Publications by authors named "Wei Xiao"

1,645 Publications

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Phase 2 multicenter study of enzalutamide in metastatic castration resistant prostate cancer to identify mechanisms driving resistance.

Clin Cancer Res 2021 Apr 13. Epub 2021 Apr 13.

GU Oncology, Dana-Farber Cancer Institute

Purpose: Enzalutamide is a second-generation androgen receptor (AR) inhibitor which has improved overall survival (OS) in metastatic castration resistant prostate cancer (CRPC). However, nearly all patients develop resistance. We designed a phase 2 multicenter study of enzalutamide in metastatic CRPC incorporating tissue and blood biomarkers to dissect mechanisms driving resistance.

Experimental Design: Eligible patients with metastatic CRPC underwent a baseline metastasis biopsy and then initiated enzalutamide 160 mg daily. A repeat metastasis biopsy was obtained at radiographic progression from the same site when possible. Blood for circulating tumor cell (CTC) analysis was collected at baseline and progression. The primary objective was to analyze mechanisms of resistance in serial biopsies. Whole exome sequencing was performed on tissue biopsies. CTC samples underwent RNA sequencing.

Results: 65 patients initiated treatment, of whom 22 (33.8%) had received prior abiraterone. Baseline biopsies were enriched for alterations in (mutations, amplifications) and tumor suppression genes (, , and ) which were observed in 73.1% and 92.3% of baseline biopsies, respectively. Progression biopsies revealed increased amplifications (64.7% at progression versus 53.9% at baseline) and alterations (64.7% at progression versus 38.5% at baseline). Genomic analysis of baseline and progression CTC samples demonstrated increased AR splice variants, AR regulated-genes, and neuroendocrine markers at progression.

Conclusions: Our results demonstrate that a large proportion of enzalutamide-treated patients have baseline and progression alterations in the AR pathway and tumor suppressor genes. We demonstrate an increased number of alterations post-enzalutamide highlighting importance of serial tumor sampling in CRPC.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4616DOI Listing
April 2021

Ocean surface energy balance allows a constraint on the sensitivity of precipitation to global warming.

Nat Commun 2021 04 9;12(1):2115. Epub 2021 Apr 9.

School of the Environment, Yale University, New Haven, CT, USA.

Climate models generally predict higher precipitation in a future warmer climate. Whether the precipitation intensification occurred in response to historical warming continues to be a subject of debate. Here, using observations of the ocean surface energy balance as a hydrological constraint, we find that historical warming intensified precipitation at a rate of 0.68 ± 0.51% K, which is slightly higher than the multi-model mean calculation for the historical climate (0.38 ± 1.18% K). The reduction in ocean surface albedo associated with melting of sea ice is a positive contributor to the precipitation temperature sensitivity. On the other hand, the observed increase in ocean heat storage weakens the historical precipitation. In this surface energy balance framework, the incident shortwave radiation at the ocean surface and the ocean heat storage exert a dominant control on the precipitation temperature sensitivity, explaining 91% of the inter-model spread and the spread across climate scenarios in the Intergovernmental Panel on Climate Change Fifth Assessment Report.
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http://dx.doi.org/10.1038/s41467-021-22406-7DOI Listing
April 2021

The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance.

BMC Biol 2021 Apr 8;19(1):67. Epub 2021 Apr 8.

Department of Biochemistry and Molecular Biology, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.

Background: Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche.

Results: In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies.

Conclusions: These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.
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http://dx.doi.org/10.1186/s12915-021-00998-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034193PMC
April 2021

Ag and Ag Nanoclusters: Toward Active-Site Tailoring of Nanocluster Surface Structures.

Inorg Chem 2021 Apr 7. Epub 2021 Apr 7.

Department of Chemistry and Centre for Atomic Engineering of Advanced Materials, Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials, Anhui University, Hefei 230601, P.R. China.

The determination of active sites in metal nanoclusters is of great significance for the in-depth understanding of the structural evolution and the mechanism of physicochemical properties. In this work, the surface active Ag(SR) units of the AgCl(S-Adm) nanocluster are determined, and the active-site tailoring of this nanocluster gives rise to two derivative nanoclusters, i.e., the structure-maintained AgCl(S-Adm)(S--CH) and the structure-growth AgCl(S-Adm)(DPPP). Both Ag and Ag nanoclusters exhibit almost the same cluster framework, but the Ag(S-Adm) active units are regulated to Ag(S-Adm)(DPPP)Cl with the transformation from Ag to Ag. The surface active sites on Ag are rationalized by analyzing its crystal structure and the ligand-exchange-induced cluster transformation. This study provides some inspiration toward the active-site tailoring of nanocluster surface structures, which is significant for the preparation of new cluster-based nanomaterials with customized structures and enhanced performance.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00355DOI Listing
April 2021

Tracing the Origins of Blueberries by Their Mineral Element Contents and Sr/Sr Ratios.

Biol Trace Elem Res 2021 Apr 6. Epub 2021 Apr 6.

College of Agriculture, Guizhou University, Guiyang, 550025, Guizhou, China.

This study investigated the feasibility of using the mineral element contents and Sr/Sr ratios of blueberries to trace their origins. The contents of 28 mineral elements, including K, Al, and Mg, were determined in 104 blueberry samples from three blueberry-producing areas in Guizhou Province, China. Also determined were both the Sr/Sr ratios in 48 blueberry samples as well as the type of soil in which the blueberries were grown. Cluster analysis of Sr/Sr ratios, stepwise discriminant analysis of mineral element contents, and combined discriminant analyses of Sr/Sr ratios and mineral element contents were done. The results show that ten elements (Ca, Cr, Cs, Mg, Mn, P, Rb, Sb, Th, and Y) were selected by linear discriminant analysis, which could be used to establish the provenance traceability model of blueberries in Guizhou. The original accuracy of linear discriminant analysis was 89.4%, and the accuracy of cross-validation was 83.6%. When Sr/Sr ratios were used for tracing, the accuracies of both the original discrimination and the cross-validation were 81.3% as determined by linear discriminant analysis, and the accuracy rate of origin discrimination was 81.25% by cluster analysis. The results of combined discrimination were the best: the accuracy of the original discrimination was 95.8%, and the accuracy of cross-validation was 93.8%. Mineral element contents and Sr/Sr ratios can be used to trace the origins of blueberries, and combining them can significantly improve the discrimination accuracy. Fisher linear discriminant analysis had the greatest accuracy followed by cluster analysis, while principal component analysis was relatively poor in the research of Guizhou blueberry origin traceability.
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http://dx.doi.org/10.1007/s12011-021-02701-6DOI Listing
April 2021

Unmasking CSF protein corona: Effect on targeting capacity of nanoparticles.

