Publications by authors named "Ying Wang"

10,587 Publications

  • Page 1 of 1

Supramolecular and Physically Double-Cross-Linked Network Strategy toward Strong and Tough Elastic Fibers.

ACS Macro Lett 2020 Nov 28;9(11):1655-1661. Epub 2020 Oct 28.

Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.

The strength and toughness are two trade-off properties of a material, yet can achieve strong and tough materials by introducing sacrificial bonds into a system. Here, we present a four-component multiblock copolymer (mBCP) approach toward strong and tough elastic fibers, by introducing terpyridine moieties into poly(ether ester) mBCP elastomers. After coordination with Fe(II), supramolecular cross-links are formed within the physically cross-linked thermoplastic elastomers. The toughening elastic fibers with a double-cross-linked network structure show high tensile strength (ca. 300 MPa) and toughness (ca. 100 MJ m). In addition, they display excellent resilience with enhanced self-healing properties. Our strategy provides a promising way for the development of strong and tough elastomers by introducing metal-ligand sacrificial bonds into mBCPs elastomers.
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http://dx.doi.org/10.1021/acsmacrolett.0c00579DOI Listing
November 2020

CDC25C is a prognostic biomarker and correlated with mitochondrial homeostasis in pancreatic adenocarcinoma.

Bioengineered 2022 May;13(5):13089-13107

Department of Central Laboratory, Affiliated Hangzhou first people's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Pancreatic adenocarcinoma (PAAD) is a common digestive tract malignant tumor with an extremely poor prognosis. The survival and prognosis may significantly improve if it is diagnosed early. Therefore, identifying biomarkers for early diagnosis is still considered a great clinical challenge in PAAD. Cell Division Cycle 25C (CDC25C), a cardinal cell cycle regulatory protein, directly mediates the G2/M phase and is intimately implicated in tumor development. In the current study, we aim to explore the possible functions of CDC25C and determine the potential role of CDC25C in the early diagnosis and prognosis of PAAD. Expression analysis indicated that CDC25C was overexpressed in PAAD . In addition, survival analysis revealed a strong correlation between the enhanced expression of CDC25C and poor survival in PAAD. Furthermore, pathway analysis showed that CDC25C is related to TP53 signaling pathways, glutathione metabolism, and glycolysis. Mechanically, our in vitro experiments verified that CDC25C was capable of promoting cell viability and proliferation. CDC25C inhibition increases the accumulation of ROS, inhibits mitochondrial respiration, suppresses glycolysis metabolism and reduces GSH levels. To summarize, CDC25C may be involved in energy metabolism by maintaining mitochondrial homeostasis. Our results suggested that CDC25C is a potential biological marker and promising therapeutic target of PAAD.
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http://dx.doi.org/10.1080/21655979.2022.2078940DOI Listing
May 2022

Functional Analysis of Serum Long Noncoding RNAs in Patients with Atrial Fibrillation.

Dis Markers 2022 16;2022:2799123. Epub 2022 May 16.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Objectives: Long noncoding RNAs (lncRNAs) are closely related to diverse diseases. However, its role in atrial fibrillation (AF) pathogenesis needs further exploration.

Design: We performed microarray analysis on the serum samples from 70 healthy volunteers and 70 AF patients. This study was aimed at detecting the levels of serum lncRNAs and mRNAs and bioinformatically analyze them to establish potential marker(s) for AF diagnosis. Receiver operating curve (ROC) and area under the curve (AUC) were employed to address the AF diagnostic power of lncRNAs.

Results: In the AF serum samples, 753 lncRNAs and 802 mRNAs ( ≤ 0.05; fold change ≥ 2) were upregulated, and 315 lncRNAs and 153 mRNAs were downregulated, as opposed to healthy serum samples. Using bioinformatic analysis, we analyzed the top 4 differentially expressed (DE) lncRNAs, namely, , , , and , and found that the PI3K-AKT cell proliferation signaling pathway was most affected. This was in accordance with our functional analysis of DE mRNAs and adjacent lncRNAs. Notably, the elevated serum levels were strongly associated with AF incidence.

Conclusions: Our work highlights the role of lncRNAs in AF pathogenesis and provides a novel serum biomarker for AF diagnosis.
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http://dx.doi.org/10.1155/2022/2799123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126683PMC
May 2022

Influence of different regimens of volumetric therapy on perioperative intestinal flora in the surgical patients with pancreas tumor, a randomized controlled trial study.

BMC Anesthesiol 2022 May 25;22(1):162. Epub 2022 May 25.

Department of Anesthesiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

Background: It is not clear whether the perioperative intestinal microenvironment of patients undergoing pancreatic tumor surgery is affected by intraoperative fluid therapy.

Method: Fifty-eight patients who underwent a confined excision of pancreas mass at this center were enrolled. The patients were grouped according to the random number table in these two groups: the liberal fluid infusion (LFI) group and the goal-directed fluid therapy (GDFT) group. Perioperative anesthesia management was carried out by the same team of anesthesiologists according to a preset anesthetic protocol. Fecal samples were collected twice: within 2 days before the surgery and at 6 to 8 days postoperatively. The collected fecal samples were sequenced through microbial diversity high-throughput 16 s-rDNA; and the differential changes of intestinal flora were analyzed.

Results: Main components of flora in the sample were significantly different between LFI and GDFT groups. As shown by the difference in species, in GDFT group, more constituent bacteria participated in the metabolism inside human body and the restoration of coagulation function, including: prevotella, roseburia, lachnospiracea, dialister and clostridium (P < 0.05); in LFI group, more constituent bacteria were opportunistic pathogenic bacteria, including: enterococcus, pseudomonas aeruginosa, and acinetobacter baumannii (P < 0.05).

