Publications by authors named "Li Q"

41,898 Publications

A Bayesian method for synthesizing multiple diagnostic outcomes of COVID-19 tests.

R Soc Open Sci 2021 Sep 15;8(9):201867. Epub 2021 Sep 15.

JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.

The novel coronavirus disease 2019 (COVID-19) has spread worldwide and threatened human life. Diagnosis is crucial to contain the spread of SARS-CoV-2 infections and save lives. Diagnostic tests for COVID-19 have varying sensitivity and specificity, and the false-negative results would have substantial consequences to patient treatment and pandemic control. To detect all suspected infections, multiple testing is widely used. However, it may be challenging to build an assertion when the testing results are inconsistent. Considering the situation where there is more than one diagnostic outcome for each subject, we proposed a Bayesian probabilistic framework based on the sensitivity and specificity of each diagnostic method to synthesize a posterior probability of being infected by SARS-CoV-2. We demonstrated that the synthesized posterior outcome outperformed each individual testing outcome. A user-friendly web application was developed to implement our analytic framework with free access via http://www2.ccrb.cuhk.edu.hk/statgene/COVID_19/. The web application enables the real-time display of the integrated outcome incorporating two or more tests and calculated based on Bayesian posterior probability. A simulation-based assessment demonstrated higher accuracy and precision of the Bayesian probabilistic model compared with a single-test outcome. The online tool developed in this study can assist physicians in making clinical evaluations by effectively integrating multiple COVID-19 tests.
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http://dx.doi.org/10.1098/rsos.201867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441124PMC
September 2021

Involvement of bradykinin and bradykinin B1 receptor in patients with endometriosis.

Exp Ther Med 2021 Nov 1;22(5):1240. Epub 2021 Sep 1.

Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050091, P.R. China.

Endometriosis (EM), a benign aseptic inflammatory disease, is associated with the presence of endometrial foci. Pain, one of its typical symptoms, has been reported as a constant stressor, but the etiology and pathogenesis of EM-associated pain are unclear. In the present study, eutopic and ectopic endometrium samples from women with EM (n=50) and normal endometrium samples from control subjects (n=20) were collected. Serum levels of prostaglandin E (PGE), prostaglandin F2α (PGF2α) and bradykinin (BK) were measured using commercial ELISA kits. The expression of the BKB1 receptor (BKB1R) protein was evaluated by immunohistochemical staining and western blot assay. The mRNA expression of BKB1R was measured by reverse transcription-quantitative PCR. The results revealed that there was a substantial increase in the protein and mRNA expression of BKB1R, as well as the release of PGE, PGF2α and BK in the blood, in the EM group compared with that in the control group. Moreover, PGE, PGF2α and BK levels were significantly correlated with each other, as well as with the pain intensity of EM. The increased expression levels of BKB1R protein and mRNA were positively correlated with the pain degree of EM. Thus, these data indicated that BK and BKB1R were involved in the pathological onset of EM-associated pain and that they may play an important role in EM-related pain by inducing PGE and PGF2α. The data indicate a potential new therapeutic target for EM-related pain.
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http://dx.doi.org/10.3892/etm.2021.10675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438668PMC
November 2021

Moxibustion improves ovarian function based on the regulation of the androgen balance.

Exp Ther Med 2021 Nov 30;22(5):1230. Epub 2021 Aug 30.

Traditional Chinese Medicine Department, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu 221006, P.R. China.

