Publications by authors named "Wen Huang"

650 Publications

Complete mitochondrial genome of a tropical sea cucumber, .

Mitochondrial DNA B Resour 2021 31;6(10):2788-2790. Epub 2021 Aug 31.

Laboratory of Aquatic Sciences, Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture in Rural Affairs, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China.

In this study, we report the complete mitochondrial genome of The mitogenome was 16,247 base pairs (58.55% A + T content) in length, comprising a total of 37 genes, including 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. To resolve the phylogenetic position of , we analyzed all mitochondrial protein-coding genes from 27 species within the Echinodermata. The results showed that belonged to the family and was more closely related to tropical species ( and ) than to other species. Our results will be useful for evolutionary analysis of sea cucumber species.
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http://dx.doi.org/10.1080/23802359.2021.1967218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425741PMC
August 2021

Landscape of Immune Microenvironment Under Immune Cell Infiltration Pattern in Breast Cancer.

Front Immunol 2021 27;12:711433. Epub 2021 Aug 27.

Department of Nephrology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Increasing evdence supports the suggestion that the immune cell infiltration (ICI) patterns play a pivotal role in tumor progression in breast cancer (BRCA). Nonetheless, there has been no comprehensive analysis of the ICI patterns effects on the clinical outcomes and immunotherapy.

Methods: Multiomic data for BRCA samples were downloaded from TCGA. ESTIMATE algorithm, ssGSEA method, and CIBERSORT analysis were used to uncover the landscape of the tumor immune microenvironment (TIME). BRCA subtypes based on the ICI pattern were identified by consensus clustering and principal-component analysis was performed to obtain the ICI scores to quantify the ICI patterns in individual tumors. Their prognostic value was validated by the Kaplan-Meier survival curves. Gene set enrichment analysis (GSEA) was applied for functional annotation. Immunophenoscore (IPS) was employed to explore the immunotherapeutic role of the ICI scores. Finally, the mutation data was analyzed by using the "maftools" R package.

Results: Three different immune infiltration patterns with a distinct prognosis and biological signature were recognized among 1,198 BRCA samples. The characteristics of TIME under these three patterns were highly consistent with three known immune profiles: immune- excluded, immune-desert, and immune-inflamed phenotypes, respectively. The identification of the ICI patterns within individual tumors based on the ICI score, developed under the ICI-related signature genes, contributed into dissecting biological processes, clinical outcome, immune cells infiltration, immunotherapeutic effect, and genetic variation. High ICI score subtype, characterized with a suppression of immunity, suggested an immune-exhausted phenotype. Abundant effective immune cells were discovered in the low ICI score patients, which corresponded to an immune-activated phenotype and might present an immunotherapeutic advantage. Immunophenoscore was implemented as a surrogate of immunotherapeutic outcome, low-ICI scores samples obtained a significantly higher immunophenoscore. Enrichment of the JAK/STAT and VEGF signal pathways were activated in the ICI low-score subgroup. Finally, the synergistic effect between the ICI score and the tumor mutation burden (TMB) was confirmed.

Conclusion: This work comprehensively elucidated that the ICI patterns served as an indispensable player in complexity and diversity of TIME. Quantitative identification of the ICI patterns in individual tumor will contribute into mapping the landscape of TIME further optimizing precision immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.711433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429934PMC
August 2021

LncRNA LINC00520 aggravates cell proliferation and migration in lung adenocarcinoma via a positive feedback loop.

BMC Pulm Med 2021 Sep 8;21(1):287. Epub 2021 Sep 8.

Department of Oncology, Sir Run Run Hospital of Nanjing Medical University, 109 Longmian Avenue, Jiangning District, Nanjing, China.

Background: Lung adenocarcinoma (LUAD) is the most common histological subtype of primary lung cancer. To identify the biomarker of diagnosis for LUAD is of great significance. Long non-coding RNAs (lncRNAs) were previously revealed to exert vital effects in numerous cancers. LncRNA long intergenic non-protein coding RNA 520 (LINC00520) served as an oncogene in various cancers. Therefore, our study was specially designed to probe the role of LINC00520 in LUAD.

Results: LINC00520 expression was detected by RT-qPCR. Next, function of LINC00520 in LUAD was verified by in vitro loss-of-function experiments. DNA pull down, ChIP, RIP, and luciferase reporter assays were conducted to reveal the regulatory mechanism of LINC00520. We found that LINC00520 was upregulated in LUAD. Additionally, LINC00520 upregulation is associated with the poor prognosis for patients with LUAD. Furthermore, LINC00520 downregulation suppressed LUAD cell proliferation and migration and induced cell apoptosis. Forkhead box P3 (FOXP3) is identified as the transcription factor to transcriptionally activate LINC00520. Moreover, LINC00520 positively upregulated FOXP3 expression via sponging miR-3611 in LUAD cells. Subsequently, rescue experiments delineated that miR-3611 downregulation or FOXP3 overexpression reversed the effects of silenced LINC00520 on proliferative and migratory capabilities in LUAD cells.

Conclusion: This study innovatively indicated that lncRNA LINC00520 facilitated cell proliferative and migratory abilities in LUAD through interacting with miR-3611 and targeting FOXP3, which may provide a potential novel insight for treatment of LUAD.
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http://dx.doi.org/10.1186/s12890-021-01657-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425021PMC
September 2021

Superhydrophilic nickel cyclotetraphosphate for the hydrogen evolution reaction in acidic solution.

Dalton Trans 2021 Sep 2. Epub 2021 Sep 2.

Anhui Laboratory of Clean Catalytic Engineering, Anhui Polytechnic University, China.

Nickel cyclotetraphosphate grown on carbon cloth (NiPO/CC) is synthesized an anion exchange reaction method and it shows excellent hydrogen evolution reaction (HER) activity and strong working stability in acid due to the merits of its unique polymer-like structure, mesoporous characteristics, and superhydrophilic surface.
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http://dx.doi.org/10.1039/d1dt02194jDOI Listing
September 2021

Correction to: LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis.

