Publications by authors named "Jia Wen"

144 Publications

Community Composition and Spatial Distribution of N-Removing Microorganisms Optimized by Fe-Modified Biochar in a Constructed Wetland.

Authors:
Wen Jia Liuyan Yang

Int J Environ Res Public Health 2021 Mar 13;18(6). Epub 2021 Mar 13.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.

Microbial nitrogen (N) removal capability can be significantly enhanced in a horizontal subsurface flow constructed wetland (HSCW) amended by Fe-modified biochar (FeB). To further explore the microbiological mechanism of FeB enhancing N removal, - and -denitrifier community diversities, as well as spatial distributions of denitrifiers and anaerobic ammonium oxidation (anammox) bacteria, were investigated in HSCWs (C-HSCW: without biochar and FeB; B-HSCW: amended by biochar; FeB-HSCW: amended by FeB) treating tailwater from a wastewater treatment plant, with C-HSCW without biochar and FeB and B-HSCW amended by biochar as control. The community structures of - and -denitrifiers in FeB-HSCW were significantly optimized for improved N removal compared with the two other HSCWs, although no significant differences in their richness and diversity were detected among the HSCWs. The spatial distributions of the relative abundance of genes involved in denitrification and anammox were more heterogeneous and complex in FeB-HSCW than those in other HSCWs. More and larger high-value patches were observed in FeB-HSCW. These revealed that FeB provides more appropriate habitats for N-removing microorganisms, which can prompt the bacteria to use the habitats more differentially, without competitive exclusion. Overall, the Fe-modified biochar enhancement of the microbial N-removal capability of HSCWs was a result of optimized microbial community structures, higher functional gene abundance, and improved spatial distribution of N-removing microorganisms.
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http://dx.doi.org/10.3390/ijerph18062938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000742PMC
March 2021

An unexpected role for p53 in regulating cancer cell-intrinsic PD-1 by acetylation.

Sci Adv 2021 Mar 31;7(14). Epub 2021 Mar 31.

State Key Laboratory of Medical Molecular Biology and Department of Medical Genetics, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.

Cancer cell-intrinsic programmed cell death protein-1 (PD-1) has emerged as a tumor regulator in an immunity-independent manner, but its precise role in modulating tumor behaviors is complex, and how PD-1 is regulated in cancer cells is largely unknown. Here, we identified PD-1 as a direct target of tumor suppressor p53. Notably, p53 acetylation at K120/164 played a critical role in p53-mediated PD-1 transcription. Acetylated p53 preferentially recruited acetyltransferase cofactors onto PD-1 promoter, selectively facilitating PD-1 transcription by enhancing local chromatin acetylation. Reexpression of PD-1 in cancer cells inhibited tumor growth, whereas depletion of cancer cell-intrinsic PD-1 compromised p53-dependent tumor suppression. Moreover, histone deacetylase inhibitor (HDACi) activated PD-1 in an acetylated p53-dependent manner, supporting a synergistic effect by HDACi and p53 on tumor suppression via stimulating cancer cell-intrinsic PD-1. Our study reveals a mechanism for activating cancer cell-intrinsic PD-1 and indicates that p53-mediated PD-1 activation is critically involved in tumor suppression in an immunity-independent manner.
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http://dx.doi.org/10.1126/sciadv.abf4148DOI Listing
March 2021

Optimization of Tilmicosin-Loaded Nanostructured Lipid Carriers Using Orthogonal Design for Overcoming Oral Administration Obstacle.

Pharmaceutics 2021 Feb 25;13(3). Epub 2021 Feb 25.

Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing 210095, China.

Tilmicosin (TMS) is widely used to treat bacterial infections in veterinary medicine, but the clinical effect is limited by its poor solubility, bitterness, gastric instability, and intestinal efflux transport. Nanostructured lipid carriers (NLCs) are nowadays considered to be a promising vector of therapeutic drugs for oral administration. In this study, an orthogonal experimental design was applied for optimizing TMS-loaded NLCs (TMS-NLCs). The ratios of emulsifier to mixed lipids, stearic acid to oleic acid, drugs to mixed lipids, and cold water to hot emulsion were selected as the independent variables, while the hydrodynamic diameter (HD), drug loading (DL), and entrapment efficiency (EE) were the chosen responses. The optimized TMS-NLCs had a small HD, high DL, and EE of 276.85 ± 2.62 nm, 9.14 ± 0.04%, and 92.92 ± 0.42%, respectively. In addition, a low polydispersity index (0.231 ± 0.001) and high negative zeta potential (-31.10 ± 0.00 mV) indicated the excellent stability, which was further demonstrated by uniformly dispersed spherical nanoparticles under transmission electron microscopy. TMS-NLCs exhibited a slow and sustained release behavior in both simulated gastric juice and intestinal fluid. Furthermore, MDCK-chAbcg2/Abcb1 cell monolayers were successfully established to evaluate their absorption efficiency and potential mechanism. The results of biodirectional transport showed that TMS-NLCs could enhance the cellular uptake and inhibit the efflux function of drug transporters against TMS in MDCK-chAbcg2/Abcb1 cells. Moreover, the data revealed that TMS-NLCs could enter the cells mainly via the caveolae/lipid raft-mediated endocytosis and partially via macropinocytosis. Furthermore, TMS-NLCs showed the same antibacterial activity as free TMS. Taken together, the optimized NLCs were the promising oral delivery carrier for overcoming oral administration obstacle of TMS.
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http://dx.doi.org/10.3390/pharmaceutics13030303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996536PMC
February 2021

In-vitro and in-vivo monitoring of gold(III) ions from intermediate metabolite of sodium aurothiomalate through water-soluble ruthenium (II) complex-based luminescent probe.

Bioorg Chem 2021 Feb 19;110:104749. Epub 2021 Feb 19.

