Publications by authors named "Zhe Zhang"

1,677 Publications

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Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts.

BMC Genomics 2021 Jun 15;22(1):445. Epub 2021 Jun 15.

Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, 510642, Guangzhou, China.

Background: In mammals, the ovary is the essential system of female reproduction for the onset of puberty, and the abnormal puberty has negative outcomes on health. CircRNA is a non-coding RNA produced by non-canonical alternative splicing (AS). Several studies have reported that circRNA is involved in the gene regulation and plays an important role in some human diseases. However, the contribution of circRNA has received little known within the onset of puberty in ovary.

Results: Here, the profiles of ovarian circRNAs across pre-, in- and post-pubertal stages were established by RNA-sEq. In total, 972 circRNAs were identified, including 631 stage-specific circRNAs and 8 tissue-specific circRNAs. The biological functions of parental genes of circRNAs were enriched in steroid biosynthesis, autophagy-animal, MAPK signaling pathway, progesterone-mediated oocyte maturation and ras signaling pathway. Moreover, 5 circRNAs derived from 4 puberty-related genes (ESR1, JAK2, NF1 and ARNT) were found in this study. The A3SS events were the most alternative splicing, but IR events were likely to be arose in post-pubertal ovaries. Besides, the circRNA-miRNA-gene networks were explored for 10 differentially expressed circRNAs. Furthermore, the head-to-tail exon as well as the expressions of 10 circRNAs were validated by the divergent RT-qPCR and sanger sequencing.

Conclusions: In summary, the profiles of ovarian circRNAs were provided during pubertal transition in gilts, and these results provided useful information for the investigation on the onset of puberty at the ovarian-circRNAs-level in mammals.
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http://dx.doi.org/10.1186/s12864-021-07786-wDOI Listing
June 2021

Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omics.

Genomics Proteomics Bioinformatics 2021 Jun 9. Epub 2021 Jun 9.

BGI-Shenzhen, Shenzhen 518083, China.

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, and cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancy, delivery histories, cesarean section, and breast-feeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breast-feeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiome, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.
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http://dx.doi.org/10.1016/j.gpb.2021.01.005DOI Listing
June 2021

K63-linked ubiquitination of DYRK1A by TRAF2 alleviates Sprouty 2-mediated degradation of EGFR.

Cell Death Dis 2021 Jun 11;12(6):608. Epub 2021 Jun 11.

Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Dual specificity tyrosine phosphorylation regulated kinase 1A, DYRK1A, functions in multiple cellular pathways, including signaling, endocytosis, synaptic transmission, and transcription. Alterations in dosage of DYRK1A leads to defects in neurogenesis, cell growth, and differentiation, and may increase the risk of certain cancers. DYRK1A localizes to a number of subcellular structures including vesicles where it is known to phosphorylate a number of proteins and regulate vesicle biology. However, the mechanism by which it translocates to vesicles is poorly understood. Here we report the discovery of TRAF2, an E3 ligase, as an interaction partner of DYRK1A. Our data suggest that TRAF2 binds to PVQE motif residing in between the PEST and histidine repeat domain (HRD) of DYRK1A protein, and mediates K63-linked ubiquitination of DYRK1A. This results in translocation of DYRK1A to the vesicle membrane. DYRK1A increases phosphorylation of Sprouty 2 on vesicles, leading to the inhibition of EGFR degradation, and depletion of TRAF2 expression accelerates EGFR degradation. Further, silencing of DYRK1A inhibits the growth of glioma cells mediated by TRAF2. Collectively, these findings suggest that the axis of TRAF2-DYRK1A-Sprouty 2 can be a target for new therapeutic development for EGFR-mediated human pathologies.
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http://dx.doi.org/10.1038/s41419-021-03887-2DOI Listing
June 2021

MicroRNA miR-29a Inhibits Colon Cancer Progression by Downregulating B7-H3 Expression: Potential Molecular Targets for Colon Cancer Therapy.

Mol Biotechnol 2021 Jun 7. Epub 2021 Jun 7.

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

MiR-29a belongs to one of the subtypes of miRNAs known as non-coding single-stranded RNAs and is preferentially expressed in normal tissues. B7-H3, a member of the B7/CD28 immunoglobulin superfamily, was shown to be overexpressed in several solid malignant tumors, including colon cancer. In addition, it is associated with tumor progression and poor prognosis. We used immunohistochemical and Western blotting to assess B7-H3 protein expression levels in colon cancer and adjacent normal tissues and then compared their relationships with clinicopathological factors. Quantitative real-time reverse-transcription PCR was used to assess B7-H3 and miRNA-29a mRNA expression levels, and then their relationship and clinical significance were evaluated. In addition, colon cancer Caco-2 cells, which constitutively overexpress B7-H3, were transfected with lentivirus particles for miR-29a upregulation. Invasion and migration assays were carried out in vitro along with the establishment of a subcutaneous xenograft model in vivo to determine the role of miRNA-29a in colon cancer progression. The B7-H3 protein showed elevated expression in colon carcinoma and was relevant to TNM staging, lymph node metastasis, and reduced survival. Meanwhile, miR-29a was preferentially expressed in normal colon tissues, while B7-H3 transcript levels had no marked differences between tumor and normal tissue specimens. In vitro, miR-29a upregulation resulted in reduced B7-H3 expression. Furthermore, miR-29a upregulation reduced the invasive and migratory abilities of colon carcinoma cells. In animal models, upregulation of miR-29a slowed down the growth of subcutaneous xenotransplanted tumors and resulted in prolonged survival time. MiR-29a downregulates B7-H3 expression and accordingly inhibits colon cancer progression, invasion, and migration, indicating miR-29a and B7-H3 might represent novel molecular targets for advanced immunotherapy in colon cancer.
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http://dx.doi.org/10.1007/s12033-021-00348-1DOI Listing
June 2021

Proteomics, Personalized Medicine and Cancer.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.