Mol Cancer 2021 Aug 28;20(1):110. Epub 2021 Aug 28.

Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Building 25, Room 513, 1665 Kongjiang Road, Shanghai, 200092, China.

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http://dx.doi.org/10.1186/s12943-021-01386-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400894PMC
August 2021

Mesoscale Mechanisms in Viscoplastic Deformation of Metals and Their Applications to Constitutive Models.

Materials (Basel) 2021 Aug 19;14(16). Epub 2021 Aug 19.

Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100088, China.

Deformation of metals has attracted great interest for a long time. However, the constitutive models for viscoplastic deformation at high strain rates are still under intensive development, and more physical mechanisms are expected to be involved. In this work, we employ the newly-proposed methodology of mesoscience to identify the mechanisms governing the mesoscale complexity of collective dislocations, and then apply them to improving constitutive models. Through analyzing the competing effects of various processes on the mesoscale behavior, we have recognized two competing mechanisms governing the mesoscale complex behavior of dislocations, i.e., maximization of the rate of plastic work, and minimization of the elastic energy. Relevant understandings have also been discussed. Extremal expressions have been proposed for these two mesoscale mechanisms, respectively, and a stability condition for mesoscale structures has been established through a recently-proposed mathematical technique, considering the compromise between the two competing mechanisms. Such a stability condition, as an additional constraint, has been employed subsequently to close a two-phase model mimicking the practical dislocation cells, and thus to take into account the heterogeneous distributions of dislocations. This scheme has been exemplified in three increasingly complicated constitutive models, and improves the agreements of their results with experimental ones.
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http://dx.doi.org/10.3390/ma14164667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399072PMC
August 2021

Does social trust stimulate university technology transfer? Evidence from China.

PLoS One 2021 25;16(8):e0256551. Epub 2021 Aug 25.

School of Finance, Southwestern University of Finance and Economics, Chengdu, China.

This paper examines the effect of social trust on university technology transfer. A large sample of Chinese universities from the 2007-2017 period was used. We find that social trust facilitates university technology transfer. The finding remain valid after a series of robustness. The mechanism test shows that social trust facilitates university technology transfer by improving the level of university-industry cooperative innovation. Our study suggests that social trust is an important factor that affects university technology transfer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256551PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386828PMC
August 2021

Correction to: Immunological significance of prognostic alternative splicing signature in hepatocellular carcinoma.

Cancer Cell Int 2021 Aug 24;21(1):448. Epub 2021 Aug 24.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No 109. Xueyuan West Road, Wenzhou, 325000, Zhejiang, China.

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http://dx.doi.org/10.1186/s12935-021-02139-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383396PMC
August 2021

Diagnostic value of combined pleural interleukin-33, adenosine deaminase and peripheral blood tuberculosis T cell spot detection TB for tuberculous pleurisy.

BMC Infect Dis 2021 Aug 23;21(1):861. Epub 2021 Aug 23.

Department of Nephrology Medicine, The Second Affiliated Hospital of Wenzhou Medical University, 109, Xueyuan Western Road, Wenzhou, 325027, Zhejiang, People's Republic of China.

Background: To investigate the correlation between pleural fluid interleukin-33 (IL-33) and adenosine deaminase (ADA) and peripheral blood tuberculosis T cell spot detection (T-SPOT.TB), and the combined value of the three tests for the diagnosis of tuberculous pleurisy.

Methods: 79 patients with pleural effusion admitted from June 2017 to December 2018 were enrolled. They were divided into tuberculous pleural effusion (TPE) group (57 cases, 72.2%) and malignant pleural effusion group (17 cases, 21.5%), pneumonia-like pleural effusion group (5 cases, 6.3%). Correlation between pleural fluid IL-33, pleural effusion ADA and peripheral blood T-SPOT.TB was analyzed, comparison of the three separate and combined diagnostic efficacy was also performed.

Results: The levels of IL-33, ADA and peripheral blood T-SPOT.TB in patients with TPE were significantly higher than those in non-TPE (P < 0.001). The level of pleural fluid IL-33 was positively correlated with pleural effusion ADA and peripheral blood T-SPOT.TB. The Area under the ROC curve (AUC) of TPE diagnosed by pleural IL-33, ADA and peripheral blood T-SPOT.TB were 0.753, 0.912 and 0.865, respectively. AUC for combined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB is the largest, with a value of 0.962. Specificity is 100% and sensitivity is 88.5%.

Conclusion: Combined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB can improve the diagnostic efficacy of tuberculous pleurisy.
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http://dx.doi.org/10.1186/s12879-021-06575-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381589PMC
August 2021

Landscape of Prognostic m6A RNA Methylation Regulators in Hepatocellular Carcinoma to Aid Immunotherapy.

Front Cell Dev Biol 2021 5;9:669145. Epub 2021 Aug 5.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy with a high mortality worldwide. N6-methyladenosine (m6A) may participate extensively in tumor progression. To reveal the landscape of tumor immune microenvironment (TIME), ESTIMATE analysis, ssGSEA algorithm, and the CIBERSORT method were used. Taking advantage of consensus clustering, two different HCC categories were screened. We analyzed the correlation of clustering results with TIME and immunotherapy. Then, we yielded a risk signature by systematical bioinformatics analyses. Immunophenoscore (IPS) was implemented to estimate the immunotherapeutic significance of risk signature. The m6A-based clusters were significantly correlated with overall survival (OS), immune score, immunological signature, immune infiltrating, and ICB-associated genes. Risk signature possessed robust prognostic validity and significantly correlated with TIME context. IPS was employed as a surrogate of immunotherapeutic outcome, and patients with low-risk scores showed significantly higher immunophenoscores. Collectively, m6A-based clustering subtype and signature was a robust prognostic indicator and correlated with TIME and immunotherapy, providing novel insight into antitumor management and prognostic prediction in HCC.
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http://dx.doi.org/10.3389/fcell.2021.669145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375309PMC
August 2021

A human forebrain organoid model of fragile X syndrome exhibits altered neurogenesis and highlights new treatment strategies.