J Control Release 2021 Apr 3;333:352-361. Epub 2021 Apr 3.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610064, PR China. Electronic address:

Among biological fluids, cerebrospinal fluid (CSF) not only protects and support brain, but also plays a pivotal role in intracerebral interaction of various nano-drug carriers. However, it is still uncertain how protein corona from CSF affects the targeting capability of functionalized nanoparticles (NPs). So, two types of polystyrene NPs, including PEGylated polystyrene NPs (PN) and transferrin (Tf)-modified PN (PT), were used to obtain protein corona-coated NPs, by incubating with CSF in vivo and in vitro. Strikingly, both the corona-coated NPs recovered in vivo and in vitro completely lost their active targeting characteristics towards bEnd.3 and C6 cells. Charge-, clathrin- and energy-mediated endocytosis contributed to the improved uptake efficiency of PT, whereas this enhancement in uptake of PT was disappeared after the formation of CSF protein corona. Moreover, serum albumin, which were found both in vivo and in vitro CSF corona, could mediate and facilitate the internalization of corona-coated NPs. Overall, these results have distinctly confirmed that the formation of CSF protein corona could cause the loss of active targeting specificity by shielding the targeting groups on the surface of polystyrene NPs and alter their cellular uptake by other non-specific internalization pathways.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.001DOI Listing
April 2021

Bracovirus-mediated innexin hemichannel closure in cell disassembly.

iScience 2021 Apr 8;24(4):102281. Epub 2021 Mar 8.

School of Life Sciences, Yunnan University, Kunming 650500, P.R. China.

Cell-cell communication is necessary for cellular immune response. Hemichannel closure disrupts communication between intracellular and extracellular environments during polydnavirus-induced immunosuppression in invertebrates. However, the effects of hemichannel closure on cellular immune response are unclear. Here, we examined apoptotic body formation triggered by hemichannel closure in hemocytes of infected with bracovirus from the parasitic wasp, . We showed that Microplitis bicoloratus bracovirus (MbBV) induced apoptotic cell disassembly, accompanied by hemichannel closure. Hemocyte apoptotic body formation was caused by the dysregulation of the innexins (Inxs), Inx1, Inx2, Inx3, and Inx4, during the MbBV-mediated inhibition of pI3K/AKT signaling and activation of caspase-3, which cleaved gap junction Inx proteins. Our results showed that hemichannel opening or closure in response to various stimuli, which induces the modulation of Inx levels, could inhibit or activate apoptotic body formation, respectively. Therefore, the "hemichannel open and close" model may regulate the cellular immune response.
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http://dx.doi.org/10.1016/j.isci.2021.102281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008186PMC
April 2021

Serum IP-10 and IL-7 levels are associated with disease severity of coronavirus disease 2019.

Cytokine 2021 06 19;142:155500. Epub 2021 Mar 19.

Institute of Disease Control and Prevention, Chinese People's Liberation Army, Beijing, China. Electronic address:

We quantified the serum levels of 34 cytokines/chemokines in 30 patients with SARS-CoV-2 infection. Elevated levels of IP-10 and IL-7 were detected in the acute and convalescent stages of the infection and were highly associated with disease severity.
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http://dx.doi.org/10.1016/j.cyto.2021.155500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973056PMC
June 2021

[Therapeutic effect of acupuncture combined with medication on chronic prostatitis of damp and heat stasis].

Zhongguo Zhen Jiu 2021 Feb;41(2):149-52

Zhongshan Hospital Affiliated to Guangzhou University of CM.

Objective: To observe the clinical therapeutic effect of electroacupuncture (EA) combined with tamsulosin hydrochloride sustained release capsule on chronic prostatitis (CP) of damp and heat stasis.

Methods: A total of 70 patients with CP of damp and heat stasis were randomized into an acupuncture plus medication group (35 cases, 4 cases dropped off) and a medication group (35 cases, 5 cases dropped off). In the medication group, tamsulosin hydrochloride sustained release capsule was given orally, 0.2 mg a time, once each night. On the basis of treatment in the medication group, EA was applied at Guanyuan (CV 4), Sanyinjiao (SP 6) and Yinglingquan (SP 9), with disperse-dense wave, 5 mA in intensity for 30 min. Treatment for 30 days was as one course, and totally 3 courses were required in both groups. Before treatment, 1, 2, 3 months into treatment and at the follow-up of 2 months after treatment, the TCM syndrome score and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score were observed, and the clinical efficacy was evaluated in both groups.

Results: Compared before treatment, the TCM syndrome scores of 3 months into treatment and follow-up were decreased in the acupuncture plus medication group (<0.01), and were lower than those in the medication group (<0.05). Compared before treatment, the NIH-CPSI scores of 3 months into treatment and follow-up were decreased in both groups (<0.01), and those in the acupuncture plus medication group were lower than the medication group (<0.05). The total effective rate was 90.3% (28/31) in the acupuncture plus medication group, which was superior to 80.0% (24/30) in the medication group (<0.05).

Conclusion: Acupuncture combined with medication can improve the clinical symptoms in patients with CP of damp and heat stasis, and its therapeutic effect is superior to simple western medication.
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http://dx.doi.org/10.13703/j.0255-2930.20200219-0004DOI Listing
February 2021

Identification of Survival-Associated Gene Signature in Lung Cancer Coexisting With COPD.

Front Oncol 2021 9;11:600243. Epub 2021 Mar 9.

