Publications by authors named "Feng Zhu"

1,578 Publications

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RSL1D1 modulates cell senescence and proliferation via regulation of PPARγ mRNA stability.

Life Sci 2022 Aug 5:120848. Epub 2022 Aug 5.

Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, People's Republic of China. Electronic address:

Aims: In this study, we will examine if RSL1D1 influences PPARγ expression and explore the underlying mechanism that RSL1D1 regulates PPARγ expression. Moreover, the significance of RSL1D1-PPARγ pathway in cell senescence and proliferation will also be determined.

Main Methods: Our main methods include western blotting, immunoprecipitation (IP), real-time PCR, RNA Immunoprecipitation (RIP), biotin-labeled RNA pull down assay, dual luciferase reporter gene assay, senescence-associated β-galactosidase staining, cell proliferation assay, colony formation assay, wound healing assay, blood biochemistry test and Oil red O staining.

Key Findings: By analyzing gene chip results we find that the expression of RSL1D1 and PPARγ might be correlated. Then we show that RSL1D1 is a posttranscriptional regulator of PPARγ. RSL1D1 overexpression elevates, while RSL1D1 knockdown inhibits, PPARγ mRNA and protein expression levels. Mechanistically, we find that RSL1D1 directly interacts with the 3'-untranslated region of PPARγ mRNA, and then promotes its stability and increases PPARγ protein expression level. We further demonstrate that RSL1D1 modulates cellular senescence and cell proliferation partially via PPARγ-regulated downstream target genes such as PTEN/p27, NF-κB, GLUT4, and ACL. Moreover, we find that RSL1D1 regulates PPARγ expression and function in a HuR-dependent manner. Last, we show that RSL1D1 knockout in mouse adipose tissue shortens mouse lifespan and leads to hepatic damage which may impair liver damage repair function.

Significance: Collectively, our findings unveil a novel posttranscriptional regulation of PPARγ by RSL1D1 and uncover a critical role of RSL1D1-PPARγ-PPARγ downstream target genes in regulating cellular senescence and cell proliferation.
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http://dx.doi.org/10.1016/j.lfs.2022.120848DOI Listing
August 2022

Autophagy modulates the metabolism and growth of tomato fruit during development.

Hortic Res 2022 13;9:uhac129. Epub 2022 Jun 13.

Max-Planck-Institute of Molecular Plant Physiology, 14476 Potsdam-Golm, Germany.

Although autophagy is a conserved mechanism operating across eukaryotes, its effects on crops and especially their metabolism has received relatively little attention. Indeed, whilst a few recent studies have used systems biology tools to look at the consequences of lack of autophagy in maize these focused on leaf tissues rather than the kernels. Here we utilized RNA interference (RNAi) to generate tomato plants that were deficient in the autophagy-regulating protease . Plants displayed an early senescence phenotype yet relatively mild changes in the foliar metabolome and were characterized by a reduced fruit yield phenotype. Metabolite profiling indicated that metabolites of -RNAi tomato leaves just exhibited minor alterations while that of fruit displayed bigger difference compared to the WT. In detail, many primary metabolites exhibited decreases in the -RNAi lines, such as proline, tryptophan and phenylalanine, while the representative secondary metabolites (quinic acid and 3-caffeoylquinic acid) were present at substantially higher levels in -RNAi green fruits than in WT. Moreover, transcriptome analysis indicated that the most prominent differences were in the significant upregulation of organelle degradation genes involved in the proteasome or chloroplast vesiculation pathways, which was further confirmed by the reduced levels of chloroplastic proteins in the proteomics data. Furthermore, integration analysis of the metabolome, transcriptome and proteome data indicated that ATG4 significantly affected the lipid metabolism, chlorophyll binding proteins and chloroplast biosynthesis. These data collectively lead us to propose a more sophisticated model to explain the cellular co-ordination of the process of autophagy.
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http://dx.doi.org/10.1093/hr/uhac129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343920PMC
June 2022

iTRAQ-based quantitative proteomic analysis of the liver regeneration termination phase after partial hepatectomy in mice.

J Proteomics 2022 Jul 29:104688. Epub 2022 Jul 29.

Core Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, China. Electronic address:

Liver regeneration (LR) is an important biological process after liver injury. As the "brake" in the process of LR, the termination phase of LR not only suppresses the continuous increase in liver volume but also effectively promotes the recovery of liver function. However, the mechanisms underlying the termination phase of LR are still not clear. In our study, we used isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis to determine the protein expression profiles of livers in the termination phase of mouse LR after partial hepatectomy (PH). We found that the expression of 197 proteins increased gradually during LR; in addition, 187 proteins were upregulated and 264 proteins were downregulated specifically in the termination phase of LR. The GO analysis of the proteins revealed the upregulation of "cell-cell adhesion" and "translation" and the downregulation of the "oxidation-reduction process". The KEGG pathway analysis showed that "biosynthesis of antibiotics" and "ribosomes" were significantly upregulated, while "metabolic pathways" were significantly downregulated. These analyses indicated that the termination phase of LR mainly focuses on restoring cellular structure and function. Differentially expressed proteins such as SNX5 were also screened out from biological processes. SIGNIFICANCE: The key regulatory factors in the termination phase of LR were studied by iTRAQ-based proteomics to lay a foundation for further study of the molecular mechanism and biomarkers of the termination phase of LR. This study will guide the clinical perioperative management of patients after hepatectomy.
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http://dx.doi.org/10.1016/j.jprot.2022.104688DOI Listing
July 2022

A self-amplifying USP14-TAZ loop drives the progression and liver metastasis of pancreatic ductal adenocarcinoma.

Cell Death Differ 2022 Jul 29. Epub 2022 Jul 29.

Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, Hubei, China.