Conclusion: For surgical patients with pancreas tumor, there are significant differences of intestinal flora in diversity between GDFT and LFI. GDFT seems to play a more important role in protection and restoration of intestinal flora.

Clinical Trial Registration: ChiCTR2000035187 .
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http://dx.doi.org/10.1186/s12871-022-01693-7DOI Listing
May 2022

The Hippo pathway mediates Semaphorin signaling.

Sci Adv 2022 May 25;8(21):eabl9806. Epub 2022 May 25.

Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.

Semaphorins were originally identified as axonal guidance molecules, but they also control processes such as vascular development and tumorigenesis. The downstream signaling cascades of Semaphorins in these biological processes remain unclear. Here, we show that the class 3 Semaphorins (SEMA3s) activate the Hippo pathway to attenuate tissue growth, angiogenesis, and tumorigenesis. restoration in lung cancer cells with loss of heterozygosity suppresses cancer cell growth via activating the core Hippo kinases LATS1/2 (large tumor suppressor kinase 1/2). Furthermore, SEMA3 also acts through LATS1/2 to inhibit angiogenesis. We identified p190RhoGAPs as essential partners of the SEMA3A receptor PlexinA in Hippo regulation. Upon SEMA3 treatment, PlexinA interacts with the pseudo-guanosine triphosphatase (GTPase) domain of p190RhoGAP and simultaneously recruits RND GTPases to activate p190RhoGAP, which then stimulates LATS1/2. Disease-associated etiological factors, such as genetic lesions and oscillatory shear, diminish Hippo pathway regulation by SEMA3. Our study thus discovers a critical role of Hippo signaling in mediating SEMA3 physiological function.
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http://dx.doi.org/10.1126/sciadv.abl9806DOI Listing
May 2022

[Advances in several important antimicrobial lipopeptids from spp.]

Sheng Wu Gong Cheng Xue Bao 2022 May;38(5):1768-1783

The Innovative Academy of Seed Design, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

spp. are probiotics and can secrete a variety of natural antimicrobiol active substances, of which lipopeptides are an important class. Up to now, about 90 lipopeptides have been identified, and most of them are cyclic lipopeptides. surfactin, iturin, fengycin, bacillomycin and polymyxins are widely studied, and the first three have huge potential for application due to their properties of surfactants and anti-fungal, anti-bacterial, anti-viral, anti-tumor and anti-inflammatory functions. In this paper, the research progress in the structure, function, synthesis regulation, separation, purification and production of surfactin, iturin and fengycin was reviewed. Synthetic biology is a vital means to increase the yield of lipopeptides, and in the future, lipopeptides can be used in crop cultivation, animal farming, food, medicine and petroleum industries as well as environmental protection. Future research should be strengthened on the discovery of new lipopeptides, synthesis of high-activity lipopeptides, economical production of lipopeptides on a large scale and their safety evaluation.
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http://dx.doi.org/10.13345/j.cjb.220001DOI Listing
May 2022

Water quality criteria for lanthanum for freshwater aquatic organisms derived via species sensitivity distributions and interspecies correlation estimation models.

Ecotoxicology 2022 May 24. Epub 2022 May 24.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China.

The increasing exploitation and application of rare earth elements (REEs) may induce hazardous risks to freshwater aquatic organisms. Due to the lack of water quality criteria (WQC) and sufficient reliable toxicity data, little information is available on the ecological risk of REEs in surface water. In this study, lanthanum (La) toxicity data were collected from published toxicological studies, and the data quality was assessed using a toxicological data reliability assessment tool. To obtain more toxicity data, Daphnia magna, Cyprinus carpio, and Dania rerio embryos were selected as surrogate species, and an interspecies correlation estimation (ICE) model was used to predict the toxicity of La for untested species. The species sensitivity distributions (SSDs) of La toxicity and WQC were investigated. Differences were observed in the hazardous concentrations for 5% of species (HC), but no statistically significant differences were noted in the SSD curves between the measured acute toxicity data and the predicted data. For the SSDs constructed from the measured toxicity data, the ICE-predicted toxicity data and all acute data supplemented with the ICE-predicted data, the acute WQC values of La were 88, 1022 and 256 μg/L, respectively. According to the SSD and corresponding HC of chronic toxicity data, the chronic WQC was 14 μg/L. The results provide a scientific reference for establishing WQC for freshwater aquatic organisms and ecological risk assessments of REEs.
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http://dx.doi.org/10.1007/s10646-022-02557-zDOI Listing
May 2022

Mptx2 defends against peritoneal infection by methicillin-resistant staphylococcus aureus.

Int Immunopharmacol 2022 May 21;108:108856. Epub 2022 May 21.

Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address:

Methicillin-resistant Staphylococcus aureus (MRSA) has an increasing prevalence of multi-drug resistance. There is an urgent need for developing novel approaches to combat MRSA infection. Mucosal pentraxin 2 (Mptx2) is predicted to be a member of the pentraxin family, but its biological function is still unknown. This study is aimed to explore the roles of Mptx2 in MRSA-associated peritoneal infection. The recombinant Mptx2 protein is used to evaluate its antibacterial activity. Biofilm formation assay and macrophage phagocytic experiment are performed to explore the involved mechanisms. The effects of Mptx2 on peritoneal infection are investigated in a MRSA-induced peritoneal infected model. We here show that addition of Mptx2 suppresses the growth and biofilm formation of MRSA in vitro. Enzyme-linked immunosorbent assay (ELISA) binding analysis shows that Mptx2 protein directly binds to the MRSA. Additionally, Mptx2 supplementation promotes macrophages to phagocytize and clear the MRSA. In the MRSA-infected peritonitis model, Mptx2 administration reduces MRSA loading in peritoneal organs and alleviates peritoneal damage. Mptx2 knockout aggravates MRSA infection-induced peritoneal injury. In conclusion, our findings reveal that Mptx2 has bactericidal activity against MRSA both in vitro and in vivo, which may shed light on the discovery and development of novel strategies for MRSA-infected peritonitis.
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http://dx.doi.org/10.1016/j.intimp.2022.108856DOI Listing
May 2022

Mining cell-cell signaling in single-cell transcriptomics atlases.

