed in sputum autoantibodies between COPD and asymptomatic smokers in either cohort. In contrast, 16% of detectable sputum IgG autoantibodies were decreased in COPD subjects compared to healthy controls in the ADEPT cohort. Compared to asymptomatic smokers, approximately 13% of detectable serum IgG and 40% of detectable serum IgM autoantibodies were differentially expressed in GIRH COPD subjects. Of the differentially expressed specificities, anti-nuclear autoantibodies were predominately decreased. A weak correlation between increased serum IgM anti-tissue autoantibodies and a measure of airspace enlargement was observed. The differential expression of specificities varied between the cohorts. In closing, using a comprehensive autoantibody array, we demonstrate that autoantibodies are present in COPD subjects, asymptomatic smokers and healthy controls. Cohorts displayed high levels of heterogeneity, precluding the utilisation of autoantibodies for diagnostic purposes.
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http://dx.doi.org/10.1152/ajplung.00518.2020DOI Listing
April 2021

Distinct diagnostic and prognostic values of Glypicans gene expression in patients with hepatocellular carcinoma.

BMC Cancer 2021 Apr 26;21(1):462. Epub 2021 Apr 26.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6#, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

Backgroud: In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC).

Methods: The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database.

Results: Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44-2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05).

Conclusions: Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.
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http://dx.doi.org/10.1186/s12885-021-08104-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073913PMC
April 2021

Discovery of a highly efficient nitroaryl group for detection of nitroreductase and imaging of hypoxic tumor cells.

Org Biomol Chem 2021 Apr;19(15):3469-3478

State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

Hypoxia is a pathological hallmark of solid tumors. Detection of hypoxia is therefore of great interest for tumor diagnosis and treatment. As a well-established biomarker of hypoxia, nitroreductase (NTR) has been widely exploited in the development of hypoxia-responsive fluorescent probes on the basis of its enzymatic activity to reduce nitroaryl groups. However, studies on the relationship between the nitroaryl structure and the probe performance for optimal probe design are still rare. Here we report a comparative investigation of nitroaryl groups and identification of the optimal nitroaryl structure for developing new fluorescent probes with extremely high efficiency in the detection of NTR and the imaging of hypoxic tumor cells. Specifically, we synthesized a series of resorufin-based fluorescent probes containing different nitroaryl groups, compared their fluorescence responses to NTR, and identified 2-nitro-N-methyl-imidazolyl as the optimal nitroaryl group that is much more efficient than the most widely used 4-nitrophenyl for NTR detection. The structure-performance relationship was then studied by theoretical molecular docking, revealing the unique features of 2-nitro-N-methyl-imidazolyl in binding and reaction with NTR. We further incorporated the 2-nitro-N-methyl-imidazolyl group into a near-infrared (NIR) hemicyanine fluorophore and developed a NIR fluorescent probe NFP-7 for the detection of NTR and hypoxic tumor cells. NFP-7 exhibits a strong fluorescence increase toward NTR in vitro with an ultrafast (within 40 seconds to fluorescence maximum) and ultrasensitive (0.2 ng mL-1 detection limit) response. NFP-7 has also been demonstrated for imaging the degree of hypoxia in live tumor cells and, more importantly, in a murine tumor model. Our study provides important insights into hypoxia probe development and new tools for hypoxia imaging.
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http://dx.doi.org/10.1039/d1ob00356aDOI Listing
April 2021

Site-Specific Lipidation Enhances IFITM3 Membrane Interactions and Antiviral Activity.

ACS Chem Biol 2021 05 22;16(5):844-856. Epub 2021 Apr 22.

Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, New York, New York 10065, United States.

Interferon-induced transmembrane proteins (IFITMs) are -palmitoylated proteins in vertebrates that restrict a diverse range of viruses. -palmitoylated IFITM3 in particular engages incoming virus particles, prevents their cytoplasmic entry, and accelerates their lysosomal clearance by host cells. However, how -palmitoylation modulates the structure and biophysical characteristics of IFITM3 to promote its antiviral activity remains unclear. To investigate how site-specific -palmitoylation controls IFITM3 antiviral activity, we employed computational, chemical, and biophysical approaches to demonstrate that site-specific lipidation of cysteine 72 enhances the antiviral activity of IFITM3 by modulating its conformation and interaction with lipid membranes. Collectively, our results demonstrate that site-specific -palmitoylation of IFITM3 directly alters its biophysical properties and activity in cells to prevent virus infection.
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http://dx.doi.org/10.1021/acschembio.1c00013DOI Listing
May 2021

A Comparative Study of Deep Neural Network-Aided Canonical Correlation Analysis-Based Process Monitoring and Fault Detection Methods.