Respiratory Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.

Chronic obstructive pulmonary disease (COPD) and lung cancer often coexist, which is associated with a worse prognosis. Thousands of biomarkers related to the survival of lung cancer have been investigated. However, those which can predict the survival of lung cancer coexisting with COPD are currently lacking. The present study aimed to identify novel gene signatures to predict the survival of patients with lung cancer coexisting COPD. RNA-sequence data of lung cancer and control accompanying with matched clinical information were retrieved from the Cancer Genome Atlas (TCGA). Differently expressed genes (DEGs) associated with lung cancer coexisting COPD were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Univariate and multivariate Cox regression analyses were applied to identify survival-associated DEGs and to construct survival-associated gene signature. Kaplan-Meier survival analysis and calibration plots of the nomogram were performed to test the predictive accuracy of the gene signature. qPCR was performed to validate the genes in the prognostic signature. Sequence data from 70 patients with lung cancer coexisting COPD, 127 with lung cancer alone and 108 control tissues were included for analysis. A total of 2424 DEGs were identified when comparing lung cancer coexisting COPD with controls. The biological process was primarily associated with DNA-binding transcription activator activity, peptidase inhibitor activity, endopeptidase inhibitor activity, et al. KEGG pathways were mainly enriched in neuroactive ligand-receptor interaction, cell cycle, and infection. A survival-associated gene signature consisting of , and was identified and represented as risk score. The high-risk score group had significantly worse survival than the low-risk score group ( < 0.001). Areas under receiver operating characteristic curves were 0.943, 0.773, 0.888 for predicting overall survival at 1-, 3-, and 5-year, respectively. The risk score was an independent predictor of survival, independent of clinical factors. High conformity of the actual survival and the nomogram-predicted probability of survival by applying the risk score. Upregulation of the five genes in patients with lung cancer coexisting COPD were confirmed by qPCR in an independent cohort. Our study constructed and validated a novel prognostic gene signature for predicting survival of patient with lung cancer coexisting COPD, which may contribute to the clinical treatment decisions.
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http://dx.doi.org/10.3389/fonc.2021.600243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006292PMC
March 2021

Guizhi Fuling Capsule ameliorates endometrial hyperplasia through promoting p62-Keap1-NRF2-mediated ferroptosis.

J Ethnopharmacol 2021 Mar 24;274:114064. Epub 2021 Mar 24.

Department of Gynecology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, 310012, China; Center for Uterine Cancer Diagnosis & Therapy Research in Zhejiang Province, Hangzhou, 310012, China. Electronic address:

Ethnopharmacological Relevance: Guizhi Fuling Capsule (GFC) is a classical traditional Chinese medicine officially recorded in Synopsis of the Golden Chamber and has long been used to treat gynecological diseases in China. However, scientific evidence for the anti-endometrial hyperplasia potential of GFC used in traditional medicine is lacking.

Aim Of The Study: This study evaluated whether GFC protects against endometrial hyperplasia and its potential mechanism in mice.

Methods And Materials: We used estrogen (estradiol) to induce endometrial hyperplasia in mice. C57BL/6 mice were treated with estradiol subcutaneously for 21 days, and GFC (75 mg/kg and 150 mg/kg) was given intragastric administration from the first day of the modeling. H&E staining is used to evaluate endometrial tissue structure change. Malondialdehyde was measured to explore lipid peroxidation. Western blot, immunohistochemistry and immunofluorescence were performed to observe the expressions of GPX4, p62, Keap1 and NRF2.

Results: The degree of ferroptosis in endometrial tissue of patients with endometrial hyperplasia was lower than normal endometrial tissue. In addition, ferroptosis inducer imidazole ketone erastin could improve endometrial hyperplasia in mice. Interestingly, GFC significantly alleviated endometrial hyperplasia through triggering ferroptosis. Furthermore, GFC inhibited p62-Keap1-NRF2 pathway in estradiol-induced endometrial hyperplasia model.

Conclusions: GFC may attenuate estrogen-induced endometrial hyperplasia in mice through triggering ferroptosis via inhibiting p62-Keap1-NRF2 pathway. These findings suggest that GFC might act as a promising traditional Chinese medicine to treat endometrial hyperplasia.
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http://dx.doi.org/10.1016/j.jep.2021.114064DOI Listing
March 2021

CD46 splice variant enhances translation of specific mRNAs linked to an aggressive tumor cell phenotype in bladder cancer.

Mol Ther Nucleic Acids 2021 Jun 24;24:140-153. Epub 2021 Feb 24.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.

CD46 is well known to be involved in diverse biological processes. Although several splice variants of CD46 have been identified, little is known about the contribution of alternative splicing to its tumorigenic functions. In this study, we found that exclusion of CD46 exon 13 is significantly increased in bladder cancer (BCa) samples. In BCa cell lines, enforced expression of CD46-CYT2 (exon 13-skipping isoform) promoted, and CD46-CYT1 (exon 13-containing isoform) attenuated, cell growth, migration, and tumorigenicity in a xenograft model. We also applied interaction proteomics to identify exhaustively the complexes containing the CYT1 or CYT2 domain in EJ-1 cells. 320 proteins were identified that interact with the CYT1 and/or CYT2 domain, and most of them are new interactors. Using an internal ribosome entry site (IRES)-dependent reporter system, we established that CD46 could regulate mRNA translation through an interaction with the translation machinery. We also identified heterogeneous nuclear ribonucleoprotein (hnRNP)A1 as a novel CYT2 binding partner, and this interaction facilitates the interaction of hnRNPA1 with IRES RNA to promote IRES-dependent translation of HIF1a and c-Myc. Strikingly, the splicing factor SRSF1 is highly correlated with CD46 exon 13 exclusion in clinical BCa samples. Taken together, our findings contribute to understanding the role of CD46 in BCa development.
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http://dx.doi.org/10.1016/j.omtn.2021.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972933PMC
June 2021

Direct Z-scheme CuInS/BiMoO heterostructure for enhanced photocatalytic degradation of tetracycline under visible light.

J Hazard Mater 2021 Mar 5;415:125591. Epub 2021 Mar 5.