Curr Opin Cell Biol 2022 May 21;76:102101. Epub 2022 May 21.

Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address:

Recent advances in single-cell RNA sequencing (scRNA-seq) techniques lead to an explosion of single-cell atlases from diverse biological contexts. The information of cell-cell signaling events, which underlie multicellular organism function, is embedded in these atlases. Here, we review current strategies of mining cell-cell signaling events from single-cell transcriptomics datasets and highlight examples where functions of predicted cell-cell signaling events from single-cell atlases are further pursued to yield new insights into biological processes.
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http://dx.doi.org/10.1016/j.ceb.2022.102101DOI Listing
May 2022

Short Hexapeptide Optimized from Rice-Derived Peptide 1 Shows Promising Anti-hyperuricemia Activities.

J Agric Food Chem 2022 May 24. Epub 2022 May 24.

Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, Yunnan 650504, China.

Plant-derived peptides are a treasure trove for new-generation anti-hyperuricemia drugs. In the current study, we optimized a short hexapeptide rice-derived peptide 1 (RDP1)-M3 (AAAAGA) according to the anti-hyperuricemia RDP1 peptide identified from rice in our previous research. Results showed that RDP1-M3 exerted better hyperuricemia-alleviating and xanthine oxidase (XOD)-inhibiting potency in mice than RDP1. The biodistribution of RDP1-M3 was also analyzed. RDP1-M3 directly decreased XOD and uric acid levels in vivo and in vitro. In addition, RDP1-M3 reduced the expression of urate transporter 1 and glucose transporter 9, increased the level of organic anion transporter 1, reduced the expression of NOD-like receptor superfamily pyrin 3 inflammasomes, and reduced the levels of interleukin-1β and tumor necrosis factor-α of hyperuricemic mice. Thus, our results indicated that the optimized short hexapeptide RDP1-M3 may be a candidate drug for anti-hyperuricemia.
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http://dx.doi.org/10.1021/acs.jafc.2c00354DOI Listing
May 2022

Electrochemical deposition of lithium coating on titanium implant with enhanced early stage osseointegration.

J Biomed Mater Res B Appl Biomater 2022 May 23. Epub 2022 May 23.

Department of Implantology, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, Zhejiang, China.

Recently, a large number of studies have reported that lithium (Li) displayed a positive effect on osteogenesis. However, only a few studies have investigated the Li-incorporated surfaces through electrochemical deposition. In this study, electrochemical deposition was conducted on a CHI600E electrochemical workstation. The characterization of electrochemical deposition (ECD) and ECD-Li surfaces were detected by field-emission scanning electron microscopy with energy-dispersive spectrometer. rBMSCs were cultured on two surfaces for subsequent adhesion, proliferation and live/dead assay. To evaluate the effects of Li-incorporated implants by electrochemical deposition on osseointegration in vivo, teeth extraction of two premolars and one first molar in bilateral mandible were performed on six male beagle dogs. After 3 months, ZDI and ZDI-Li implants were inserted into the bilateral mandible of each beagle dog. Micro Computed Tomography (Micro-CT) and hard tissue sectioning analysis were carried out to evaluate the osseointegration at 4- and 8-weeks post-implantation. Results showed that ECD-Li surface promoted adhesion and proliferation of BMSCs in the early stage. More importantly, through micro-CT analysis, the values of bone volume/total volume (BV/TV) (0.374 ± 0.015), bone-implant contact (BIC) (0.831 ± 0.025), and Tb.Th (0.412 ± 0.007) in ZDI-Li group was significantly higher than those of ZDI group (0.302 ± 0.009, 0.700 ± 0.023, 0.353 ± 0.001, p < .01) at 4 weeks. Similarly, ZDI-Li group manifested more bone contact with the implant surfaces at 4 weeks based on hard tissue sectioning analysis, whereas no significant difference was detected between two groups at 8 weeks. Therefore, incorporating Li into implant surface through ECD could enhance early osseointegration in vivo.
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http://dx.doi.org/10.1002/jbm.b.35085DOI Listing
May 2022

Clinical Efficacy of Soluble Thrombomodulin, Tissue Plasminogen Activator Inhibitor complex, Thrombin-Antithrombin complex,α2-Plasmininhibitor-Plasmin complex in Pediatric Sepsis.

Clin Appl Thromb Hemost 2022 Jan-Dec;28:10760296221102929

Department of Critical Care Medicine, 426116Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: To investigated the clinical efficacy of Soluble thrombomodulin (sTM), tissue plasminogen activator inhibitor complex (t-PAI·C),thrombin-antithrombin complex (TAT),α2-plasmininhibitor-plasmin complex (PIC) in pediatric sepsis and pediatrics sepsis-induced coagulopathy (pSIC).

Methods: We prospectively collected patient data with sepsis diagnosed in the PICU of Shanghai Children's Medical Center from June 2019 to June 2021. sTM,t-PAI·C, TAT,PIC and classical coagulation laboratory tests (CCTs) were evaluated on the day of sepsis diagnosis.