The effect of androgens on follicular development and female reproduction has become an active research topic. Moxibustion is a Traditional Chinese Medicine therapy that has been reported to be able to prevent and treat numerous ovary-related problems. However, studies on the effect of moxibustion for diminished ovarian reserve (DOR) on androgen balance are still lacking. The present study aimed to assess the efficacy of moxibustion intervention prior to disease onset and at the early stage of disease in a rat model of DOR and explore the mechanisms of its effect on ovarian function. A total of 32 rats were randomly divided into four groups: Blank group, Model group (a drug-induced model of DOR), Moxibustion group 1 and Moxibustion group 2. Moxibustion was performed on the BL23 and RN4 acupoints of female rats daily for a total of 20 days (once a day, five times a week for a total of 4 weeks). The two moxibustion groups were established with different intervention times: One group was subjected to pre-disease intervention and the other group to early-disease intervention. The ovarian function was evaluated by detecting anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), testosterone (T), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT) and androgen receptor (AR) levels in the serum or the ovary samples. To further investigate the downstream regulatory factors for AR after moxibustion treatment for pre-disease or early-disease intervention, FSH receptor (FSHR) and microRNA (miR)-125b expression in ovaries were also analyzed. The results indicated that AMH and DHT levels were reduced in the model group compared with those in the blank group, while FSH, T and DHEA levels were increased. AMH and DHT levels were increased in Moxibustion group 1 compared with those in the model group, while FSH, T and DHEA levels were reduced. There was no difference in E2 levels between Moxibustion group 1 and the model group. Compared with that in the model group, the AR content in the ovary was increased in Moxibustion group 1. There was no difference in FSHR mRNA in the ovaries between Moxibustion group 1 and the model group. miR-125b levels were significantly increased in Moxibustion group 1 as compared with those in the model group. Furthermore, AMH and DHT levels were increased in Moxibustion group 2 compared with those in the model group, while FSH, T and DHEA levels were reduced. E2 levels were significantly decreased in Moxibustion group 2 compared with those in the model group. The relative mRNA expression of AR, FSHR and miR-125b was decreased following establishment of the model. Compared with that in the model group, the AR content in the ovary was increased in Moxibustion group 2. In comparison with the blank and model groups, the FSHR content in the ovary of Moxibustion group 2 was significantly increased. miR-125b levels were not obviously altered in Moxibustion group 2 as compared with those in the model group. In addition, there was no significant difference in AMH, FSH, T and DHEA levels between the two moxibustion groups. E2 and DHT levels were higher in Moxibustion group 1 than in Moxibustion group 2. There was no difference in AR mRNA expression between the two moxibustion groups. FSHR mRNA levels were lower in Moxibustion group 1 than in Moxibustion group 2, while miR-125b mRNA levels were higher in Moxibustion group 1 than in Moxibustion group 2. In conclusion, the present study suggested that moxibustion intervention prior to disease onset and at the early disease stage was able to improve ovarian function via modulation of the AR-mediated stable equilibrium of androgens. However, the effects and mechanisms of moxibustion intervention for pre-disease and early-disease intervention of DOR appear to be different. The appropriate duration of treatment and the time-effect relationship require to be further studied.
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http://dx.doi.org/10.3892/etm.2021.10664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438671PMC
November 2021

Transcriptional and Hormonal Responses in Ethephon-Induced Promotion of Femaleness in Pumpkin.

Front Plant Sci 2021 1;12:715487. Epub 2021 Sep 1.

College of Horticulture and Landscape, Henan Institute of Science and Technology, Xinxiang, China.

The number and proportion of female flowers per plant can directly influence the yield and economic benefits of cucurbit crops. Ethephon is often used to induce female flowers in cucurbits. However, the mechanism through which it affects floral sex differentiation in pumpkin is unknown. We found that the application of ethephon on shoot apical meristem of pumpkin at seedling stage significantly increased the number of female flowers and expedited the appearance of the first female flower. These effects were further investigated by transcriptome and hormone analyses of plants sprayed with ethephon. A total of 647 differentially expressed genes (DEGs) were identified, among which 522 were upregulated and 125 were downregulated. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis indicated that these genes were mainly enriched in plant hormone signal transduction and 1-aminocyclopropane-1-carboxylate oxidase (ACO). The results suggests that ethylene is a trigger for multiple hormone signaling, with approximately 4.2% of the identified DEGs involved in ethylene synthesis and multiple hormone signaling. Moreover, ethephon significantly reduced the levels of jasmonic acid (JA), jasmonoyl-L-isoleucine (JA-ILE), and para-topolin riboside (pTR) but increased the levels of 3-indoleacetamide (IAM). Although the level of 1-aminocyclopropanecarboxylic acid was not changed, the expression of genes, which code for the enzyme catalyzing the key rate-limiting step in ethylene production, was significantly upregulated after ethephon treatment. The results indicate that the ethephon affects the transcription of ethylene synthesis and signaling genes, and other hormone signaling genes, especially auxin responsive genes, and modulates the levels of auxin, jasmonic acid, and cytokinin (CK), which may together contribute to femaleness.
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http://dx.doi.org/10.3389/fpls.2021.715487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442687PMC
September 2021

Cytotoxic T-Cell Trafficking Chemokine Profiles Correlate With Defined Mucosal Microbial Communities in Colorectal Cancer.

Front Immunol 2021 1;12:715559. Epub 2021 Sep 1.

Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China.