Key Laboratory of Xinjiang Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, China. Electronic address:

Real-time monitoring of drug metabolism in vivo is of great significance to drug development and toxicology research. The purpose of this study is to establish a rapid and visual in vivo detection method for the detection of an intermediate metabolite of the gold (I) drug. Gold (I) drugs such as sodium aurothiomalate (AuTM) have anti-inflammatory effects in the treatment of rheumatoid arthritis. Gold(III) ions (Au) are the intermediate metabolite of gold medicine, and they are also the leading factor of side effects in the treatment of patients. However, the rapid reduction of Au to Au by thiol proteins in organisms limits the in-depth study of metabolism of gold drugs in vivo. Here we describe a luminescence Au probe (RA) based on ruthenium (II) complex for detecting Au in vitro and in vivo. RA with large Stokes shift, good water solubility and biocompatibility was successfully applied to detect Au in living cells and vivo by luminescence imaging, and to trap the fluctuation of Au level produced by gold (I) medicine. More importantly, the luminescent probe was used to the detection of the intermediate metabolites of gold (I) drugs for the first time. Overall, this work offers a new detection tool/method for a deeper study of gold (I) drugs metabolite.
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http://dx.doi.org/10.1016/j.bioorg.2021.104749DOI Listing
February 2021

Nonconservative integration and diversity of a new family of integrative and conjugative elements associated with antibiotic resistance in zoonotic pathogen Streptococcus suis.

Vet Microbiol 2021 Mar 19;254:109009. Epub 2021 Feb 19.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

Macrolide and tetracycline resistance in streptococci is mainly caused by acquisition of integrative and conjugative elements (ICEs) of the ICESa2603 family carrying erm(B) and tet(O). But the characteristics about the transferability and physiological consequences of ICEs with triplet serine integrases are still rare. This study tested the transferability of ICESsuYZDH1_SSU0877, a novel erm(B)- and tet(O)-carrying ICESa2603 family-like ICE with triplet serine integrases, and evaluated the physiological consequences after ICE transferred and integrated into recipient. The prevalence of ICESsuYZDH1-like ICEs in S. suis was analyzed based on 1334 genomic sequences available in GenBank and examined in 330 clinical isolates in China. Nonconservative transfer was observed by integrating of ICESsuYZDH1 into SSU1797 gene besides the primary SSU0877 site. Imperfect direct repeats of 2-/4-nt (5'-TC-3'/5'-TCCC-3') and (5'-GC-3'/5'-TCCC-3') were observed at SSU0877 and SSU1797 sites, respectively. The transconjugant suffered a weak fitness cost with stunted growth and less competition with recipient strain. Successive passages indicate the ICESsuYZDH1 could be persist and endued stable resistant phenotype. Comprehensive analysis of the ICESsuYZDH1-like ICEs from both public genome database and our clinical isolates revealed the widespread and diversity of the ICEs by integration at the sites of SSU0877, SSU0468, SSU1262, and SSU1797. The ICESsuYZDH1-like ICEs could stably co-exist within the host chromosome at more than one attachment sites, which is probably mediated by the triplet serine integrases. Nonconservative integration and diversity of the ICESsuYZDH1 family of ICEs might have contributed to the evolution of ICEs and the dissemination of macrolide and tetracycline resistance in S. suis.
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http://dx.doi.org/10.1016/j.vetmic.2021.109009DOI Listing
March 2021

Metal selectivity and effects of co-existing ions on the removal of Cd, Cu, Ni, and Cr by ZIF-8-EGCG nanoparticles.

Authors:
Jia Wen Xiaohong Hu

J Colloid Interface Sci 2021 May 13;589:578-586. Epub 2021 Jan 13.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082, PR China.

Recently, the developments of MOFs and their applications on heavy metal removal have attracted much attention. In this paper, we focused on the influence of co-existing ions on the adsorbability of epigallocatechin gallate (EGCG) modified ZIF-8 in a multi-metal system (Cd(II), Cu(II), Ni(II), and Cr(VI)). It was found that the adsorption of Cd(II), Cu(II), Ni(II), and Cr(VI) on the ZIF-8-EGCG fitted well with the pseudo second-order kinetic model and Langmuir isotherm. The adsorption selectivity of ZIF-8-EGCG in the mixed metal solution followed the order of Cu(II) ≫ Cr(VI) > Cd(II) > Ni(II). Besides, Cu(II) was the most attractive substance with a maximum capacity of 232.97 mg·g. Copper also disturbed the adsorption of Cd(II) and Ni(II) and contributed the most to the Cr(VI) removal. The natural anions (e.g., Cl, NO, AsO, SO) significantly impeded Cr(VI) adsorption, while low concentrations of natural cations (e.g., K, Na, Ca, and Mg) facilitated the adsorption of Cd(II), Cu(II) and Ni(II).
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http://dx.doi.org/10.1016/j.jcis.2021.01.021DOI Listing
May 2021

MACC1 Contributes to the Development of Osteosarcoma Through Regulation of the HGF/c-Met Pathway and Microtubule Stability.

Front Cell Dev Biol 2020 23;8:825. Epub 2020 Dec 23.

Department of Orthopedics, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.