Nat Neurosci 2021 Aug 19. Epub 2021 Aug 19.

Department of Psychiatry and Behavioral Scieces, Emory University School of Medicine, Atlanta, GA, USA.

Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP), an RNA-binding protein that can regulate the translation of specific mRNAs. In this study, we developed an FXS human forebrain organoid model and observed that the loss of FMRP led to dysregulated neurogenesis, neuronal maturation and neuronal excitability. Bulk and single-cell gene expression analyses of FXS forebrain organoids revealed that the loss of FMRP altered gene expression in a cell-type-specific manner. The developmental deficits in FXS forebrain organoids could be rescued by inhibiting the phosphoinositide 3-kinase pathway but not the metabotropic glutamate pathway disrupted in the FXS mouse model. We identified a large number of human-specific mRNAs bound by FMRP. One of these human-specific FMRP targets, CHD2, contributed to the altered gene expression in FXS organoids. Collectively, our study revealed molecular, cellular and electrophysiological abnormalities associated with the loss of FMRP during human brain development.
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http://dx.doi.org/10.1038/s41593-021-00913-6DOI Listing
August 2021

Piezo1 initiates platelet hyperreactivity and accelerates thrombosis in hypertension.

J Thromb Haemost 2021 Aug 19. Epub 2021 Aug 19.

Laboratory of Ethnopharmacology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Thrombosis is the pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten human life and health. Among them, nearly half of cardiovascular disease patients suffer from severe hypertension complications. Hypertension is thought to cause abnormal platelet activation and increases the risk of thrombosis, but the related mechanism is still vague.

Objectives: This study hypothesized that the abnormal hemodynamics of blood under hypertension might affect platelet function and accelerate thrombosis by activating mechanoreceptor Piezo1.

Methods: To assess the activation effect of hypertension on mechanoreceptor Piezo1, we injected Piezo1 agonist Yoda1 and antagonist GsMTx-4 through the tail vein, then examined the platelet activation status and thrombosis.

Results: Our results displayed that antagonist GsMTx-4 effectively inhibited calcium influx caused by hypertension and agonist Yoda1. Anti-thrombotic studies proved that the inhibition of Piezo1 effectively inhibited arterial thrombosis and reduced the infarct size of stroke in hypertensive mice.

Conclusions: Our study explains the activation of mechanoreceptor Piezo1 under hypertension is the key to abnormal platelet activation and thrombosis while providing novel platelet intervention strategies to prevent thrombosis.
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http://dx.doi.org/10.1111/jth.15504DOI Listing
August 2021

Immunological Value of Prognostic Signature Based on Cancer Stem Cell Characteristics in Hepatocellular Carcinoma.

Front Cell Dev Biol 2021 2;9:710207. Epub 2021 Aug 2.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Liver cancer stem cells, characterized by self-renewal and initiating cancer cells, were decisive drivers of progression and therapeutic resistance in hepatocellular carcinoma (HCC). However, a comprehensive understanding of HCC stemness has not been identified. RNA sequencing information, corresponding clinical annotation, and mutation data of HCC were downloaded from The Cancer Genome Atlas-LIHC project. Two stemness indices, mRNA expression-based stemness index (mRNAsi) and epigenetically regulated-mRNAsi, were used to comprehensively analyze HCC stemness. Estimation of Stromal and Immune Cells in Malignant Tumors using Expression Data and single-sample gene-set enrichment analysis algorithm were performed to characterize the context of tumor immune microenvironment (TIME). Next, differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify significant mRNAsi-related modules with hub genes. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment pathways were analyzed to functionally annotate these key genes. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to establish a prognostic signature. Kaplan-Meier survival curves and receiver operating characteristic (ROC) analysis were applied for prognostic value validation. Seven algorithms (XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT, and CIBERSORT-ABS) were utilized to draw the landscape of TIME. Finally, the mutation data were analyzed by employing "maftools" package. mRNAsi was significantly elevated in HCC samples. mRNAsi escalated as tumor grade increased, with poor prognosis presenting the higher stemness index. The stemness-related (greenyellow) modules with 175 hub genes were screened based on DEGs and WGCNA. A prognostic signature was established using LASSO analysis of prognostic hub genes to classify samples into two risk subgroups, which exhibited good prognostic performance. Additionally, prognostic risk-clinical nomogram was drawn to estimate risk quantitatively. Moreover, risk score was significantly associated with contexture of TIME and immunotherapeutic targets. Finally, potential interaction between risk score with tumor mutation burden (TMB) was elucidated. This work comprehensively elucidated that stemness characteristics served as a crucial player in clinical outcome, complexity of TIME, and immunotherapeutic prediction from both mRNAsi and mRNA level. Quantitative identification of stemness characteristics in individual tumor will contribute into predicting clinical outcome, mapping landscape of TIME further optimizing precision immunotherapy.
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http://dx.doi.org/10.3389/fcell.2021.710207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365341PMC
August 2021

A bioenergetic shift is required for spermatogonial differentiation.

Cell Discov 2020 Aug 18;6(1):56. Epub 2020 Aug 18.

Department of Animal Sciences, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI, 48824, USA.

A bioenergetic balance between glycolysis and mitochondrial respiration is particularly important for stem cell fate specification. It however remains to be determined whether undifferentiated spermatogonia switch their preference for bioenergy production during differentiation. In this study, we found that ATP generation in spermatogonia was gradually increased upon retinoic acid (RA)-induced differentiation. To accommodate this elevated energy demand, RA signaling concomitantly switched ATP production in spermatogonia from glycolysis to mitochondrial respiration, accompanied by increased levels of reactive oxygen species. Disrupting mitochondrial respiration significantly blocked spermatogonial differentiation. Inhibition of glucose conversion to glucose-6-phosphate or pentose phosphate pathway also repressed the formation of c-Kit differentiating germ cells, suggesting that metabolites produced from glycolysis are required for spermatogonial differentiation. We further demonstrated that the expression levels of several metabolic regulators and enzymes were significantly altered upon RA-induced differentiation, with both RNA-seq and quantitative proteomic analyses. Taken together, our data unveil a critically regulated bioenergetic balance between glycolysis and mitochondrial respiration that is required for spermatogonial proliferation and differentiation.
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http://dx.doi.org/10.1038/s41421-020-0183-xDOI Listing
August 2020

Involvement of kisspeptin in androgen-induced hypothalamic endoplasmic reticulum stress and its rescuing effect in PCOS rats.