IEEE Trans Neural Netw Learn Syst 2021 Apr 22;PP. Epub 2021 Apr 22.

Multivariate analysis is an important kind of method in process monitoring and fault detection, in which the canonical correlation analysis (CCA) makes use of the correlation change between two groups of variables to distinguish the system status and has been greatly studied and applied. For the monitoring of nonlinear dynamic systems, the deep neural network-aided CCA (DNN-CCA) has received much attention recently, but it lacks a general definition and comparative study of different network structures. Therefore, this article first introduces four deep neural network (DNN) models that are suitable to combine with CCA, and the general form of DNN-CCA is given in detail. Then, the experimental comparison of these methods is conducted through three cases, so as to analyze the characteristics and distinctions of CCA aided by each DNN model. Finally, some suggestions on method selection are summarized, and the existed open issues in the current DNN-CCA form and future directions are discussed.
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http://dx.doi.org/10.1109/TNNLS.2021.3072491DOI Listing
April 2021

Human hand as a powerless and multiplexed infrared light source for information decryption and complex signal generation.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

With the increasing pursuit of intelligent systems, the integration of human components into functional systems provides a promising route to the ultimate human-compatible intelligent systems. In this work, we explored the integration of the human hand as the powerless and multiplexed infrared (IR) light source in different functional systems. With the spontaneous IR radiation, the human hand provides a different option as an IR light source. Compared to engineered IR light sources, the human hand brings sustainability with no need of external power and also additional level of controllability to the functional systems. Besides the whole hand, each finger of the hand can also independently provide IR radiation, and the IR radiation from each finger can be selectively diffracted by specific gratings, which helps the hand serve as a multiplexed IR light source. Considering these advantages, we show that the human hand can be integrated into various engineered functional systems. The integration of hand in an encryption/decryption system enables both unclonable and multilevel information encryption/decryption. We also demonstrate the use of the hand in complex signal generation systems and its potential application in sign language recognition, which shows a simplified recognition process with a high level of accuracy and robustness. The use of the human hand as the IR light source provides an alternative sustainable solution that will not only reduce the power used but also help move forward the effort in the integration of human components into functional systems to increase the level of intelligence and achieve ultimate control of these systems.
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http://dx.doi.org/10.1073/pnas.2021077118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054021PMC
April 2021

CytoTalk: De novo construction of signal transduction networks using single-cell transcriptomic data.

Sci Adv 2021 Apr 14;7(16). Epub 2021 Apr 14.

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Single-cell technology enables study of signal transduction in a complex tissue at unprecedented resolution. We describe CytoTalk for de novo construction of cell type-specific signaling networks using single-cell transcriptomic data. Using an integrated intracellular and intercellular gene network as the input, CytoTalk identifies candidate pathways using the prize-collecting Steiner forest algorithm. Using high-throughput spatial transcriptomic data and single-cell RNA sequencing data with receptor gene perturbation, we demonstrate that CytoTalk has substantial improvement over existing algorithms. To better understand plasticity of signaling networks across tissues and developmental stages, we perform a comparative analysis of signaling networks between macrophages and endothelial cells across human adult and fetal tissues. Our analysis reveals an overall increased plasticity of signaling networks across adult tissues and specific network nodes that contribute to increased plasticity. CytoTalk enables de novo construction of signal transduction pathways and facilitates comparative analysis of these pathways across tissues and conditions.
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http://dx.doi.org/10.1126/sciadv.abf1356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046375PMC
April 2021

Everolimus regulates the activity of gemcitabine-resistant pancreatic cancer cells by targeting the Warburg effect via PI3K/AKT/mTOR signaling.