With a 5-year survival rate of approximately 10%, pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies in humans. A poor understanding of the underlying biology has resulted in a lack of effective targeted therapeutic strategies. Tissue microarray and bioinformatics analyses have revealed that the downstream transcriptional coactivator of the Hippo pathway, transcriptional coactivator with PDZ-binding motif (TAZ), might be a therapeutic target in PDAC. Since pharmacological inhibition of TAZ is challenging, we performed unbiased deubiquitinase (DUB) library screening to explore the pivotal regulators of TAZ ubiquitination as potential targets in PDAC models. We found that USP14 contributed to Yes-associated protein (YAP)/TAZ transcriptional activity and stabilized TAZ but not YAP. Mechanistically, USP14 catalyzed the K48-linked deubiquitination of TAZ to promote TAZ stabilization. Moreover, TAZ facilitated the transcription of USP14 by binding to the TEA domain transcription factor (TEAD) 1/4 response element in the promoter of USP14. USP14 was found to modulate the expression of TAZ downstream target genes through a feedback mechanism and ultimately promoted cancer progression and liver metastasis in PDAC models in vitro and in vivo. In addition, depletion of USP14 led to proteasome-dependent degradation of TAZ and ultimately arrested PDAC tumour growth and liver metastasis. A strong positive correlation between USP14 and TAZ expression was also detected in PDAC patients. The small molecule inhibitor of USP14 catalytic activity, IU1, inhibited the development of PDAC in subcutaneous xenograft and liver metastasis models. Overall, our data strongly suggested that the self-amplifying USP14-TAZ loop was a previously unrecognized mechanism causing upregulated TAZ expression, and identified USP14 as a viable therapeutic target in PDAC.
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http://dx.doi.org/10.1038/s41418-022-01040-wDOI Listing
July 2022

How Is Professional Identity Associated with Teacher Career Satisfaction? A Cross-Sectional Design to Test the Multiple Mediating Roles of Psychological Empowerment and Work Engagement.

Int J Environ Res Public Health 2022 Jul 25;19(15). Epub 2022 Jul 25.

Research Center of Tin Ka Ping Moral Education, Zhejiang Normal University, Jinhua 321004, China.

(1) Purpose: Previous studies investigated the positive relationship between professional identity and career satisfaction in teachers, but the underlying reasons were not explored. Therefore, the present study explores the mediating effects of two variables, namely, psychological empowerment and work engagement on the relationship between professional identity and career satisfaction. (2) Method: The present study used the professional identity scale, psychological empowerment scale, Utrecht Work Engagement scale and career satisfaction scale to investigate 2104 teachers (Mage = 39.50 years, SD = 8.74) in a province in China. The demographic variables (e.g., gender, age, teaching age) were controlled as covariates to conduct conservative predictions. (3) Result: (a) professional identity is positively related to career satisfaction; (b) psychological empowerment and career satisfaction play parallel mediator roles between professional identity and career satisfaction; (c) psychological empowerment and career satisfaction play serial mediator roles between professional identity and career satisfaction. (4) Limitations: Data were collected by participant self-report. This method may lead to recall bias. Further, we adopted a cross-sectional rather than experimental or longitudinal design, thus precluding causal conclusions. Lastly, it would be useful to validate our findings with a national sample. (5) Conclusions: The present study indicates that the relationship between professional identity is positively associated with teacher career satisfaction. More importantly, professional identity can indirectly make an impact on teacher career satisfaction through the single mediating effects of psychological empowerment and work engagement, and the chain mediating effect, by improving the level of psychological empowerment, and thereby increasing work engagement.
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http://dx.doi.org/10.3390/ijerph19159009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332691PMC
July 2022

Prenatal Detection of Novel Compound Heterozygous Splice Site Variants of the Gene in a Fetus with Postaxial Polydactyly Type A.

Genes (Basel) 2022 Jul 11;13(7). Epub 2022 Jul 11.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Postaxial polydactyly (PAP) is a common abnormality characterized by extra digits on hands and/or feet. To date, sequence variants in seven genes have been identified in non-syndromic PAP. In the present study, a fetus manifesting non-syndromic postaxial polydactyly type A (PAPA) was found by fetal ultrasonography. To better evaluate fetal prognosis, SNP array analysis and trio whole-exome sequencing (trio-WES) were performed to identify the underlying etiology. Although SNP array analysis revealed no abnormality, trio-WES identified compound heterozygous splice site variants in , c.-1-2A>T and c.2247-2A>G in intron 2 and intron 12, respectively. These two splice site variants were absent in control databases and were predicted to influence splicing by in silico analysis. To confirm the potential pathogenicity of the variants, in vitro splicing assays using minigene and RNA from peripheral leukocytes of the heterozygous parents were conducted. Minigene and RT-PCR assays demonstrated that the c.-1-2A>T variant led to the loss of the initiation codon, and the c.2247-2A>G variant mainly resulted in exon 13 skipping. Prenatal WES and subsequent functional studies are important approaches for defining the genetic etiology of fetuses with PAPA and are also essential for accurate genetic counseling and decision making. Taken together, this study expands the spectrum of variations in PAPA patients and increases the knowledge of the molecular consequences of splice site variants.
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http://dx.doi.org/10.3390/genes13071230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316509PMC
July 2022

Hearing loss and depressive symptoms in older Chinese: whether social isolation plays a role.

BMC Geriatr 2022 07 26;22(1):620. Epub 2022 Jul 26.

School of Public Health, Sun Yat-Sen University, No. 74 Zhongshan 2ndRoad, Guangzhou, Guangdong Province, China.

Background: Existing evidence links hearing loss to depressive symptoms, with the extent of association and underlying mechanisms remaining inconclusive. We conducted a cross-sectional study to examine the association of hearing loss with depressive symptoms and explored whether social isolation mediated the association.