Biochim Biophys Acta Mol Basis Dis 2021 Aug 10;1867(12):166242. Epub 2021 Aug 10.

Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. Electronic address:

Endoplasmic reticulum (ER) stress, with adaptive unfolded protein response (UPR), is a key link between obesity, insulin resistance and type 2 diabetes, all of which are often present in the most common endocrine-metabolic disorder in women of reproductive age, polycystic ovary syndrome (PCOS), which is characterized with hyperandrogenism. However, the link between excess androgen and endoplasmic reticulum (ER) stress/insulin resistance in patients with polycystic ovary syndrome (PCOS) is unknown. An unexpected role of kisspeptin was reported in the regulation of UPR pathways and its involvement in the androgen-induced ER stress in hypothalamic neuronal cells. To evaluate the relationship of kisspeptin and ER stress, we detected kisspeptin and other factors in blood plasm of PCOS patients, rat models and hypothalamic neuronal cells. We detected higher testosterone and lower kisspeptin levels in the plasma of PCOS than that in non-PCOS women. We established a PCOS rat model by dihydrotestosterone (DHT) chronic exposure, and observed significantly downregulated kisspeptin expression and activated UPR pathways in PCOS rat hypothalamus compared to that in controls. Inhibition or knockdown of kisspeptin completely mimicked the enhancing effect of DHT on UPR pathways in a hypothalamic neuronal cell line, GT1-7. Kp10, the most potent peptide of kisspeptin, effectively reversed or suppressed the activated UPR pathways induced by DHT or thapsigargin, an ER stress activator, in GT1-7 cells, as well as in the hypothalamus in PCOS rats. Similarly, kisspeptin attenuated thapsigargin-induced Ca response and the DHT- induced insulin resistance in GT1-7 cells. Collectively, the present study has revealed an unexpected protective role of kisspeptin against ER stress and insulin resistance in the hypothalamus and has provided a new treatment strategy targeting hypothalamic ER stress and insulin resistance with kisspeptin as a potential therapeutic agent.
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http://dx.doi.org/10.1016/j.bbadis.2021.166242DOI Listing
August 2021

Effects of drying on the structural characteristics and antioxidant activities of polysaccharides from .

J Food Sci Technol 2021 Sep 6;58(9):3622-3631. Epub 2021 May 6.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070 Hubei China.

We investigated the structural characteristics and antioxidant activities of two types of neutral polysaccharides and two types of acidic polysaccharides from under different drying methods. Fresh were processed with freeze-vacuum drying (FVD) and hot-air drying (HAD). Polysaccharides from the dried (SRP) were purified using a DEAE-52 cellulose column to obtain two types of neutral SRPs (FSRP-1 and HSRP-1) and two types of acidic SRPs (FSRP-2 and HSRP-2). We found that drying can affect the structural characteristics and antioxidant activities of SRPs. Varied monosaccharide compositions were found in FSRP-1, FSRP-2, HSRP-1 and HSRP-2, and HAD-treated SRP had more glucose and less galactose. The (1 → 6)-α-D-Galp linkage was the primary chain in FSRP-1 and HSRP-1, whereas the (1 → 3)-β-D-Glcp was the backbone structure in FSRP-2 and HSRP-2. Our results thus suggest that hot air drying changed the β-configuration in polysaccharides. FSRP-1, FSRP-2, HSRP-1 and HSRP-2 had positive ferric ion reducing antioxidant power and scavenging activities on ABTS and hydroxyl radicals, whereas HSRP exhibited a stronger antioxidant activity than that of FSRP. Hot-air dried could therefore be recommended as a suitable candidate for use in the preparation of antioxidant polysaccharides as functional foods.
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http://dx.doi.org/10.1007/s13197-021-05120-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292488PMC
September 2021

Altered complexity in resting-state fNIRS signal in autism: a multiscale entropy approach.

Physiol Meas 2021 Aug 27;42(8). Epub 2021 Aug 27.

South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510006, People's Republic of China.

Feature extraction and recognition in brain signal processing is of great significance for understanding the neurological mechanism of autism spectrum disorder (ASD). Resting-state (RS) functional near-infrared spectroscopy measurement provides a way to investigate the possible alteration in ASD-related complexity of resting-state (RS) functional near-infrared spectroscopy (fNIRS) signals and to explore the relationship between brain functional connectivity and complexity.Using the multiscale entropy (MSE) of fNIRS signals recorded from the bilateral temporal lobes (TLs) on 25 children with ASD and 22 typical development (TD) children, the pattern of brain complexity was assessed for both the ASD and TD groups.The quantitative analysis of MSE revealed the increased complexity in RS-fNIRS in children with ASD, particularly in the left temporal lobe. The complexity in the RS signal and resting state functional connectivity (RSFC) were also observed to exhibit negative correlation in the medium magnitude.These results indicated that the MSE might serve as a novel measure for RS-fNIRS signals in characterizing and understanding ASD.
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http://dx.doi.org/10.1088/1361-6579/ac184dDOI Listing
August 2021

Reconstruction of the evolutionary biogeography reveal the origins and diversification of oysters (Bivalvia: Ostreidae).

Mol Phylogenet Evol 2021 Jul 22;164:107268. Epub 2021 Jul 22.

