Publications by authors named "Lu Xia"

322 Publications

SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis.

J Cell Mol Med 2021 Jul 24. Epub 2021 Jul 24.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

High myopia is one of the leading causes of visual impairment worldwide with high heritability. We have previously identified the genetic contribution of SLC39A5 to nonsyndromic high myopia and demonstrated that disease-related mutations of SLC39A5 dysregulate the TGF-β pathway. In this study, the mechanisms underlying SLC39A5 involvement in the pathogenesis of high myopia are determined. We observed the morphogenesis and migration abnormalities of the SLC39A5 knockout (KO) human embryonic kidney cells (HEK293) and found a significant injury of ECM constituents. RNA-seq and qRT-PCR revealed the transcription decrease in COL1A1, COL2A1, COL4A1, FN1 and LAMA1 in the KO cells. Further, we demonstrated that TGF-β signalling, the regulator of ECM, was inhibited in SLC39A5 depletion situation, wherein the activation of receptor Smads (R-Smads) via phosphorylation was greatly blocked. SLC39A5 re-expression reversed the phenotype of TGF-β signalling and ECM synthesis in the KO cells. The fact that TGF-β signalling was zinc-regulated and that SLC39A5 was identified as a zinc transporter urged us to check the involvement of intracellular zinc in TGF-β signalling impairment. Finally, we determined that insufficient zinc chelation destabilized Smad proteins, which naturally inhibited TGF-β signalling. Overall, the SLC39A5 depletion-induced zinc deficiency destabilized Smad proteins, which inhibited the TGF-β signalling and downstream ECM synthesis, thus contributing to the pathogenesis of high myopia. This discovery provides a deep insight into myopic development.
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http://dx.doi.org/10.1111/jcmm.16803DOI Listing
July 2021

Evidence for methanobactin "Theft" and novel chalkophore production in methanotrophs: impact on methanotrophic-mediated methylmercury degradation.

ISME J 2021 Jul 21. Epub 2021 Jul 21.

Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, MI, 48109-2125, USA.

Aerobic methanotrophy is strongly controlled by copper, and methanotrophs are known to use different mechanisms for copper uptake. Some methanotrophs secrete a modified polypeptide-methanobactin-while others utilize a surface-bound protein (MopE) and a secreted form of it (MopE*) for copper collection. As different methanotrophs have different means of sequestering copper, competition for copper significantly impacts methanotrophic activity. Herein, we show that Methylomicrobium album BG8, Methylocystis sp. strain Rockwell, and Methylococcus capsulatus Bath, all lacking genes for methanobactin biosynthesis, are not limited for copper by multiple forms of methanobactin. Interestingly, Mm. album BG8 and Methylocystis sp. strain Rockwell were found to have genes similar to mbnT that encodes for a TonB-dependent transporter required for methanobactin uptake. Data indicate that these methanotrophs "steal" methanobactin and such "theft" enhances the ability of these strains to degrade methylmercury, a potent neurotoxin. Further, when mbnT was deleted in Mm. album BG8, methylmercury degradation in the presence of methanobactin was indistinguishable from when MB was not added. Mc. capsulatus Bath lacks anything similar to mbnT and was unable to degrade methylmercury either in the presence or absence of methanobactin. Rather, Mc. capsulatus Bath appears to rely on MopE/MopE* for copper collection. Finally, not only does Mm. album BG8 steal methanobactin, it synthesizes a novel chalkophore, suggesting that some methanotrophs utilize both competition and cheating strategies for copper collection. Through a better understanding of these strategies, methanotrophic communities may be more effectively manipulated to reduce methane emissions and also enhance mercury detoxification in situ.
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http://dx.doi.org/10.1038/s41396-021-01062-1DOI Listing
July 2021

Ambient climate determines the directional trend of community stability under warming and grazing.

Glob Chang Biol 2021 Jul 6. Epub 2021 Jul 6.

Key Laboratory of Adaptation and Evolution of Plateau Biotac, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China.

Changes in ecological processes over time in ambient treatments are often larger than the responses to manipulative treatments in climate change experiments. However, the impacts of human-driven environmental changes on the stability of natural grasslands have been typically assessed by comparing differences between manipulative plots and reference plots. Little is known about whether or how ambient climate regulates the effects of manipulative treatments and their underlying mechanisms. We collected two datasets, one a 36-year long-term observational dataset from 1983 to 2018, and the other a 10-year manipulative asymmetric warming and grazing experiment using infrared heaters with moderate grazing from 2006 to 2015 in an alpine meadow on the Tibetan Plateau. The 36-year observational dataset shows that there was a nonlinear response of community stability to ambient temperature with a positive relationship between them due to an increase in ambient temperature in the first 25 years and then a decrease in ambient temperature thereafter. Warming and grazing decreased community stability with experiment duration through an increase in legume cover and a decrease in species asynchrony, which was due to the decreasing background temperature through time during the 10-year experiment period. Moreover, the temperature sensitivity of community stability was higher under the ambient treatment than under the manipulative treatments. Therefore, our results suggested that ambient climate may control the directional trend of community stability while manipulative treatments may determine the temperature sensitivity of the response of community stability to climate relative to the ambient treatment. Our study emphasizes the importance of the context dependency of the response of community stability to human-driven environmental changes.
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http://dx.doi.org/10.1111/gcb.15786DOI Listing
July 2021

Heterostructured Pd/Ti/Pd Thin Films as Highly Efficient Catalysts for Methanol and Formic Acid Oxidation.

ACS Appl Mater Interfaces 2021 Jul 2;13(27):31725-31732. Epub 2021 Jul 2.