The involvement of gut microbiota in T-cell trafficking into tumor tissue of colorectal cancer (CRC) remains to be further elucidated. The current study aimed to evaluate the expression of major cytotoxic T-cell trafficking chemokines (CTTCs) and chemokine-associated microbiota profiles in both tumor and adjacent normal tissues during CRC progression. We analyzed the expression of chemokine C-X-C motif ligands 9, 10, and 11 (, , and ), and C-C motif ligand 5 (), characterized gut mucosa-associated microbiota (MAM), and investigated their correlations in CRC patients. Our results showed that the expression of , and was significantly higher in tumor than in adjacent normal tissues in 136 CRC patients. Notably, the high expression of in tumor tissues was associated with enhanced CD8 T-cell infiltration and improved survival. Moreover, the MAM in tumor tissues showed reduction of microbial diversity and increase of oral bacteria. Microbial network analysis identified differences in microbial composition and structure between tumor and adjacent normal tissues. In addition, stronger associations between oral bacteria and other gut microbes were observed. Furthermore, the correlation analysis between the defined MAM and individual CTTCs showed that the CTTCs' correlated operational taxonomic units (OTUs) in tumor and adjacent normal tissues rarely overlap with each other. Notably, all the enriched OTUs were positively correlated with the CTTCs in either tumor or adjacent normal tissues. Our findings demonstrated stronger interactions between oral bacteria and gut microbes, and a shifted correlation pattern between MAM and major CTTCs in tumor tissues, underlining possible mechanisms of gut microbiota-host interaction in CRC.
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http://dx.doi.org/10.3389/fimmu.2021.715559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442671PMC
September 2021

A taxonomic study of from China, with six new species.

MycoKeys 2021 24;83:39-67. Epub 2021 Aug 24.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550004, China Guizhou Medical University Guiyang China.

During an investigation of Xylariaceae from 2019 to 2020, isolates representing eight (Xylariacese) species were collected from Yunnan, Guizhou and Hainan Provinces in China. Morphological and multi-gene phylogenetic analyses, based on combined ITS, α-actin, and β-tubulin sequences, confirmed that six of them are new to science, viz. , , , , and ; one is a new record () for China and one is a known species (). Morphological descriptions and illustrations of all species are detailed. In addition, the characteristics of are summarised and prevailing contradictions in generic concepts are discussed.
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http://dx.doi.org/10.3897/mycokeys.83.69906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408098PMC
August 2021

Metabolite profiles in the peritoneal cavity of endometriosis patients and mouse models.

Reprod Biomed Online 2021 Jul 8. Epub 2021 Jul 8.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, People's Republic of China. Electronic address:

Research Question: Which metabolites are altered in the peritoneal cavity of women with endometriosis? Could the mouse endometriosis model simulate these alterations?

Design: Thirteen women with endometriosis and seven women with other benign gynaecological diseases, who underwent laparoscopic surgery, were included in this study. None had received hormonal therapy for 3 months before surgery. For the animal experiments, six and five mice were included in the endometriosis and control groups, respectively. Peritoneal fluid from the patients and peritoneal lavage fluid from the mice was collected and analysed. Non-targeted metabolomics via liquid chromatography with tandem mass spectrometry was used to identify the altered metabolites in the peritoneal fluid of endometriosis patients and mouse models. MetaboAnalyst 4.0 was used to visualize the data.

Results: Several metabolites in the peritoneal cavity were significantly altered in both humans and mice with endometriosis. Concentrations of lysophosphatidylcholine (LysopC) (P=0.017 in patients and P=0.041 in the mouse model) and derivatives of phosphoethanolamine (1-arachidonoyl-sn-glycero-3-phosphoethanolamine in patients, P=0.027; 1-oleoyl-sn-glycero-3-phosphoethanolamine in patients, P=0.0086; and phosphorylethanolamine in the mouse model, P=0.0027) were significantly up-regulated in both, whereas concentrations of acylcarnitines (l-palmitoylcarnitine, P=0.047; and stearoylcarnitine, P=0.029) and kynurenine (P=0.045) were significantly increased only in humans. The human and mouse samples shared three altered enriched metabolite sets.

Conclusions: Women with endometriosis show an altered metabolic state in the abdominal cavity. The endometriosis mouse model shared half of the significantly altered metabolite sets found in the abdominal cavity of humans.
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http://dx.doi.org/10.1016/j.rbmo.2021.06.029DOI Listing
July 2021

LINC00323 mediates the role of M1 macrophage polarization in diabetic nephropathy through PI3K/AKT signaling pathway.