As of 2020 the human genome and proteome are both at >90% completion based on high stringency analyses. This has been largely achieved by major technological advances over the last 20 years and has enlarged our understanding of human health and disease, including cancer, and is supporting the current trend towards personalized/precision medicine. This is due to improved screening, novel therapeutic approaches and an increased understanding of underlying cancer biology. However, cancer is a complex, heterogeneous disease modulated by genetic, molecular, cellular, tissue, population, environmental and socioeconomic factors, which evolve with time. In spite of recent advances in treatment that have resulted in improved patient outcomes, prognosis is still poor for many patients with certain cancers (e.g., mesothelioma, pancreatic and brain cancer) with a high death rate associated with late diagnosis. In this review we overview key hallmarks of cancer (e.g., autophagy, the role of redox signaling), current unmet clinical needs, the requirement for sensitive and specific biomarkers for early detection, surveillance, prognosis and drug monitoring, the role of the microbiome and the goals of personalized/precision medicine, discussing how emerging omics technologies can further inform on these areas. Exemplars from recent onco-proteogenomic-related publications will be given. Finally, we will address future perspectives, not only from the standpoint of perceived advances in treatment, but also from the hurdles that have to be overcome.
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http://dx.doi.org/10.3390/cancers13112512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196570PMC
May 2021

Naringin attenuates cerebral ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress.

Transl Neurosci 2021 Jan 13;12(1):190-197. Epub 2021 May 13.

Department of Radiology, Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.

Objective: This investigation was carried out with an aim of exploring neuroprotection by naringin (Nar) in rats with cerebral ischemia-reperfusion (CI/R) injury and its mechanism.

Methods: Rats were grouped into ischemia-reperfusion (I/R), sham operation (Sham), nimodipine control (NIM), and different doses of Nar (Nar-L, Nar-M, Nar-H) groups. With Zea Longa score for assessment of neurological deficits, dry and wet method for measurement of brain tissue water content, and (2,3,5-triphenyltetrazolium chloride) TTC staining for determination of cerebral infarction volume, the related parameters were obtained and compared. Subsequently, ELISA was introduced to detect levels of proinflammatory cytokines (TNF-α, IL-8) and anti-inflammatory cytokine (IL-10) in the serum as well as superoxide dismutase (SOD) and malondialdehyde (MDA) activities in brain tissue. Western blot was applied to evaluate endoplasmic reticulum stress (ERS)-related proteins expression, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12, and activating transcription factor 6 (ATF-6).

Results: Nar significantly alleviated nerve injury and decreased brain tissue water content and brain infraction volume in CI/R injury rats in a concentration-dependent manner. Reduction of TNF-α, IL-8 as well as MDA content and elevation of IL-10 as well as SOD activity were confirmed to be caused by Nar treatment in a concentration-dependent manner. Meanwhile, ERS-related proteins also markedly decreased in the Nar groups.

Conclusion: Nar may achieve neuroprotection and alleviation of CI/R injury by anti-inflammation, anti-oxidation, and inhibiting ERS, and its efficacy is concentration-dependent.
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http://dx.doi.org/10.1515/tnsci-2020-0170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134799PMC
January 2021

Surface-Modified Phthalocyanine-Based Two-Dimensional Conjugated Metal-Organic Framework Films for Polarity-Selective Chemiresistive Sensing.

Angew Chem Int Ed Engl 2021 May 25. Epub 2021 May 25.

Technische Universitat Dresden, Department of Chemistry and Food Chemistry, Mommsenstrasse 4, 01062, Dresden, GERMANY.

Two-dimensional conjugated metal-organic frameworks (2D c -MOFs) are emerging as new-generation electroactive materials for chemiresistive sensors. However, selective sensing with fast response/recovery remains a challenge. Here, we report for the first time phthalocyanine-based Ni 2 [MPc(NH) 8 ] 2D c -MOF films as active layers for polarity-selective chemiresisitors toward water and volatile organic compounds (VOCs). We demonstrate that surface-hydrophobic-modification by grafting aliphatic alkyl chains on 2D c -MOF films reduces the amount of diffused analytes into the MOF backbone, thus resulting in a considerably accelerated recovery progress (from ~ 50 to ~ 10 s) during humidity sensing. Toward VOCs, the sensors deliver a polarity-selective response among alcohols while no signal is recorded for the low-polar aprotic hydrocarbons. Typically, the octadecyltrimethoxysilane-modified Ni 2 [MPc(NH) 8 ] based sensor displays high-performance methanol sensing with fast response (36 s)/recovery (13 s) and a detection limit as low as 10 ppm, which surpass the reported chemiresistors based on MOFs, conducting polymers, metal disulfides, and black phosphorus at room temperature.
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http://dx.doi.org/10.1002/anie.202104461DOI Listing
May 2021

Down-regulation LncRNA-SNHG15 contributes to proliferation and invasion of bladder cancer cells.

BMC Urol 2021 May 20;21(1):83. Epub 2021 May 20.

Department of Urology, The First Hospital of China Medical University, 155 Nanjing North Street, Shenyang, Liaoning, 110001, P.R. China.

Objectives: The aim of this study was to investigate the effect of lncRNA-SNHG15 in bladder carcinoma using cell lines experiments and the relationship between clinical characteristics and lncRNA-SNHG15 expression was analyzed.

Methods: Bladder cancer tissues and near-cancer tissues were collected. The real-time PCR (RT-PCR) was used to detect the expression of lncRNA-SNHG15 in tissues and cell lines. The expression of lncRNA-SNHG15 was downregulated by interference (siRNA), as detected by RT-PCR, that was used to determine the efficiency of the interference. CCK-8 and Transwell assays were used to evaluate the effect of lncRNA-SNHG15 on the proliferation and invasion capability of bladder cancer cells. The t-test was used for Statistical analyses, which were carried out using the Statistical Graph pad 8.0.1.224 software.