Osteosarcoma (OS) is the most prevalent human bone malignancy, and presents a global annual morbidity of approximately five cases per million. Notably, precise and efficient targeted therapy has become the most promising strategy for the treatment of OS; however, there is still an urgent need for the identification of suitable therapeutic targets. Metastasis-associated in colon cancer 1 (MACC1) was first identified in colon tumors by differential display RT-PCR, and was shown to be involved in the regulation of colon tumor growth and metastasis through the hepatocyte growth factor (HGF)/c-Met signaling pathway. Additionally, MACC1 overexpression has been reported to induce the growth of several types of cancers, including glioblastoma multiforme and gastric cancer. However, whether MACC1 also plays a role in the progression of OS remains unclear. In this study, we found that MACC1 was highly expressed in human OS tissues, as well as in U-2OS and MG-63 cells, when compared with normal tissues and osteoblasts, respectively. Our data further indicated that MACC1 expression was correlated with several clinicopathological features of OS. Through assays, we found that MACC1 depletion markedly suppressed the proliferative ability of both OS cells and endothelial cells, and inhibited the angiogenic capacity of endothelial cells. Similarly, MACC1 depletion inhibited tumor growth, metastasis, and angiogenesis in mice. Mechanistically, we found that MACC1 could bind to the promoter, and enhanced the proliferation of both OS cells and endothelial cells through the HGF/c-Met signaling pathway. Furthermore, we show that MACC1 also promoted angiogenesis by regulating microtubule dynamics, thereby promoting the progression of OS. Our results indicate that MACC1 may be a new and promising therapeutic target for the treatment of OS.
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http://dx.doi.org/10.3389/fcell.2020.00825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793648PMC
December 2020

Recent Applications of Carbon Nanomaterials for microRNA Electrochemical Sensing.

Chem Asian J 2021 Jan 18;16(2):114-128. Epub 2020 Dec 18.

College of Pharmaceutical Science, Hebei University Institute of Life Science and Green Development, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Baoding, 071002, P. R. China.

MicroRNA (miRNA) is an important tumor marker in the human body, and its early detection has a great influence on the survival rate of patients. Although there are many detection methods for miRNA at present such as northern blotting, real-time quantitative polymerase chain reaction, microarrays, and others, electrochemical biosensors have the advantages of low detection cost, small instrument size, simple operation, non-invasive detection and low consumption of reagents and solvents, and thus they play an important role in the early detection of cancer. In addition, with the development of nanotechnology, nano-biosensors show great potential. The application of various nanomaterials in the development of electrochemical biosensor has greatly improved the detection sensitivity of electrochemical biosensor. Among them, carbon nanomaterials which have unique electrical, optical, physical and chemical properties have attracted increasing attention. In particular, they have a large surface area, good biocompatibility and conductivity. Therefore, carbon nanomaterials combined with electrochemical methods can be used to detect miRNA quickly, easily and sensitively. In this review, we systematically review recent applications of different carbon nanomaterials (carbon nanotubes, graphene and its derivatives, graphitic carbon nitride, carbon dots, graphene quantum dots and other carbon nanomaterials) for miRNA electrochemical detection. In addition, we demonstrate the future prospects of electrochemical biosensors modified by carbon nanomaterials for the detection of miRNAs, and some suggestions for their development in the near future.
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http://dx.doi.org/10.1002/asia.202001260DOI Listing
January 2021

Mobilization or immobilization? The effect of HDTMA-modified biochar on As mobility and bioavailability in soil.

Ecotoxicol Environ Saf 2021 Jan 3;207:111565. Epub 2020 Nov 3.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082, PR China.

Biochar plays an essential role in soil remediation, but its effect on the arsenic remediation has been controversial. In this study, hexadecyl trimethyl ammonium bromide (HDTMA-Br) modified or unmodified biochar on As mobility and bioavailability in soil were studied. The sequential extraction experiment showed that As in the original soil mainly existed in the occluded form (78.24%), followed by Fe‒As (20.72%) and Al‒As (0.88%) forms. With the addition of the modified and unmodified biochars, the contents of Ca‒As and Fe‒As increased by 0.36 - 0.95% and 2.06 - 3.36%, respectively, suggesting the increased potential toxicity of As. The NaHPO extraction result showed that the unmodified biochar increased the As availability by 3.23 - 22.76%, whereas the HDTMA-modified biochar reduced the As availability by 4.80 - 13.41%. Pot experiment showed that the unmodified and modified biochar increased the biomass of Brassica pekinensis, and the modified biochar (HB5) decreased the uptake of As by plants by 80.77% compared to the unmodified biochar. In particular, the plant achieved better growth in the modified biochar treatment (average height 8.31 cm) than in the unmodified biochar treatment (average height 6.97 cm). Therefore, both biochars facilitated phase transformation of As from the stable to the mobile states in the soil. Nevertheless, the HDTMA-modified biochar had an effect on alleviating As bioavailability and toxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111565DOI Listing
January 2021

Construction of immune-related gene pairs signature to predict the overall survival of osteosarcoma patients.

Aging (Albany NY) 2020 11 16;12(22):22906-22926. Epub 2020 Nov 16.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.

The purpose of this study is to establish the prognosis of osteosarcoma patients based on the characteristics of immune-related gene pairs. We used the lasso Cox regression model to construct and verify the signature consisting of 14 immune-related gene pairs. This signature can accurately predict the overall survival of osteosarcoma patients and is an independent prognostic factor for osteosarcoma patients. For this we constructed a signature-based nomogram. The results of the nomogram show that our signature can bring clinical net benefits. We then assessed the abundance of infiltrating immune cells in each sample, and combine the results of the gene set enrichment analysis of a single sample to explore the differences in the immune microenvironment between IRPG signature groups. The result of gene set enrichment analysis shows the strong relationship between signature and immune system. Finally, we evaluated the relationship between signature and immunotherapy efficiency using algorithms such as TIMI and SubMap to explore patients who might benefit from immunotherapy. In conclusion, our signature can predict the overall survival rate of osteosarcoma patients and provide potential guidance for exploring patients who may benefit from immunotherapy.
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http://dx.doi.org/10.18632/aging.104017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746392PMC
November 2020

[Transcriptome analysis of "Langmei" fruits and key enzyme genes structure and function prediction involved in citric acid biosynthesis].

Zhongguo Zhong Yao Za Zhi 2020 Oct;45(19):4606-4616

Anhui University of Chinese Medicine Hefei 230012, China.