JST-ERATO Yamauchi Materials Space-Tectonics Project, International Center for Young Researchers (ICYS), and International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan. Electronic address:

The construction of direct Z-scheme heterojunctions with high photocatalytic degradation ability is a theme of importance in both environmental and materials sciences, but still retains many unresolved challenges. In this article, we report the construction of Z-scheme CuInS/BiMoO heterostructure by in-situ hydrothermal reactions, demonstrating superior photocatalytic activity towards the degradation of tetracycline under visible light, compared to their individual components: that is to say 8 and 2.5 times those of CuInS and BiMoO, respectively. The photocatalytic performance of CuInS/BiMoO heterostructure is mainly ascribed to the effective charge transfer at the interface through the construction of a direct Z-scheme heterojunction, combined with a ternary sulfide semiconductor absorbing light in the useful region of the solar spectrum. This photocatalyst provides new insights on the fundamental aspects governing the mechanisms responsible for multicomponent photodegradation, while constituting already a promising candidate for practical environmental applications.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125591DOI Listing
March 2021

Engineered Polyploid Yeast Strains Enable Efficient Xylose Utilization and Ethanol Production in Corn Hydrolysates.

Front Bioeng Biotechnol 2021 5;9:655272. Epub 2021 Mar 5.

Beijing Key Laboratory of Plant Gene Resources and Biotechnology for Carbon Reduction and Environmental Improvement, College of Life Sciences, Capital Normal University, Beijing, China.

The reported haploid strain F106 can utilize xylose for ethanol production. After a series of and/or mutations were introduced into F106, the mutant was found to outperform others. The corresponding haploid, diploid, and triploid strains were then constructed and their fermentation performance was compared. Strains F106-KR and the diploid produced an ethanol yield of 0.45 and 0.48 g/g total sugars, respectively, in simulated corn hydrolysates within 36 h. Using non-detoxicated corncob hydrolysate as the substrate, the ethanol yield with the triploid was approximately sevenfold than that of the diploid at 40°C. After a comprehensive evaluation of growth on corn stover hydrolysates pretreated with diluted acid or alkali and different substrate concentrations, ethanol yields of the triploid strain were consistently higher than those of the diploid using acid-pretreatment. These results demonstrate that the yeast chromosomal copy number is positively correlated with increased ethanol production under our experimental conditions.
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http://dx.doi.org/10.3389/fbioe.2021.655272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973232PMC
March 2021

Adipose-derived stem cell sheets combined with β-tricalcium phosphate/collagen-I fiber scaffold improve cell osteogenesis.

Exp Ther Med 2021 May 1;21(5):452. Epub 2021 Mar 1.

Department of Stomatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.

Transplantation of cell-based material is a promising approach for the treatment of critical bone defects. However, it is still limited by the lack of suitable scaffold material or abundant seeding cell sources. The present study aimed to establish a novel composite of an adipose-derived stem cell (ADSC) sheet and a synthetic porous β-tricalcium phosphate/collagen-I fiber (β-TCP/COL-I) scaffold to enhance osteogenic activity. ADSCs were isolated from 3-week-old female Sprague Dawley rats and the ADSC sheets were prepared in an osteoinductive medium. The study groups included the ADSC sheets/scaffold, scattered ADSCs/scaffold, ADSC sheet alone and scaffold alone. Scanning electron microscopy and energy-dispersive spectrometry were used to observe cell-scaffold interactions and analyze the relative calcium content on the composites' surface. Alizarin red S staining was used to examine the calcium deposition. ELISA and reverse transcription-quantitative PCR were used to detect the expression levels of alkaline phosphatase (ALP), osteocalcin (OCN) and osteopontin (OPN). The results revealed that ADSCs were able to tightly adhere to the β-TCP/COL-I scaffold with no cytotoxicity. The calcifying nodules reaction was positive on ADSC sheets and gradually increased after osteogenic induction. In addition, the β-TCP/COL-I scaffold combined with ADSC sheets was able to significantly enhance the expression levels of ALP, OCN and OPN and increase the superficial relative calcium content compared to scattered ADSCs/scaffold or the ADSC sheet alone (P<0.05). The results indicated that ADSCs possess a strong osteogenic potential, particularly in the cell-sheet form and when compounded with the β-TCP/COL-I scaffold, compared to scattered ADSCs with a β-TCP/COL-I scaffold or an ADSC sheet alone. This novel composite may be a promising candidate for bone engineering.
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http://dx.doi.org/10.3892/etm.2021.9882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967868PMC
May 2021

Deciphering the Pharmacological Mechanisms of Guizhi-Fuling Capsule on Primary Dysmenorrhea Through Network Pharmacology.

Front Pharmacol 2021 3;12:613104. Epub 2021 Mar 3.

Department of Automation, Institute for TCM-X, MOE Key Laboratory of Bioinformatics/Bioinformatics Division, BNRIST, Tsinghua University, Beijing, China.

Guizhi-Fuling capsule (GZFLC), originated from a classical traditional Chinese herbal formula Guizhi-Fuling Wan, has been clinically used for primary dysmenorrhea in China. Nonetheless, the underlying pharmacological mechanisms of GZFLC remain unclear. The integration of computational and experimental methods of network pharmacology might be a promising way to decipher the mechanisms. In this study, the target profiles of 51 representative compounds of GZFLC were first predicted by a high-accuracy algorithm, drugCIPHER-CS, and the network target of GZFLC was identified. Then, potential functional modules of GZFLC on primary dysmenorrhea were investigated using functional enrichment analysis. Potential bioactive compounds were recognized by hierarchical clustering analysis of GZFLC compounds and first-line anti-dysmenorrhea drugs. Furthermore, the potential anti-dysmenorrhea mechanisms of GZFLC were verified through enzyme activity assays and immunofluorescence tests. Moreover, effects of GZFLC on primary dysmenorrhea were evaluated in oxytocin-induced dysmenorrhea murine model. In the network target analysis, GZFLC may act on five functional modules of pain, inflammation, endocrine, blood circulation and energy metabolism. Integrating computational and experimental approaches, we found that GZFLC significantly inhibited the writhing response and reduced the degree of uterine lesions in oxytocin-induced dysmenorrhea murine model. Furthermore, GZFLC may partially alleviate primary dysmenorrhea by inhibiting cyclooxygenase 2 (COX2) and downregulating MAPK signaling pathway. Consequently, GZFLC presented pain relief and sustained benefits for primary dysmenorrhea. This study could provide a scientific approach for deciphering pharmacological mechanisms of herbal formulae through network pharmacology.
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http://dx.doi.org/10.3389/fphar.2021.613104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966503PMC
March 2021

NOGEA: A Network-oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning.