Results: Fifty-nine children were enrolled, There were significant differences in t-PAI·C (P = 0.001), Plt (P < 0.001), PT (P < 0.001), INR (P < 0.001), aPTT (P < 0.001), and TT (P = 0.048) between the pSIC and non-pSIC groups, logistic regression analysis showed that Plt (P = 0.032) was an independent risk factor for pSIC. Logistic regression analysis showed that sTM (P = 0.007) and Plt (P = 0.016) were independent risk factors for the outcome in pediatrics sepsis following discharge. The AUC of sTM combined with Plt on the mortality outcome of children with sepsis at discharge was 0.889 (95%CI: 0.781,0.956). which was better than that for PRISM III (AUC, 0.723), pSOFA (AUC, 0.764), and blood Lac (AUC, 0.717) when sepsis was diagnosed in the PICU.

Conclusions: The t-PAI·C increased in children with pSIC. The prediction of sepsis outcome using sTM combined with Plt was better than with PRISM III, pSOFA, or Lac.Further research is still needed in the future to explore the clinical value of sTM, TAT, PIC, and t-PAI·C in diagnosis and outcome of pediatrics sepsis and pSIC.
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http://dx.doi.org/10.1177/10760296221102929DOI Listing
May 2022

Editorial: Innate Immunity in Kidney Injury, Repair and Fibrosis.

Front Immunol 2022 5;13:909654. Epub 2022 May 5.

Chinese Academy of Sciences (CAS) Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.

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http://dx.doi.org/10.3389/fimmu.2022.909654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119139PMC
May 2022

Identification of Angiogenesis-Related Prognostic Biomarkers Associated With Immune Cell Infiltration in Breast Cancer.

Front Cell Dev Biol 2022 6;10:853324. Epub 2022 May 6.

Department of Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.

This study aimed to explore the prognostic value of angiogenesis-related genes (ARGs) and their association with immune cell infiltration (ICI) in breast cancer (BC). Transcriptome data of BC were obtained from the TCGA and GEO databases. Differentially expressed ARGs were identified by the limma package. The identification of key genes and construction of the risk score model were performed by univariate and multivariate Cox regression algorithms. The prognostic value of the risk score was assessed by ROC curves and nomogram. GO, KEGG pathway, and GSEA were used to investigate the biological functions of differentially expressed genes (DEGs), and CIBERSORT, ssGSEA, and xCell algorithms were performed to estimate the ICI in high-risk and low-risk groups. The correlations between prognostic biomarkers and differentially distributed immune cells were assessed. Moreover, a ceRNA regulatory network based on prognostic biomarkers was constructed and visualized by Cytoscape software. A total of 18 differentially expressed ARGs were identified between tumor and adjacent normal tissue samples. TNFSF12, SCG2, COL4A3, and TNNI3 were identified as key prognostic genes by univariate and multivariate Cox regression analyses. The risk score model was further constructed based on the four-gene signature and validated in GSE7390 and GSE88770 datasets. ROC curves and nomogram indicated that the risk score had good accuracy for determining BC patient survival. Biological function analysis showed that DEGs in high- and low-risk groups had a high enrichment in immune-related biological processes and signaling pathways. Moreover, significantly different ICIs were found between high- and low-risk groups, such as memory B cells, CD8 T cells, resting memory CD4 T cells, follicular helper T cells, regulatory T cells, monocytes, M2 macrophages, and neutrophils, and each prognostic biomarker was significantly correlated with one or more immune cell types. The current study identified novel prognostic ARGs and developed a prognostic model for predicting survival in patients with BC. Furthermore, this study indicated that ICI may act as a bond between angiogenesis and BC. These findings enhance our understanding of angiogenesis in BC and provide novel guidance on developing therapeutic targets for BC patients.
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http://dx.doi.org/10.3389/fcell.2022.853324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121305PMC
May 2022

Chronic Obstructive Pulmonary Disease With Asthma-Like Features in the General Population in China.

Front Med (Lausanne) 2022 6;9:876240. Epub 2022 May 6.

State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.

Background: Patients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population.

Methods: COPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV >15% and >400 ml after bronchodilator.

Results: COPD with concomitant features of asthma was found in 1.62% (95% CI 1.31-2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0-17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, < 0.001), and with a lower post-bronchodilator FEV%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months.

Conclusions: COPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.
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http://dx.doi.org/10.3389/fmed.2022.876240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120624PMC
May 2022

LLRHNet: Multiple Lesions Segmentation Using Local-Long Range Features.

Front Neuroinform 2022 5;16:859973. Epub 2022 May 5.

College of Information and Management Science, Henan Agricultural University, Zhengzhou, China.

The encoder-decoder-based deep convolutional neural networks (CNNs) have made great improvements in medical image segmentation tasks. However, due to the inherent locality of convolution, CNNs generally are demonstrated to have limitations in obtaining features across layers and long-range features from the medical image. In this study, we develop a local-long range hybrid features network (LLRHNet), which inherits the merits of the iterative aggregation mechanism and the transformer technology, as a medical image segmentation model. LLRHNet adopts encoder-decoder architecture as the backbone which iteratively aggregates the projection and up-sampling to fuse local low-high resolution features across isolated layers. The transformer adopts the multi-head self-attention mechanism to extract long-range features from the tokenized image patches and fuses these features with the local-range features extracted by down-sampling operation in the backbone network. These hybrid features are used to assist the cascaded up-sampling operations to local the position of the target tissues. LLRHNet is evaluated on two multiple lesions medical image data sets, including a public liver-related segmentation data set (3DIRCADb) and an in-house stroke and white matter hyperintensity (SWMH) segmentation data set. Experimental results denote that LLRHNet achieves state-of-the-art performance on both data sets.
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http://dx.doi.org/10.3389/fninf.2022.859973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119082PMC
May 2022

Total ice content and lipid saturation determine adipose tissue cryolipolysis by injection of ice-slurry.