Prunus mume "Langmei" is a relict tree species, which fruit has good medicinal value. To understand the biosynthesis pathway of citric acid, the Illumina HiSeq XTen high-throughput sequencing technology was used to get the transcriptome from "Langmei". A total of 38 936 unigenes were obtained by assembling the fruit transcripts, of which 28 311 unigenes were successfully annotated in public databases, 15 193 unigenes were mapped to 265 KEGG metabolic pathways, and 18 908 unigenes were classified into 59 GO functional subclasses, 103 unigenes encoding 15 key enzymes involved in citric acid synthesis pathway were identified and analyzed. The structural model of citrate synthetase in "Langmei" showed that it was a homodimer and the secondary structure of each monomer was mainly composed of alpha helixes. Moreover, the residues in the active site of the citrate synthetase were highly conserved. This study provides a valuable resource for identifying candidate genes involved in the citric acid biosynthesis pathway, and will promote the development and sustainable utilization of genetic resources of "Langmei".
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200627.102DOI Listing
October 2020

Simultaneous immobilization of As and Cd in a mining site soil using HDTMA-modified zeolite.

Environ Sci Pollut Res Int 2021 Feb 7;28(8):9935-9945. Epub 2020 Nov 7.

College of Environmental Science and Engineering, Hunan University, Changsha, 410082, People's Republic of China.

Arsenic (As) and cadmium (Cd) co-contamination has been a typical problem in Chinese agricultural land adjacent to historical metal mining and smelting activities. Remediation of As and Cd in soil has encountered many difficulties owing to the distinct nature of the two metal(loid)s. In this study, we developed a remediation scheme by adding a hexadecyltrimethylammonium (HDTMA)-modified zeolite to a mining site soil and evaluated the immobilization effect. The result of the increased surface zeta potential indicates that the HDTMA modification conferred the zeolite with adsorbability towards As through the cationic surfactant head. The addition of the highest dosage of HDTMA-modified zeolite (10%) to the contaminated soil greatly improved soil organic matter by 1.4 times, partly due to the elevated C loading on the zeolite from HDTMA. Sequential extraction results show that the addition of HDTMA-modified zeolite not only increased the residual fraction of As (by 2.7-5.9%) but also reduced the toxicity-related fraction (by 2.3-2.7%) when compared to the unmodified zeolite and blank treatments. The oxidizable fractions of Cd in the modified zeolite treatment were significantly higher than that in the blank soil. Besides, the exchangeable fractions of Cd were all significantly reduced in the zeolite treatments. Enzyme activity assays show that the HDTMA-modified zeolite treatment could greatly improve soil microbial environment. The physiologically based extraction test (PBET) also proved that the bioavailability of As and Cd was reduced after the modified zeolite treatment.
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http://dx.doi.org/10.1007/s11356-020-11477-6DOI Listing
February 2021

Association of CNVs with methylation variation.

NPJ Genom Med 2020 24;5:41. Epub 2020 Sep 24.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115 USA.

Germline copy number variants (CNVs) and single-nucleotide polymorphisms (SNPs) form the basis of inter-individual genetic variation. Although the phenotypic effects of SNPs have been extensively investigated, the effects of CNVs is relatively less understood. To better characterize mechanisms by which CNVs affect cellular phenotype, we tested their association with variable CpG methylation in a genome-wide manner. Using paired CNV and methylation data from the 1000 genomes and HapMap projects, we identified genome-wide associations by methylation quantitative trait locus (mQTL) analysis. We found individual CNVs being associated with methylation of multiple CpGs and vice versa. CNV-associated methylation changes were correlated with gene expression. CNV-mQTLs were enriched for regulatory regions, transcription factor-binding sites (TFBSs), and were involved in long-range physical interactions with associated CpGs. Some CNV-mQTLs were associated with methylation of imprinted genes. Several CNV-mQTLs and/or associated genes were among those previously reported by genome-wide association studies (GWASs). We demonstrate that germline CNVs in the genome are associated with CpG methylation. Our findings suggest that structural variation together with methylation may affect cellular phenotype.
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http://dx.doi.org/10.1038/s41525-020-00145-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519119PMC
September 2020

Cell-type-specific 3D epigenomes in the developing human cortex.

Nature 2020 11 14;587(7835):644-649. Epub 2020 Oct 14.

Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.

Lineage-specific epigenomic changes during human corticogenesis have been difficult to study owing to challenges with sample availability and tissue heterogeneity. For example, previous studies using single-cell RNA sequencing identified at least 9 major cell types and up to 26 distinct subtypes in the dorsal cortex alone. Here we characterize cell-type-specific cis-regulatory chromatin interactions, open chromatin peaks, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational samples of the human cortex. We show that chromatin interactions underlie several aspects of gene regulation, with transposable elements and disease-associated variants enriched at distal interacting regions in a cell-type-specific manner. In addition, promoters with increased levels of chromatin interactivity-termed super-interactive promoters-are enriched for lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of transcription. Finally, we develop CRISPRview, a technique that integrates immunostaining, CRISPR interference, RNAscope, and image analysis to validate cell-type-specific cis-regulatory elements in heterogeneous populations of primary cells. Our findings provide insights into cell-type-specific gene expression patterns in the developing human cortex and advance our understanding of gene regulation and lineage specification during this crucial developmental window.
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http://dx.doi.org/10.1038/s41586-020-2825-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704572PMC
November 2020

Chinese herbal medicine reduces mortality in patients with severe and critical Coronavirus disease 2019: a retrospective cohort study.

Front Med 2020 Dec 14;14(6):752-759. Epub 2020 Sep 14.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.

This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076-0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023-1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028-0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19.
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http://dx.doi.org/10.1007/s11684-020-0813-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488644PMC
December 2020

Targeted antimicrobial peptide delivery in vivo to tumor with near infrared photoactivated mesoporous silica nanoparticles.