Genomics Proteomics Bioinformatics 2021 Mar 17. Epub 2021 Mar 17.

College of Life Science, Northwest University, Xi'an 710069, China; College of Life Science, Northwest A & F University, Yangling 712100, China; State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang 222001, China. Electronic address:

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes on the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and repositioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.
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http://dx.doi.org/10.1016/j.gpb.2020.06.023DOI Listing
March 2021

Elamipretide (SS-31) Improves Functional Connectivity in Hippocampus and Other Related Regions Following Prolonged Neuroinflammation Induced by Lipopolysaccharide in Aged Rats.

Front Aging Neurosci 2021 1;13:600484. Epub 2021 Mar 1.

Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Neuroinflammation has been recognized as a major cause for neurocognitive diseases. Although the hippocampus has been considered an important region for cognitive dysfunction, the influence of hippocampal neuroinflammation on brain functional connectivity (FC) has been rarely studied. In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment. Systemic and hippocampal inflammation were determined using ELISA, while astrocyte responses during hippocampal neuroinflammation were determined by interleukin 1 beta (IL-1β)/tumor necrosis factor alpha (TNFα) double staining immunofluorescence. Oxidative stress was determined by reactive oxidative species (ROS), electron transport chain (ETC) complex, and superoxide dismutase (SOD). Short- (<7 days) and long-term (>30 days) learning and spatial working memory were tested by the Morris water maze (MWM). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyze the brain FC by placing seed voxels on the left and right hippocampus. Compared with the vehicle group, rats with the LPS exposure showed an impaired MWM performance, higher oxidative stress, higher levels of inflammatory cytokines, and astrocyte activation in the hippocampus. The neuroimaging examination showed decreased FC on the right orbital cortex, right olfactory bulb, and left hippocampus on day 3, 7, and 31, respectively, after treatment. In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance. Neuroimaging examination showed increased FC on the left-parietal association cortex (L-PAC), left sensory cortex, and left motor cortex on day 7 with the right flocculonodular lobe on day 31 as compared with those without SS-31 treatment. Our study demonstrated that inhibiting neuroinflammation in the hippocampus not only reduces inflammatory responses in the hippocampus but also improves the brain FC in regions related to the hippocampus. Furthermore, early anti-inflammatory treatment with SS-31 has a long-lasting effect on reducing the impact of LPS-induced neuroinflammation.
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http://dx.doi.org/10.3389/fnagi.2021.600484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956963PMC
March 2021

Concurrent vs sequential chemoradiotherapy for patients with advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials.

Authors:
Wei Xiao Mei Hong

Medicine (Baltimore) 2021 Mar;100(11):e21455

Nanjing Chest Hospital, Nanjing, Jiangsu Province, China.

Background: Chemotherapy in combination with thoracic radiotherapy yields significant results in patients with advanced non-small-cell lung cancer (NSCLC) compared with thoracic radiotherapy alone. However, whether concurrent or sequential delivery of chemotherapy combined with thoracic radiotherapy is optimal remains unclear. Herein, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of concurrent vs sequential chemoradiotherapy in patients with NSCLC.

Methods: PubMed, EmBase, and Cochrane Library were systematically searched for RCTs focusing on concurrent and sequential chemoradiotherapy for patients with NSCLC. The pooled-effect estimate was calculated using the random-effects model. Sensitivity, subgroup, and publication biases were also evaluated. A total of 14 RCTs (2634 patients with NSCLC) were selected for the final meta-analysis.

Results: Compared with sequential chemoradiotherapy, concurrent chemoradiotherapy did not increase the 1-year survival rates; however, concurrent chemoradiotherapy significantly increased the 2-, 3-, 4-, and 5-year survival rates. Moreover, although there were no significant differences between concurrent and sequential chemoradiotherapy in terms of distant relapse and locoregional plus distant relapse, concurrent chemoradiotherapy significantly reduced the risk of locoregional relapse. Furthermore, concurrent chemoradiotherapy yielded positive results with respect to overall response rates. Unfortunately, concurrent chemoradiotherapy could result in esophagitis, nausea/vomiting, and reduced leukocyte and platelet counts in patients with NSCLC.

Conclusion: Compared with sequential chemoradiotherapy, concurrent chemoradiotherapy may be significantly beneficial in terms of long-term survival and locoregional relapse, although it increases the risk of grade 3 (or greater) adverse events.
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http://dx.doi.org/10.1097/MD.0000000000021455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982214PMC
March 2021

Hepatitis B virus X protein promotes vimentin expression via LIM and SH3 domain protein 1 to facilitate epithelial-mesenchymal transition and hepatocarcinogenesis.

Cell Commun Signal 2021 Mar 15;19(1):33. Epub 2021 Mar 15.

Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.

Background: Hepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC). Vimentin is an EMT-related molecular marker. However, the importance of vimentin in the pathogenesis of HCC mediated by HBX has not been well determined.

Methods: The expression of vimentin induced by HBX, and the role of LIM and SH3 domain protein 1 (LASP1) in HBX-induced vimentin expression in hepatoma cells were examined by western blot and immunohistochemistry analysis. Both the signal pathways involved in the expression of vimentin, the interaction of HBX with vimentin and LASP1, and the stability of vimentin mediated by LASP1 in HBX-positive cells were assessed by western blot, Co-immunoprecipitation, and GST-pull down assay. The role of vimentin in EMT, proliferation, and migration of HCC cells mediated by HBX and LASP1 were explored with western blot, CCK-8 assay, plate clone formation assay, transwell assay, and wound healing assay.