Mol Med 2021 04 13;27(1):38. Epub 2021 Apr 13.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Gemcitabine (GEM) resistance remains a significant clinical challenge in pancreatic cancer treatment. Here, we investigated the therapeutic utility of everolimus (Evr), an inhibitor of mammalian target of rapamycin (mTOR), in targeting the Warburg effect to overcome GEM resistance in pancreatic cancer.

Methods: The effect of Evr and/or mTOR overexpression or GEM on cell viability, migration, apoptosis, and glucose metabolism (Warburg effect) was evaluated in GEM-sensitive (GEM) and GEM-resistant (GEM) pancreatic cancer cells.

Results: We demonstrated that the upregulation of mTOR enhanced cell viability and favored the Warburg effect in pancreatic cancer cells via the regulation of PI3K/AKT/mTOR signaling. However, this effect was counteracted by Evr, which inhibited aerobic glycolysis by reducing the levels of glucose, lactic acid, and adenosine triphosphate and suppressing the expression of glucose transporter 1, lactate dehydrogenase-B, hexokinase 2, and pyruvate kinase M2 in GEM and GEM cells. Evr also promoted apoptosis by upregulating the pro-apoptotic proteins Bax and cytochrome-c and downregulating the anti-apoptotic protein Bcl-2. GEM was minimally effective in suppressing GEM cell activity, but the therapeutic effectiveness of Evr against pancreatic cancer growth was greater in GEM cells than that in GEM cells. In vivo studies confirmed that while GEM failed to inhibit the progression of GEM tumors, Evr significantly decreased the volume of GEM tumors while suppressing tumor cell proliferation and enhancing tumor apoptosis in the presence of GEM.

Conclusions: Evr treatment may be a promising strategy to target the growth and activity of GEM-resistant pancreatic cancer cells by regulating glucose metabolism via inactivation of PI3K/AKT/mTOR signaling.
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http://dx.doi.org/10.1186/s10020-021-00300-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045370PMC
April 2021

Development of a preoperative prognostic scoring system to predict benefits of hepatic resection in advanced hepatocellular carcinoma patients.

Biosci Rep 2021 Apr;41(4)

Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Guangxi Medical University Cancer Hospital, Nanning, China.

Objective: The present study aimed to identify risk factors for overall survival in advanced hepatocellular carcinoma (HCC) patients and establish a scoring system to select patients who would benefit from hepatic resection.

Methods: Survival curves were analyzed using the Kaplan-Meier method and log-rank test. The prognostic scoring system was developed from training cohort using a Cox-regression model and validated in a external validation cohort Results: There were 401 patients in the training cohort, 163 patients in the external validation cohorts. The training cohort median survival in all patients was 12 ± 1.07 months, rate of overall survival was 49.6% at 1 year, 25.0% at 3 years, and 18.0% at 5 years. A prognostic scoring system was established based on age, body mass index, alkaline phosphatase, tumor number and tumor capsule. Patients were classified as low- risk group(≤3.5) or high-risk group(>3.5). High-risk patients had a median survival of 9 months, compared with 23 months in low-risk patients. The area under the receiver operating characteristic curve (AUC) of the prognostic scoring system was 0.747 (0.694-0.801), which is significantly better than AFP, Child-Pugh and ALBI. The AUC of validation cohorts was 0.716 (0.63-0.803).

Conclusion: A prognostic scoring system for hepatic resection in advanced HCC patients has been developed based entirely on preoperative variables. Patients classified as low risk using this system may experience better prognosis after hepatic resection.
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http://dx.doi.org/10.1042/BSR20201928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035620PMC
April 2021

Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer.

J Exp Clin Cancer Res 2021 Apr 8;40(1):124. Epub 2021 Apr 8.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China.

Background: Pancreatic cancer is a malignant tumor and ranks the sixth in incidence among cancers. Circular RNA (circRNA) has been reported to regulate the progression of pancreatic cancer. However, the effects of circ-membrane bound O-acyltransferase domain containing 2 (circ-MBOAT2) on regulating pancreatic cancer process were unclear.