Lasers Surg Med 2022 May 21. Epub 2022 May 21.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objectives: Cryolipolysis uses tissue cooling to solidify lipids, preferentially damaging lipid-rich cells. Topical cooling is popular for the reduction of local subcutaneous fat. Injection of biocompatible ice-slurry is a recently introduced alternative. We developed and verified a quantitative model that simulates the heat exchange and phase changes involved, offering insights into ice-slurry injection for treating subcutaneous fat.

Methods: Finite element method was used to model the spatial and temporal progression of heat transfer between adipose tissue and injected ice-slurry, estimating dose-response relationships between properties of the slurry and size of tissue affected by cryolipolysis. Phase changes of both slurry and adipose tissue lipids were considered. An in vivo swine model was used to validate the numerical solutions. Oils with different lipid compositions were exposed to ice-slurry in vitro to evaluate the effects of lipid freezing temperature. Microscopy and nuclear magnetic resonance (NMR) were performed to detect lipid phase changes.

Results: A ball of granular ice was deposited at the injection site in subcutaneous fat. Total injected ice content determines both the effective cooling region of tissue, and the duration of tissue cooling. Water's high latent heat of fusion enables tissue cooling long after slurry injection. Slurry temperature affects the rate of tissue cooling. In swine, when 30 ml slurry injection at -3.5°C was compared to 15 ml slurry injection at -4.8°C (both with the same total ice content), the latter led to almost twice faster tissue cooling. NMR showed a large decrease in diffusion upon lipid crystallization; saturated lipids with higher freezing temperatures were more susceptible to solidification after ice-slurry injection.

Conclusions: Total injected ice content determines both the volume of tissue treated by cryolipolysis and the cooling duration after slurry injection, while slurry temperature affects the cooling rate. Lipid saturation, which varies with diet and anatomic location, also has an important influence.
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http://dx.doi.org/10.1002/lsm.23557DOI Listing
May 2022

Intra-articular opening wedge osteotomy for varus ankle arthritis with computer-assisted planning and patient-specific surgical guides: a retrospective case series.

BMC Musculoskelet Disord 2022 May 21;23(1):483. Epub 2022 May 21.

Tianjin Hospital, Tianjin, 300211, China.

Background: Computer-assisted preoperative planning, combined with PSI has become an effective technique for treating complex limb deformities. The purpose of this study was to evaluate the efficacy and safety of the novel technique in corrective osteotomy for intra-articular varus ankle deformities associated with osteoarthritis and ankle instability.

Methods: Nineteen patients with intra-articular varus ankle arthritis were reviewed between April 2017 and June 2019, including ten men and nine women with a mean age of 58.3 ± 9.9 years (range, 38 to 76 years). All patients underwent intra-articular opening wedge osteotomy assisted by 3D virtual planning and PSI. Weight-bearing radiographs were used to assess the radiographic results, including TAS angle, TT angle, TMM angle, TC angle, TLS angle, opening-wedge angle, and wedge height. Functional outcomes were assessed by the AOFAS score, VAS score, and ROM of the ankle.

Results: The average follow-up time was 32.2 ± 9.0 months (range, 22 to 47 months). The average union time was 4.4 ± 0.9 months (range, 3.0 to 6.5 months). The TAS angle significantly changed from 84.1 ± 4.6° preoperatively to 87.7 ± 3.1° at the 1-year follow-up and 86.2 ± 2.6° at the latest follow-up. Similarly, the TT angle, TMM angle and TC angle changed significantly at the 1-year follow-up compared with the preoperative assessment and remained stable until the last follow-up. However, the TLS was not corrected significantly. The postoperative obtained opening-wedge angle, and wedge height showed no significant change with preoperative planning. The overall complication rate was 15.8%. The mean VAS score improved from 5.3 ± 0.6 to 2.7 ± 0.7. The mean AOFAS score improved from 56.2 ± 7.6 to 80.6 ± 4.6. However, the ROM showed no significant change.

Conclusions: Accurate correction and satisfactory functional recovery were attained with computer-assisted planning and PSI in the corrective osteotomy of intra-articular varus ankle deformities.
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http://dx.doi.org/10.1186/s12891-022-05437-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123770PMC
May 2022

CuO induced Au nanochains for highly sensitive dual-mode detection of hydrogen sulfide.

J Hazard Mater 2022 May 13;436:129144. Epub 2022 May 13.

State Key Laboratory of Heavy Oil Processing, College of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China. Electronic address:

Colorimetric and chemoresistive gas sensing methods have aroused great interest in HS monitoring due to their unique merits of naked-eye readout, and highly sensitive and rapid detection. However, combining these two methods for gas detection, especially utilizing one material as their common sensing material is a grand challenge because they are inconsistent in sensing mechanism. Taking advantage of the strong chemical affinity of CuO for HS and the excellent performance of localized surface plasmon resonance (LSPR) of Au nanoparticles (NPs) in the visible regions and its ability as a noble metal to enhance gas sensing property, the CuO-Au nanochains (NCs) were prepared for dual-mode detection of HS gas. The CuO-Au chemoresistive gas sensor shows a 5-fold higher response than CuO sensor at room temperature with a low detection limit of 10 ppb. Such good performance is attributed to the spillover effect and catalytic activity of Au NPs, and the enhanced HS adsorption after Au loading as revealed by density functional theory calculation. Test strips containing CuO-Au produced for gaseous HS detection show superior color gradient changes (blue, yellow, and brown). Finally, the practicability of the method was validated by real-time monitoring HS released from cell culture.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129144DOI Listing
May 2022

Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes.