Department of Marine Organism Taxonomy and Phylogeny, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, Shandong 266071, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, Shandong 266071, China. Electronic address:

Oysters (Bivalvia: Ostreidae Rafinesque, 1815) live in the intertidal and shallow subtidal areas worldwide. Despite their long evolutionary histories, abundant fossil records, global distribution, and ecological significance, a systematic time-dependent biogeographical analysis of this family is still lacking. Using combined mitochondrial (COI and 16S rRNA) and nuclear (18S rRNA, 28S rRNA, H3 and ITS2) gene makers for 80% (70/88) of the recognized extant Ostreidae, we reconstructed the global phylogenetic and biogeographical relationships throughout the evolutionary history of oysters. The result provided a holistic view of the origin, migration and dispersal patterns of Ostreidae. The phylogenetic results and fossil evidence indicated that Ostreidae originated from the circum-Arctic region in the Early Jurassic. The widening of the Atlantic Ocean and changes in the Tethys Ocean further facilitated their subsequent diversification during the Cretaceous and the Palaeogene periods. In particular, Crassostrea and Saccostrea exhibited relatively low dispersal abilities and their major diversifications were consistent with the tectonic events. Environmental adaptations and reproductive patterns, therefore, should play key roles in the formation of oyster distribution patterners, rather than the dispersal ability of their planktonic larvae. The diversity dynamics inferred by standard phylogenetic are consistent with the fossil record, however, further systematic classification, especially for fossil genus Ostrea, would enhance our understanding on extant and fossil oysters. The present study of the historical biogeography of oysters provides new insights into the evolution and speciation of oysters. Our findings also provide a foundation for the assessment of evolutionary patterns and ecological processes in intertidal and inshore life.
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http://dx.doi.org/10.1016/j.ympev.2021.107268DOI Listing
July 2021

A bivalent cyclic RGD-siRNA conjugate enhances the antitumor effect of apatinib via co-inhibiting VEGFR2 in non-small cell lung cancer xenografts.

Drug Deliv 2021 Dec;28(1):1432-1442

Department of Pharmacy, The Seventh Affiliated Hospital, Southern Medical University, Foshan, Guangdong, China.

The vascular endothelial growth factor receptor 2 (VEGFR2) is considered to be a pivotal target for anti-tumor therapy against angiogenesis of non-small cell lung cancer (NSCLC). However, effective and low-toxicity targeted therapies to inhibit VEGFR2 are still lacking. Here, biRGD-siVEGFR2 conjugate comprising murine VEGFR2 siRNA and [cyclo(Arg-Gly-Asp-D-Phe-Lys)-Ahx]-Glu-PEG-MAL (biRGD) peptide which selectively binds to integrin αvβ3 receptors expressing on neovascularization endothelial cell was synthesized. The anti-tumor activity and renal toxicity of biRGD-siVEGFR2 or its combination therapy with low-dose apatinib were investigated on NSCLC xenografts. The immunogenicity of biRGD-siVEGFR2 was also evaluated in C57BL/6J mice. , intravenously injected biRGD-siVEGFR2 substantially inhibited NSCLC growth with a marked reduction of vessels and a down-regulation of VEGFR2 in tumor tissue. Furthermore, biRGD-siVEGFR2 in combination with low-dose apatinib achieved powerful anti-tumor effect with less nephrotoxicity compared with the regular dose of apatinib. Besides, no obvious immunogenicity of biRGD-siVEGFR2 was found. These findings demonstrate that biRGD-siVEGFR2 conjugate can be used as a new candidate for the treatment of NSCLC and its combination therapy with apatinib may also provide a novel strategy for cancer treatment in clinic.
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http://dx.doi.org/10.1080/10717544.2021.1937381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274511PMC
December 2021

Prenatal ethanol exposure increases maternal bile acids through placental transport pathway.

Toxicology 2021 06 2;458:152848. Epub 2021 Jul 2.

Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. Electronic address:

High maternal serum bile acid level is common and sometimes harmful to the gravida. This study aimed to confirm the bile acid phenotypic change caused by prenatal ethanol exposure (PEE) and elucidate its placental mechanism. Pregnant Wistar rats were administered intragastrically with ethanol 4 g/kg⋅d from gestational day 9-20. Total bile acids (TBA) were detected in maternal, fetal serum and placental tissues, increasing significantly in the serum but no significant change in the placental tissues. Meta-analysis was performed and verified the efficacy of the PEE-induced model based on published data from several relevant studies. Mining of microarray data from human and rat placental sources identified the involvement of bile acid metabolism and its significant genes, which were verified by RT-qPCR and western blotting on tissues and treated BeWo cells with the administration of FXR/PXR siRNAs or FXR/PXR agonists. Our examination, consistent with microarray data and wet experiments, showed that organic anion transporter polypeptide-related protein 2B1 (Oatp2b1), multidrug resistance-associated proteins 3 (Mrp3) and breast cancer resistance protein (Bcrp) expression were increased, while nuclear receptor farnesoid X receptor (Fxr) was decreased but pregnane X receptor (Pxr) was increased. Furthermore, the interventional experiments confirmed that FXR regulated Bcrp while PXR regulated Oatp2b1 and Mrp3. In summary, PEE could induce high bile acid level in maternal serum and its mechanism is associated with the high expression of BCRP/MRP3/OATP2B1 in the placenta through up-regulating PXR and down-regulating FXR, thereby leading to an excessive bile acid transport to maternal blood via the placenta. Our study provides a novel perspective in terms of placenta, explaining the increased maternal blood bile acids under the toxicity of PEE.
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http://dx.doi.org/10.1016/j.tox.2021.152848DOI Listing
June 2021

Multi-omics analysis reveals prognostic value of tumor mutation burden in hepatocellular carcinoma.

Cancer Cell Int 2021 Jul 3;21(1):342. Epub 2021 Jul 3.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No 109. Xueyuan West Road, Wenzhou, 325000, Zhejiang, China.

Background: Hepatocellular carcinoma (HCC) was the sixth common malignancies characteristic with highly aggressive in the world. It was well established that tumor mutation burden (TMB) act as indicator of immunotherapeutic responsiveness in various tumors. However, the role of TMB in tumor immune microenvironment (TIME) is still obscure.