Results: Vimentin expression was increased in both HBX-positive hepatoma cells and HBV-related HCC tissues, and the expression of vimentin was correlated with HBX in HBV-related HCC tissues. Functionally, vimentin was contributed to the EMT, proliferation, and migration of hepatoma cells mediated by HBX. The mechanistic analysis suggested that HBX was able to enhance the expression of vimentin through LASP1. On the one hand, PI3-K, ERK, and STAT3 signal pathways were involved in the upregulation of vimentin mediated by LASP1 in HBX-positive hepatoma cells. On the other hand, HBX could directly interact with vimentin and LASP1, and dependent on LASP1, HBX was capable of promoting the stability of vimentin via protecting it from ubiquitination mediated protein degradation. Besides these, vimentin was involved in the growth and migration of hepatoma cells mediated by LASP1 in HBX-positive hepatoma cells.

Conclusion: Taken together, these findings demonstrate that, dependent on LASP1, vimentin is crucial for HBX-mediated EMT and hepatocarcinogenesis, and may serve as a potential target for HBV-related HCC treatment. Video abstract.
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http://dx.doi.org/10.1186/s12964-021-00714-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958410PMC
March 2021

Bulbar Conjunctival Microvascular Alterations in Thyroid-Associated Ophthalmopathy Patients with Different Activities.

Curr Eye Res 2021 Mar 15:1-6. Epub 2021 Mar 15.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

: To evaluate the morphologic and hemodynamic changes of bulbar conjunctival vessels in thyroid-associated ophthalmopathy (TAO) patients and the correlations with the activity.: Patients diagnosed as TAO with different clinical activity scores (CAS) and healthy participants were recruited. All subjects underwent a complete ophthalmic examination and functional slit-lamp biomicroscope. Vascular variables including the vessel density, vessel complexity, average diameter, blood flow velocity and blood flow rate in microvascular networks were measured. The correlations among microvascular parameters, CAS and exophthalmos were analyzed. Areas under the receiver operating characteristic curves (AUROCs) were applied to evaluate the diagnostic accuracy of microvascular alterations for active TAO.: A total of 46 eyes were enrolled in our study. The vessel complexity and blood flow velocity increased in the active TAO group significantly compared with the inactive group and healthy controls ( < .05). Meanwhile, the vessel complexity and blood flow rate were positively correlated with CAS (r = 0.641 and r = 0.526). Bulbar conjunctival microvascular parameters performed a good ability in distinguishing the active stage of TAO (AUROC = 0.793).: Increasing bulbar conjunctival vessel complexity and blood flow were evident in TAO with severe inflammation. The measurements of bulbar conjunctival microvasculature could be a reference to evaluate activity in TAO.
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http://dx.doi.org/10.1080/02713683.2020.1849729DOI Listing
March 2021

Dim Red Light During Scotophase Enhances Mating of a Moth Through Increased Male Antennal Sensitivity Against the Female Sex Pheromone.

Front Genet 2021 24;12:611476. Epub 2021 Feb 24.

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.

Insects are behaviorally and physiologically affected by different light conditions, including photoperiod, light intensity, and spectrum. Light at night has important influences on nocturnal insects, including most moth species. Moth copulation and mating usually occur at night. Although a few studies examine changes in insect mating under artificial light at night, detailed influences of light, such as that of monochromatic light, on moth mating remain largely unknown. In this study, on the basis of long-term insects rearing experience, dim red light (spectrum range: 610-710nm, with a peak at 660nm; 2.0 Lux) during scotophase was hypothesized to enhance mating in the yellow peach moth, . To test the hypothesis, the mating of moths under dim red, blue, and white lights during scotophase was observed. Under the dim red light, the enhancement of mating in was observed. In addition, the electroantennografic response of males against the female sex pheromone increased with red light treatment during scotophase. In an analysis of the differentially expressed genes in the antennae of males under red light and dark conditions, the expression levels of two odorant-binding protein (OBP) genes, and , were up-regulated. Two genes were then expressed in , and the recombinant proteins showed strong binding to female pheromone components in fluorescence-binding assays. Thus, the results of this study indicated that dim red light at night enhanced the mating of . One of the mechanisms for the enhancement was probably an increase in the antennal sensitivity of males to the female sex pheromone under red light that was caused by increases in the expression levels of pheromone-binding protein genes in male antennae.
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http://dx.doi.org/10.3389/fgene.2021.611476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943464PMC
February 2021

Minimize the Xylitol Production in by Balancing the Xylose Redox Metabolic Pathway.

Front Bioeng Biotechnol 2021 26;9:639595. Epub 2021 Feb 26.

Key Laboratory of Plant Gene Resources and Biotechnology for Carbon Reduction and Environmental Improvement, College of Life Sciences, Capital Normal University, Beijing, China.

Xylose is the second most abundant sugar in lignocellulose, but it cannot be used as carbon source by budding yeast . Rational promoter elements engineering approaches were taken for efficient xylose fermentation in budding yeast. Among promoters surveyed, exhibited the best performance. The promoter is suppressed in the presence of glucose and derepressed by xylose, making it a promising candidate to drive xylose metabolism. However, simple ectopic expression of both key xylose metabolic genes and by the promoter resulted in massive accumulation of the xylose metabolic byproduct xylitol. Through the -driven expression of a reported redox variant, , along with optimized expression of and the downstream pentose phosphate pathway genes, a balanced xylose metabolism toward ethanol formation was achieved. Fermented in a culture medium containing 50 g/L xylose as the sole carbon source, xylose is nearly consumed, with less than 3 g/L xylitol, and more than 16 g/L ethanol production. Hence, the combination of an inducible promoter and redox balance of the xylose utilization pathway is an attractive approach to optimizing fuel production from lignocellulose.
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http://dx.doi.org/10.3389/fbioe.2021.639595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953151PMC
February 2021

Garlic (Allium sativum) based interplanting alters the heavy metals absorption and bacterial diversity in neighboring plants.