Cardiovasc Diabetol 2022 May 20;21(1):80. Epub 2022 May 20.

Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Rd, Shenzhen, 518000, China.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular outcomes in stable coronary artery disease with diabetes. We aimed to assess the relationship between PCSK9 and major adverse cardiovascular events (MACEs) in ST-segment elevation myocardial infarction (STEMI) patients with or without diabetes, as well as the relationships between PCSK9 and metabolism, inflammation and platelet activation markers.

Methods: A total of 1027 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) and without prior lipid-lowering therapy were consecutively enrolled and the baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients were followed up for the occurrence of MACEs. The associations of PCSK9 with metabolism, inflammation and platelet activation markers and MACEs were evaluated.

Results: PCSK9 levels were positively correlated with triglycerides, high-sensitivity C reactive protein, soluble CD40 ligand and soluble P-selectin levels, and the correlations were stronger in diabetic patients than in non-diabetic patients. In diabetic patients receiving ticagrelor, PCSK9 levels were positively correlated with maximal platelet aggregation measured by light transmittance aggregometry and maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots measured by thrombelastography in the maintenance phase of treatment, whereas no correlations were found in non-diabetic patients. During a median follow-up of 2.0 years, 155 (15.1%) MACEs occurred. The Kaplan-Meier analysis displayed that the patients with high PCSK9 levels had lower event-free survival rate than those with low PCSK9 levels (P = 0.030). When participants were categorized into 4 subgroups according to PCSK9 levels and diabetes status, high PCSK9 levels plus diabetes subgroup had the lowest cumulative event-free survival rate (P = 0.043). Multivariable Cox regression analysis revealed that high PCSK9 levels were independently associated with MACEs in diabetic patients (hazard ratio 2.283, 95% confidence interval: 1.094-4.764, P = 0.028), but not in the whole cohort or non-diabetic patients.

Conclusions: The study showed that high PCSK9 levels were independently associated with MACEs in STEMI patients with diabetes undergoing primary PCI, and the association may be due to stronger correlations of PCSK9 with inflammation and platelet activation markers in diabetic patients.
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http://dx.doi.org/10.1186/s12933-022-01519-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123773PMC
May 2022

Detection and Prevention of Virus Infection.

Adv Exp Med Biol 2022 ;1368:21-52

Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

The pathogenic mechanism of viral infection is a complex process involving viral mutation, viral integration, and various aspects of the interaction between the viral genome and the host. Moreover, the virus mutation will lead to the failure of related vaccines, leading to the increasing of vaccine development costs and difficulties in virus prevention. With the accumulation of various types of data, using bioinformatics methods to mine the potential viral characteristics of the pathogenic process can help virus detection and diagnosis, to take intervention measures to prevent disease development or develop effective antiviral therapies. In this chapter, we first outlined traditional approaches and emerging technologies of virus detection and prevention, and then summarized the latest developments in the bioinformatics methods application in different fields of virus researches. The emergence of artificial intelligence provides advanced analysis techniques for revealing key factors of virus infection and has been widely used in the virology community. In particular, we highlight machine learning and deep learning algorithms to identify factors/categories from complex multidimensional data and uncover novel patterns of virus or disease risk prediction.
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http://dx.doi.org/10.1007/978-981-16-8969-7_2DOI Listing
May 2022

Physicochemical characteristics and immunoregulatory activities of polysaccharides from five cultivars of Chrysanthemi Flos.

Food Sci Nutr 2022 May 24;10(5):1391-1400. Epub 2022 Apr 24.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency Tianjin University Tianjin China.

This study compared the physicochemical characteristics and immunomodulatory activities of chrysanthemums' polysaccharides (JPs) from five cultivars. Significant differences were found in the molecular weights, the ratios of monosaccharide compositions, and morphological properties. Polysaccharides of Gongju (GJP) had the lowest molecular weight populations and polysaccharides of Boju (BJP) had the highest. showed that GJP and polysaccharides of Qiju had looser and uniform surface structures, which are beneficial for being developed into instant products. Immunoregulatory assay revealed that JPs enhanced the phagocytosis and proliferation of RAW264.7 cells without obvious cytotoxicity, and upregulated the release level of TNF-, IFN-, and NO. Immune-enhancing activity correlated with their molecular weights, the contents of glucuronic acid and arabinose, and microstructure, which performed differently according to different cultivars. The results suggested that BJP and polysaccharides of Hangbaiju are more suitable to be developed as new functional foods for enhancing immunity, and provided a reference for selection based on the immunization requirements.
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http://dx.doi.org/10.1002/fsn3.2720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094477PMC
May 2022

Modulation of biological motion perception in humans by gravity.

Nat Commun 2022 May 19;13(1):2765. Epub 2022 May 19.