School of Materials, Sun Yat-sen University, Shenzhen 510817, China.

Finding a highly efficient catalyst for proton exchange membrane fuel cells is still the subject of extensive research. This article describes heterostructured Pd/Ti/Pd bimetallic thin films prepared using a strain-release technology as electrocatalysts for fuel cells. With their particular structure, these materials exhibit intriguing electrocatalytic activity toward the oxidation of both methanol and formic acid, yielding current densities of 0.17 and 0.56 A mg, much superior to that of the commercial Pd black catalyst. Moreover, the Pd/Ti/Pd thin films display a low onset oxidation potential and extremely high current retention in both acidic and alkaline media. The carbon monoxide poisoning resistance is also significantly enhanced, thus contributing to ultrahigh stability in the long-term electrocatalytic processes. Their encouraging performance implies that such composites could be potential materials for energy conversion in the fuel cell field.
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http://dx.doi.org/10.1021/acsami.1c07846DOI Listing
July 2021

Identification and functional analysis of a sex-biased transcriptional factor Foxl2 in the bay scallop Argopecten irradians irradians.

Comp Biochem Physiol B Biochem Mol Biol 2021 Jun 24;256:110638. Epub 2021 Jun 24.

Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; College of Marine Science and Engineering, Qingdao Agricultural University, Qingdao 266109, China. Electronic address:

Transcription factor Foxl2 is an evolutionarily conserved gene playing pivotal roles in regulation of early ovarian differentiation and maintenance in animals. However, the Foxl2 gene has not been thoroughly studied in hermaphroditic scallops. In this study, we cloned and characterized a Foxl2 (designated as AiFoxl2) from the bay scallop Argopecten irradians irradians. The open reading frame of AiFoxl2 was 1122 bp encoding 373 amino acids residues and contained a conserved forkhead box domain. Quantitative real-time PCR showed that AiFoxl2 was mainly expressed in the ovary. Moreover, the highest expression of AiFoxl2 in the ovary was detected at proliferative stage and growing stage, while the lowest level was found at resting stage. During the embryonic and larval development, expression of AiFoxl2 was found first in fertilized eggs, increased significantly at the blastula stage, and reached peak value at the D-larvae stage. When AiFoxl2 was knocked down, testis development-related genes (Dmrt1, Sox7 and Sox9) were up-regulated significantly while the ovary development-related genes (Vg, HSD14, and GATA-1) were down-regulated manifestly. These findings suggested that AiFoxl2 was a female-related gene in A. i. irradians and may be involved in regulation of ovarian development and differentiation.
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http://dx.doi.org/10.1016/j.cbpb.2021.110638DOI Listing
June 2021

Protective Predictors Associated With Posttraumatic Stress and Psychological Distress in Chinese Nurses During the Outbreak of COVID-19.

Front Psychol 2021 26;12:684222. Epub 2021 May 26.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.

The novel coronavirus disease 2019 (COVID-19) posed an unprecedented threat to Chinese healthcare professionals. Nevertheless, few studies notably focused on the mental health conditions of nurses and explored protective factors to prevent posttraumatic stress and psychological distress. This study aimed to explore the prevalence and the predictive factors especially defensive predictors associated with posttraumatic stress and psychological distress in nurses during the COVID-19 pandemic. In this online study, 1,728 nurses (~77.5% came from the COVID-19 pandemic frontline) were included in the final analysis. Posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (PCL-5) and Self-Reporting Questionnaire (SRQ) was used to assess posttraumatic stress and psychological distress. The results demonstrated that the prevalence of posttraumatic stress and psychological distress in nurses throughout China between February 1, 2020 and February 13, 2020 was 39.12 and 24.36%, respectively. Multivariate logistic regression indicated that insomnia, high panic intensity, and high impact of the COVID-19 pandemic were risk predictors of posttraumatic stress and psychological distress in nurses. Married participants had a 1.58 times increased risk of having posttraumatic stress when compared with the single participants. Frontline medical staff were more likely to suffer from psychological distress. The adequate exercise was a protective predictor of psychological distress [adjusted odds ratio (AOR) = 0.655, 95% CI = 0.486-0.883], but not with posttraumatic stress. High-quality diet was a protective predictor of posttraumatic stress (AOR = 0.112, 95% CI = 0.037-0.336) and psychological distress (AOR = 0.083, 95% CI = 0.028-0.247). Our study revealed the prevalence and factors associated with posttraumatic stress and psychological distress in nurses during the COVID-19 pandemic. Low panic intensity, low level of impact, satisfactory sleep, adequate exercise, and better diet were protective factors of posttraumatic stress and psychological distress. It indicated that the psychological status of nurses (particularly those from the COVID-19 pandemic frontline) should be monitored, and protective factors associated with posttraumatic stress and psychological distress should be increased.
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http://dx.doi.org/10.3389/fpsyg.2021.684222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189291PMC
May 2021

High rate of completion for weekly rifapentine plus isoniazid treatment in Chinese children with latent tuberculosis infection-A single center study.

PLoS One 2021 11;16(6):e0253159. Epub 2021 Jun 11.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Three months of weekly rifapentine plus isoniazid (3HP) is a short course regimen for latent tuberculosis infection treatment with satisfied safety and efficacy. However, research on its use in children is limited. In this study, we evaluated the completion rate and safety of the 3HP regimen among children in China. Participants aged 1-14 years receiving 3HP for TB prevention at Shanghai Public Health Clinical Center were followed from December 2019 to November 2020 to evaluate the safety and completion rate of the treatment. Thirty-one children were eligible for inclusion, but five were excluded from the analysis (three were treated with a lower than recommended dose, and two were lost to follow-up). Of the 26 children included in the analysis, the treatment completion rate was 100%. Adverse drug reactions (ADRs) were reported in 38.5% (10/26) of the patients. The most common ADRs were gastrointestinal symptoms (19.2%,5/26), and all ADRs were rated as Grade 1. The 3HP regimen has a high completion rate, and it seems well tolerated in our study population. However, further randomized controlled clinical trial with larger sample size are warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253159PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195436PMC
June 2021

SCF is functionally linked to obesity and metabolic syndrome.