Sci Rep 2021 Mar 12;11(1):5833. Epub 2021 Mar 12.

School of Life Science and Engineering, Southwest University of Science and Technology, 59# Qinglong Road, Fucheng District, Mianyang, 621010, Sichuan, China.

Heavy metals are naturally occurring elements that have a high atomic weight and let out in the environment by agriculture, industry, mining and therapeutic expertise and thrilling amassing of these elements pollutes the environment. In this study we have investigated the potential of garlic interplanting in promoting hyper accumulation and absorption of heavy metals to provide a basis for phytoremediation of polluted land. Monoculture and inter-plantation of garlic were conducted to investigate the absorption of cadmium and lead contamination in the land. A group of experiments with single planting (monoculture) of Lolium perenne, Conyza canadensis and Pteris vittata as accumulators were used. The results have shown that garlic has a potential as a hyper accumulate and absorb heavy metals. It was found that the accumulation of Cd and Pb was much higher with inter-planting. Garlic boosts up the absorption of heavy metals in Lolium perenne of Cd 66% and Pb 44% respectively. The Inter-planting of garlic with Pteris vittata promotes the Cd 26% and Pb 15%. While the maximum accumulation of Lead 87% and Cadmium 77% occurred in Conyza canadensis herb plant. The bacterial diversity in the soil was analyzed for each experimental soil and was found that the Proteobacteria, Acidobacteria, Actinobacteria, Firmicutes, and Planctomycetes were commonly abundant in both single planting (monoculture) of ryegrass and interplanting ryegrass with garlic habitats. Variances were observed in the bacterial floral composition of single (monoculture) and intercropping (interplant) soils. Relative abundance of bacterial taxa revealed that the proportion of Proteobacteria, Acidobacteria, and Actinobacteria in the inter-planting group was slightly higher, while Firmicutes and Planctomycetes were low. This study provides the evidence to control the heavy metals contaminated soils with weed species. Growth promotion and heavy metal uptake of neighboring plants proved the specific plant-plant and plant-microbial associations with garlic plants. This inter-planting strategy can be used to improve heavy metal absorption.
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http://dx.doi.org/10.1038/s41598-021-85269-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971001PMC
March 2021

Transparent, smooth, and sustainable cellulose-derived conductive film applied for the flexible electronic device.

Carbohydr Polym 2021 May 16;260:117820. Epub 2021 Feb 16.

College of Material Engineering, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, PR China; National Forestry and Grassland Administration Key Laboratory of Plant Fiber Functional Materials, PR China. Electronic address:

A high-performance flexible conductive substrate is one of the key components for developing promising wearable devices. Concerning this, a sustainable, flexible, transparent, and conductive cellulose/ZnO/AZO (CZA) film was developed in this study. The cellulose was used as the transparent substrate. The added AZO was as the conductive layer and ZnO functioned as an interface buffer layer. Results showed that the interface buffer layer of ZnO effectively alleviated the intrinsic incompatibility of organic cellulose and inorganic AZO, resulting in the improvement of the performance of CZA film. In compared with the controlled cellulose/AZO (CA) film with 365 Ω/sq sheet resistance and 87% transmittance, this CZA film featured a low conductive sheet resistance of 115 Ω/sq and high transmittance of 89%, as well as low roughness of 1.85 nm Moreover, the existence of conducive ZnO buffer layer enabled the conductivity of CZA film to be stable under the bending treatment. Herein, a flexible electronic device was successfully prepared with the biomass materials, which would be available by a roll-to-roll production process.
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http://dx.doi.org/10.1016/j.carbpol.2021.117820DOI Listing
May 2021

Computed Tomography Imaging Predictors of Intracerebral Hemorrhage Expansion.

Curr Neurol Neurosci Rep 2021 Mar 12;21(5):22. Epub 2021 Mar 12.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Purpose Of Review: Hematoma expansion (HE) is strongly associated with poor clinical outcome and is a compelling target for improving outcome after intracerebral hemorrhage (ICH). Non-contrast computed tomography (NCCT) is widely used in clinical practice due to its faster acquisition at the presence of acute stroke. Recently, imaging markers on NCCT are increasingly used for predicting HE. We comprehensively review the current evidence on HE prediction using NCCT and provide a summary for assessment of these markers in future research studies.

Recent Findings: Predictors of HE on NCCT have been described in reports of several studies. The proposed markers, including swirl sign, blend sign, black hole sign, island sign, satellite sign, and subarachnoid extension, were all significantly associated with HE and poor outcome in their small sample studies after ICH. In summary, the optimal management of ICH remains a therapeutic dilemma. Therefore, using NCCT markers to select patients at high risk of HE is urgently needed. These markers may allow rapid identification and provide potential targets for anti-HE treatments in patients with acute ICH.
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http://dx.doi.org/10.1007/s11910-021-01108-zDOI Listing
March 2021

Comparison of Radical Surgery and Radiotherapy for the Treatment of Early-Stage Cervical Carcinoma: A Meta-Analysis.

Oncol Res Treat 2021 11;44(4):176-183. Epub 2021 Mar 11.

Department of General Surgery, Jingdong Zhongmei Hospital, Beijing, China,

Objective: To compare the efficacy and safety of radical surgery with radiotherapy in patients with early-stage cervical carcinoma.

Methods: PubMed, Web of Science, and Embase were systematically reviewed, and studies comparing radical surgery with radiotherapy were included. The main efficacy outcomes included overall survival (OS), and disease-free survival (DFS). Safety endpoints were adverse events. Hazard ratios (HR) or risk ratios (RR) with 95% CI were used to pool the estimates.