Methods: Eight thousand nine hundred sixty-two participants from Guangzhou Biobank Cohort Study were included. Data on self-reported hearing status, the 15-item Geriatric Depression Scale (GDS-15), social isolation and potential confounders were collected by face-to-face interview.

Results: The mean (standard deviation) age of participants was 60.2 (7.8) years. The prevalence of poor and fair hearing was 6.8% and 60.8%, respectively. After adjusting for age, sex, household income, education, occupation, smoking, alcohol use, self-rated health, comorbidities, compared with participants who had normal hearing, those with poor hearing (β = 0.74, 95% confidence interval (CI) 0.54, 0.94) and fair hearing (β = 0.59, 95% CI 0.48, 0.69) had higher scores of GDS-15. After similar adjustment, those with poor hearing (odds ratio (OR) = 2.13, 95% CI 1.65, 2.74) or fair hearing (OR = 1.68, 95% CI 1.43, 1.99) also showed higher odds of depressive symptoms. The association of poor and fair hearing with depressive symptoms attenuated slightly but not substantially after additionally adjusting for social isolation. In the mediation analysis, the adjusted proportion of the association mediated through social isolation was 9% (95% CI: 6%, 22%).

Conclusion: Poor hearing was associated with a higher risk of depressive symptoms, which was only partly mediated by social isolation. Further investigation of the underlying mechanisms is warranted.
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http://dx.doi.org/10.1186/s12877-022-03311-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316428PMC
July 2022

HSPA5 Inhibitor Meliorate DSS-Induced Colitis through HSPA1A/CHIP.

Dis Markers 2022 13;2022:7115181. Epub 2022 Jul 13.

Department of Integrated Chinese and Western Medicine, Union Hospital Affiliate to Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei 430022, China.

Objective: Ulcerative colitis (UC) is closely related to immune response, in which Treg cells (Tregs) suppress the autoimmune response of effector T cells to maintain homeostasis. As a marker of endoplasmic reticulum stress (ERS), HSPA5 was highly expressed in the colon tissue of UC patients. This study is aimed at evaluating the therapeutic effect of HSPA5 inhibitor (HA15) on dextran sulfate sodium- (DSS-) induced ulcerative colitis in mice and explored the effect and related mechanism of HSPA5 inhibitor on the differentiation and function of Tregs.

Methods: Thirty-two C57BL/6 mice were randomly divided into four groups (8 mice per group): normal control group, DSS model group, HSPA5 inhibitor (HA15) group (intraperitoneal injection), and dexamethasone (DXM) group (intraperitoneal injection). Except for the blank control group, the other groups were induced with 3% DSS for 7 days and then given corresponding intervention therapy for 7 days.

Results: The disease activity index (DAI) score, colon length, histopathological changes, and scores of DSS-induced mice show that HA15 could significantly improve the degree of inflammation in ulcerative colitis. Moreover, HA15 can better inhibit the expression of HSPA5, HSPA1A, and CHIP in the colon and increase the level of FOXP3 mRNA. Finally, the content of Treg cells and the levels of IL-10 and TGF-1 were significantly increased, and the levels of IL-6 were significantly reduced.

Conclusions: HA15 can improve the differentiation and function of Treg cells by inhibiting the HSPA1A/CHIP pathway, thereby improving ulcerative colitis. Therefore, inhibiting the expression of HSPA5 may serve as a new approach to treat ulcerative colitis.
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http://dx.doi.org/10.1155/2022/7115181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300310PMC
July 2022

REGLIV: Molecular regulation data of diverse living systems facilitating current multiomics research.

Comput Biol Med 2022 Jul 14;148:105825. Epub 2022 Jul 14.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou, 330110, China. Electronic address:

Multiomics is a powerful technique in molecular biology that facilitates the identification of new associations among different molecules (genes, proteins & metabolites). It has attracted tremendous research interest from the scientists worldwide and has led to an explosive number of published studies. Most of these studies are based on the regulation data provided in available databases. Therefore, it is essential to have molecular regulation data that are strictly validated in the living systems of various cell lines and in vivo models. However, no database has been developed yet to provide comprehensive molecular regulation information validated by living systems. Herein, a new database, Molecular Regulation Data of Living System Facilitating Multiomics Study (REGLIV) is introduced to describe various types of molecular regulation tested by the living systems. (1) A total of 2996 regulations describe the changes in 1109 metabolites triggered by alterations in 284 genes or proteins, and (2) 1179 regulations describe the variations in 926 proteins induced by 125 endogenous metabolites. Overall, REGLIV is unique in (a) providing the molecular regulation of a clearly defined regulatory direction other than simple correlation, (b) focusing on molecular regulations that are validated in a living system not simply in an in vitro test, and (c) describing the disease/tissue/species specific property underlying each regulation. Therefore, REGLIV has important implications for the future practice of not only multiomics, but also other fields relevant to molecular regulation. REGLIV is freely accessible at: https://idrblab.org/regliv/.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105825DOI Listing
July 2022

Tetrahedral framework nucleic acids promote diabetic wound healing via the Wnt signalling pathway.

Cell Prolif 2022 Jul 22:e13316. Epub 2022 Jul 22.

Burn Institute of PLA, Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, China.

Objectives: To determine the therapeutic effect of tetrahedral framework nucleic acids (tFNAs) on diabetic wound healing and the underlying mechanism.

Materials And Methods: The tFNAs were characterized by polyacrylamide gel electrophoresis (PAGE), atomic force microscopy (AFM), transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential assays. Cell Counting Kit-8 (CCK-8) and migration assays were performed to evaluate the effects of tFNAs on cellular proliferation and migration. Quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the effect of tFNAs on growth factors. The function and role of tFNAs in diabetic wound healing were investigated using diabetic wound models, histological analyses and western blotting.