Methods: The expression levels of circ-MBOAT2, microRNA-433-3p (miR-433-3p) and glutamic-oxaloacetic transaminase 1 (GOT1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). GOT1 protein expression was determined by western blot analysis. Cell proliferation was illustrated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and cell colony formation assay. Cell apoptosis was demonstrated by flow cytometry analysis. Cell invasion and migration were investigated by transwell invasion and wound-healing assays. Glutamine catabolism was explained by detecting glutamine consumption, alpha ketoglutarate (α-KG) production and glutamate production. In vivo assay was performed to illustrate the impacts of circ-MBOAT2 silencing on tumor formation in vivo. The binding relationship between miR-433-3p and circ-MBOAT2 or GOT1 was predicted by circinteractome or starbase online databases, and identified by dual-luciferase reporter assay.

Results: Circ-MBOAT2 and GOT1 expression were significantly upregulated, while miR-433-3p expression was downregulated in pancreatic cancer tissues and cells compared with normal pancreatic tissues or cells. Circ-MBOAT2 silencing repressed cell proliferation, migration, invasion and glutamine catabolism, whereas promoted cell apoptosis in pancreatic cancer. Additionally, circ-MBOAT2 acted as a sponge of miR-433-3p, which was found to be associate with GOT1. MiR-433-3p inhibitors hindered circ-MBOAT2 silencing-mediated impacts on pancreatic cancer progression and glutamine catabolism. Furthermore, circ-MBOAT2 silencing repressed tumor formation in vivo.

Conclusion: Circ-MBOAT2 modulated tumor development and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. This finding suggests that circ-MBOAT2 may be a therapeutic target for pancreatic cancer.
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http://dx.doi.org/10.1186/s13046-021-01894-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034179PMC
April 2021

COVID-19 infection in patients with connective tissue disease: A multicity study in Hubei province, China.

MedComm (Beijing) 2021 Mar 4;2(1):82-90. Epub 2021 Feb 4.

Department of Rheumatology and Immunology Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan Hubei China.

Novel Coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID-19 patients hospitalized in 23 centers affiliated to Hubei COVID-19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID-19 infection (= 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts ( values were 0.033, < 0.001, and 0.071, respectively). Hydroxychloroquine therapy and low- to medium-dose glucocorticoids before COVID-19 diagnosis reduced the progression of COVID-19 to severe/critical conditions (= 0.001 for hydroxychloroquine; = 0.006 for glucocorticoids). Our data suggests that COVID-19 in CTD patients may be more severe compared to patients with AS or gout.
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http://dx.doi.org/10.1002/mco2.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013216PMC
March 2021

Psychological Distress Reported by Primary Care Physicians in China During the COVID-19 Pandemic.

Psychosom Med 2021 05;83(4):380-386

From the Department of General Practice (Zeng, Peng, Hao, Zou), Chengdu Fifth People's Hospital, Chengdu University of TCM, Chengdu; Family Medicine Centre (Lin), The First Affiliated Hospital of Shantou University Medical College, Shantou; The Department of General Practice (Liao), West China Hospital, Sichuan University, Chengdu; The Department of Geriatric Medicine (Chen), Chengdu Fifth People's Hospital, Chengdu University of TCM, Chengdu, China; and The Department of Primary Care and Public Health (Hayhoe), Imperial College London, London, United Kingdom.

Objective: Primary care physicians (PCPs) play a key role in responding to the COVID-19 epidemic. The objective of this study was to explore the influencing factors associated with self-reported psychological distress among a sample of PCPs in China in relation to COVID-19.

Methods: An online survey was distributed to a sample of PCPs in Chengdu city between February 10 and February 13, 2020. The survey consisted of three sections: demographic characteristics, COVID-19-related questions, and the General Health Questionnaire-12 (GHQ-12). After 5 months, a follow-up survey investigating the change of the GHQ-12 was conducted.

Results: A total of 712 PCPs completed the baseline survey (11.8% of those invited), 55.6% were female and 74.4% were aged between 30 and 49 years. High levels of psychological distress (GHQ-12 ≥3) were observed in 29.2% and were associated with low preparedness, high work impact, working with infected residents, personal life impact, and concerns, as well as older age and being married (p values < .05). Logistic regression analysis showed that psychological distress was associated with low preparedness (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.87-0.96), high work impact (OR = 1.11, 95% CI = 1.03-1.20), personal life impact (OR = 1.12, 95% CI = 1.07-1.17), and safety-related concerns (OR = 1.09, 95% CI = 1.02-1.16). At the 5-month assessment point, high psychological distress was less frequent (21.8%).