EMBO Rep 2021 Jul 11;22(7):e52036. Epub 2021 Jun 11.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.

Dysregulation of lipid metabolism could lead to the development of metabolic disorders. We report here that the F-box protein JFK promotes excessive lipid accumulation in adipose tissue and contributes to the development of metabolic syndrome. JFK transgenic mice develop spontaneous obesity, accompanied by dyslipidemia, hyperglycemia, and insulin resistance, phenotypes that are further exacerbated under high-fat diets. In contrast, Jfk knockout mice are lean and resistant to diet-induced metabolic malfunctions. Liver-specific reconstitution of JFK expression in Jfk knockout mice leads to hepatic lipid accumulation resembling human hepatic steatosis and nonalcoholic fatty liver disease. We show that JFK interacts with and destabilizes ING5 through assembly of the SCF complex. Integrative transcriptomic and genomic analysis reveals that the SCF -ING5 axis interferes with AMPK activity and fatty acid β-oxidation, leading to the suppression of hepatic lipid catabolism. Significantly, JFK is upregulated and AMPKα1 is down-regulated in liver tissues from NAFLD patients. These results reveal that SCF is a bona fide E3 ligase for ING5 and link the SCF -ING5 axis to the development of obesity and metabolic syndrome.
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http://dx.doi.org/10.15252/embr.202052036DOI Listing
July 2021

UHRF2 commissions the completion of DNA demethylation through allosteric activation by 5hmC and K33-linked ubiquitination of XRCC1.

Mol Cell 2021 07 9;81(14):2960-2974.e7. Epub 2021 Jun 9.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. Electronic address:

The transition of oxidized 5-methylcytosine (5mC) intermediates into the base excision repair (BER) pipeline to complete DNA demethylation remains enigmatic. We report here that UHRF2, the only paralog of UHRF1 in mammals that fails to rescue Uhrf1 phenotype, is physically and functionally associated with BER complex. We show that UHRF2 is allosterically activated by 5-hydroxymethylcytosine (5hmC) and acts as a ubiquitin E3 ligase to catalyze K33-linked polyubiquitination of XRCC1. This nonproteolytic action stimulates XRCC1's interaction with the ubiquitin binding domain-bearing RAD23B, leading to the incorporation of TDG into BER complex. Integrative epigenomic analysis in mouse embryonic stem cells reveals that Uhrf2-fostered TDG-RAD23B-BER complex is functionally linked to the completion of DNA demethylation at active promoters and that Uhrf2 ablation impedes DNA demethylation on latent enhancers that undergo poised-to-active transition during neuronal commitment. Together, these observations highlight an essentiality of 5hmC-switched UHRF2 E3 ligase activity in commissioning the accomplishment of active DNA demethylation.
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http://dx.doi.org/10.1016/j.molcel.2021.05.022DOI Listing
July 2021

Fluoride exposure and children's intelligence: Gene-environment interaction based on SNP-set, gene and pathway analysis, using a case-control design based on a cross-sectional study.

Environ Int 2021 Oct 4;155:106681. Epub 2021 Jun 4.

Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

Background: Excessive fluoride exposure has been associated with intelligence loss, but little is known about gene-fluoride interactions on intelligence at SNP-set, gene and pathway level.

Objectives: Here we conducted a population-based study in Chinese school-aged children to estimate the associations of fluoride from internal and external exposures with intelligence as well as to explore the gene-fluoride interactions on intelligence at SNP-set, gene and neurodevelopmental pathway level.

Methods: A total of 952 resident children aged 7 to 13 were included in the current study. The fluoride contents in drinking water, urine, hair and nail were measured using the ion-selective electrode method. LASSO Binomial regression was conducted to screen the intelligence-related SNP-set. The gene-fluoride interactions at gene and pathway levels were detected by the Adaptive Rank Truncated Product method.

Results: The probability of high intelligence was inversely correlated with fluoride contents in water, urine, hair and nail (all P < 0.001). The SNP-set based on rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 was related to high intelligence (P = 0.001) alone and by interaction with water, urinary and hair fluoride (P = 0.030, 0.040, 0.010), separately. In gene level, CLU and TOMM40 interacted with hair fluoride (both P = 0.017) on intelligence. In pathway level, Alzheimer disease pathway, metabolic pathway, signal transduction pathway, sphingolipid signaling pathway and PI3K-AKT signaling pathway interacted with fluoride on intelligence in men.

Conclusions: Our study suggests that fluoride is inversely associated with intelligence. Moreover, the interactions of fluoride with mitochondrial function-related SNP-set, genes and pathways may also be involved in high intelligence loss.
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http://dx.doi.org/10.1016/j.envint.2021.106681DOI Listing
October 2021

OVOL2 attenuates the expression of MAP3K8 to suppress epithelial mesenchymal transition in colorectal cancer.

Pathol Res Pract 2021 May 25;224:153493. Epub 2021 May 25.

Laboratory of Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China; Department of Clinical Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China. Electronic address:

Background: Inactivation of members of the OVO-like family of C2H2 zinc-finger transcription factor 2 (OVOL2) is increased after colorectal cancer (CRC) metastasis. This study investigated the functional roles and clinical relevance of OVOL2 and its downstream factors in colorectal carcinogenesis.