Int J Pharm 2020 Oct 13;588:119767. Epub 2020 Aug 13.

School of Life Science, Liaoning Normal University, Dalian 116081, China; Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116081, China. Electronic address:

Antimicrobial peptide PA-C1b (chensinin-1b conjugated with palmitic acid) showed potent anticancer activity with no obvious hemolytic activity, which made it a potential agent for treating cancers. However, after in vivo administration, peptides can be degraded by proteases because there is no effective protection. In this study, a tumor-targeting photoresponsive antimicrobial peptide delivery system was developed, and the peptide PA-C1b labeled with the dye sulfo-cyanine7 (Cy7) was loaded into mesoporous silica nanoparticles (MSNs). The final MSN@Cy7-PA-C1b nanoparticles were wrapped by graphene oxide (GO), and then folic acid was conjugated to the surface of the MSNs for targeting purposes. The final MSN@Cy7-PA-C1b@FA-GO nanoparticles were constructed to allow light-mediated peptide release and folate receptor-targeted cancer therapy. The Cy7 dye serves as a real-time indicator, and GO acts as a gatekeeper to prevent leakage of the loaded peptides in the absence of near-infrared light irradiation. Upon light irradiation, the GO wrapping detaches, and the photoresponsive peptide delivery system works well both in in vitro cell experiments and during in vivo administration in mouse tumor experiments. The construction of the MSN@Cy7-PA-C1b@FA-GO platform provides a novel approach to deliver antimicrobial peptides in vivo for the treatment of infections by pathogenic microorganisms and cancers.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119767DOI Listing
October 2020

[Analysis of medication regularity and pharmacodynamic characteristics of traditional Chinese medicine treatment in 444 severe cases of COVID-19].

Zhongguo Zhong Yao Za Zhi 2020 Jul;45(13):3007-3012

Wuhan Hospital of Traditional Chinese and Western Medicine Wuhan 430022, China.

The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no effective intervention for the severe patients, and their prognosis is poor. It is worth noting that in the fight against COVID-19, China has always put equal emphasis on both Chinese and Western medicine. Traditional Chinese medicine has played an important role in the whole process. It is of great significance to discuss the rules and characteristics of the prescription of traditional Chinese medicine in the treatment of COVID-19. In this study, information was collected from 444 severe COVID-19 patients who were admitted to a hospital designated to treat patients with severe COVID-19 in Wuhan before March 20, 2020. We collected traditional Chinese medicine prescriptions for patients with severe COVID-19, referred to Chinese Pharmacopoeia to standardize the names of traditional Chinese medicine, and extract the property, flavor and channel tropism of traditional Chinese medicines to analyze the rules of the prescriptions. IBM SPSS Modeler 18.0 software was used to conduct correlation analysis of traditional Chinese medicine. Effective traditional Chinese medicines against COVID-19 was identified by the TCMATCOV platform. In the end, 1 532 effective prescriptions were included. Among them, the high-frequency drugs are Poria, Astragali Radix, Pogostemonis Herba, Armeniacae Semen Amarum, Atractylodis Macrocephalae Rhizoma, Pinelliae Rhizoma, Glycyrrhizae Radix et Rhizoma, Magnoliae Officinalis Cortex, Ephedrae Herba, Cinna-momi Ramulus. Most of the drugs have the following functions: resolving dampness, replenishing deficiency, resolving phlegm, cough, and asthma. The core combinations are Pogostemonis Herba-Poria, Astragali Radix-Pogostemonis Herba-Poria, Amomi Fructus-Poria, Amomi Fructus-Pogostemonis Herba, Amomi Fructus-Astragali Radix. The majority of the medicines are with cold and warm properties, and the proportions are 41.03% and 38.46%, respectively. The medicinal flavors are mainly concentrated in sweet and bitter, and the proportions are 34.71% and 30.58%, respectively. The meridian of the drug is more into the lung, stomach and spleen, with lung accounting for 22.87%. From the analysis of high-frequency drugs to the core combinations, one can see that the main treatment principle for severe COVID-19 is to remove internal and external dampness, protect the spleen and stomach, remove evil energy, and support righteousness. TCMATCOV platform was used to calculate the network disturbances of the high-frequency drugs. It was found that the traditional Chinese medicine with a high disturbance score accounted for a high proportion of the classic anti-COVID-19 prescriptions used by clinicians. Among them, the drugs with top scores are Ephedrae Herba, Citri Reticulatae Pericarpium, Eupatorii Herba, Platycodonis Radix, Cinnamomi Ramulus, Astragali Radix, Magnoliae Officinalis Cortex, Atractylodis Macrocephalae Rhizoma, Pogostemonis Herba, Scutellariae Radix. After a further exploration of the action targets, it was showed that disease-specific factor TNF was the target of the above ten drugs, and traditional Chinese medicine can exert anti-inflammatory and immune-modulating effects.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200427.501DOI Listing
July 2020

Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT.

Oncotarget 2020 Jul 7;11(27):2611-2624. Epub 2020 Jul 7.

Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India.

Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are central to metastatic aggressiveness and therapy resistance in solid tumors. While molecular determinants of both processes have been extensively characterized, the heterogeneity in the response of tumor cells to EMT and MET inducers has come into focus recently, and has been implicated in the failure of anti-cancer therapies. Recent experimental studies have shown that some cells can undergo an irreversible EMT depending on the duration of exposure to EMT-inducing signals. While the irreversibility of MET, or equivalently, resistance to EMT, has not been studied in as much detail, evidence supporting such behavior is slowly emerging. Here, we identify two possible mechanisms that can underlie resistance of cells to undergo EMT: epigenetic feedback in ZEB1/GRHL2 feedback loop and stochastic partitioning of biomolecules during cell division. Identifying the ZEB1/GRHL2 axis as a key determinant of epithelial-mesenchymal plasticity across many cancer types, we use mechanistic mathematical models to show how GRHL2 can be involved in both the abovementioned processes, thus driving an irreversible MET. Our study highlights how an isogenic population may contain subpopulation with varying degrees of susceptibility or resistance to EMT, and proposes a next set of questions for detailed experimental studies characterizing the irreversibility of MET/resistance to EMT.
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http://dx.doi.org/10.18632/oncotarget.27651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343638PMC
July 2020

Fe-modified biochar enhances microbial nitrogen removal capability of constructed wetland.