Results: Cellular proliferation and migration were enhanced after treatment with tFNAs in a high-glucose environment. The expression of growth factors was also facilitated by tFNAs in vitro. During in vivo experiments, tFNAs accelerated the healing process in diabetic wounds and promoted the regeneration of the epidermis, capillaries and collagen. Moreover, tFNAs increased the secretion of growth factors and activated the Wnt pathway in diabetic wounds.

Conclusions: This study indicates that tFNAs can accelerate diabetic wound healing and have potential for the treatment of diabetic wounds.
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http://dx.doi.org/10.1111/cpr.13316DOI Listing
July 2022

Identification and subcellular localization analysis of membrane protein Ycf 1 in the microsporidian .

PeerJ 2022 8;10:e13530. Epub 2022 Jul 8.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu, China.

Microsporidia are obligate intracellular parasites that can infect a wide range of vertebrates and invertebrates including humans and insects, such as silkworm and bees. The microsporidium can cause pebrine in , which is the most destructive disease in the sericulture industry. Although membrane proteins are involved in a wide range of cellular functions and part of many important metabolic pathways, there are rare reports about the membrane proteins of microsporidia up to now. We screened a putative membrane protein Ycf 1 from the midgut transcriptome of the -infected silkworm. Gene cloning and bioinformatics analysis showed that the gene contains a complete open reading frame (ORF) of 969 bp in length encoding a 322 amino acid polypeptide that has one signal peptide and one transmembrane domain. Indirect immunofluorescence results showed that Ycf 1 protein is distributed on the plasma membrane. Expression pattern analysis showed that the gene expressed in all developmental stages of . Knockdown of the gene by RNAi effectively inhibited the proliferation of . These results indicated that Ycf 1 is a membrane protein and plays an important role in the life cycle of .
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http://dx.doi.org/10.7717/peerj.13530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272817PMC
July 2022

Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Attenuate Myocardial Infarction Injury via miR-24-3p-Promoted M2 Macrophage Polarization.

Adv Biol (Weinh) 2022 Jul 11:e2200074. Epub 2022 Jul 11.

Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science, Soochow University, Suzhou, 215000, China.

Exosomes derived from human umbilical cord mesenchymal stem cells (UMSC-Exos) have shown encouraging effects in regulating inflammation and attenuating myocardial injury. Macrophages are regulated dynamically in response to environmental cues. However, the underlying mechanisms by which UMSC-Exos regulate macrophage polarization are still not well understood. Herein, it is aimed to explore the effects of UMSC-Exos on macrophage polarization and their roles in cardiac repair after myocardial infarction (MI). These results show that UMSC-Exos improve cardiac function by increasing M2 macrophage polarization and reducing excessive inflammation. RNA-sequencing results identify Plcb3 as a key gene involved in UMSC-Exo-facilitated M2 macrophage polarization. Further bioinformatic analysis identifies exosomal miR-24-3p as a potential effector mediating Plcb3 downregulation in macrophages. Increasing miR-24-3p expression in macrophages effectively enhances M2 macrophage polarization by suppressing Plcb3 expression and NF-κB pathway activation in the inflammatory environment. Furthermore, reducing miR-24-3p expression in UMSC-Exos attenuates the effects of UMSC-Exos on M2 macrophage polarization. This study demonstrates that the cardiac therapeutic effects of UMSC-Exos are at least partially through promoting M2 macrophage polarization in an inflammatory microenvironment. Mechanistically, exosomal miR-24-3p is found to inhibit Plcb3 expression and NF-κB pathway activation to promote M2 macrophage polarization.
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http://dx.doi.org/10.1002/adbi.202200074DOI Listing
July 2022

Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities.

Gut 2022 Jul 11. Epub 2022 Jul 11.

Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore

Objective: Gastric cancer (GC) comprises multiple molecular subtypes. Recent studies have highlighted mesenchymal-subtype GC (Mes-GC) as a clinically aggressive subtype with few treatment options. Combining multiple studies, we derived and applied a consensus Mes-GC classifier to define the Mes-GC enhancer landscape revealing disease vulnerabilities.

Design: Transcriptomic profiles of ~1000 primary GCs and cell lines were analysed to derive a consensus Mes-GC classifier. Clinical and genomic associations were performed across >1200 patients with GC. Genome-wide epigenomic profiles (H3K27ac, H3K4me1 and assay for transposase-accessible chromatin with sequencing (ATAC-seq)) of 49 primary GCs and GC cell lines were generated to identify Mes-GC-specific enhancer landscapes. Upstream regulators and downstream targets of Mes-GC enhancers were interrogated using chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing, CRISPR/Cas9 editing, functional assays and pharmacological inhibition.

Results: We identified and validated a 993-gene cancer-cell intrinsic Mes-GC classifier applicable to retrospective cohorts or prospective single samples. Multicohort analysis of Mes-GCs confirmed associations with poor patient survival, therapy resistance and few targetable genomic alterations. Analysis of enhancer profiles revealed a distinctive Mes-GC epigenomic landscape, with as a master regulator of Mes-GC enhancers and Mes-GCs exhibiting preferential sensitivity to TEAD1 pharmacological inhibition. Analysis of Mes-GC super-enhancers also highlighted kinase as a downstream target, with synergistic effects observed between NUAK1 inhibition and cisplatin treatment.

Conclusion: Our results establish a consensus Mes-GC classifier applicable to multiple transcriptomic scenarios. Mes-GCs exhibit a distinct epigenomic landscape, and TEAD1 inhibition and combinatorial NUAK1 inhibition/cisplatin may represent potential targetable options.
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http://dx.doi.org/10.1136/gutjnl-2021-326483DOI Listing
July 2022

Testing and multiscale modeling of a foam-based lung surrogate subjected to underwater shock loading.