Methods: Transcriptome RNA sequencing (RNA-seq) of HCT116 cells overexpressing OVOL2 and SW480 cells silencing OVOL2 were conducted. We cross-checked the Chromatin Immunoprecipitation sequencing (ChIP-seq, GSM1239518) positive peaks and RNA-seq differential expression genes (DEGs). In vitro functional assays, including wound-healing assay and transwell assay, were performed. The RNA expression (n = 597) and protein expression (n = 93) of OVOL2- mitogen-activated protein kinase kinase kinase 8 (MAP3K8)-C-X-C Motif Chemokine Ligand 16 (CXCL16) were evaluated in human CRC and adjacent normal tissues. CXCL16 levels in cell culture supernatants and serum samples obtained from 29 colon polyps patients and 24 CRC patients were measured using ELISA.

Results: We found that OVOL2 inhibited the migration and epithelial mesenchymal transition (EMT) of CRC cells by blocking the MAP3K8/AKT/NF-κB signaling pathway, and also decreased levels of CXCL16, a chemokine downstream of the MAP3K8/AKT/NF-κB signaling pathway. Furthermore, patient tumor tissue samples showed a lower level of in situ OVOL2 (P = 0.005) and higher CXCL16 (P = 0.001) levels, compared to adjacent normal tissues. Survival analyses revealed that both OVOL2 (logrank P = 0.063) and CXCL16 (logrank P = 0.048) were associated with overall survival (OS) and were independent prognostic factors for CRC. Additionally, OVOL2 and CXCL16 were found to be prognostically relevant (logrank P = 0.038). CXCL16 may serve as a potential diagnostic biomarker for CRC (P = 0.010).

Conclusions: The OVOL2/ MAP3K8/CXCL16 axis is a key player in colonic tumorigenesis and metastasis, and may be a potential diagnostic and prognostic biomarker.
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http://dx.doi.org/10.1016/j.prp.2021.153493DOI Listing
May 2021

Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development.

Cell Biosci 2021 May 22;11(1):95. Epub 2021 May 22.

Country Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, People's Republic of China.

Background: Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese.

Results: Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism.

Conclusions: This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.
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http://dx.doi.org/10.1186/s13578-021-00604-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141238PMC
May 2021

Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders.

J Autism Dev Disord 2021 May 10. Epub 2021 May 10.

National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Xiangya Road, Kaifu District, Changsha, 410013, Hunan, China.

The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.11%, 34.40%, 33.31%, 10.98% and 6.91% of patients with ID, EE, UDD, ASD and SCZ, respectively. Consistent with phenotype similarity and heterogeneity in different NPDs, they show different degree of genetic association. Cross-disorder analysis of DNMs prioritized 321 candidate genes (FDR < 0.05) and showed that genes shared in more disorders were more likely to exhibited specific expression pattern, functional pathway, genetic convergence, and genetic intolerance.
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http://dx.doi.org/10.1007/s10803-021-05031-7DOI Listing
May 2021

A Niemann-pick C1 disease child with BCG-itis: a case report and analysis.

BMC Pediatr 2021 05 4;21(1):218. Epub 2021 May 4.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Background: Niemann-Pick C disease is a rare autosomal recessive lysosomal lipid storage disorder. Some primary immunodeficiency diseases patients developed regional disease or disseminated disease after vaccinating BCG. It is unclear whether NPC gene deficiency is associated with Mycobacteria infection.

Case Presentation: We report and discuss a case of a child who presented at the age of 6 months with NPC1 and BCG-itis. The patient was treated with Miglustat and the symptom of lymphadenopathy was improved.

Conclusions: We reasonably speculate that NPC1 is a susceptibility gene of Mtb infection and mainly affects innate immunity. Once diagnosed, the infant should not be vaccinated with BCG and early treated.
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http://dx.doi.org/10.1186/s12887-021-02671-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094597PMC
May 2021

LINC00665 promotes HeLa cell proliferation, migration, invasion and epithelial-mesenchymal transition by activating the WNT-CTNNB1/β‑catenin signaling pathway.

Sheng Li Xue Bao 2021 Apr;73(2):233-243

Laboratory of Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.

There is increasing evidence that long non-coding RNA (lncRNA) plays critical roles in cancer progression. However, the role of long non-coding RNA 00665 (LINC00665) in most cancers is poorly understood. The purpose of the present study was to reveal the functional role of LINC00665 in cervical cancer cells. HeLa cells were subjected to LINC00665 short hairpin RNA (shRNA) or control shRNA treatment to investigate the metastasis and proliferation phenotype of cervical cancer cells in vitro and in vivo. Transcriptome sequencing experiments of HeLa cells in LINC00665 silencing or control group were conducted, and the differentially expressed genes (DEGs) were screened. The DEGs were subjected to Metascape database functional analysis and gene set enrichment analysis. Epithelial-mesenchymal transition (EMT) related markers and a key element of WNT/β‑catenin pathway, CTNNB1 (catenin beta 1), were detected by Western blot and immunofluorescence assay. The results showed that silencing LINC00665 reduced cell viability of Hela cells, up-regulated protein expression level of E-cadherin, down-regulated protein expression levels of N-cadherin, Vimentin and CTNNB1, and inhibited cell migration and invasion of HeLa cells. Bioinformatics analysis results showed that LINC00665 might promote EMT by activating WNT-CTNNB1/β‑catenin signaling pathway. These results indicate that LINC00665 has functions in transcriptional EMT regulation via WNT-CTNNB1/β‑catenin signaling pathway and therefore can be developed as a therapeutic target for cervical cancer.
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April 2021

Genome sequence, transcriptome, and annotation of rodent malaria parasite Plasmodium yoelii nigeriensis N67.