Sci Total Environ 2020 Oct 20;740:139534. Epub 2020 May 20.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China. Electronic address:

To improve the nitrogen removal capability of constructed wetlands, the biochar, produced from bamboo, activated with HCl and coated with Fe (FeCl·6HO), and then was added as a substrate into the systems. Three horizontal subsurface flow constructed wetlands (HSCWs) was established to treat the low C/N tailwater from the wastewater treatment plant: C-HSCW (quartz sand + soil), B-HSCW (quartz sand + soil + unmodified biochar), and FeB-HSCW (quartz sand + soil + Fe-modified biochar). Under different combinations of hydraulic retention time and nitrogen loading, the FeB-HSCW revealed extremely effective nitrogen removal, compared to the C-HSCW and B-HSCW. The highest removal efficiencies of NO-N (95.30%), TN (86.68%), NH-N (86.33%), NO-N (79.35%) and COD (63.36%) were obtained in FeB-HSCW with the hydraulic retention time of 96 h. and low influent nitrogen loading (C/N of 2.5). Nitrogen mass balance analysis showed that microbial processes played the most important role of nitrogen removal in HSCWs and the Fe-modified biochar significantly enhanced the microbial nitrogen removal. A total of 128.40 g nitrogen was removed by microorganisms in FeB-HSCW (average removal rate of 2.52 g N/(m·d)), much higher than that in other two HSCWs. The contributions of microorganisms, substrate storage and plant uptake on the total amount of nitrogen removal in the FeB-HSCW was 92.69%, 2.97% and 4.34%, respectively. Moreover, FeB significantly increased the abundances of genes involved in nitrogen removal. The copy numbers of bacterial 16S rRNA and amx, as well as of genes nirS, nirK, nosZ-I, nosZ-II, and hzsA were 1.3- to 27.8-fold higher in the FeB-HSCW than that in the other two HSCWs. Thus, Fe-modified biochar provides a feasible and effective amendment for constructed wetlands to improve the nitrogen removal, particularly nitrate-N, for low C/N wastewaters by enhancing the microbial nitrogen removal capacity (mainly of the denitrification).
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http://dx.doi.org/10.1016/j.scitotenv.2020.139534DOI Listing
October 2020

Phosphoinositide 3-kinase γ deficiency attenuates kidney injury and fibrosis in angiotensin II-induced hypertension.

Nephrol Dial Transplant 2020 09;35(9):1491-1500

Division of Nephrology, Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.

Background: We have shown that the CXCL16/CXCR6 axis plays a critical role in recruiting inflammatory cells and bone marrow-derived fibroblasts into the kidney leading to renal injury and fibrosis. However, the underlying signaling mechanisms are not known.

Methods: In the present study, we examined the role of phosphoinositide-3 kinase γ (PI3Kγ) signaling in the recruitment of inflammatory cells and bone marrow-derived fibroblasts into the kidney and development of renal injury and fibrosis in an experimental model of hypertension induced by angiotensin II.

Results: Blood pressure was comparable between wild-type (WT) and PI3Kγ knockout (KO) mice at baseline. Angiotensin II treatment led to an increase in blood pressure that was similar between WT and PI3Kγ KO mice. Compared with WT mice, PI3Kγ KO mice were protected from angiotensin II-induced renal dysfunction and injury and developed less proteinuria. PI3Kγ deficiency suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the kidney and inhibited total collagen deposition and extracellular matrix protein production in the kidney in response to angiotensin II. PI3Kγ deficiency inhibited the infiltration of F4/80+ macrophages and CD3+ T cells into the kidney and reduced gene expression levels of pro-inflammatory cytokines in the kidney following angiotensin II treatment. Finally, inhibition of PI3Kγ suppressed CXCL16-induced monocyte migration in vitro.

Conclusion: These results indicate that PI3Kγ mediates the influx of macrophages, T cells and bone marrow-derived fibroblasts into the kidney resulting in kidney injury and fibrosis.
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http://dx.doi.org/10.1093/ndt/gfaa062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778344PMC
September 2020

MnO-Based nanosystems for cancer therapy.

Chem Commun (Camb) 2020 Jul 4;56(52):7065-7079. Epub 2020 Jun 4.

Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Science, Hebei University, Baoding 071002, China.

Cancer is one of the most dangerous diseases worldwide, the treatment of which is still a great problem. The increasing demand of clinical biomedicine and fast development of nanotechnology have quickly promoted the generation of diverse nanosystems for various cancer therapies. As one kind of redox active transition-metal dioxide nanomaterials, manganese dioxide (MnO) and its nanocomposites have emerged as a novel class of nanomaterials that show superior advantages and unprecedented performances in cancer therapy due to their large surface area, good absorption and degradation ability, strong fluorescence quenching ability, high oxidation and catalytic activity, etc. According to different morphologies of MnO, MnO can be divided into MnO nanosheets, MnO quantum dots (QDs), MnO nanocrystals, MnO nanowires, etc. In this review, the synthesis of MnO, especially MnO nanosheets, is first introduced, followed by an introduction of the classification of MnO nanomaterials. Then, recent cancer therapeutic applications of MnO and its nanocomposites are comprehensively overviewed, which are categorized into three parts: chemotherapy, phototherapy and synergistic therapy. In addition, treatment of other diseases based on MnO and its nanocomposites is also discussed. Finally, some crucial unresolved problems, probable challenges and future perspectives about the rational design and construction of MnO-based nanosystems for further biomedical applications are also discussed.
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http://dx.doi.org/10.1039/d0cc02782kDOI Listing
July 2020

Identification of single nucleotide pleomorphisms associated with periodontal disease in head and neck cancer irradiation patients by exome sequencing.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 Jul 22;130(1):32-42.e4. Epub 2020 May 22.