Method: The mutation data was analyzed by employing "maftools" package. Weighted gene co-expression network analysis (WGCNA) was implemented to determine candidate module and significant genes correlated with TMB value. Differential analysis was performed between different level of TMB subgroups employing R package "limma". Gene ontology (GO) enrichment analysis was implemented with "clusterProfiler", "enrichplot" and "ggplot2" packages. Then risk score signature was developed by systematical bioinformatics analyses. K-M survival curves and receiver operating characteristic (ROC) plot were further analyzed for prognostic validity. To depict comprehensive context of TIME, XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT, and CIBERSORT-ABS algorithm were employed. Additionally, the potential role of risk score on immune checkpoint blockade (ICB) immunotherapy was further explored. The quantitative real-time polymerase chain reaction was performed to detect expression of HTRA3.

Results: TMB value was positively correlated with older age, male gender and early T status. A total of 75 intersection genes between TMB-related genes and differentially expressed genes (DEGs) were screened and enriched in extracellular matrix-relevant pathways. Risk score based on three hub genes significantly affected overall survival (OS) time, infiltration of immune cells, and ICB-related hub targets. The prognostic performance of risks score was validated in the external testing group. Risk-clinical nomogram was constructed for clinical application. HTRA3 was demonstrated to be a prognostic factor in HCC in further exploration. Finally, mutation of TP53 was correlated with risk score and do not interfere with risk score-based prognostic prediction.

Conclusion: Collectively, a comprehensive analysis of TMB might provide novel insights into mutation-driven mechanism of tumorigenesis further contribute to tailored immunotherapy and prognosis prediction of HCC.
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http://dx.doi.org/10.1186/s12935-021-02049-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254981PMC
July 2021

MSCs‑derived exosomes attenuate ischemia-reperfusion brain injury and inhibit microglia apoptosis might via exosomal miR-26a-5p mediated suppression of CDK6.

Mol Med 2021 07 2;27(1):67. Epub 2021 Jul 2.

Department of Neurology, Xinqiao Hospital, Third Military Medical University (Army Medical University), No. 188 Xinqiaozheng Street, Chongqing, 400038, People's Republic of China.

Background: This study aimed to explore the role of mesenchymal stromal cells (MSCs)-derived exosomes (MSCs-Exo) in the cerebral ischemia-reperfusion (I/R) injury.

Methods: Exosomes were isolated from MSCs of adult C57BL/6J mice by the gradient centrifugation method. The expression of miR-26a-5p and CDK6 in MSCs-Exo and mice brain tissues were evaluated by qRT-PCR and western blot. miR-26a-5p mimics and miR-NC were transfected into MSCs, and exosomes were isolated from the MSCs stably expressing miR-26a-5p. Then MSCs-Exo-miR-26a-5p mimics or MSCs-Exo-miR-NC was injected into mice through the tail vein, or added into medium to stimulate BV-2 cells. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometry. The apoptosis in brain tissues was evaluated by TUNEL staining assay. Bioinformatics analysis and luciferase reporter assay were performed to determine the binding relationship between miR-26a-5p and CDK6.

Results: miR-26a-5p was downregulated and CDK6 was upregulated in MSCs-Exo of MCAO-mice and OGD-induced MSCs. MSCs-Exo-miR-26a-5p mimics significantly reduced cell apoptosis of OGD-injured BV-2 cells. MSCs-Exo-miR-26a-5p mimics significantly reduced the infarct volume of MCAO-induced mice. Luciferase reporter assay revealed that CDK-6 was a target of miR-26a-5p. In addition, MSCs-Exo-miR-26a-5p mimics significantly decreased the expression of CDK6 in both OGD-induced BV-2 cells and the brain tissues of MCAO-treated mice.

Conclusion: Our results indicated that MSCs‑Exo attenuated I/R injury in mice by inhibiting microglia apoptosis might via exosomal miR-26a-5p mediated suppression of CDK6. Our study shed light on the application of MSC-Exo as a potential therapeutic tool for cerebral I/R injury.
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http://dx.doi.org/10.1186/s10020-021-00324-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254277PMC
July 2021

Single-cell RNA-sequencing atlas reveals an MDK-dependent immunosuppressive environment in ErbB pathway-mutated gallbladder cancer.

J Hepatol 2021 Jun 23. Epub 2021 Jun 23.

Department of Gastroenterology Surgery, Songjiang Central Hospital Affiliated to The First People's Hospital of Shanghai Jiao Tong University, Shanghai, 201600, China.

Background & Aims: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Herein, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression.

Methods: We engaged single-cell RNA-sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBCs and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA-sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between tissues with or without ErbB pathway mutations.

Results: We identified 16 cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and regulatory T cells were predominant in tumors with ErbB pathway mutations. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The tumors with ErbB pathway mutations harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than tumors without ErbB pathway mutations. Increased MDK resulted in an interaction with its receptor LRP1, which is expressed by tumor-infiltrating macrophages, and promoted immunosuppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on regulatory T cells was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival in patients with GBC.

Conclusions: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus, unveiling novel cellular and molecular targets for cancer therapy.

Lay Summary: We employed single-cell RNA-sequencing and functional assays to uncover the transcriptomic heterogeneity and intercellular crosstalk present in gallbladder cancer. We found that ErbB pathway mutations reduced anti-cancer immunity and led to cancer development. ErbB pathway mutations resulted in immunosuppressive macrophage differentiation and regulatory T cell activation, explaining the reduced anti-cancer immunity and worse overall survival observed in patients with these mutations.
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http://dx.doi.org/10.1016/j.jhep.2021.06.023DOI Listing
June 2021

Improvement of Fatigue Symptoms and Endurance Capacity by the Combined Administration of L., Nakai, and Bunge.

J Med Food 2021 Jun;24(6):577-585

Department of Food and Biotechnology, Korea University, Sejong, Korea.