J Mech Behav Biomed Mater 2022 Sep 5;133:105356. Epub 2022 Jul 5.

Innovision, LLC., Dayton, OH, USA.

A combined experimental and computational study was conducted to investigate the structural response of a foam-based lung simulant subjected to underwater pressure wave. In the physical experiments, a lung surrogate made from porous medium was exposed to underwater pressure wave in an impact force - driven testing tube. The pressures in the water and surrogate deformation profile were recorded throughout the event. A numerical model of the underwater shock tube was developed using finite element (FE) method and validated against experimental data. An arbitrary Lagrangian-Eulerian (ALE) fluid-structure coupling algorithm was then utilized to simulate the interaction between the underwater pressure wave and the lung surrogate. Based on the numerical model, a multiscale modeling strategy was used to link the surrogate responses in macro and micro scales. The modeling process consists of two steps, namely (1) macro scale FE modeling to predict the overall surrogate reponse; and (2) micro scale Representative Volume Element (RVE) modeling for the detailed microstructure response. The strain tensors computed in Step (1) were applied to the RVE as the boundary condtions in Step (2) to calculate its response in the micro scale. With this multiscale modeling approach, a parametric study was carried out to study the influence of waveform on the RVE strain response. The results indicate that for current input pressure levels, the strain response within the foam surrogate model is more sensitive to the overpressure than the duration of pulse. The modeling approach developed in this work can potentially serve as a basis for further numerical models to gain a deeper insight into the mechanism of underwater blast-induced lung injury.
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http://dx.doi.org/10.1016/j.jmbbm.2022.105356DOI Listing
September 2022

Characterizing serum amino acids in schizophrenic patients: Correlations with gut microbes.

J Psychiatr Res 2022 Jul 5;153:125-133. Epub 2022 Jul 5.

Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China; Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China. Electronic address:

Amino acid abnormalities have been suggested to be a key pathophysiological mechanism in schizophrenia (SZ). Recently, gut microbes were found to be critically involved in mental and metabolic diseases. However, the relationship between serum amino acid levels and gut microbes in SZ is rarely studied. Here, we analyzed serum amino acid levels in 76 untreated SZ patients and 79 healthy controls (HC). Serum levels of 10 amino acids were significantly altered in patients with SZ. We further classified the cut-off values for serum arginine, leucine, glutamine, and methionine levels to distinguish SZ patients from controls. These classifiers were shown to be effective in another validation cohort (49 SZ and 48 HC). The correlation between serum amino acids and clinical symptoms and cognitive functions was also analyzed. Arginine, leucine, glutamine, and methionine levels were significantly correlated with clinical symptoms and cognitive impairments in SZ patients. By metagenome shotgun sequencing of fecal samples, we found that patients with SZ with a low level of serum amino acids have higher richness and evenness of the gut microbiota. At the genus level, the abundances of Mitsuokella and Oscillibacter are significantly abnormal. At the mOTU level, 15 mOTUs in the low-level SZ group were significantly different from the HC group. In addition, Mitsuokella multacida was correlated with glutamine and methionine, respectively. Our research revealed that alterations in serum amino acid levels are critically related to changes in gut microbiota composition in SZ patients. These findings may shed light on new strategies for the diagnosis and treatment of SZ.
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http://dx.doi.org/10.1016/j.jpsychires.2022.07.006DOI Listing
July 2022

Fatigue Driving Detection Method Based on Combination of BP Neural Network and Time Cumulative Effect.

Sensors (Basel) 2022 Jun 22;22(13). Epub 2022 Jun 22.

School of Mechanical Engineering, Yangzhou University, Yangzhou 225127, China.

Fatigue driving has always received a lot of attention, but few studies have focused on the fact that human fatigue is a cumulative process over time, and there are no models available to reflect this phenomenon. Furthermore, the problem of incorrect detection due to facial expression is still not well addressed. In this article, a model based on BP neural network and time cumulative effect was proposed to solve these problems. Experimental data were used to carry out this work and validate the proposed method. Firstly, the Adaboost algorithm was applied to detect faces, and the Kalman filter algorithm was used to trace the face movement. Then, a cascade regression tree-based method was used to detect the 68 facial landmarks and an improved method combining key points and image processing was adopted to calculate the eye aspect ratio (EAR). After that, a BP neural network model was developed and trained by selecting three characteristics: the longest period of continuous eye closure, number of yawns, and percentage of eye closure time (PERCLOS), and then the detection results without and with facial expressions were discussed and analyzed. Finally, by introducing the Sigmoid function, a fatigue detection model considering the time accumulation effect was established, and the drivers' fatigue state was identified segment by segment through the recorded video. Compared with the traditional BP neural network model, the detection accuracies of the proposed model without and with facial expressions increased by 3.3% and 8.4%, respectively. The number of incorrect detections in the awake state also decreased obviously. The experimental results show that the proposed model can effectively filter out incorrect detections caused by facial expressions and truly reflect that driver fatigue is a time accumulating process.
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http://dx.doi.org/10.3390/s22134717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269348PMC
June 2022

HS release rate strongly affects particle size and settling performance of metal sulfides in acidic wastewater: The role of homogeneous and heterogeneous nucleation.