Authors:
Kun Li Qiang Li

Hum Immunol 2021 Sep 15. Epub 2021 Sep 15.

Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road 246, Harbin 150086, Heilongjiang, China. Electronic address:

Objective: To explore the effect of LINC00323 on the polarization of M1 macrophages in diabetic nephropathy. To study the effect and biological mechanism of LINC00323 on the occurrence and development of diabetic nephropathy.

Methods: We used clinical samples to analyze the correlation between macrophage polarization and the occurrence and development of diabetic nephropathy. In addition, we used bioinformatics to analyze the key molecules of macrophage polarization. We then verified the key pathways that promote the M1 polarization of macrophages at the level of cell biology. And we verify the effectiveness of treatment against this target in animal experiments.

Results: We analyzed in clinical samples that the expression of inflammatory factors (TNF-α and IL-6) increased in patients with diabetic nephropathy. In addition, we found that the expression of M1 marker protein CD86 increased through PCR and western blot analysis. We found a key target (LINC00323) through bioinformatics. The expression of LINC00323 in patients' blood samples is also at a high level. We further explored the mechanism of LINC00323 involved in the polarization of M1 macrophages at the level of cellular molecular biology, and found that it is closely related to the PI3K/AKT signaling pathway. In animal models, we found that inhibiting the expression of LINC00323 can reduce the damage of diabetic nephropathy.

Conclusion: We found that LINC00323 mediates the polarization of M1 macrophages through the PI3K/AKT signaling pathway. LINC00323 plays an important role in the occurrence and development of diabetic nephropathy.
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http://dx.doi.org/10.1016/j.humimm.2021.08.010DOI Listing
September 2021

Wernicke encephalopathy following advanced caecum cancer.

Rev Esp Enferm Dig 2021 Sep 20. Epub 2021 Sep 20.

Gastrointestinal Surgery, The First Affiliated of Wannan Medical College, China.

A 26-year-old lactating mother presented with a 3-week history of abdominal pain, constipation and vomiting. She denied a history of alcohol abuse or other gastrointestinal problem. Contrast-enhanced CT revealed a small bowel obstruction caused by caecum cancer. Therefore, she underwent a right hemicolectomy and ileocolic anastomosis. Post-operatively, she gradually developed drowsiness, fainting and a rapid heart rate of 130. But blood tests were all normal. On the fourteenth postoperative day, she experienced two episodes of generalized tonic-clonic seizure. Neurologic examination revealed nystagmus, ophthalmoplegia and gait ataxia. She complained of impaired memory and blurred vision. Brain magnetic resonance image (MRI) showed bilaterally symmetric hyperintensities in paramedial thalami surrounding the third ventricle, dorsal brainstem and periaqueductal region in the axial T2-FLAIR images . Wernicke's encephalopathy (WE) was suspected and the patient was treated with Vitamin B1 immediately. Her symptoms improved rapidly, and a brain MRI two weeks later demonstrated marked resolution of the hyperintensities.
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http://dx.doi.org/10.17235/reed.2021.8343/2021DOI Listing
September 2021

miR-2337 induces TGF-β1 production in granulosa cells by acting as an endogenous small activating RNA.

Cell Death Discov 2021 Sep 18;7(1):253. Epub 2021 Sep 18.

College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, China.

Transforming growth factor-β1 (TGF-β1) is essential for ovarian function and female fertility in mammals. Herein, we identified three completely linked variants, including two known variants referred to as c.1583A > G and c.1587A > G and the novel variant c.2074A > C in the porcine TGF-β1 3'-UTR. An important role of these variants in Yorkshire sow fertility was revealed. Variants c.1583A > G and c.1587A > G were located at the miRNA response element (MRE) of miR-2337 and affected miR-2337 regulation of TGF-β1 3'-UTR activity. Interestingly, miR-2337 induces, not reduces the transcription and production of TGF-β1 in granulosa cells (GCs). Mechanistically, miR-2337 enhances TGF-β1 promoter activity via the MRE motif in the core promoter region and alters histone modifications, including H3K4me2, H3K4me3, H3K9me2, and H3K9ac. In addition, miR-2337 controls TGF-β1-mediated activity of the TGF-β signaling pathway and GC apoptosis. Taken together, our findings identify miR-2337 as an endogenous small activating RNA (saRNA) of TGF-β1 in GCs, while miR-2337 is identified as a small activator of the TGF-β signaling pathway which is expected to be a new target for rescuing GC apoptosis and treating low fertility.
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http://dx.doi.org/10.1038/s41420-021-00644-4DOI Listing
September 2021

Multiple fluorescence response behaviors towards antibiotics and bacteria based on a highly stable Cd-MOF.