Result: The expression of lncRNA-SNHG15 was up regulated in 5637, UMUC3 and T24 cell lines compared with corresponding normal controls (P < 0.05). Up regulation was positively related to tumor stage (P = 0.015). And tumor size (P = 0.0465). The down-regulation of lncRNA-SNHG15 with siRNA significantly inhibited UMUC3 and T24 cell proliferation and invasion.

Conclusion: This study showed that lncRNA-SNHG15 is overexpressed in bladder cancer tissues and (5637, UMUC3 T24) cell lines. Up regulation was positively related to tumor stage (P = 0.015), and tumor size (P = 0.0465). Down-regulation of lncRNA-SNHG15 by siRNA significantly inhibited UMUC3 and T24 cell proliferation and invasion, indicating a potential molecular target for future tumor targeted therapy.
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http://dx.doi.org/10.1186/s12894-021-00852-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139049PMC
May 2021

Tai Chi postural training for dyskinesia rehabilitation: a study protocol for a randomised controlled trial in convalescent ischaemic stroke patients.

BMJ Open 2021 05 18;11(5):e046003. Epub 2021 May 18.

Department of Rehabilitation, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China.

Introduction: Acute ischaemic stroke (AIS) is not only seriously damaging to the physical and mental health of patients, but also has become a major social public health problem. Effective dyskinesia rehabilitation treatment in convalescence is of great significance for AIS patients' prognosis and quality of life. Tai Chi (TC) shows great potential in improving motor function. This trial aims to evaluate the clinical efficacy of modified TC postural training (TPT), and to explore the related central-peripheral neurotransmitter mechanisms.

Methods/design: The proposed study will be a multicentre randomised controlled trial. The trial will randomise 120 eligible AIS patients in a 1:1 ratio to receive TPT or Bobath rehabilitation training. Each training session will last 40 min and will be implemented once a day and five times per week (from Monday to Friday) in a duration of 4 weeks. After finishing the 4-week treatment, another 3-month follow-up period will be seen. Root mean square generated from the surface electromyogram (sEMG) will be the primary outcome. Other sEMG time-domain parameters and frequency-domain parameters and clinical scales assessment will be the secondary outcomes. Peripheral blood samples will be collected at baseline and at the end of 4-week treatment, which will be used to explore the related therapeutic mechanisms. Intention-to-treat analysis and per-protocol analysis will both be implemented in this trial.

Ethics And Dissemination: The study has been approved by Ethics Committee of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, being granted approval numbers DZMEC-KY-2020-22. The research results will be disseminated through (open access) peer-reviewed publications and presentations at conferences.

Trial Registration Number: ChiCTR2000032999.
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http://dx.doi.org/10.1136/bmjopen-2020-046003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137247PMC
May 2021

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Signal Transduct Target Ther 2021 05 17;6(1):194. Epub 2021 May 17.

Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.
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http://dx.doi.org/10.1038/s41392-021-00603-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127508PMC
May 2021

Genome-Wide Detection of Runs of Homozygosity in Laiwu Pigs Revealed by Sequencing Data.

Front Genet 2021 29;12:629966. Epub 2021 Apr 29.

Department of Animal Science, College of Animal Sciences, Zhejiang University, Hangzhou, China.

Laiwu pigs, distinguished by their high intramuscular fat of 7-9%, is an indigenous pig breed of China, and recent studies also found that Laiwu pigs showed high resistance to Porcine circovirus type 2. However, with the introduction of commercial varieties, the population of Laiwu pigs has declined, and some lineages have disappeared, which could result in inbreeding. Runs of homozygosity (ROH) can be used as a good measure of individual inbreeding status and is also normally used to detect selection signatures so as to map the candidate genes associated with economically important traits. In this study, we used data from Genotyping by Genome Reducing and Sequencing to investigate the number, length, coverage, and distribution patterns of ROH in 93 Chinese Laiwu pigs and identified genomic regions with a high ROH frequency. The average inbreeding coefficient calculated by pedigree was 0.021, whereas that estimated by all detected ROH segments was 0.133. Covering 13.4% of the whole genome, a total of 7,508 ROH segments longer than 1 Mb were detected, whose average length was 3.76 Mb, and short segments (1-5 Mb) dominated. For individuals, the coverage was in the range between 0.56 and 36.86%. For chromosomes, SSC6 had the largest number ( = 688), and the number of ROH in SSC12 was the lowest ( = 215). Thirteen ROH islands were detected in our study, and 86 genes were found within those regions. Some of these genes were correlated with economically important traits, such as meat quality (, , , , and ), immunity capacity (, , , , and ), production (, , and ), and reproduction ( and ). A total of six significant Gene Ontology terms and nine significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, most of which were correlated with disease resistance and biosynthesis processes, and one KEGG pathway was related to lipid metabolism. In addition, we aligned all of the ROH islands to the pig quantitative trait loci (QTL) database and finally found eight QTL related to the intramuscular fat trait. These results may help us understand the characteristics of Laiwu pigs and provide insight for future breeding strategies.
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http://dx.doi.org/10.3389/fgene.2021.629966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116706PMC
April 2021

Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker.

Bioorg Chem 2021 Jul 1;112:104956. Epub 2021 May 1.

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China. Electronic address:

A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85-110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔG = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
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http://dx.doi.org/10.1016/j.bioorg.2021.104956DOI Listing
July 2021

Alteration of MDM2 by the small molecule YF438 exerts anti-tumor effects in triple-negative breast cancer.

Cancer Res 2021 May 13. Epub 2021 May 13.

Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University

Triple-negative breast cancer (TNBC) exhibits a high mortality rate and is the most aggressive subtype of breast cancer. As previous studies have shown that histone deacetylases (HDAC) may represent molecular targets for TNBC treatment, we screened a small library of synthetic molecules and identified a potent HDAC inhibitor (HDACi), YF438, which exerts effective anti-TNBC activity both in vitro and in vivo. Proteomic and biochemical studies revealed that YF438 significantly downregulated MDM2 expression. In parallel, loss of MDM2 expression or blocking MDM2 E3 ligase activity rendered TNBC cells less sensitive to YF438 treatment, revealing an essential role of MDM2 E3 ligase activity in YF438-induced inhibition of TNBC. Mechanistically, YF438 disturbed the interaction between HDAC1 and MDM2, induced the dissociation of MDM2-MDMX, and subsequently increased MDM2 self-ubiquitination to accelerate its degradation, which ultimately inhibited growth and metastasis of TNBC cells. In addition, analysis of clinical tissue samples demonstrated high expression levels of MDM2 in TNBC, and MDM2 protein levels closely correlated with TNBC progression and metastasis. Collectively, these findings show that MDM2 plays an essential role in TNBC progression and targeting the HDAC1-MDM2-MDMX signaling axis with YF438 may provide a promising therapeutic option for TNBC. Furthermore, this novel underlying mechanism of a hydroxamate-based HDACi in inducing MDM2 highlights the need for further development of HDACi for TNBC treatment.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-0922DOI Listing
May 2021

METTL13 inhibits progression of clear cell renal cell carcinoma with repression on PI3K/AKT/mTOR/HIF-1α pathway and c-Myc expression.

J Transl Med 2021 05 13;19(1):209. Epub 2021 May 13.

Department of Urology, First Hospital of China Medical University, School of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang City, 110004, Liaoning Province, People's Republic of China.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal malignancy. Methyltransferase like 13 (METTL13) functions as an oncogene in most of human cancers, but its function and mechanism in ccRCC remains unreported.

Methods: qRT-PCR, western blotting and immunohistochemistry were used to detect METTL13's expression in tissues. The effects of METTL13 on ccRCC cells' growth and metastasis were determined by both functional experiments and animal experiments. Weighted gene co-expression network analysis (WGCNA) was performed to annotate METTL13's functions and co-immunoprecipitation (co-IP) was used to determine the interaction between METTL13 and c-Myc.

Results: METTL13 was underexpressed in ccRCC tissues compared to normal kidney tissues and its low expression predicted poor prognosis for ccRCC patients. The in vitro studies showed that knockdown and overexpression of METTL13 respectively led to increase and decrease in ccRCC cells' proliferation, viability, migratory ability and invasiveness as well as epithelial-mesenchymal transition (EMT). The in vivo experiment demonstrated the inhibitory effect that METTL13 had on ccRCC cells' growth and metastasis. Bioinformatic analyses showed various biological functions and pathways METTL13 was involved in. In ccRCC cells, we observed that METTL13 could negatively regulate PI3K/AKT/mTOR/HIF-1α pathway and that it combined to c-Myc and inhibited c-Myc protein expression.

Conclusions: In general, our finding suggests that high expression of METTL13 is associated with favorable prognosis of ccRCC patients. Meanwhile, METTL13 can inhibit growth and metastasis of ccRCC cells with participation in multiple potential molecular mechanisms. Therefore, we suggest METTL13 can be a new diagnostic and therapeutic target for ccRCC in the future.
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http://dx.doi.org/10.1186/s12967-021-02879-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120818PMC
May 2021

Broadband tunable orbital angular momentum mode converter based on a conventional single-mode all-fiber configuration.

Opt Express 2021 May;29(10):15595-15603

A broadband tunable orbital angular momentum (OAM) mode converter based on a helical long-period fiber grating (HLPFG) inscribed in a conventional single-mode fiber (SMF) is experimentally demonstrated. The proposed all-fiber OAM mode converter is based on the core-cladding mode dual resonance near the dispersion turning point (DTP). The converter can operate with a bandwidth of 303.9 nm @ -3 dB and 182.2 nm @ -10 dB, which is, as far as we know, the widest bandwidth for a conventional SMF. Furthermore, the bandwidth of the OAM mode can be dynamically tuned within a large dynamic range (>80 nm) by simply twisting the fiber clockwise (CW) or counterclockwise (CCW). The dynamic tunability of the bandwidth of the proposed OAM mode generator may find vital applications in large-capacity optical fiber communication systems.
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http://dx.doi.org/10.1364/OE.421967DOI Listing
May 2021

Dynamic functional connectivity and its anatomical substrate reveal treatment outcome in first-episode drug-naïve schizophrenia.

Transl Psychiatry 2021 May 12;11(1):282. Epub 2021 May 12.

Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Zhejiang, China.

Convergent evidence has suggested a significant effect of antipsychotic exposure on brain structure and function in patients with schizophrenia, yet the characteristics of favorable treatment outcome remains largely unknown. In this work, we aimed to examine how large-scale brain networks are modulated by antipsychotic treatment, and whether the longitudinal changes could track the improvements of psychopathologic scores. Thirty-four patients with first-episode drug-naïve schizophrenia and 28 matched healthy controls were recruited at baseline from Shanghai Mental Health Center. After 8 weeks of antipsychotic treatment, 24 patients were re-scanned. Through a systematical dynamic functional connectivity (dFC) analysis, we investigated the schizophrenia-related intrinsic alterations of dFC at baseline, followed by a longitudinal study to examine the influence of antipsychotic treatment on these abnormalities by comparing patients at baseline and follow-up. A structural connectivity (SC) association analysis was further carried out to investigate longitudinal anatomical changes that underpin the alterations of dFC. We found a significant symptomatic improvement-related increase in the occurrence of a dFC state characterized by stronger inter-network integration. Furthermore, symptom reduction was correlated with increased FC variability in a unique connectomic signature, particularly in the connections within the default mode network and between the auditory, cognitive control, and cerebellar network to other networks. Additionally, we observed that the SC between the superior frontal gyrus and medial prefrontal cortex was decreased after treatment, suggesting a relaxation of normal constraints on dFC. Taken together, these findings provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network. Moreover, our identified neuroimaging markers tied to the neurobiology of schizophrenia could be used as potential indicators in predicting the treatment outcome of antipsychotics.
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http://dx.doi.org/10.1038/s41398-021-01398-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115129PMC
May 2021

Quantitative analysis of soil sustainability after applying stabilizing amendments in long-term Cd-contaminated paddy soils.