BMC Genomics 2021 Apr 26;22(1):303. Epub 2021 Apr 26.

Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892-8132, USA.

Background: Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated.

Results: We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains.

Conclusions: The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.
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http://dx.doi.org/10.1186/s12864-021-07555-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072299PMC
April 2021

Influence of the carbon source concentration on the nitrate removal rate in groundwater.

Environ Technol 2021 May 8:1-11. Epub 2021 May 8.

College of Earth Science and Engineering, Shandong University of Science and Technology, Qingdao, People's Republic of China.

At present, groundwater nitrate pollution in China is serious. The use of microorganisms for biological denitrification has been widely applied, and it is a universal and efficient in situ groundwater remediation technique, but this approach is influenced by many factors. In this study, glucose was adopted as the carbon source, four different concentrations of 0, 2, 5 and 10 g/L were considered, and natural groundwater with a nitrate concentration of 300.8 mg/L was employed as the experimental solution. The effect of the carbon source concentration on the nitrate removal rate in groundwater was examined through heterotrophic anaerobic denitrification experiments. The results showed that the nitrate removal rate could be improved by the addition of an external carbon source in the process of biological denitrification, and an optimal concentration was observed. At a glucose concentration of 2 g/L, the denitrification effect was the best.
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http://dx.doi.org/10.1080/09593330.2021.1921053DOI Listing
May 2021

GPCards: An integrated database of genotype-phenotype correlations in human genetic diseases.

Comput Struct Biotechnol J 2021 22;19:1603-1611. Epub 2021 Mar 22.

National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Genotype-phenotype correlations are the basis of precision medicine of human genetic diseases. However, it remains a challenge for clinicians and researchers to conveniently access detailed individual-level clinical phenotypic features of patients with various genetic variants. To address this urgent need, we manually searched for genetic studies in PubMed and catalogued 8,309 genetic variants in 1,288 genes from 17,738 patients with detailed clinical phenotypic features from 1,855 publications. Based on genotype-phenotype correlations in this dataset, we developed an user-friendly online database called GPCards (http://genemed.tech/gpcards/), which not only provided the association between genetic diseases and disease genes, but also the prevalence of various clinical phenotypes related to disease genes and the patient-level mapping between these clinical phenotypes and genetic variants. To accelerate the interpretation of genetic variants, we integrated 62 well-known variant-level and gene-level genomic data sources, including functional predictions, allele frequencies in different populations, and disease-related information. Furthermore, GPCards enables automatic analyses of users' own genetic data, comprehensive annotation, prioritization of candidate functional variants, and identification of genotype-phenotype correlations using custom parameters. In conclusion, GPCards is expected to accelerate the interpretation of genotype-phenotype correlations, subtype classification, and candidate gene prioritisation in human genetic diseases.
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http://dx.doi.org/10.1016/j.csbj.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042245PMC
March 2021

Safety Evaluation of Recombinant Fusion Protein RP22 as a Skin Test Reagent for Tuberculosis Diagnosis: A Phase I Clinical Trial.

Infect Dis Ther 2021 Jun 7;10(2):925-937. Epub 2021 Apr 7.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Introduction: This phase I clinical trial was conducted to evaluate the safety of RP22 as a skin test reagent for tuberculosis (TB) diagnosis and to explore the appropriate dosage.

Methods: We used a randomized, double-blind, placebo-controlled identification allergen (IA) skin test. A total of 72 healthy adult volunteers with negative chest X-ray results were randomized into six groups and given a QuantiFERON-TB Gold (QFT) test. Of the 12 participants in each group, eight received RP22 and four received placebo. The doses of RP22 in the six experimental groups ranged from 0.1 to 4.0 μg in a single intradermal injection of 0.1 ml. Skin reactions and adverse events were recorded at intervals.

Results: All doses of RP22 except the highest were well tolerated and safe. No serious adverse events associated with the injection were observed in all groups. There were 11 participants who had positive QFT results, eight had a skin reaction with a redness or induration area diameter of greater than 10 mm at 48-72 h, one had no skin reaction. Among the 60 negative-QFT participants, none had a reaction area diameter of greater than 10 mm.

Conclusion: The RP22 skin test was well tolerated and safe, it could play a key role in screening for latent tuberculosis infection (LTBI) by providing a much-wanted alternative to the tuberculin skin test (TST) and interferon-γ release assays (IGRAs).
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http://dx.doi.org/10.1007/s40121-021-00435-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116472PMC
June 2021

mutations in folate-related genes associated with common developmental disorders.

Comput Struct Biotechnol J 2021 1;19:1414-1422. Epub 2021 Mar 1.