Conclusions: COVID-19 has resulted in high levels of distress in approximately 30% of PCPs in China. Factors associated with high psychological distress levels include low preparedness and high levels of work impact, personal life impact, and concerns. These findings highlight the importance of enhancing psychological health throughout the course of infectious pandemics.
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http://dx.doi.org/10.1097/PSY.0000000000000939DOI Listing
May 2021

B cells, antibody-secreting cells, and virus-specific antibodies respond to herpes simplex virus 2 reactivation in skin.

J Clin Invest 2021 May;131(9)

Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Tissue-based T cells are important effectors in the prevention and control of mucosal viral infections; less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in inflammatory infiltrates in skin biopsy specimens from study participants during symptomatic herpes simplex virus 2 (HSV-2) reactivation and early healing. Both CD20+ B cells, most of which are antigen inexperienced based on their coexpression of IgD, and ASCs - characterized by dense IgG RNA expression in combination with CD138, IRF4, and Blimp-1 RNA - were found to colocalize with T cells. ASCs clustered with CD4+ T cells, suggesting the potential for crosstalk. HSV-2-specific antibodies to virus surface antigens were also present in tissue and increased in concentration during HSV-2 reactivation and healing, unlike in serum, where concentrations remained static over time. B cells, ASCs, and HSV-specific antibody were rarely detected in biopsies of unaffected skin. Evaluation of samples from serial biopsies demonstrated that B cells and ASCs followed a more migratory than resident pattern of infiltration in HSV-affected genital skin, in contrast to T cells. Together, these observations suggest the presence of distinct phenotypes of B cells in HSV-affected tissue; dissecting their role in reactivation may reveal new therapeutic avenues to control these infections.
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http://dx.doi.org/10.1172/JCI142088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087200PMC
May 2021

UXT antisense RNA 1 sever as a novel prognostic long non-coding RNA in early stage pancreatic ductal adenocarcinoma patients after receiving pancreaticoduodenectomy.

J Cancer 2021 21;12(7):2122-2139. Epub 2021 Feb 21.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

The principal objective of this project was to investigate the prognostic value of UXT antisense RNA 1 (UXT-AS1) in pancreatic ductal adenocarcinoma (PDAC), as well as its biological function mechanisms and the screening of targeted drugs using The Cancer Genome Atlas (TCGA) PDAC genome-wide RNA sequencing (RNA-seq) dataset. We used TCGA 112 early stage PDAC patients to screen the prognostic value of UXT-AS1. Biological functions and mechanisms of UXT-AS1 were investigated by co-expression analysis, differentially expressed genes (DEGs) and gene set enrichment analysis, while targeted drug screening was investigated by connectivity Map (CMap). By analyzing the dataset from TCGA cohort, we found that UXT-AS1 was significantly up-regulated in pancreatic cancer tissues. Multivariate survival analysis demonstrated that PDAC patients with high UXT-AS1 expression had an unfavourable prognosis (adjusted P=0.033, HR=1.830, 95%CI=1.051-3.188). Genome-wide co-expression analysis and gene set enrichment analysis suggested that UXT-AS1 may act as a pivotal part in PDAC by participating in nuclear factor kappa beta, regulation of tumor necrosis factor, cell adhesion, T cell receptor signaling pathway, and numerous immune-related biological processes and signaling pathways. Functional enrichment analysis of DEGs between high- and low-UXT-AS1 expression groups suggested that these DEGs were significant enriched in B cell receptor complex, response to drug chemical carcinogenesis and drug metabolism-cytochrome P450. CMap analysis revealed that quipazine and terazosin may be targeted drugs for UXT-AS1 in PDAC. Our current study has identified UXT-AS1 as a novel biomarker for the prognosis of early stage PDAC. We also clarified its biological functional mechanisms and identified two targeted drugs of UXT-AS1 in PDAC.
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http://dx.doi.org/10.7150/jca.46084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974525PMC
February 2021