Environ Pollut 2021 May 3;286:117205. Epub 2021 May 3.

College of Water Resource & Hydropower, Sichuan University, Chengdu, Sichuan, 610065, China.

Considering the biomagnification in food chains, cadmium (Cd) contamination in paddy fields has become concerning. The remediation of soil cadmium by the addition of amendments is a common agricultural practice. However, it remains ambiguous whether amendment use decreases soil environmental quality (SEQ) and sustainability. In this study, five compound amendments with different pH were utilized in long-term Cd-contaminated paddy soils. The SEQ of all treatments was quantitatively assessed according to a comprehensive evaluation mathematical model (Criteria Importance Through Inter-criteria Correlation (CRITIC)-Technique for Order Preference by Similarity to Ideal Solution (TOPSIS)), and the indicators involved in microbial functional gene (MFG) abundance, soil physicochemical and microbiological properties (CMP) and soil microbial function (N-related enzyme and transformation rate, N-ET) were measured. The results show that the SQE and remediation effect (expressed by the decrease in available Cd (A), %) in our treatments were alkaline > natural > acidic except for D alkaline treatment. The significant contradiction between soil SQE and remediation effect in D treatment attribute to its dose effects, which inhibiting microbial nitrogen assimilation and dissimilation and therefore counteracts the promoting effect of the decrease in A. Based on this discussion, three alkaline amendments (A, B and D) with similar effective remediation effect were employed in four other Cd-contaminated soils. Results indicated that both negative effect (D treatment) and promoting effect (A and B treatment) existed in the next 3 years.
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http://dx.doi.org/10.1016/j.envpol.2021.117205DOI Listing
May 2021

Efficient removal of tetracycline by a hierarchically porous ZIF-8 metal organic framework.

Environ Res 2021 07 7;198:111254. Epub 2021 May 7.

State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University, Chengdu, 610065, China; College of Water Resource and Hydropower, Sichuan University, Chengdu, 610065, China.

Most reported metal organic frameworks (MOFs) have microporous structures and defective active sites, limiting their practical application to macromolecular substances. A hierarchical porous zeolitic imidazolate framework-8 (ZIF-8) was prepared using poly(diallyldimethylammonium chloride) (PDDA) as a structure-directing agent under facile "aqueous room-temperature" conditions to increase the mass transfer and adsorption capacity tetracycline hydrochloride (TCH). The ZIF-8 pore structure and morphology were synchronously tuned by controlling the PDDA molecular weight and dosage. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Bruner-Emmett-Teller (BET), scanning electron microscopy (SEM), NH-temperature-programmed desorption (NH-TPD) and adsorption results revealed abundant pore structures and open metal sites in the prepared materials, along with excellent TCH adsorption performance compared with ZIF-8, despite decreased BET surface areas. Initial screens revealed large adsorption capacities of hierarchical porous ZIF-8P3(4) (976.8 mg g) due to the presence of more abundant unsaturated metal sites than ZIF-8 and novel hierarchical porous structures. Therefore, TCH adsorption on ZIF-8 and ZIF-8P3(4), including the kinetics, isotherms, thermodynamics and pH effect, was studied. The adsorption process follows pseudo-second-order kinetics and the Freundlich models better, indicating multilayer adsorption of TCH on the surface of the two absorbents. Adsorption behavior test, FTIR, XPS, BET and XRD results show that TCH adsorption on ZIF-8 and ZIF-8P3(4) most likely involves coordination bonds, electrostatic and π-π interactions, hydrogen bonds, and pore-filling effects. This study provides new insights into the template preparation of MOFs with high adsorption performance as potentially economical adsorbents to remove organic matter from contaminated water.
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http://dx.doi.org/10.1016/j.envres.2021.111254DOI Listing
July 2021

Identifying functioning and nonfunctioning adrenal tumors based on blood serum surface-enhanced Raman spectroscopy.

Anal Bioanal Chem 2021 May 8. Epub 2021 May 8.

Department of Urology, First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, China.

Adrenal tumors are common tumors in urology and they can be further divided into functioning and nonfunctioning tumors according to whether there is uncommon endocrine function. In clinical practice, the early identification and accurate assessment of adrenal tumors are essential for the guidance of subsequent treatment. However, a nonfunctioning adrenal tumor often lacks obvious clinical symptoms, making it difficult to be timely and precisely diagnosed by conventional examinations. Therefore, a rapid and accurate method for identifying the functioning and nonfunctioning adrenal tumors is urgently required to achieve precise treatment of adrenal tumors. In this study, surface-enhanced Raman spectroscopy was investigated as a diagnostic tool to identify the blood serum samples from healthy volunteers as well as the patients with functioning and nonfunctioning adrenal tumors. Based on the SERS peak analysis, abnormal glycolysis, DNA/RNA, and amino acid metabolites were found to be potential biomarkers for identifying patients with adrenal tumors, while metabolites related to disordered protein catabolism and excessive hormone secretion were expected to further differentiate functioning adrenal tumors from nonfunctioning adrenal tumors. In addition, principal component analysis followed by support vector machine (PCA-SVM) was further applied on those serum SERS measurements, and the classification accuracies of 96.8% and 84.5% were achieved for differentiating healthy group versus adrenal tumor group and functioning adrenal tumor group versus nonfunctioning adrenal tumor group, respectively. The results have demonstrated the prodigious potential of precise adrenal tumor diagnosis by using the blood serum surface-enhanced Raman spectroscopy technique.
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http://dx.doi.org/10.1007/s00216-021-03381-wDOI Listing
May 2021

Dietary patterns and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Background: Dietary factors, such as consumption of preserved foods, fresh vegetables, and fruits, have been linked to the risk of nasopharyngeal carcinoma (NPC). However, little is known about associations between dietary patterns and the risk of NPC in NPC-endemic areas.