J Hazard Mater 2021 Sep 11;423(Pt B):127132. Epub 2021 Sep 11.

Key Laboratory of Synthetic and Natural Functional Molecule of Ministry of Education, Shaanxi Key Laboratory of Physico-Inorganic Chemistry, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, PR China. Electronic address:

The abuse of antibiotics has triggered the rise of drug-resistance bacteria, which has seriously threatened public health globally. As a result, carrying out efficient and accurate antibiotic and bacteria identification are quite significant but challenge. Herein, an unprecedented Cd-MOF-based sensor, [CdL] [1, HL = 4-(2-methyl-1H-benzo[d]imidazol-1-yl) isophthalic acid] with multiple fluorescence response behaviours towards antibiotics and bacteria was developed. Single-crystal X-ray diffraction revealed that 1 is a mesomeric 2D bilayer, which is comprised of two opposite chiral mono-layers, each assembled by left-handed or right-handed helixes. More interestingly, 1 represented multiplex detection capability towards antibiotics and bacteria through two detection behaviors: toward nitro-antibiotics and chlortetracycline (CTC) via fluorescent quenching, while toward Staphylococcus albus (S. albus) via fluorescent enhancement. Remarkably, 1 showed a low limit of detection (LOD, 47 CFU/mL) accompanied with specificity in the detection of S. albus compared to other bacteria, such as Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumonia, Pseudomonas aeruginosa and Escherichia coli. In addition, the LOD could reach to ppm level for nitro-antibiotics and CTC. Moreover, the practical application of 1 was further reinforced through the detection of nitro-antibiotics and CTC, as well as S. albus in fetal calf serum and river water.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127132DOI Listing
September 2021

CD39+ Fibroblasts Enhance Myofibroblast Activation by Promoting IL-11 Secretion in Hypertrophic Scars.

J Invest Dermatol 2021 Sep 16. Epub 2021 Sep 16.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai. Electronic address:

Fibroblasts (Fbs) are critical to hypertrophic scar (HTS) formation and were recently demonstrated to be highly heterogeneous. However, Fb heterogeneity in HTSs has not been fully elucidated. Here, we observed an increased fraction of CD39+ Fbs in HTS after screening four Fb subtypes (CD26+, CD36+, FAP+, and CD39+). CD39+ Fbs, enriched in the upper dermis, were positively correlated with scar severity. The transcriptional analysis of CD39+ and CD39- Fbs sorted from HTS revealed that IL-11 was more highly expressed in CD39+ Fbs. We then demonstrated that IL-11 was upregulated in HTSs and that its expression was induced by TGF-β1 in vitro. TGF-β1 also stimulated the expression of CD39 at the transcriptional and protein levels, mediating the maintenance of the CD39-positive phenotype. Furthermore, IL-11 facilitated myofibroblast activation and extracellular matrix production in both CD39+ and CD39- Fbs. Interestingly, CD39+ Fbs secreted more IL-11 upon TGF-β1 treatment and were less responsive to IL-11 than CD39- Fbs. Notably, a CD39 inhibitor effectively reduced stretch-induced scar formation and attenuated bleomycin-induced skin fibrosis, suggesting an antiscarring approach by targeting CD39+ Fbs.
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http://dx.doi.org/10.1016/j.jid.2021.07.181DOI Listing
September 2021

The Evolution of Image Reconstruction in PET: From Filtered Back-Projection to Artificial Intelligence.

PET Clin 2021 Oct;16(4):533-542

Department of Radiology, Center for Advanced Medical Computing and Analysis, Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

PET can provide functional images revealing physiologic processes in vivo. Although PET has many applications, there are still some limitations that compromise its precision: the absorption of photons in the body causes signal attenuation; the dead-time limit of system components leads to the loss of the count rate; the scattered and random events received by the detector introduce additional noise; the characteristics of the detector limit the spatial resolution; and the low signal-to-noise ratio caused by the scan-time limit (eg, dynamic scans) and dose concern. The early PET reconstruction methods are analytical approaches based on an idealized mathematical model.
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http://dx.doi.org/10.1016/j.cpet.2021.06.004DOI Listing
October 2021

Ethnicity-stratified analysis of the association between XRCC3 Thr241Met polymorphism and leukemia: an updated meta-analysis.