Fatigue is a common phenomenon usually observed in healthy, as well as in nonhealthy, individuals that affects their performance and quality of life. Efficient supplementation to relieve fatigue is of significant importance. This study was designed to investigate the efficacy of three prescreened natural resources ( L. [CEL], Nakai [AGN], and Bunge [AMB]) against fatigue symptoms induced by heavy exercise. Effects on muscle fatigue and endurance capacity during exercise were investigated in C2C12 myoblasts and exercised mice. A combination of CEL, AGN, and AMB (CEL:AGN:AMB, 1:2:1) treatment in myoblasts reduced intracellular reactive oxygen species levels induced by hydrogen peroxide by ∼20 times ( < .001). The optimal mixture extract combination was determined as CEL:AGN:AMB, 1:2:1 (CAA), which was recombined by applying the extraction yield of individual substance for study. Compared to the exercise control (EC) group, the serum lactate dehydrogenase level decreased by ∼40% due to CAA administration. The proliferator-activated receptor gamma coactivator 1-alpha protein expression increased significantly ( < .05) after CAA administration compared to that observed in the normal control group. In parallel, CAA treatment significantly ( < .05) enhanced the maximum running time compared to the EC group. Overall, combinatorial administration exhibited greater efficacy compared to each individual treatment, indicating that CAA could be used as an efficient ergogenic and antifatigue supplement.
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http://dx.doi.org/10.1089/jmf.2020.4743DOI Listing
June 2021

Memristive Artificial Synapses for Neuromorphic Computing.

Nanomicro Lett 2021 Mar 6;13(1):85. Epub 2021 Mar 6.

New Energy Technology Engineering Laboratory of Jiangsu Province and School of Science, Nanjing University of Posts and Telecommunications (NJUPT), Nanjing, 210023, People's Republic of China.

Neuromorphic computing simulates the operation of biological brain function for information processing and can potentially solve the bottleneck of the von Neumann architecture. This computing is realized based on memristive hardware neural networks in which synaptic devices that mimic biological synapses of the brain are the primary units. Mimicking synaptic functions with these devices is critical in neuromorphic systems. In the last decade, electrical and optical signals have been incorporated into the synaptic devices and promoted the simulation of various synaptic functions. In this review, these devices are discussed by categorizing them into electrically stimulated, optically stimulated, and photoelectric synergetic synaptic devices based on stimulation of electrical and optical signals. The working mechanisms of the devices are analyzed in detail. This is followed by a discussion of the progress in mimicking synaptic functions. In addition, existing application scenarios of various synaptic devices are outlined. Furthermore, the performances and future development of the synaptic devices that could be significant for building efficient neuromorphic systems are prospected.
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http://dx.doi.org/10.1007/s40820-021-00618-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006524PMC
March 2021

Evolution of Photoluminescent CdS Magic-Size Clusters Assisted by Adding Small Molecules with Carboxylic Group.

ACS Omega 2021 Jun 28;6(22):14458-14466. Epub 2021 May 28.

Engineering Research Center in Biomaterials, Sichuan University, Chengdu, Sichuan 610065, P. R. China.

We report our investigation on the formation of photoluminescent CdS magic-size clusters (MSCs), which exhibit absorption peaking at 373 nm, along with sharp band edge emission at ∼385 nm. Denoted as MSC-373, the MSCs were synthesized from the reaction of cadmium oleate (Cd(OA)) and S powder in 1-octadecene at room temperature, together with the addition of acetic acid (HOAc) or acetate salts (M(OAc), M = Zn and Mn) during the prenucleation stage (120 °C). The morphology of as-synthesized MSC-373 was dot-like, which could be altered to flake-like morphology after purification. We found the formation of MSC-373 was related to the ligand exchange, resulting from the addition of small molecules with carboxylic group. The addition of HOAc not only promotes the formation of CdS MSC-373 but suppresses the formation of MSC-311 and nucleation and growth of quantum dots (QDs). When the amount of HOAc addition was increased, another photoluminescent CdS MSCs, namely, MSC-406, evolved. This study provides an overall understanding of the CdS MSC-373 and introduces a new approach to synthesize photoluminescent CdS MSCs.
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http://dx.doi.org/10.1021/acsomega.1c01362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190887PMC
June 2021

Immunological Significance of Prognostic DNA Methylation Sites in Hepatocellular Carcinoma.

Front Mol Biosci 2021 26;8:683240. Epub 2021 May 26.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Hepatocellular carcinoma (HCC) is a tumor with high morbidity and high mortality worldwide. DNA methylation, one of the most common epigenetic changes, might serve a vital regulatory role in cancer. To identify categories based on DNA methylation data, consensus clustering was employed. The risk signature was yielded by systematic bioinformatics analyses based on the remarkably methylated CpG sites of cluster 1. Kaplan-Meier analysis, variable regression analysis, and ROC curve analysis were further conducted to validate the prognosis predictive ability of risk signature. Gene set enrichment analysis (GSEA) was performed for functional annotation. To uncover the context of tumor immune microenvironment (TIME) of HCC, we employed the ssGSEA algorithm and CIBERSORT method and performed TIMER database exploration and single-cell RNA sequencing analysis. Additionally, quantitative real-time polymerase chain reaction was employed to determine the LRRC41 expression and preliminarily explore the latent role of LRRC41 in prognostic prediction. Finally, mutation data were analyzed by employing the "maftools" package to delineate the tumor mutation burden (TMB). HCC samples were assigned into seven subtypes with different overall survival and methylation levels based on 5'-cytosine-phosphate-guanine-3' (CpG) sites. The risk prognostic signature including two candidate genes (LRRC41 and KIAA1429) exhibited robust prognostic predictive accuracy, which was validated in the external testing cohort. Then, the risk score was significantly correlated with the TIME and immune checkpoint blockade (ICB)-related genes. Besides, a prognostic nomogram based on the risk score and clinical stage presented powerful prognostic ability. Additionally, LRRC41 with prognostic value was corroborated to be closely associated with TIME characterization in both expression and methylation levels. Subsequently, the correlation regulatory network uncovered the potential targets of LRRC41 and KIAA1429. Finally, the methylation level of KIAA1429 was correlated with gene mutation status. In summary, this is the first to identify HCC samples into distinct clusters according to DNA methylation and yield the CpG-based prognostic signature and quantitative nomogram to precisely predict prognosis. And the pivotal player of DNA methylation of genes in the TIME and TMB status was explored, contributing to clinical decision-making and personalized prognosis monitoring of HCC.
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http://dx.doi.org/10.3389/fmolb.2021.683240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187884PMC
May 2021

Combining Lactate Dehydrogenase and Fibrinogen: Potential Factors to Predict Therapeutic Efficacy and Prognosis of Patients with Small-Cell Lung Cancer.