National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Folate deficiency is an environmental risk factor for several developmental disorders. mutations (DNMs) also play important etiological roles in various developmental disorders. However, it remains unclear whether DNMs in folate-related genes (FRGs) contribute to developmental disorders. We obtained a list of 1,821 FRGs from folate metabolism pathways and the Comparative Toxicogenomics Database, along with data concerning DNMs in 15,404 cases and 3,391 controls from the Gene4Denovo database. We used a TADA-Denovo model to prioritize candidate disease-associated FRGs, and characterized these genes in terms of genic intolerance, functional networks, and expression patterns. Compared with the controls, FRGs were significantly enriched in likely damaging DNMs (ldDNMs) in patients with developmental disorders (1.54 ≤ odds ratio ≤ 3.39,  ≤ 0.0075). Furthermore, FRGs with ldDNMs rather than with likely non-damaging DNMs (lndDNMs) overlapped significantly among the five developmental disorders included in the datasets. The TADA-Denovo model prioritized 96 candidate disease-associated FRGs, which were intolerant to genetic variants. Their functional networks mainly involved pathways associated with chromatin modification, organ development, and signal transduction pathways. , , , and emerged as hub FRGs from the protein-protein interaction network. These candidate disease-associated FRGs are preferentially expressed in the excitatory neurones during embryonic development, and in the cortex, cerebellum, striatum, and amygdala during foetal development. Overall, these findings show that DNMs in FRGs are associated with the risk of developmental disorders. Further research on these DNMs may facilitate the discovery of developmental disorder biomarkers and therapeutic targets, enabling detailed, personalized, and precise folate treatment plan.
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http://dx.doi.org/10.1016/j.csbj.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966843PMC
March 2021

Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter.

Cell Discov 2021 Mar 23;7(1):16. Epub 2021 Mar 23.

Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China.

LAT1 (SLC7A5) is one of the representative light chain proteins of heteromeric amino acid transporters, forming a heterodimer with its heavy chain partner 4F2hc (SLC3A2). LAT1 is overexpressed in many types of tumors and mediates the transfer of drugs and hormones across the blood-brain barrier. Thus, LAT1 is considered as a drug target for cancer treatment and may be exploited for drug delivery into the brain. Here, we synthesized three potent inhibitors of human LAT1, which inhibit transport of leucine with IC values between 100 and 250 nM, and solved the cryo-EM structures of the corresponding LAT1-4F2hc complexes with these inhibitors bound at resolution of up to 2.7 or 2.8 Å. The protein assumes an outward-facing occluded conformation, with the inhibitors bound in the classical substrate binding pocket, but with their tails wedged between the substrate binding site and TM10 of LAT1. We also solved the complex structure of LAT1-4F2hc with 3,5-diiodo-L-tyrosine (Diiodo-Tyr) at 3.4 Å overall resolution, which revealed a different inhibition mechanism and might represent an intermediate conformation between the outward-facing occluded state mentioned above and the outward-open state. To our knowledge, this is the first time that the outward-facing conformation is revealed for the HAT family. Our results unveil more important insights into the working mechanisms of HATs and provide a structural basis for future drug design.
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http://dx.doi.org/10.1038/s41421-021-00247-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988154PMC
March 2021

Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2.

Cell Res 2021 06 18;31(6):717-719. Epub 2021 Mar 18.

Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China.

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http://dx.doi.org/10.1038/s41422-021-00490-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972335PMC
June 2021

Effects of polyacrylamide molecular weight and mass concentration on water transport characteristics of iron tailings.

Sci Rep 2021 Mar 18;11(1):6252. Epub 2021 Mar 18.

College of Resources and Environment, Shanxi Agricultural University, Taigu, 030801, Shanxi, China.

Iron tailings have few macropores which severely inhibit infiltration and transport of soil water. Polyacrylamide (PAM) can regulate soil water, but it is rarely used when remediating tailings matrix. In this research, PAM of four molecular weights of 300w, 600w, 800w, and 1000w were selected as amendments, and were each applied at five mass concentrations of 0% (CK), 0.01%, 0.04%, 0.08%, and 0.16% to observe their effects on water transport in iron tailings using column simulations in the laboratory. After adding PAM, the water retention and saturated water content of iron tailings increased significantly (P < 0.05). With increases in PAM molecular weight and mass concentration, the saturated hydraulic conductivity showed a downward trend, but the saturated hydraulic conductivity increased after a dry-wet cycle. With the increase of PAM mass concentration, adding PAM of 1000w molecular weight to iron tailing decreased infiltration capacity, but treatments of other molecular weights all initially increased then decreased infiltration capacity. The greatest improvement on infiltration capacity of iron tailings was observed with the addition of PAM of 300w molecular weight and 0.01% mass concentration. Adding PAM increased the vertical depth of the saturation zone of iron tailings (P < 0.05) with a maximum depth of 20.83 cm. The Kostiakov model more accurately simulated water infiltration of iron tailings compared with the Horton and Philip models. On the whole, when PAM of low molecular weight and concentration was added to iron tailings, PAM increased stable infiltration, saturated water content, and water retention. It also inhibited saturated hydraulic conductivity of iron tailings. Therefore, in practice, it is necessary to select the appropriate molecular weight and mass concentration of PAM according to the dominant limiting factors and remediation needs of the matrix.
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http://dx.doi.org/10.1038/s41598-021-85338-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973773PMC
March 2021

Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies.

Cell Res 2021 05 17;31(5):517-525. Epub 2021 Mar 17.

Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, Zhejiang, 310024, China.

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.
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http://dx.doi.org/10.1038/s41422-021-00487-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966918PMC
May 2021

Recurrent hemorrhage risk associated with medial target medullary artery anastomosis from the periventricular collateral vessel in adult patients with moyamoya disease.

BMC Neurol 2021 Mar 6;21(1):102. Epub 2021 Mar 6.

Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Background: Although the association between periventricular target collateral anastomosis and recurrent ipsilateral hemorrhage has been evaluated in adult patients with moyamoya disease (MMD), no studies have investigated the relationship between target anastomotic territory and recurrent ipsilateral hemorrhage. The goal of this study was to assess this association.