BMC Med Genomics 2021 Sep 18;14(1):229. Epub 2021 Sep 18.

Department of Hematology, The Fifth Affiliated Hospital of Zunyi Medical University, Zhufeng Avenue 1439, Zhuhai, 519000, China.

Background: Presently, whether X-ray repair cross complementing group 3 (XRCC3) Thr241Met polymorphism is correlated to leukemia risk remains controversial. Because of this reason, the objective of current study is to explore whether XRCC3 Thr241Met polymorphism confers risk to leukemia.

Methods: Two independent authors systematically and comprehensively searched Pubmed, Embase, the Cochrane library, Google academic, China National Knowledge Infrastructure (CNKI). Search time is from database foundation to March 2021.

Results: Overall, significant associations between leukemia risk and XRCC3 Thr241Met polymorphism were found in Caucasian population by allele contrast (T vs. C: OR 1.20, 95% CI 1.02-1.40), homozygote comparison (TT vs. CC: OR 1.35, 95% CI 1.05-1.73), and recessive genetic model (TT vs. TC/CC: OR 1.31, 95% CI 1.04-1.64).

Conclusions: The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for leukemia in Caucasian population.
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http://dx.doi.org/10.1186/s12920-021-01076-wDOI Listing
September 2021

Application of a combinatorial approach for soil organic carbon mapping in hills.

J Environ Manage 2021 Sep 16;300:113718. Epub 2021 Sep 16.

College of Resources, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address:

Accurate mapping of soil organic carbon (SOC) is critical to improve C management and develop sustainable management policies. However, it is constrained by local variations of the model parameters under complex topography, especially in hills. This study applied a methodological framework to optimize the spatial prediction of SOC in the hilly areas during 1981-2012 by quantifying the relative importance of environmental factors, which include both qualitative factors and quantitative variables. Results showed that SOC increased twofold with a moderate spatial dependence during the past 32 years. During this period, land use patterns, soil groups, topographic factors, and vegetation coverage had significant impacts on the SOC changes (p < 0.01). Specifically, the impact of land use patterns has exceeded the impact of soil groups and became the dominant factor affecting SOC changes. Meanwhile, impacts from the topographic factors and vegetation coverage have substantially declined. Based on those results, a combinatorial approach (LS_RBF_HASM) was developed to map SOC using radial basis function neural network (RBF) and high accuracy surface modelling (HASM), and to generate more detailed spatial mapping relationships between SOC and the affecting factors. Compared with ordinary kriging (OK), land use-soil group units (LS) and HASM combined (LS_HASM), multiple linear regression (MLR) and HASM combined with LS (LS_MLR_HASM); LS_RBF_HASM showed a better performance with a decline of 6.3%-37.7% prediction errors and more accurate spatial patterns due to the quantitative combination of auxiliary environmental variables and more information on the SOC variations within local factors captured by RBF and HASM. Additionally, MLR may partially undermine the relationship of the internal spatial structure due to the highly nonlinear relation between SOC and environmental variables. This methodological framework highlights the optimization of more environmental factors and the calculation of spatial variability within local factors and provides a more accurate approach for SOC mapping in hills.
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http://dx.doi.org/10.1016/j.jenvman.2021.113718DOI Listing
September 2021

Viral infections and the efficacy of PD-(L)1 inhibitors in virus-related cancers: Head and neck squamous cell carcinoma and hepatocellular carcinoma.

Int Immunopharmacol 2021 Sep 17;100:108128. Epub 2021 Sep 17.

Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address:

Purpose: This study aimed to test the interaction between viral infections and immune checkpoint inhibitor (ICI) efficacy for two virus-associated tumors, head and neck squamous carcinoma (HNSCC) and hepatocellular carcinoma (HCC), by conducting a systematic review and meta-analysis.

Methods: We searched databases from inception until December 30, 2020 to identify phase 2 or 3 randomized clinical trials involving ICI treatments with data on hazard ratios (HRs) for survival according to viral infection status. We evaluated the heterogeneity between patients with and without viral infections using an interaction test. Subgroup analyses were conducted to explore variations in the efficacy of immunotherapy according to viral infection status.