Objectives: We aimed to evaluate whether dietary patterns are associated with NPC risk.

Methods: We studied 2554 newly diagnosed NPC patients aged 20-74 y living in 3 endemic regions of southern China, and 2648 population-based controls frequency-matched to case patients by age, sex, and region, between 2010 and 2014. Dietary components were derived from food frequency data in adulthood and adolescence using principal component analysis. Four dietary components were identified and highly similar in adulthood and adolescence. We used multivariable unconditional logistic regression to calculate ORs with 95% CIs for the association between dietary patterns and NPC risk.

Results: Compared with the lowest quartile, individuals in the highest quartile of the "plant-based factor" in adulthood had a 52% (OR: 0.48; 95% CI: 0.38, 0.59) decreased risk of NPC, and those in the highest quartile of the "animal-based factor" had a >2-fold (OR: 2.26; 95% CI: 1.85, 2.77) increased risk, with a monotonic dose-response trend (P-trend < 0.0001). Similar but weaker associations were found in adolescence. High intakes of the "preserved-food factor" were associated with increased NPC risk in both periods, although stronger associations were found in adolescence. Results from joint analysis and sensitivity analyses indicated that dietary factors in adulthood might be more stable and robust predictors of NPC risk than those in adolescence.

Conclusions: Our results deliver compelling evidence that plant- and animal-based dietary factors are associated with NPC risk, and provide more insights on the associations of diets and cancer risk that may assist healthy diet recommendations.
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http://dx.doi.org/10.1093/ajcn/nqab114DOI Listing
May 2021

Photocatalytic upgrading of lignin oil to diesel precursor and hydrogen.

Angew Chem Int Ed Engl 2021 May 7. Epub 2021 May 7.

Dalian University of Technology, Zhang Dayu school of chemistry, zhongshan road 457, dalian, China, 116024, Dalian, CHINA.

Producing renewable biofuels from biomass is a promising way to meet future energy demand. Here, we demonstrated a lignin to diesel route via dimerization of the lignin oil followed by hydrodeoxygenation. The lignin oil undergoes C-C bond dehydrogenative coupling over Au/CdS photocatalyst under visible light irradiation, co-generating diesel precursors and hydrogen. The Au nanoparticles loaded on CdS can effectively restrain the recombination of photogenerated electrons and holes, thus improving the efficiency of the dimerization reaction. About 2.4 mmol g catal -1 h -1 dimers and 1.6 mmol g catal -1 h -1 H 2 were generated over Au/CdS, which is about 12 times and 6.5 times over CdS, respectively. The diesel precursors are finally converted into C16-C18 cycloalkanes or aromatics via hydrodeoxygenation reaction using Pd/C or porous CoMoS catalyst, respectively. The conversion of pine sawdust to diesel was performed to demonstrate the feasibility of the lignin-to-diesel route.
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http://dx.doi.org/10.1002/anie.202105692DOI Listing
May 2021

Lansoprazole Alone or in Combination With Gefitinib Shows Antitumor Activity Against Non-small Cell Lung Cancer A549 Cells and .

Front Cell Dev Biol 2021 20;9:655559. Epub 2021 Apr 20.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China.

Lansoprazole (Lpz) is an FDA-approved proton pump inhibitor (PPI) drug for the therapy of acid-related diseases. Aiming to explore the new application of old drugs, we recently investigated the antitumor effect of Lpz. We demonstrated that the PPI Lpz played a tumor suppressive role in non-small cell lung cancer (NSCLC) A549 cells. Mechanistically, Lpz induced apoptosis and G0/G1 cell cycle arrest by inhibiting the activation of signal transducer and activator of transcription (Stat) 3 and the phosphoinositide 3-kinase (PI3K)/Akt and Raf/ERK pathways. In addition, Lpz inhibited autophagy by blocking the fusion of autophagosomes with lysosomes. Furthermore, Lpz in combination with gefitinib (Gef) showed a synergistic antitumor effect on A549 cells, with enhanced G0/G1 cell cycle arrest and apoptosis. The combination inhibited Stat3 phosphorylation, PI3K/Akt and Raf/ERK signaling, affecting cell cycle-related proteins such as p-Rb, cyclin D1 and p27, as well as apoptotic proteins such as Bax, Bcl-2, caspase-3, and poly (ADP-ribose) polymerase (PARP). , coadministration with Lpz and Gef significantly attenuated the growth of A549 nude mouse xenograft models. These findings suggest that Lpz might be applied in combination with Gef for NSCLC therapy, but further evidence is required.
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http://dx.doi.org/10.3389/fcell.2021.655559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093516PMC
April 2021

Evaluation of the Association of Polymorphisms With Palbociclib-Induced Neutropenia: Pharmacogenetic Analysis of PALOMA-2/-3.

Oncologist 2021 May 5. Epub 2021 May 5.

Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background: The most frequently reported treatment-related adverse event in clinical trials with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib is neutropenia. Allelic variants in ABCB1 and ERCC1 might be associated with early occurrence (i.e., end of week 2 treatment) of grade 3/4 neutropenia. Pharmacogenetic analyses were performed to uncover associations between single nucleotide polymorphisms (SNPs) in these genes, patient baseline characteristics, and early occurrence of grade 3/4 neutropenia.