Methods: Consecutive adult MMD patients who had experienced initial intracranial hemorrhage and undergone conservative treatment were included. Two readers assessed angiographic results to identify the target anastomotic territory (medial medullary artery, lateral medullary artery, multiple medullary arteries, or nonmedullary artery) responsible for the hemorrhage. Cox proportional hazard regression models were used to estimate the risk of recurrent hemorrhage.

Results: In the 36 hemispheres with initial hemorrhage, the target anastomotic territory was in the anastomotic territory of the medial medullary artery in 10 (27.8%), lateral medullary artery in 15 (41.7%), multiple medullary arteries in 2 (5.6%), and a nonmedullary artery in 9 (25.0%) hemispheres. During 45.1 ± 40.0 months of follow-up, recurrent ipsilateral hemorrhage occurred in 44.4% (16/36) of hemispheres. The target anastomotic territories responsible for the recurrent event were in the anastomotic territory of the medial medullary artery in 9 (56.3%) hemispheres, lateral medullary artery in 6 (37.5%) hemispheres, and multiple medullary arteries in 1 (6.3%) hemisphere. The anastomotic territory of the medial medullary artery was associated with recurrent hemorrhage before (HR = 2.94; 95% CI, 1.07-8.08; p = 0.037) and after (HR = 6.65; 95% CI, 1.32-33.60; p = 0.022) adjustments were made for confounding factors.

Conclusions: The incidence of recurrent ipsilateral hemorrhage varies with the target anastomotic territory in adult patients with MMD. Medial target medullary artery anastomosis is a significant risk factor for recurrent ipsilateral hemorrhage.
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http://dx.doi.org/10.1186/s12883-021-02130-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936479PMC
March 2021

Transcriptomic analyses provide insights into the adaptive responses to heat stress in the ark shells, Scapharca subcrenata.

Comp Biochem Physiol Part D Genomics Proteomics 2021 06 15;38:100813. Epub 2021 Feb 15.

Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; Qingdao Agricultural University, Qingdao 266109, China. Electronic address:

The ark shell, Scapharca subcrenata, is susceptible to high temperature which may lead to mass mortality in hot summers. Herein, we conducted the transcriptomic analyses of haemocytes in ark shells under thermal stress, to reveal the underlying molecular mechanisms of heat resistance in these animals. The results showed that a total of 7773, 11,500 and 13,046 unigenes were expressed differentially at 12, 24 and 48 h post thermal stress, respectively. The expression levels of key DEGs as revealed by RNA-seq were confirmed by quantitative real-time PCR. GO and KEGG enrichment analyses showed that the DEGs were mainly associated with apoptosis, NF-kappa B signaling pathway, TNF signaling pathway and RIG-I-like receptor signaling pathway. Among the DEGs, 40 were candidate heat stress response-related genes and 169 were identified to be involved in antioxidant defense, cell detoxification, protein metabolism and endoplasmic reticulum stress responses. It seemed that ark shells may adapt to short term thermal stress through regulation of protein metabolism, DNA replication and anti-apoptotic system. However, if the stress sustains, it may cause irreparable injury gradually in the animals due to oxygen limitation and metabolic dysregulation. Noteworthily, the expression of DEGs involved in protein biosynthesis and proteolysis was significantly elevated in ark shells under heat stress. These findings may provide preliminary insights into the molecular response of ark shells to acute thermal stress and lay the groundwork for marker-assisted selection of heat-resistant strains in S. subcrenata.
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http://dx.doi.org/10.1016/j.cbd.2021.100813DOI Listing
June 2021

Agarose-resolvable InDel markers based on whole genome re-sequencing in cucumber.

Sci Rep 2021 Feb 16;11(1):3872. Epub 2021 Feb 16.

Molecular Biology Laboratory of Jiangsu Green Port Modern Agriculture Development Company, Suqian, 223800, Jiangsu, China.

Insertion and Deletion (InDel) are common features in genomes and are associated with genetic variation. The whole-genome re-sequencing data from two parents (X1 and X2) of the elite cucumber (Cucumis sativus) hybrid variety Lvmei No.1 was used for genome-wide InDel polymorphisms analysis. Obtained sequence reads were mapped to the genome reference sequence of Chinese fresh market type inbred line '9930' and gaps conforming to InDel were pinpointed. Further, the level of cross-parents polymorphism among five pairs of cucumber breeding parents and their corresponding hybrid varieties were used for evaluating hybrid seeds purity test efficiency of InDel markers. A panel of 48 cucumber breeding lines was utilized for PCR amplification versatility and phylogenetic analysis of these markers. In total, 10,470 candidate InDel markers were identified for X1 and X2. Among these, 385 markers with more than 30 nucleotide difference were arbitrary chosen. These markers were selected for experimental resolvability through electrophoresis on an Agarose gel. Two hundred and eleven (211) accounting for 54.81% of markers could be validated as single and clear polymorphic pattern while 174 (45.19%) showed unclear or monomorphic genetic bands between X1 and X2. Cross-parents polymorphism evaluation recorded 68 (32.23%) of these markers, which were designated as cross-parents transferable (CPT) InDel markers. Interestingly, the marker InDel114 presented experimental transferability between cucumber and melon. A panel of 48 cucumber breeding lines including parents of Lvmei No. 1 subjected to PCR amplification versatility using CPT InDel markers successfully clustered them into fruit and common cucumber varieties based on phylogenetic analysis. It is worth noting that 16 of these markers were predominately associated to enzymatic activities in cucumber. These agarose-based InDel markers could constitute a valuable resource for hybrid seeds purity testing, germplasm classification and marker-assisted breeding in cucumber.
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http://dx.doi.org/10.1038/s41598-021-83313-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886880PMC
February 2021

Fungal-induced glycolysis in macrophages promotes colon cancer by enhancing innate lymphoid cell secretion of IL-22.