Results: Six phase 3 trials with 3672 patients (1382 with viral infections [38%] and 2115 without viral infections [57%]) were included. Among these patients, the pooled HR for survival was 0.69 (95% confidence interval [CI], 0.60-0.79) for those with viral infections and 0.84 (95% CI, 0.77-0.91) for those without infections after ICI treatment. Patients with viral infections achieved a better prognosis after ICI therapy than those without infections (P = 0.018). This was evident in patients with hepatitis B virus-associated HCC (P = 0.016), but not in patients with hepatitis C virus-associated HCC (P = 0.081) or in patients with human papillomavirus-positive HNSCC (P = 0.67).

Conclusion: Patients with advanced HNSCC and HCC, regardless of viral infection status, could benefit from ICI treatment. Patients with hepatitis B virus-associated HCC were more likely to benefit from ICI treatment than patients without viral infections.

Registration: Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews on March 27, 2020 (registration number CRD42020155326).
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http://dx.doi.org/10.1016/j.intimp.2021.108128DOI Listing
September 2021

LncRNA DLGAP1-AS1 accelerates glioblastoma cell proliferation through targeting miR-515-5p/ROCK1/NFE2L1 axis and activating Wnt signaling pathway.

Brain Behav 2021 Sep 18:e2321. Epub 2021 Sep 18.

Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Introduction: Glioblastoma (GBM), the primary malignant tumor in the central nervous system, features high aggressiveness and mortality. Long noncoding RNAs (lncRNAs) can exert the crucial function in regulating various human diseases, including GBM. However, the function and mechanism of lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) in GBM remain still unknown.

Methods: DLGAP1-AS1 expression in GBM cells was detected by RT-qPCR. Functional assays were conducted to determine GBM cell proliferation and apoptosis. RIP, RNA pull down, and luciferase reporter assay were applied for measuring the interplay of DLGAP1-AS1 with other RNAs.

Results: DLGAP1-AS1 was distinctly upregulated in GBM cells. DLGAP1-AS1 depletion inhibited cell proliferation, but induced apoptosis. MiR-515-5p could be sponged by DLGAP1-AS1 in GBM cells and to repress cell proliferation in GBM. Further, Rho-associated coiled-coil containing protein kinase 1 (ROCK1) and Nuclear factor erythroid-2 like 1 (NFE2L1) were confirmed as the target gene of miR-515-5p. Wnt signaling pathway could be activated by DLGAP1-AS1 via regulating ROCK1 and NFE2L1 expression. Rescue assays proved that overexpression of both ROCK1 and NFE2L1 could totally reverse the inhibitory effect of silencing DLGAP1-AS1 on GBM cell proliferation.

Conclusion: LncRNA DLGAP1-AS1 accelerated cell proliferation in GBM via targeting miR-515-5p/ROCK1/NFE2L1 axis and activating Wnt signaling pathway.
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http://dx.doi.org/10.1002/brb3.2321DOI Listing
September 2021

Recent progress of electrocatalysts for oxygen reduction in fuel cells.

J Colloid Interface Sci 2021 Sep 6;607(Pt 1):791-815. Epub 2021 Sep 6.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education of the People's Republic of China, School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, P. R. China. Electronic address:

Oxygen reduction reaction (ORR) has gradually been in the limelight in recent years because of its great application potential for fuel cells and rechargeable metal-air batteries. Therefore, significant issues are increasingly focused on developing effective and economical ORR electrocatalysts. This review begins with the reaction mechanisms and theoretical calculations of ORR in acidic and alkaline media. The latest reports and challenges in ORR electrocatalysis are traced. Most importantly, the latest advances in the development of ORR electrocatalysts are presented in detail, including platinum group metal (PGM), transition metal, and carbon-based electrocatalysts with various nanostructures. Furthermore, the development prospects and challenges of ORR electrocatalysts are speculated and discussed. These insights would help to formulate the design guidelines for highly-active ORR electrocatalysts and affect future research to obtain new knowledge for ORR mechanisms.
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http://dx.doi.org/10.1016/j.jcis.2021.09.008DOI Listing
September 2021

Design of a defined grain distribution brazed diamond grinding wheel for ultrasonic assisted grinding and experimental verification.

Ultrasonics 2021 Sep 9;118:106577. Epub 2021 Sep 9.

School of Mechanical Engineering, Jiangsu University of Technology, Changzhou 213001, China.