Materials And Methods: ABCB1 (rs1045642, rs1128503) and ERCC1 (rs3212986, rs11615) were analyzed in germline DNA from palbociclib-treated patients from PALOMA-2 (n = 584) and PALOMA-3 (n = 442). SNP, race, and cycle 1 day 15 (C1D15) absolute neutrophil count (ANC) data were available for 652 patients. Univariate and multivariable analyses evaluated associations between SNPs, patient baseline characteristics, and early occurrence of grade 3/4 neutropenia. Analyses were stratified by Asian (n = 122) and non-Asian (n = 530) ethnicity. Median progression-free survival (mPFS) was estimated using the Kaplan-Meier method. The effect of genetic variants on palbociclib pharmacokinetics was analyzed.

Results: ABCB1 and ERCC1_rs11615 SNP frequencies differed between Asian and non-Asian patients. Multivariable analysis showed that low baseline ANC was a strong independent risk factor for C1D15 grade 3/4 neutropenia regardless of race (Asians: odds ratio [OR], 6.033, 95% confidence interval [CI], 2.615-13.922, p < .0001; Non-Asians: OR, 6.884, 95% CI, 4.138-11.451, p < .0001). ABCB1_rs1128503 (C/C vs. T/T: OR, 0.57, 95% CI, 0.311-1.047, p = .070) and ERCC1_rs11615 (A/A vs. G/G: OR, 1.75, 95% CI, 0.901-3.397, p = .098) were potential independent risk factors for C1D15 grade 3/4 neutropenia in non-Asian patients. Palbociclib mPFS was consistent across genetic variants; exposure was not associated with ABCB1 genotype.

Conclusion: This is the first comprehensive assessment of pharmacogenetic data in relationship to exposure to a CDK4/6 inhibitor. Pharmacogenetic testing may inform about potentially increased likelihood of patients developing severe neutropenia (NCT01740427, NCT01942135).

Implications For Practice: Palbociclib plus endocrine therapy improves hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer outcomes, but is commonly associated with neutropenia. Genetic variants in ABCB1 may influence palbociclib exposure, and in ERCC1 are associated with chemotherapy-induced severe neutropenia. Here, the associations of single nucleotide polymorphisms in these genes and baseline characteristics with neutropenia were assessed. Low baseline absolute neutrophil count was a strong risk factor (p < .0001) for grade 3/4 neutropenia. There was a trend indicating that ABCB1_rs1128503 and ERCC1_rs11615 were potential risk factors (p < .10) for grade 3/4 neutropenia in non-Asian patients. Pharmacogenetic testing could inform clinicians about the likelihood of severe neutropenia with palbociclib.
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http://dx.doi.org/10.1002/onco.13811DOI Listing
May 2021

Pentraxin 3 is a diagnostic and prognostic marker for ovarian epithelial cancer patients based on comprehensive bioinformatics and experiments.

Cancer Cell Int 2021 Apr 6;21(1):193. Epub 2021 Apr 6.

Department of Pathology, Shenyang KingMed Center for Clinical Laboratory Co., Ltd, Shenyang, 110164, China.

Background: Ovarian epithelial cancer is one of the leading malignant tumors in gynecology and lacks effective diagnostic and prognostic markers. Our study aims to screen and verify ovarian epithelial cancer biomarkers.

Methods: GSE18520 and GSE26712 were downloaded from the GEO database. The "limma" and "WGCNA" packages were used to explore hub genes. The Kaplan-Meier Plotter database was used for survival analysis of the hub genes. Immunohistochemical analysis was used to identify the expression level of Pentraxin 3 in ovarian epithelial cancer samples.

Results: In this study, we integrated and analyzed two datasets, GSE18520 and GSE26712, and a total of 238 differentially expressed genes (DEGs) were screened out. Enrichment analysis showed that these DEGs were related to collagen-containing extracellular matrix and other pathways. Further application of WGCNA (weighted gene coexpression network analysis) identified 15 gene modules, with the purple module showing the highest correlation with ovarian epithelial cancer. Twenty-five genes were shared between the purple module and DEGs, 13 genes were related to the prognosis of ovarian epithelial cancer patients, and the PTX3 gene had the highest hazardous risk (HR) value. We performed immunohistochemical analyses on the 255 Pentraxin-3 (PTX3)-based clinical samples. PTX3 was found to be overexpressed in ovarian epithelial cancer and related to the degree of differentiation. The Cox proportional hazard model indicates that high PTX3 expression is an independent risk factor for the prognosis of ovarian epithelial cancer patients.

Conclusions: In conclusion, through WGCNA and a series of comprehensive bioinformatics analyses, PTX3 was first identified as a novel diagnostic and prognostic biomarker for ovarian epithelial cancer.
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http://dx.doi.org/10.1186/s12935-021-01854-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097951PMC
April 2021

Perineuronal net abnormalities in Slc13a4 mice are rescued by postnatal administration of N-acetylcysteine.

Exp Neurol 2021 Aug 1;342:113734. Epub 2021 May 1.