Department of Oral Medicine, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA; College of Computing and Informatics, Department of Bioinformatics and Genomics, UNC-Charlotte, Charlotte, NC, USA. Electronic address:

Objective: Periodontal disease (PD) is a common oral complication in patients with head and neck cancer (HNC) undergoing radiation therapy (RT). Our objective was to identify candidate single nucleotide polymorphisms (SNPs) associated with PD in radiation-treated patients with HNC.

Study Design: DNA was extracted from the saliva of patients with HNC (n = 69) before RT. Clinical attachment loss (CAL) increment greater than 0.2 mm over 24 months after RT was used to define PD progression. After exome sequencing, SNPs associated with post-RT PD progression were identified by using logistic regression and homozygosity analyses. The web tools STRING, the Database for Annotation, Visualization and Integrated Discovery (DAVID), GeneCodis, and Ensembl Variant Effect Predictor were used for functional analysis.

Results: Of the 48 patients with HNC with post-RT PD progression, 24 had no tooth with 5 mm or greater pocket depth before RT, whereas of the 21 patients with HNC without progression, 11 had PD initially. A total of 330 SNPs (249 genes) with over-represented homozygous genotype (98.5% variant allele) were found to be associated with post-RT PD. Sixty of these corresponded to PD-related pathways, including previously identified genes. In patients with HNC with post-RT PD progression, SNPs were found in genes (n = 10) in contrast to those without progression (n = 7).

Conclusions: The SNPs of collagen genes were identified, potentially defining susceptibility to PD in patients with HNC, and this could be further investigated to characterize PD drug targets.
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http://dx.doi.org/10.1016/j.oooo.2020.02.013DOI Listing
July 2020

Discriminative Transfer Learning for Driving Pattern Recognition in Unlabeled Scenes.

IEEE Trans Cybern 2020 May 12;PP. Epub 2020 May 12.

Driving pattern recognition based on features, such as GPS, gear, and speed information, is essential to develop intelligent transportation systems. However, it is usually expensive and labor intensive to collect a large amount of labeled driving data from real-world driving scenes. The lack of a labeled data problem in a driving scene substantially hinders the driving pattern recognition accuracy. To handle the scarcity of labeled data, we have developed a novel discriminative transfer learning method for driving pattern recognition to leverage knowledge from related scenes with labeled data to improve recognition performance in unlabeled scenes. Note that data from different scenes may have different distributions, which is a major bottleneck limiting the performance of transfer learning. To address this issue, the proposed method adopts a discriminative distribution matching scheme with the aid of pseudolabels in unlabeled scenes. It is able to reduce the intraclass distribution disagreement for the same driving pattern among labeled and unlabeled scenes while increasing the interclass distance among different patterns. Pseudolabels in unlabeled scenes are updated iteratively via an ensemble strategy that preserves the data structure while enhancing the model robustness. To evaluate the performance of the proposed method, we conducted comprehensive experiments on real-world parking lot datasets. The results show that the proposed method can substantially outperform state-of-the-art methods in driving pattern recognition.
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http://dx.doi.org/10.1109/TCYB.2020.2987632DOI Listing
May 2020

Ancient Genomes Reveal the Evolutionary History and Origin of Cashmere-Producing Goats in China.

Mol Biol Evol 2020 07;37(7):2099-2109

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.

Goats are one of the most widespread farmed animals across the world; however, their migration route to East Asia and local evolutionary history remain poorly understood. Here, we sequenced 27 ancient Chinese goat genomes dating from the Late Neolithic period to the Iron Age. We found close genetic affinities between ancient and modern Chinese goats, demonstrating their genetic continuity. We found that Chinese goats originated from the eastern regions around the Fertile Crescent, and we estimated that the ancestors of Chinese goats diverged from this population in the Chalcolithic period. Modern Chinese goats were divided into a northern and a southern group, coinciding with the most prominent climatic division in China, and two genes related to hair follicle development, FGF5 and EDA2R, were highly divergent between these populations. We identified a likely causal de novo deletion near FGF5 in northern Chinese goats that increased to high frequency over time, whereas EDA2R harbored standing variation dating to the Neolithic. Our findings add to our understanding of the genetic composition and local evolutionary process of Chinese goats.
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http://dx.doi.org/10.1093/molbev/msaa103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306693PMC
July 2020

Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia.

Nat Commun 2020 04 15;11(1):1842. Epub 2020 Apr 15.

Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.

Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.
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http://dx.doi.org/10.1038/s41467-020-15707-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160146PMC
April 2020

A parallelized strategy for epistasis analysis based on Empirical Bayesian Elastic Net models.

Bioinformatics 2020 06;36(12):3803-3810

Department of Computer and Information Sciences, Temple University, Philadelphia, PA 19122, USA.

Motivation: Epistasis reflects the distortion on a particular trait or phenotype resulting from the combinatorial effect of two or more genes or genetic variants. Epistasis is an important genetic foundation underlying quantitative traits in many organisms as well as in complex human diseases. However, there are two major barriers in identifying epistasis using large genomic datasets. One is that epistasis analysis will induce over-fitting of an over-saturated model with the high-dimensionality of a genomic dataset. Therefore, the problem of identifying epistasis demands efficient statistical methods. The second barrier comes from the intensive computing time for epistasis analysis, even when the appropriate model and data are specified.