J Hazard Mater 2022 Jun 28;438:129484. Epub 2022 Jun 28.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Beijing Key Laboratory of Industrial Wastewater Treatment and Resource Recovery, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address:

Sulfide precipitation is an extensively used method to precipitate metal and arsenic from acidic wastewater, whereas the tiny and negatively-charged metal sulfides with poor settling performance are generated. The factors and mechanisms that influence particle size and settling performance remain unclear. Herein, the effects of sulfuration factors, e.g., reagent dosage, acidity and HS release rate on the particle size and settling performance of metal sulfides were investigated, and involved mechanisms were systematically revealed. The results showed that the reagent dosage and acidity had a limited effect on particle size and settling performance while the HS release rate played a critical role. Under homogeneous conditions, the decrease in HS release rate, which can reduce the initial supersaturation and supply the sustainable supersaturation, increased the particle size of metal sulfides generated using NaS solution. Under heterogeneous conditions, the decrease in HS release rate further increased the particle size of metal sulfides generated using low-solubility CaS/FeS and further improved settling performance, in which heterogeneous nucleation played a crucial role besides supersaturation. The developed dissolution-diffusion-growth model qualitatively explained the negative relationship between HS release rate and particle growth. This work provides implications for improving the settling performance of metal sulfides in acidic wastewater.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129484DOI Listing
June 2022

Readiness of as-built horizontal curved roads for LiDAR-based automated vehicles: A virtual simulation analysis.

Accid Anal Prev 2022 Sep 2;174:106762. Epub 2022 Jul 2.

School of Civil and Environmental Engineering, Nanyang Technological University, Singapore 639798, Singapore. Electronic address:

Emerging automated vehicle (AV) technology is being deployed on as-built roadways due to its promising safety improvements. However, realistic problems concerning whether and how perception sensor-based AVs can safely adapt to the existing roadway infrastructures remain to be well addressed due to a lack of consideration of the sensor's angular resolution and detection threshold. In this study, we aim to assess whether LiDAR-based AVs (LAVs) could safely adapt to as-built horizontal curved roads from the perspective of available sight distances (ASDs) through virtual simulations. In specific, i) numerous driving scenarios featuring the design speed (V: 40 ∼ 100 km/h), circular curve radius (R: limited minimum radius ∼ common minimum radius), LAV (with LiDAR technical parameters, e.g., number of channels, N: 32, 64, 128), and the front target vehicle were simulated in PreScan/MATLAB/Simulink co-simulation platform; ii) an ASD extraction algorithm was proposed considering the point threshold for detection (N); iii) effects of V, R, N, and N on the ASD were analyzed and polynomial models were adopted to capture relationships between the ASD, V, R at different N and N; iv) the minimum speed against as-built sight obstructions along the roadside and the maximum speed against inadequate sight distance were proposed by comparing the ASD with the required stopping sight distance of human-driven vehicles and LAVs (level 3 ∼ 5), respectively; and v) speed limits (V) against inadequate sight distances for level 3 ∼ 5 LAVs were proposed. The results indicate that: i) a larger R or V, fewer N, or a higher N would cause a shorter ASD in general; ii) attention should be paid to the occlusion imposed by as-built roadside infrastructures even with more N or/and a lower N, particularly to curved roads with more rigorous geometric design controls (e.g., small V); and iii) level 3 LAVs struggle to adapt to as-built horizontal curved roads, and level 4 or 5 LAVs cannot assure adequate ASDs on high-type curved roads (e.g., large V). These findings shall help road administrators make decisions on speed limits for LAVs on as-built curved roads.
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http://dx.doi.org/10.1016/j.aap.2022.106762DOI Listing
September 2022

Ecological Disposal and Large-scale Utilization of Bauxite Residue: A Long way to go.

Bull Environ Contam Toxicol 2022 07 5;109(1):1-2. Epub 2022 Jul 5.

School of Metallurgy and Environment, Central South University, 410083, Changsha, China.

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http://dx.doi.org/10.1007/s00128-022-03578-4DOI Listing
July 2022

Case Report: A Novel Truncating Variant of Presented With X-Linked Late-Onset Adrenal Hypoplasia Congenita With Hypogonadotropic Hypogonadism.

Front Endocrinol (Lausanne) 2022 16;13:897069. Epub 2022 Jun 16.

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

Nuclear receptor subfamily 0 group B member 1 gene () encodes an orphan nuclear receptor that plays a critical role in the development and regulation of the adrenal gland and hypothalamic-pituitary-gonadal axis. In this study, we report a novel mutation in that led to adult-onset adrenal hypoplasia congenita (AHC) and pubertal development failure in a male adult. Clinical examinations revealed hyponatremia, elevated adrenocorticotropic hormone levels, reduced testosterone and gonadotropin levels, and hyper-responses to gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests. Whole-exome sequencing and Sanger sequencing were performed to identify the potential causes of AHC. Candidate variants were shortlisted based on the X-linked recessive models. Sequence analyses identified a novel hemizygous variant of c.1034delC in exon 1 of at Xp21.2, resulting in a frameshift mutation and premature stop codon formation. The c.1034delC/p.Pro345Argfs*27 in the gene was detected in the hemizygous state in affected males and in the heterozygous state in healthy female family carriers. These results expand the clinical features of AHC as well as the mutation profile of the causative gene . Further studies are needed to elucidate the biological effects of the mutation on the development and function of the adrenal gland and the hypothalamic-pituitary-gonadal axis.
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http://dx.doi.org/10.3389/fendo.2022.897069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243302PMC
June 2022

Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial.

Ann Surg 2022 Jul 4. Epub 2022 Jul 4.

The First Hospital of Jilin University, Changchun, Jilin Province, China.

Objective: To assess the safety and efficacy of antimicrobial peptide PL-5 (Peceleganan) spray in the treatment of wound infections.

Background: Antimicrobial peptide PL-5 spray is a novel topical antimicrobial agent.

Methods: We conducted a multicenter, open-label, randomized, controlled phase IIb clinical trial to evaluate the efficacy and safety of PL-5 spray, as compared with silver sulfadiazine, in patients with skin wound infections. The primary efficacy outcome was the clinical efficacy rate on the first day after ending the treatment (D8). The secondary efficacy outcome was the clinical efficacy rate on the fifth day posttreatment (D5), the bacteria clearance rate, and the overall efficacy rate at the mentioned 2 time points. The safety outcomes included adverse reactions and pharmacokinetic analysis posttreatment.