State Key Laboratory of Brain and Cognitive Sciences, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

The human visual perceptual system is highly sensitive to biological motion (BM) but less sensitive to its inverted counterpart. This perceptual inversion effect may stem from our selective sensitivity to gravity-constrained life motion signals and confer an adaptive advantage to creatures living on Earth. However, to what extent and how such selective sensitivity is shaped by the Earth's gravitational field is heretofore unexplored. Taking advantage of a spaceflight experiment and its ground-based analog via 6° head-down tilt bed rest (HDTBR), we show that prolonged microgravity/HDTBR reduces the inversion effect in BM perception. No such change occurs for face perception, highlighting the particular role of gravity in regulating kinematic motion analysis. Moreover, the reduced BM inversion effect is associated with attenuated orientation-dependent neural responses to BM rather than general motion cues and correlated with strengthened functional connectivity between cortical regions dedicated to visual BM processing (i.e., pSTS) and vestibular gravity estimation (i.e., insula). These findings suggest that the neural computation of gravity may act as an embodied constraint, presumably implemented through visuo-vestibular interaction, to sustain the human brain's selective tuning to life motion signals.
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http://dx.doi.org/10.1038/s41467-022-30347-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120521PMC
May 2022

Similarities and differences in working memory and neurometabolism of obsessive-compulsive disorder and major depressive disorder.

J Affect Disord 2022 May 16. Epub 2022 May 16.

Department of Psychiatry, First Affiliated Hospital of Jinan University, Guangzhou 510630, China. Electronic address:

Background: Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) both showed cognitive impairment, and the altered neurometabolic may associate with cognitive impairment. However, there are limited comparative working memory (WM) and neuroimaging studies on these two disorders. Therefore, we investigated the characteristics of WM and neurometabolic changes in patients with OCD and MDD.

Methods: A total of 64 unmedicated patients (32 OCD and 32 MDD), and 33 healthy controls (HC) were included to conduct WM assessment comprising Digit Span Test (DST), 2-back task and Stroop Color and Word Test (SCWT). Additionally, all subjects underwent protons magnetic resonance spectroscopy (H-MRS) to collect neurometabolic ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) in the prefrontal cortex (PFC) and lentiform nucleus (LN). Finally, differential and correlation analysis were conducted to investigate their characteristics and relationships.

Results: Compared with HC, both OCD and MDD patients exhibited a lower accuracy rate in the 2-back task, and only MDD patients performed worse in DST scores and longer reaction times in SCWT (all p < 0.05). Both OCD and MDD patients had lower NAA/Cr ratios in bilateral PFC (all p < 0.05). And the decreased NAA/Cr ratios in right PFC were positively correlated to DST scores in MDD group (r = 0.518, p = 0.003).

Conclusions: Both OCD and MDD showed WM impairment and neurometabolic alterations in PFC. Besides, MDD performed more severe and broader WM impairment compared to OCD. Moreover, the dysfunction of PFC may underlie the neural basis of WM impairment in MDD.
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http://dx.doi.org/10.1016/j.jad.2022.05.069DOI Listing
May 2022

Growth differentiation factor-15 overexpression promotes cell proliferation and predicts poor prognosis in cerebral lower-grade gliomas correlated with hypoxia and glycolysis signature.

Life Sci 2022 May 16;302:120645. Epub 2022 May 16.

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, PR China. Electronic address:

Aims: Growth differentiation factor-15 (GDF15) plays complex and controversial roles in cancer. In this study, the prognostic value and the exact biological function of GDF15 in cerebral lower-grade gliomas (LGGs) and its potential molecular targets were examined.

Main Methods: Wilcoxon signed-rank test and logistic regression were applied to analyze associations between GDF15 expression and clinical characteristics using the Cancer Genome Atlas (TCGA) database. Overall survival was analyzed using Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) and the hypoxia risk model was conducted to identify the potential molecular mechanisms underlying the effects of GDF15 on LGGs tumorigenesis. The biological function of GDF15 was examined using gain- and loss-of-function experiments, and a recombinant hGDF15 protein in LGG SW1783 cells in vitro.

Key Findings: We found that higher GDF15 expression is associated with poor clinical features in LGG patients, and an independent risk factor for overall survival among LGG patients. GSEA results showed that the poor prognostic role of GDF15 in LGGs is related to hypoxia and glycolysis signatures, which was further validated using the hypoxia risk model. Furthermore, GDF15 overexpression facilitated cell proliferation, while GDF15 siRNA inhibits cell proliferation in LGG SW1783 cells. In addition, GDF15 was upregulated upon CoCl2 treatment which induces hypoxia, correlating with the upregulation of the expressions of HIF-1α and glycolysis-related key genes in SW1783 cells.

Significance: GDF15 may promote LGG tumorigenesis that is associated with the hypoxia and glycolysis pathways, and thus could serve as a promising molecular target for LGG prevention and therapy.
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http://dx.doi.org/10.1016/j.lfs.2022.120645DOI Listing
May 2022

CAF-derived midkine promotes EMT and cisplatin resistance by upregulating lncRNA ST7-AS1 in gastric cancer.

Mol Cell Biochem 2022 May 19. Epub 2022 May 19.

Department of Geriatric Surgery, Xiangya Hospital, Central South University, No.87, Xiangya Road, Changsha, 410008, Hunan Province, People's Republic of China.