Cancer Manag Res 2021 31;13:4299-4307. Epub 2021 May 31.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China.

Background: A growing interest exists in identifying reliable and low-cost biomarkers or factors that could predict the therapeutic response, prognosis, recurrence, and survival in small-cell lung cancer (SCLC). This study aimed to investigate the better predictors of chemotherapy efficacy and prognosis in patients with SCLC receiving first-line chemotherapy and radiotherapy.

Materials And Methods: This study retrospectively retrieved the medical records of patients with SCLC treated with first-line platinum-based chemotherapy and radiotherapy from January 2016 to June 2019 in the First Affiliated Hospital of Nanjing Medical University. Plasma biochemical parameters, clinical features, and overall survival (OS) time were collected. The independent effects of plasma parameters on patient survival were assessed by conducting univariate and multivariate Cox regression analyses. The optimal cut-off values of independent risk factors in the ROC curve and Kaplan-Meier survival analysis were determined using MedCalc software.

Results: Statistically significant differences in lactate dehydrogenase (LDH) and fibrinogen (Fbg) were found between the complete remission + partial remission group and the non-responders, which consisted of stable-disease and progressive-disease groups, after first-line chemotherapy. Multivariate Cox regression analysis showed that LDH and Fbg were independent risk factors in predicting PFS (LDH HR: 1.013, 95% CI: 1.002-1.030, = 0.037; Fbg HR: 1.622, 95% CI: 1.094-2.526, = 0.017) and OS (LDH HR: 1.021, 95% CI: 1.008-1.034, = 0.001; Fbg HR: 2.168, 95% CI: 1.324-3.550, = 0.002). The AUC of LDH and Fbg was 0.77 and 0.745, respectively. The cut-off value of LDH and Fbg in predicting OS was 263 U/L and 4.03 g/L. When these two data were combined, the AUC reached 0.832, better than that of LDH and Fbg alone. The objective response rate (ORR) and OS were significantly different among these three different groups according to the addition of the assigned value ( < 0.05).

Conclusion: Combined retreatment serum LDH and Fbg levels may be a better potential biomarker for predicting the clinical efficacy of chemotherapy and the prognosis of individuals with SCLC. Combining these two parameters could improve prediction efficacy.
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http://dx.doi.org/10.2147/CMAR.S300153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178611PMC
May 2021

Efficacy of PD-1 or PD-L1 inhibitors and central nervous system metastases in advanced cancer: a meta-analysis.

Curr Cancer Drug Targets 2021 Jun 1. Epub 2021 Jun 1.

Department of gynecology and obstetrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Little is known about the efficacy of programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in patients with central nervous system (CNS) metastases.

Objective: Assess the difference in efficacy of PD-1 or PD-L1 inhibitors in patients with and without CNS metastases.

Methods: From inception to March 2020, PubMed and Embase were searched for randomized controlled trials (RCTs) about PD-1 or PD-L1 inhibitors. Only trails with available hazard ratios (HRs) for overall survival (OS) of patients with and without CNS metastases simultaneously would be included. Overall survival hazard ratios and their 95% confidence interval (CI) were calculated, and the efficacy difference between these two groups was assessed in the meantime.

Results: 4988 patients (559 patients with CNS metastases and 4429 patients without CNS metastases) from 8 RCTs were included. In patients with CNS metastases, the pooled HR was 0.76 (95%CI, 0.62 to 0.93), while in patients without CNS metastases, the pooled HR was 0.74 (95%CI, 0.68 to 0.79). There was no significant difference in efficacy between these two groups (Χ=0.06 P=0.80).

Conclusion: With no significant heterogeneity observed between patients with or without CNS metastases, patients with CNS metastases should not be excluded from PD-1 or PD-L1 blockade therapy. Future research should permit more patients with CNS metastases to engage in PD-1 or PD-L1 blockade therapy and explore the safety of PD-1 or PD-L1 inhibitors in patients with CNS metastases.
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http://dx.doi.org/10.2174/1568009621666210601111811DOI Listing
June 2021

Genetic basis of variation in cocaine and methamphetamine consumption in outbred populations of .

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Department of Genetics and Biochemistry, Clemson University, Greenwood, SC 29646;

We used to map the genetic basis of naturally occurring variation in voluntary consumption of cocaine and methamphetamine. We derived an outbred advanced intercross population (AIP) from 37 sequenced inbred wild-derived lines of the Genetic Reference Panel (DGRP), which are maximally genetically divergent, have minimal residual heterozygosity, are not segregating for common inversions, and are not infected with We assessed consumption of sucrose, methamphetamine-supplemented sucrose, and cocaine-supplemented sucrose and found considerable phenotypic variation for consumption of both drugs, in both sexes. We performed whole-genome sequencing and extreme quantitative trait locus (QTL) mapping on the top 10% of consumers for each replicate, sex, and condition and an equal number of randomly selected flies. We evaluated changes in allele frequencies among high consumers and control flies and identified 3,033 variants significantly ( < 1.9 × 10) associated with increased consumption, located in or near 1,962 genes. Many of these genes are associated with nervous system development and function, and 77 belong to a known gene-gene interaction subnetwork. We assessed the effects of RNA interference (RNAi) on drug consumption for 22 candidate genes; 17 had a significant effect in at least one sex. We constructed allele-specific AIPs that were homozygous for alternative candidate alleles for 10 single-nucleotide polymorphisms (SNPs) and measured average consumption for each population; 9 SNPs had significant effects in at least one sex. The genetic basis of voluntary drug consumption in is polygenic and implicates genes with human orthologs and associated variants with sex- and drug-specific effects.
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http://dx.doi.org/10.1073/pnas.2104131118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201854PMC
June 2021
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