Results: A total of 6 studies were included in this meta-analysis. Radical surgery was associated with comparable survival effects in OS (HR = 0.73; 95% CI 0.46-1.17; p = 0.196) and DFS (HR = 0.84; 95% CI 0.64-1.10; p = 0.207) as compared with radiotherapy. Moreover, positive lymphangiography (HR = 3.67; 95% CI 2.86-4.70; p < 0.001), adeno-carcinomatous histotype (HR = 2.53; 95% CI 1.80-3.56; p < 0.001), adenosquamous histotype (HR = 1.55; 95% CI 1.27-1.89; p < 0.001), tumor size ≥4 cm (HR = 1.60; 95% CI 1.14-2.23; p < 0.001), stage IB2 (HR = 1.71; 95% CI 1.43-2.04; p < 0.001), and stage IIA (HR = 1.85; 95% CI 1.54-2.22; p < 0.001) were all independent predictors of decreased survival. Patients treated with radical surgery had a rate of adverse events similar to that of those treated with radiotherapy (RR = 1.23; 95% CI 0.61-2.48; p = 0.557).

Conclusion: The present study suggested that radical surgery and radiotherapy offered similarly effective treatment in terms of OS and DFS in early-stage cervical carcinoma. Moreover, the complication rate between the 2 treatments was not significantly different. Considering the potential limitations of this study, more large-scale well-designed randomized controlled trials are needed to verify our findings.
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http://dx.doi.org/10.1159/000509149DOI Listing
March 2021

Ginsenoside Rb3 Alleviates CSE-induced TROP2 Upregulation Through p38 MAPK and NF-κB Pathways in BCs.

Am J Respir Cell Mol Biol 2021 Mar 11. Epub 2021 Mar 11.

Qilu Hospital, Shandong University, Respiratory Medicine, Jinan, China;

Smoking-mediated reprogramming of the phenotype and function of airway basal cells (BCs) disrupts airway homeostasis and is an early event in COPD-associated airway remodeling. Here, we examined the expression and regulation of the transmembrane glycoprotein, trophoblast antigen 2 (TROP2), a putative stem cell marker in airway BCs, in lung tissue samples from healthy smokers and healthy non-smokers and in models in culture to identify therapeutic targets. TROP2 expression was upregulated in the airway epithelia of smokers and positively correlated with the smoking index. In vitro, cigarette smoke extract (CSE) induced TROP2 expression in airway BCs in a time and dose dependent manner. The p38 MAPK and NF-κB pathways were also activated by CSE, and their specific antagonists inhibited CSE-induced TROP2 expression. A therapeutic component derived from traditional Chinese medicine, ginsenoside Rb3, inhibited CSE-induced TROP2 expression as well as activation of p38 MAPK and the NF-κB pathways in BCs in monolayer culture. Ginsenoside Rb3 furthermore prevented the increase in TROP2 expression, and antagonized CSE-induced BC hyperplasia and expression of inflammatory factors and EMT changes in an air-liquid culture (ALI) model. Thus, CSE-induced TROP2 is a possible biomarker for early changes in the epithelium of smokers, and ginsenoside Rb3 may serve as a therapeutic molecule preventing the disruption of epithelial homeostasis in COPD.
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http://dx.doi.org/10.1165/rcmb.2020-0208OCDOI Listing
March 2021

IL-38 exerts anti-inflammatory and anti-fibrotic effects in thyroid-associated ophthalmopathy.

J Clin Endocrinol Metab 2021 Mar 9. Epub 2021 Mar 9.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Context: Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease closely associated with Graves' disease (GD). IL-38, a novel cytokine in the IL-1 superfamily, has been reported to be involved in the pathogenesis of various autoimmune diseases.

Objectives: To evaluate the relationship between IL-38 and TAO disease activity and its role in inflammation and fibrosis in TAO.

Design/setting/participants: Blood samples and orbital connective tissues were collected from TAO patients and controls. Orbital fibroblasts (OFs) were isolated from patients with TAO.

Main Outcome: Measures Enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), flow cytometry, immunofluorescence, quantitative real-time PCR and western blot analysis were performed.

Results: Here, we demonstrated that IL-38 levels decreased in the circulation and orbital connective tissues of patients with TAO compared to the controls, and were negatively correlated with the clinical activity score (CAS). In vitro, potent anti-inflammatory and anti-fibrotic effects of IL-38 were observed. Furthermore, we revealed that IL-38 can counteract the phosphorylation of star molecules in multiple classical pathways.

Conclusions: IL-38 plays a protective role in TAO and is associated with its pathogenesis. Our data suggest that IL-38 may be a promising marker of TAO disease activity and a potential target for TAO therapy.
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http://dx.doi.org/10.1210/clinem/dgab154DOI Listing
March 2021

Terahertz, infrared and Raman absorption spectra of tyrosine enantiomers and racemic compound.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jun 23;254:119611. Epub 2021 Feb 23.

Research Center of Applied Physics, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China.

The application of terahertz (THz)-based techniques in biomolecule study is very promising but still in its infancy. In the present work, we employed THz time-domain spectroscopy (THz-TDS) and THz time-domain attenuated total reflection (THz-TD-ATR) spectroscopy to investigate the properties of tyrosine (Tyr) enantiomers (L- and D-Tyr) and racemate (DL-Tyr) in solid state and aqueous solutions, respectively. THz absorption spectra of solid L- and D-Tyr show similar absorption spectra with peaks at 0.95, 1.92, 2.06 and 2.60 THz, which are obviously different from the spectrum of DL-Tyr with peaks at 1.5, 2.15 and 2.40 THz. In contrast, although THz absorption spectra of L-Tyr solution and D-Tyr solution are similar and different from the spectrum of DL-Tyr solution, both of them have no observable peaks. Interestingly, it was found that the solution containing equal amounts of L- and D-Tyr has a similar spectrum as that of DL-Tyr solution, as far as the mass concentrations of the two types of solutions are kept the same. On other hand, solid L-, D- and DL-Tyr were also investigated with infrared spectroscopy and Raman spectroscopy, respectively. The results show that the spectra of L- and D-Tyr can be regarded the same but they are slightly different from the spectrum of DL-Tyr. With the aid of principal component analysis (PCA), the difference between L-/D-Tyr and DL-Tyr can be confirmed without any ambiguity. Overall, this work systematically interrogated and evaluated the performance of THz-based techniques in the detection of the chirality of tyrosine.
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http://dx.doi.org/10.1016/j.saa.2021.119611DOI Listing
June 2021