Results: In this study, we combine statistical techniques and computational techniques to scale up epistasis analysis using Empirical Bayesian Elastic Net (EBEN) models. Specifically, we first apply a matrix manipulation strategy for pre-computing the correlation matrix and pre-filter to narrow down the search space for epistasis analysis. We then develop a parallelized approach to further accelerate the modeling process. Our experiments on synthetic and empirical genomic data demonstrate that our parallelized methods offer tens of fold speed up in comparison with the classical EBEN method which runs in a sequential manner. We applied our parallelized approach to a yeast dataset, and we were able to identify both main and epistatic effects of genetic variants associated with traits such as fitness.

Availability And Implementation: The software is available at github.com/shilab/parEBEN.
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http://dx.doi.org/10.1093/bioinformatics/btaa216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320619PMC
June 2020

Feeling the Burn: Intestinal Epithelial Cells Modify Their Lipid Metabolism in Response to Bacterial Fermentation Products.

Cell Host Microbe 2020 03;27(3):314-316

Department of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address:

Intestinal epithelial absorption of dietary lipids is a major determinant of animal energy balance and metabolic health. Recent studies uncovered significant roles for intestinal microbiota in this process, but underlying mechanisms remain unresolved. Araújo et al. (2020) identify two end-products of bacterial fermentation that regulate intestinal lipid absorption and metabolism.
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http://dx.doi.org/10.1016/j.chom.2020.02.009DOI Listing
March 2020

[Discussion on registry study of acupuncture-moxibustion for malignant pleural effusion].

Zhongguo Zhen Jiu 2020 Feb;40(2):217-20

Third Affiliated Hospital of Beijing University of CM, Beijing 100029, China.

Malignant pleural effusion (MPE) is one of the common complications of tumor. Acupuncture-moxibustion therapy has several advantages for treatment of MPE. Acupuncture is regarded as a complex individualized intervention, and its characteristics of TCM is difficult to be reflected by strict randomized controlled trials. The registry study provides more possibilities for the data collection of individualized diagnosis and treatment under the guidance of the overall concept and syndrome differentiation, and is more suitable for data management and collection of large samples and multi-center trials in the real-world study. It has become an opportunity to carry out real-world study of acupuncture for MPE. There are many challenges in the registry study of acupuncture for MPE. However, it is of great significance to collect real-world data of acupuncture for MPE to improve the clinical effect of MPE and provide a new clinical research method for acupuncture in tumors and related complications.
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http://dx.doi.org/10.13703/j.0255-2930.20190221-00014DOI Listing
February 2020

Meta-Analysis of Hematological Biomarkers as Reliable Indicators of Soft Tissue Sarcoma Prognosis.

Front Oncol 2020 30;10:30. Epub 2020 Jan 30.

Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Several recent studies have reported the reliable prognostic effect of hematological biomarkers in various tumors. Yet, the prognostic value of these hematological markers in soft tissue sarcoma (STS) remains inconclusive. Thus, the aim of this meta-analysis was to check the effect of hematological markers on the prognosis of STS. We systematically searched for relevant papers published before October 2019 in the PubMed and EMBASE databases. Overall survival (OS) and disease-specific survival (DSS) were the primary outcome, whereas disease-free survival was the secondary outcome. A thorough study of hazard ratios (HR) and 95% of confidence intervals (CIs) was done for determining the prognostic significance. We performed 23 studies that comprised of 4,480 patients with STS. The results revealed that higher neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and platelet-to-lymphocyte ratio (PLR) were associated with poor OS/DFS (HR = 2.08/1.72, for NLR; HR = 1.92/1.75, for CRP, and HR = 1.86/1.61, for PLR). In contrast, a low lymphocyte-to-monocyte ratio (LMR) was relate to worse OS/DFS (HR = 2.01/1.90, for LMR). Moreover, pooled analysis illustrated that elevated NLR and CRP represents poor DSS, with HRs of 1.46 and 2.06, respectively. In addition, combined analysis revealed that higher Glasgow prognostic score (GPS) was linked to an adverse OS/DSS (HR = 2.35/2.77). Our meta-analysis suggested that hematological markers (NLR, CRP, PLR, LMR, and GPS) are one of the important prognostic indicators for patients affected by high-grade STS and patients with the STS being located in the extremity.
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http://dx.doi.org/10.3389/fonc.2020.00030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002470PMC
January 2020

LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62.

Aging Cell 2020 03 19;19(3):e13102. Epub 2020 Feb 19.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

In female mammals, the size of the initially established primordial follicle (PF) pool within the ovaries determines the reproductive lifespan of females. Interestingly, the establishment of the PF pool is accompanied by a remarkable programmed oocyte loss for unclear reasons. Although apoptosis and autophagy are involved in the process of oocyte loss, the underlying mechanisms require substantial study. Here, we identify a new role of lysine-specific demethylase 1 (LSD1) in controlling the fate of oocytes in perinatal mice through regulating the level of autophagy. Our results show that the relatively higher level of LSD1 in fetal ovaries sharply reduces from 18.5 postcoitus (dpc). Meanwhile, the level of autophagy increases while oocytes are initiating programmed death. Specific disruption of LSD1 resulted in significantly increased autophagy and obviously decreased oocyte number compared with the control. Conversely, the oocyte number is remarkably increased by the overexpression of Lsd1 in ovaries. We further demonstrated that LSD1 exerts its role by regulating the transcription of p62 and affecting autophagy level through its H3K4me2 demethylase activity. Finally, in physiological conditions, a decrease in LSD1 level leads to an increased level of autophagy in the oocyte when a large number of oocytes are being lost. Collectively, LSD1 may be one of indispensible epigenetic molecules who protects oocytes against preterm death through repressing the autophagy level in a time-specific manner. And epigenetic modulation contributes to programmed oocyte death by regulating autophagy in mice.
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http://dx.doi.org/10.1111/acel.13102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059144PMC
March 2020