EMBO J 2021 Jun 16;40(11):e105320. Epub 2021 Feb 16.

The State Key Laboratory of Pharmaceutical Biotechnology & Nanjing Stomatological Hospital, Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, China.

Incorporation of microbiome data has recently become important for prevention, diagnosis, and treatment of colorectal cancer, and several species of bacteria were shown to be associated with carcinogenesis. However, the role of commensal fungi in colon cancer remains poorly understood. Here, we report that mice lacking the c-type lectin Dectin-3 (Dectin-3 ) show increased tumorigenesis and Candida albicans burden upon chemical induction. Elevated C. albicans load triggered glycolysis in macrophages and interleukin-7 (IL-7) secretion. IL-7 induced IL-22 production in RORγt (group 3) innate lymphoid cells (ILC3s) via aryl hydrocarbon receptor and STAT3. Consistently, IL-22 frequency in tumor tissues of colon cancer patients positively correlated with fungal burden, indicating the relevance of this regulatory axis in human disease. These results establish a C. albicans-driven crosstalk between macrophages and innate lymphoid cells in the intestine and expand our understanding on how commensal mycobiota regulate host immunity and promote tumorigenesis.
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http://dx.doi.org/10.15252/embj.2020105320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167358PMC
June 2021

Histomorphology and gene expression profiles during early ovarian folliculogenesis in duck and goose.

Poult Sci 2021 Feb 21;100(2):1098-1108. Epub 2020 Oct 21.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130 Chengdu, Sichuan, China.

In contrast to the later stages of follicle development, little is known about the characteristics and mechanisms associated with early folliculogenesis in avian species. The objectives of the present study were to examine and compare the histomorphological and molecular changes of primordial, primary, and secondary follicles from duck and goose ovaries during the first 6 post-hatching week. Morphological analysis showed that the length and width of both duck and goose ovaries increased steadily during weeks 1 to 5 but increased acutely at week 6, whereas a greater increment was observed in the ovarian length of ducks than that of geese during weeks 4 to 5. Furthermore, smaller diameters of the 3 categories of follicles were observed in ducks than those in geese at the first appearance, but they reached a similar size at week 6. More importantly, secondary follicles were found in the ovaries of ducks 1 wk earlier than in those of geese. These results indicated a more rapid growth rate for ovarian follicles in ducks than in geese during early post-hatching development. At the molecular level, it was found that the mRNAs encoding follicle stimulating hormone receptor (FSHR), anti-Müllerian hormone (AMH), B-cell leukemia/lymphoma 2, and cysteine-dependent aspartate specific protease 3 (CASPASE3) were ubiquitously expressed in all ovarian follicles of ducks and geese with different expression profiles in each follicular category during the first 6 post-hatching week. Notably, transcript levels of FSHR, AMH, and CASPASE3 changed differently between ducks and geese during weeks 5 to 6, which was postulated to be one of the mechanisms inducing more rapid growth of ovarian follicles in ducks rather than in geese. In conclusion, our results revealed, for the first time, differences in early folliculogenesis, including the rate of growth of each follicular category and the timing of transition of primary to secondary follicles, between ducks and geese, and these differences could result from different expression profiles of FSHR, AMH, and CASPASE3 during early post-hatching development.
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http://dx.doi.org/10.1016/j.psj.2020.10.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858004PMC
February 2021

Effects of Salmonella enterica serovar typhimurium sseK1 on macrophage inflammation-related cytokines and glycolysis.

Cytokine 2021 Apr 26;140:155424. Epub 2021 Jan 26.

The Key Lab of Animal Disease and Public Health, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang 471023, Henan Province, People's Republic of China; Luoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471023, Henan Province, People's Republic of China.

Salmonella enterica serovar Typhimurium (S. Typhimurium), an important virulent intracellular pathogen, causes inflammatory gastroenteritis or typhoid. Macrophages play a key role in innate immunity against Salmonella. Salmonella secreted effector K1 (SseK1) encoded by SPI2 has been identified a novel translocated protein. To investigate the role of Salmonella enterica serovar Typhimurium sseK1 about the inflammation and glycolysis in macrophages, the levels of IL-1β, IL-2, IL-4, IL-6, IFN-γ and Nitric Oxide in macrophages infected by S. Typhimurium SL1344 wild-type (WT) group, ΔsseK1 mutant group and sseK1-complemented group were measured. And the glycolysis level was determined in RAW 264.7 cells infected with these different Salmonella strains. The results showed that groups infected by wild-type strain, sseK1 mutant and sseK1-complemented strain upregulated the production of IL-1β, IL-2, IL-4, IL-6, IFN-γ and NO at 3 h, 6 h and 12 h, respectively. The production of IL-1β, IL-2, IL-4, IL-6, IFN-γ and NO in wild-type strain group were significantly decreased compared with the ΔsseK1 mutant group, which suggested that sseK1 down-regulated the production of related inflammatory factors. Moreover, hexokinase, lactic acid and pyruvic acid levels significantly decreased by infection with sseK1 mutant compared to the wild-type strain. The ATP level of ΔsseK1 mutant group was remarkably increased than WT group and sseK1-complemented group. These indicated that the sseK1 enhanced the level of glycolysis of macrophages infected by S. Typhimurium. In summary, the results demonstrated that sseK1 can down-regulate the inflammation-related cytokines and enhance the glycolysis level in macrophages infected by S. Typhimurium, which may be beneficial for S. typhimurium survival in macrophages.
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http://dx.doi.org/10.1016/j.cyto.2021.155424DOI Listing
April 2021
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