This study aimed to investigate the role of cancer-associated fibroblast (CAF)-derived midkine (MK) in cisplatin (DDP) resistance. The primary cultures of CAFs and non-cancer fibroblasts (NFs) were isolated and purified. The DDP-resistant gastric cancer (GC) cells were cultured with CAF-conditioned medium. QRT-PCR and Elisa assays were employed to determine MK expression. The expression of ST7-AS1 was measured by qRT-PCR. The impact of CAFs, MK, and ST7-AS1 silencing on DDP resistance was determined by MTT and Annexin V/PI staining assay. Expression of EMT markers and PI3K/AKT was determined by Western blot and qRT-PCR. The role of MK in DDP resistance was confirmed in a xenograft model. Incubation with CAF-conditioned medium increased the IC50 to DDP. Also, incubation with CAF-conditioned medium increased cell viability, reduced cell apoptosis, and promoted EMT in DDP-resistant GC cells, which were all blocked with MK neutralization antibody treatment. MK increased the DDP resistance and upregulated the expression of ST7-AS1 in DDP-resistant GC cells. Additionally, ST7-AS1 knockdown increased the sensitivity to DDP by inhibiting EMT. Moreover, ST7-AS1 knockdown significantly decreased the phosphorylation of PI3K and AKT, and suppressed EMT, which were restored by MK addition. Finally, MK promoted tumor growth and DDP resistance in a mice model bearing the SGC-7901/DDP xenografts. CAF-derived MK promotes EMT-mediated DDP resistance via upregulation of ST7-AS1 and activation of PI3K/AKT pathway.
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http://dx.doi.org/10.1007/s11010-022-04436-xDOI Listing
May 2022

Correlation Between Angiotensin Receptor Type 1 Polymorphisms and Atherosclerotic Cerebral Infarction Risk.

Pharmgenomics Pers Med 2022 11;15:477-485. Epub 2022 May 11.

Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People's Republic of China.

Background: Emerging evidences suggest that the angiotensin receptor type 1 (AT1R) contributes heavily to the pathogenesis of atherosclerotic cerebral infarction (ACI). Herein, we examined a potential link between AT1R gene polymorphisms and ACI risk among a Southern Han Chinese population.

Methods: The rs3772616, rs275645, and rs377262 AT1R polymorphisms were genotyped in 689 ACI patients and 712 healthy controls, using the iMLDR-TM assay.

Results: The genotypic and allelic frequencies of AT1R rs3772616 differed tremendously between ACI patients and healthy controls, and the rs3772616 T allele is a risk allele for ACI. However, the rs275645 and rs377262 allelic and genotypic frequency distributions were comparable between ACI patients and controls. In addition, the G-T-T haplotype was linked to an enhanced risk of ACI. We, next, classified our study subjects based on environmental factors and revealed that the rs3772616 T allele was strongly associated with an elevated ACI risk in males, hypertensive individuals, and those over 65 years old. In addition, we observed a marked link between the rs3772616 T allele and enhanced AT1R levels.

Conclusion: Based on our research, there is a strong correlation between the AT1R rs3772616 polymorphism and enhanced ACI risk. Hence, the AT1R rs3772616 polymorphism can serve as a potential therapeutic target and bioindicator for ACI development.
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http://dx.doi.org/10.2147/PGPM.S364648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109802PMC
May 2022

Prediction of Response to Radiotherapy by Characterizing the Transcriptomic Features in Clinical Tumor Samples across 15 Cancer Types.

Comput Intell Neurosci 2022 9;2022:5443709. Epub 2022 May 9.

Radiation and Cancer Biology Laboratory, Radiation Oncology Center, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Institute and Chongqing Cancer Hospital, Chongqing University Cancer Hospital and Chongqing Cancer, Chongqing 400030, China.

Purpose: Radiotherapy (RT) is one of the major cancer treatments. However, the responses to RT vary among individual patients, partly due to the differences of the status of gene expression and mutation in tumors of patients. Identification of patients who will benefit from RT will improve the efficacy of RT. However, only a few clinical biomarkers were currently used to predict RT response. Our aim is to obtain gene signatures that can be used to predict RT response by analyzing the transcriptome differences between RT responder and nonresponder groups.

Materials And Methods: We obtained transcriptome data of 1664 patients treated with RT from the TCGA database across 15 cancer types. First, the genes with a significant difference between RT responder (R group) and nonresponder groups (PD group) were identified, and the top 100 genes were used to build the gene signatures. Then, we developed the predictive model based on binary logistic regression to predict patient response to RT.

Results: We identified a series of differentially expressed genes between the two groups, which are involved in cell proliferation, migration, invasion, EMT, and DNA damage repair pathway. Among them, MDC1, UCP2, and RBM45 have been demonstrated to be involved in DNA damage repair and radiosensitivity. Our analysis revealed that the predictive model was highly specific for distinguishing the and PD patients in different cancer types with an area under the curve (AUC) ranging from 0.772 to 0.972. It also provided a more accurate prediction than that from a single-gene signature for the overall survival (OS) of patients.

Conclusion: The predictive model has a potential clinical application as a biomarker to help physicians create optimal treatment plans. Furthermore, some of the genes identified here may be directly involved in radioresistance, providing clues for further studies on the mechanism of radioresistance.
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http://dx.doi.org/10.1155/2022/5443709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110128PMC
May 2022

Immune response in COVID-19: what is next?

Cell Death Differ 2022 May 17. Epub 2022 May 17.

The Third Affiliated Hospital of Soochow University/The First People's Hospital of Changzhou, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine of Soochow University, Medical College, Suzhou, China.

The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle and quality in unprecedented ways. A better understanding of immunity and its regulation in response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here the various virus mutations and the evolving disease manifestations along with the alterations of immune responses with specific focuses on the innate immune response, neutrophil extracellular traps, humoral immunity, and cellular immunity. Different types of vaccines were compared and analyzed based on their unique properties to elicit specific immunity. Various therapeutic strategies such as antibody, anti-viral medications and inflammation control were discussed. We predict that with the available and continuously emerging new technologies, more powerful vaccines and administration schedules, more effective medications and better public health measures, the COVID-19 pandemic will be under control in the near future.
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http://dx.doi.org/10.1038/s41418-022-01015-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110941PMC
May 2022
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