Results: A total of 220 patients from 27 hospitals in China were randomly assigned to 4 groups. On D8, the efficacy rate was 100.0%, 96.7%, 96.7% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 87.5% for the control group. The efficacy rate among the 4 groups was significantly different (P<0.05). On D5, the efficacy rate was 100.0%, 93.4%, 98.3% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 82.5% for the control group. The efficacy rate among the 4 groups was significantly different (P<0.05). The blood concentration of PL-5 was not detectable in pharmacokinetic analysis. No severe adverse event related to the application of PL-5 was reported.

Conclusions: Antimicrobial peptide PL-5 spray is safe and effective for the treatment of skin wound infections.

Trial Registration: ChiCTR2000033334.
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http://dx.doi.org/10.1097/SLA.0000000000005508DOI Listing
July 2022

Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth.

Cancer Lett 2022 Sep 30;544:215812. Epub 2022 Jun 30.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Air Force Medical University, Xi'an, China. Electronic address:

Burkitt lymphoma (BL), which is characterized by high invasiveness, is a subgroup of non-Hodgkin lymphoma. Although BL is regarded as a highly curable disease, especially for children, some patients unfortunately still do not respond adequately. The understanding of the etiology and molecular mechanisms of BL is still limited, and targeted therapies are still lacking. Here, we found that T-LAK cell-derived protein kinase (TOPK) and phosphorylated Janus kinase 2 (p-JAK2) are highly expressed in the tissues of BL patients. We report that TOPK directly binds to and is phosphorylated at Tyr74 by JAK2. Histone H3, one of the downstream targets of TOPK, is also phosphorylated in vivo and in vitro. Furthermore, we report that the phosphorylation of TOPK at Tyr74 by JAK2 plays a vital role in the proliferation of BL cells and promotes BL tumorigenesis in vivo. Phosphorylation of TOPK at Tyr74 by JAK2 enhances the stability of TOPK. Collectively, our results suggest that the JAK2/TOPK/histone H3 axis plays a key role in the proliferation of BL cells and BL tumorigenesis in vivo.
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http://dx.doi.org/10.1016/j.canlet.2022.215812DOI Listing
September 2022

Roles of ursodeoxycholic acid in the bile biochemistry and metabolomics in patients with choledocholithiasis: a prospective study.

Metabolomics 2022 07 1;18(7):46. Epub 2022 Jul 1.

Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Pudong New District, Shanghai, 200120, China.

Introduction: Recurrence after the endoscopic treatment of common bile duct stones (CBDS) is related to bile metabolism and bile compositions. Ursodeoxycholic acid (UDCA) has been proved effective in reducing the recurrence of CBDS. However, the detailed effects of UDCA on bile metabolism are still not extensively explored.

Objectives: This study aimed to analyze the role of UDCA in patients with choledocholithiasis (CDC) from the perspective of biochemistry and metabolomics.

Methods: A total of 89 patients with CDC who underwent endoscopic retrograde cholangiopancreatography were prospectively examined and randomly assigned to control and UDCA groups. The biochemical detections (cholesterol, bilirubin, and so on) were performed on the collected bile. Moreover, the metabolomics analysis was conducted based on bile from 20 patients in the UDCA group.

Results: The bile levels of cholesterol and endotoxins significantly decreased after UDCA treatment. Regarding bile metabolomics, the levels of 25 metabolites changed significantly after UDCA treatment. The pathway enrichment analysis showed that the UDCA addition evoked a common response related to phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; arachidonic acid metabolism; and terpenoid backbone biosynthesis.

Conclusions: UDCA treatment within a short time interval (7 days) did not improve the circulating laboratory values in patients with CDC who had undergone endoscopy surgery. However, relevant decreases in the bile levels of cholesterol and endotoxin were observed. UDCA evoked a common response related to lipid metabolism and amino acid metabolism, which probably reduced the bile level of cholesterol, protected hepatocytes, and corrected the abnormality of lipid metabolism caused by CDC.
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http://dx.doi.org/10.1007/s11306-022-01906-7DOI Listing
July 2022

JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis.

Int Immunopharmacol 2022 Jun 28;110:109000. Epub 2022 Jun 28.

Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiology and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of molecular biology and immunological techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theoretical basis for understanding the pathogenesis and potential therapeutic targets of UC.
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http://dx.doi.org/10.1016/j.intimp.2022.109000DOI Listing
June 2022

Somatostatin interneurons inhibit excitatory transmission mediated by astrocytic GABA and presynaptic GABA and adenosine A receptors in the hippocampus.

J Neurochem 2022 Jul 1. Epub 2022 Jul 1.

School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China.

GABAergic network activity has been established to be involved in numerous physiological processes and pathological conditions. Extensive studies have corroborated that GABAergic network activity regulates excitatory synaptic networks by activating presynaptic GABA receptors (GABA Rs). It is well documented that astrocytes express GABA Rs and respond to GABAergic network activity. However, little is known about whether astrocytic GABA Rs regulate excitatory synaptic transmission mediated by GABAergic network activity. To address this issue, we combined whole-cell recordings, optogenetics, calcium imaging, and pharmacological approaches to specifically activate hippocampal somatostatin-expressing interneurons (SOM-INs), a type of interneuron that targets pyramidal cell dendrites, while monitoring excitatory synaptic transmission in CA1 pyramidal cells. We found that optogenetic stimulation of SOM-INs increases astrocyte Ca signaling via the activation of astrocytic GABA Rs and GAT-3. SOM-INs depress excitatory neurotransmission by activating presynaptic GABA Rs and astrocytic GABA Rs, the latter inducing the release of ATP/adenosine. In turn, adenosine inhibits excitatory synaptic transmission by activating presynaptic adenosine A receptors (A Rs). Overall, our results reveal a novel mechanism that SOM-INs activation-induced synaptic depression is partially mediated by the activation of astrocytic GABA Rs.
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http://dx.doi.org/10.1111/jnc.15662DOI Listing
July 2022

Total Knee Arthroplasty Using Adjusted Restricted Kinematic Alignment for the Treatment of Severe Varus Deformity: Technical Note.