The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

Disruptions to either sulfate supply or sulfation enzymes can affect brain development and have long-lasting effects on brain function, yet our understanding of the molecular mechanisms governing this are incomplete. Perineuronal nets (PNNs) are highly sulfated, specialized extracellular matrix structures that regulate the maturation of synaptic connections and neuronal plasticity. We have previously shown that mice heterozygous for the brain sulfate transporter Slc13a4 have abnormal social interactions, memory, exploratory behaviors, stress and anxiety of postnatal origin, pointing to potential deficits in PNN biology, and implicate SLC13A4 as a critical factor required for regulating normal synaptic connectivity and function. Here, we sought to investigate aberrant PNN formation as a potential mechanism contributing to the functional deficits displayed by Slc13a4 mice. Following social interactions, we reveal reduced neuronal activation in the somatosensory cortex of Slc13a4 mice, and altered inhibitory and excitatory postsynaptic currents. In line with this, we found a reduction in parvalbumin-expressing neurons decorated with PNNs, as well as reduced expression of markers for PNN maturation. Finally, we reveal that postnatal administration of N-acetylcysteine prevented PNN abnormalities from manifesting in Slc13a4 adult animals. Collectively, these data highlight a central role for postnatal SLC13A4 in normal PNN formation, circuit function and subsequent animal behavior.
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http://dx.doi.org/10.1016/j.expneurol.2021.113734DOI Listing
August 2021

A Multitargeted Electrochemiluminescent Biosensor Coupling DNAzyme with Cascading Amplification for Analyzing Myocardial miRNAs.

Anal Chem 2021 May 4;93(20):7516-7522. Epub 2021 May 4.

School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma Xiang Road, Ma'anshan, Anhui 243032, P. R. China.

Several circulating miRNAs are associated with the pathogenic process of acute myocardial infarction (AMI). Thus, analyzing myocardial miRNAs in the circulatory system is important for the diagnosis and treatment of AMI, especially for early-stage diagnosis. Based on the characteristics of myocardial miRNAs, an ultrasensitive and multitargeted electrochemiluminescence (ECL) sensing platform was developed with a versatile probe that can couple DNAzyme with hybridization chain reaction amplification. The target miRNA and auxiliary chains form a circular unit that shears the versatile probe hairpin, and the products subsequently trigger cascading amplification; a long strand of dsDNA is then generated with many C-rich sequences that can undergo in situ reductions to generate ECL luminophore silver clusters. Using this strategy, three myocardial miRNAs are successfully detected with a detection limit as low as 29.6 aM (/ = 3). Notably, our method can detect myocardial miRNA groups composed of multiple related circulating miRNAs with high selectivity over interfering miRNAs in blood. This is extremely important for solving the problem of diverse and low abundance of infarct-associated miRNAs. Our strategy pioneers a new idea of miRNA detection, and given its versatility and sensitivity, it is promising for the diagnosis of multigene-regulated cardiovascular diseases.
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http://dx.doi.org/10.1021/acs.analchem.1c01051DOI Listing
May 2021

Corrigendum: A Weighted Gene Co-Expression Network Analysis-Derived Prognostic Model for Predicting Prognosis and Immune Infiltration in Gastric Cancer.

Front Oncol 2021 14;11:683333. Epub 2021 Apr 14.

Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China.

[This corrects the article DOI: 10.3389/fonc.2021.554779.].
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http://dx.doi.org/10.3389/fonc.2021.683333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080064PMC
April 2021

Three-Dimensional Radiomics Features From Multi-Parameter MRI Combined With Clinical Characteristics Predict Postoperative Cerebral Edema Exacerbation in Patients With Meningioma.

Front Oncol 2021 15;11:625220. Epub 2021 Apr 15.

Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, China.

Background: Postoperative cerebral edema is common in patients with meningioma. It is of great clinical significance to predict the postoperative cerebral edema exacerbation (CEE) for the development of individual treatment programs in patients with meningioma.

Objective: To evaluate the value of three-dimensional radiomics Features from Multi-Parameter MRI in predicting the postoperative CEE in patients with meningioma.

Methods: A total of 136 meningioma patients with complete clinical and radiological data were collected for this retrospective study, and they were randomly divided into primary and validation cohorts. Three-dimensional radiomics features were extracted from multisequence MR images, and then screened through Wilcoxon rank sum test, elastic net and recursive feature elimination algorithms. A radiomics signature was established based support vector machine method. By combining clinical with the radiomics signature, a clin-radiomics combined model was constructed for individual CEE prediction.

Results: Three significance radiomics features were selected to construct a radiomics signature, with areas under the curves (AUCs) of 0.86 and 0.800 in the primary and validation cohorts, respectively. Two clinical characteristics (peritumoral edema and tumor size) and radiomics signature were determined to establish the clin-radiomics combined model, with an AUC of 0.91 in the primary cohort and 0.83 in the validation cohort. The clin-radiomics combined model showed good discrimination, calibration, and clinically useful for postoperative CEE prediction.

Conclusions: By integrating clinical characteristics with radiomics signature, the clin-radiomics combined model could assist in postoperative CEE prediction before surgery, and provide a basis for surgical treatment decisions in patients with meningioma.
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http://dx.doi.org/10.3389/fonc.2021.625220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082417PMC
April 2021

ALKBH5-mediated m6A demethylation of lncRNA RMRP plays an oncogenic role in lung adenocarcinoma.

Authors:
Hui Yu Zhe Zhang

Mamm Genome 2021 Jun 1;32(3):195-203. Epub 2021 May 1.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, 138 Yi xue yuan Road, Shanghai, 200032, People's Republic of China.

Lung adenocarcinomas are more common in non-smoking males and females. In this study, we investigated the function of long non-coding RNA RMRP in lung adenocarcinoma and further explore the regulatory role of ALKBH5 in lncRNA methylation. The results showed lncRNA RMRP expression was significantly enhanced in lung adenocarcinoma tissues, and is positively correlated with poor prognosis. RMRP knockdown in lung adenocarcinoma cell lines suppressed cell proliferation, migration and invasion, and promoted cell apoptosis. In addition, ALKBH5 upregulated RMRP expression via demethylation, and ALKBH5 knockdown inhibited the tumorigenesis of lung adenocarcinoma in vitro and vivo. Given these clear patterns, suppressing RMRP through ALKBH5 manipulation may represent a promising therapeutic target for lung adenocarcinoma.
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http://dx.doi.org/10.1007/s00335-021-09872-6DOI Listing
June 2021