Orthop Surg 2022 Jun 29. Epub 2022 Jun 29.

Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.

Objective: To describe a new alignment technique of adjusted restricted kinematic alignment (arKA) for the treatment of severe varus deformity in total knee arthroplasty.

Methods: Three female patients (three severe varus knees) who underwent navigation-assisted total knee arthroplasty (TKA) using arKA from April 2020 to September 2020 were included in this study, with an average age of 71.33 years (range, 61 to 80 years). General anesthesia was given to all patients. Intraoperative observations including tibia resection angle, frontal femoral angle, axial femoral angle, medial and lateral gap in the extension and flexion positions and joint line translation were recorded. Also, operation duration and drainage volume were recorded. Radiographic parameters including the mechanical axis (α), coronal femoral component angle (β), coronal tibial component angle (γ), sagittal femoral component angle (δ), tibial posterior slope angle (ε), femoral-patella angle (θ), and femoral notching were assessed. Clinical evaluation was performed using the Hospital for Special Surgery (HSS) Score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score. Both individual and mean measurement data were displayed.

Results: The mean tibial resection was 4.00° varus (range, 3° to 5°), and the mean frontal femoral angle was 3.67° varus (range, 3° to 4°) in extension. The flexion lateral gap was wider than the medial gap with a mean laxity of 1.34 mm. Moreover, the mean axial femoral angle was 2.67° external (range, 0° to 6°) in flexion, and the mean joint line translation was 1.00 mm proximal (range, 0 to 3 mm). In addition, the mean preoperative mechanical axis was 156.22° (range, 153.65° to 158.90°) and the mean postoperative mechanical axis was 174.04° (range, 173.83° to 174.17°) with a mean correction of 17.82°. The mean femoral angle was 92.60° (range, 91.29° to 93.30°) and the mean tibial angle was 86.95° (range, 86.83° to 87.04°) in coronal plane. The HSS score improved from an average of 46.67 points (range, 42 to 51) preoperatively to 83.67 points (range, 81 to 86) at 3 months postoperatively. The mean WOMAC score was 16.33 points at 3 months postoperatively.

Conclusions: The new alignment technique of arKA aims to balance the flexion and extension gap without extensive releases of soft tissue and restore the native pre-arthritic alignment, may be a promising alignment strategy for treating severe varus deformity. However, further study and comparison with other alignment techniques is needed.
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http://dx.doi.org/10.1111/os.13354DOI Listing
June 2022

Rapid and deep response to avapritinib in heavily treated acute myeloid leukemia with t (8;21) and KIT mutation.

Ann Hematol 2022 Jun 29. Epub 2022 Jun 29.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, 215006, China.

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http://dx.doi.org/10.1007/s00277-022-04897-6DOI Listing
June 2022

ConSIG: consistent discovery of molecular signature from OMIC data.

Brief Bioinform 2022 07;23(4)

College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China.

The discovery of proper molecular signature from OMIC data is indispensable for determining biological state, physiological condition, disease etiology, and therapeutic response. However, the identified signature is reported to be highly inconsistent, and there is little overlap among the signatures identified from different biological datasets. Such inconsistency raises doubts about the reliability of reported signatures and significantly hampers its biological and clinical applications. Herein, an online tool, ConSIG, was constructed to realize consistent discovery of gene/protein signature from any uploaded transcriptomic/proteomic data. This tool is unique in a) integrating a novel strategy capable of significantly enhancing the consistency of signature discovery, b) determining the optimal signature by collective assessment, and c) confirming the biological relevance by enriching the disease/gene ontology. With the increasingly accumulated concerns about signature consistency and biological relevance, this online tool is expected to be used as an essential complement to other existing tools for OMIC-based signature discovery. ConSIG is freely accessible to all users without login requirement at https://idrblab.org/consig/.
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http://dx.doi.org/10.1093/bib/bbac253DOI Listing
July 2022

Celastrol Inhibited Human Esophageal Cancer by Activating DR5-Dependent Extrinsic and Noxa/Bim-Dependent Intrinsic Apoptosis.

Front Pharmacol 2022 8;13:873166. Epub 2022 Jun 8.

Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest digestive system cancers worldwide lacking effective therapeutic strategies. Recently, it has been found that the natural product celastrol plays an anti-cancer role in several human cancers by inducing cell cycle arrest and apoptosis. However, it remains elusive whether and how celastrol suppresses tumor growth of ESCC. In the present study, for the first time, we demonstrated that celastrol triggered both extrinsic and intrinsic apoptosis pathways to diminish the tumor growth of ESCC and . Mechanistic studies revealed that celastrol coordinatively induced DR5-dependent extrinsic apoptosis and Noxa-dependent intrinsic apoptosis through transcriptional activation of ATF4 in ESCC cells. Furthermore, we found that the FoxO3a-Bim pathway was involved in the intrinsic apoptosis of ESCC cells induced by celastrol. Our study elucidated the tumor-suppressive efficacy of celastrol on ESCC and revealed a previously unknown mechanism underlying celastrol-induced apoptosis, highlighting celastrol as a promising apoptosis-inducing therapeutic strategy for ESCC.
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http://dx.doi.org/10.3389/fphar.2022.873166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219015PMC
June 2022
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