Ultrasonic assisted grinding (UAG) is a promising manufacturing technology in processing hard and brittle materials, mostly due to its excellent machining performance. In UAG, improvements in grain trajectory interactions and overlapping stemming from kinematic characteristics were identified as the main reasons for reduced grinding forces and improved processing quality. However, in existing studies, the grinding wheels with disordered abrasive grain distributions and irregular grain protrusion heights were generally used. Consequently, it is difficult to control both the interactions between grain trajectories and overlapping. Aiming to solve this problem, a brazed diamond grinding wheel with defined grain distribution was proposed in this study. The grinding wheel matrix was designed using finite element analysis, while abrasive grain distribution was obtained by kinematic analysis of UAG. Finally, the grinding wheel was prepared using brazing technology and to verify its grinding performance, an electroplated grinding wheel with the identic matrix and abrasive grain size was prepared. Morphology analysis of both grinding wheels has shown that compared to the electroplated grinding wheel, the brazed one has both higher and more uniform grain protrusion height. In the next step, UAG and CG experiments were carried out using the brazed and electroplated grinding wheel. The effects of grain distribution and grinding parameters on the grinding force, force ratio, surface profile wave, and surface roughness were studied. The results have shown that in similar operating conditions the brazed grinding wheel produced smaller grinding force, force ratio, smoother ground surface, and lower surface roughness compared to the electroplated grinding wheel. Additionally, for both grinding wheels, the UAG reduced grinding force, force ratio, surface roughness, and profile wave height. However, it also caused a more extensive ultrasonic vibration effect on grinding compared to the electroplated grinding wheel; its reduction percentage in grinding force was larger, while surface roughness and average height difference for UAG were higher compared to CG.
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http://dx.doi.org/10.1016/j.ultras.2021.106577DOI Listing
September 2021

Highly enhanced adsorption performance to uranium(VI) by facile synthesized hydroxyapatite aerogel.

J Hazard Mater 2021 Sep 10;423(Pt B):127184. Epub 2021 Sep 10.

State Key Laboratory of Environment-friendly Energy Materials, Sichuan Co-Innovation Center for New Energetic Materials, National Co-innovation Center for Nuclear Waste Disposal and Environmental Safety, Nuclear Waste and Environmental Safety Key Laboratory of Defense, School of National Defence Science & Technology, Southwest University of Science and Technology, Mianyang 621010, PR China. Electronic address:

In order to protect environment and save uranium resources, it was necessary to find a highly efficient adsorbent for uranium recovery from wastewater. In this work, we used a freeze-drying-calcination method to synthesize HAP aerogel to effectively remove uranium. Compared with commercially available nano-hydroxyapatite, HAP aerogel presented better adsorption performance. This was because the as-prepared HAP aerogel presented continuous porous structure, which could provide more active sites for the adsorption to uranium. The uranium removal efficiency of HAP aerogel arrived 99.4% within 10 min and the maximum adsorption capacity was up to 2087.6 mg g at pH = 4.0 and 298 K. In addition, the immobilization of uranium on HAP aerogel was chemisorption, which was probably due to adsorption, dissolution-precipitation and ions exchange. These results indicated that the as-prepared HAP aerogel could be widely used as a high efficiency and potential adsorbent for the treatment of uranium-containing wastewater in the future.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127184DOI Listing
September 2021

Platelet-rich plasma attenuates interleukin-1β-induced apoptosis and inflammation in chondrocytes through targeting hypoxia-inducible factor-2α.

Tissue Cell 2021 Sep 8;73:101646. Epub 2021 Sep 8.

Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, 95 Yong an Road, Xicheng District, Beijing, 100050, China. Electronic address:

Osteoarthritis (OA) is a prevailing chronic disease in Orthopedics that characterized with severely damaged cartilage and subchondral bone, thus leading to profound disorders of synovial joints. Platelet-rich plasma (PRP) has been applied as a popular non-operative treatment option for promoting musculoskeletal healing. Our previous work demonstrated that PRP protected chondrocytes from interleukin-1β (IL-1β)-induced apoptosis in vitro. However, the underlying mechanism behind the treatment remains unclear. The current study aimed to unveil the molecular signaling underlying its protective role in chondrocytes. Rat chondrocytes were isolated from newborn Sprague Dawley rats and treated with 5 ng/mL IL-1β for 24 h. The expression of hypoxia-inducible factor 2α (HIF-2α) was determined in both mRNA and protein levels. Next, loss- and gain-of-function assays for HIF-2α were performed using small-interfering RNA (siRNA) specific for HIF-2α and adenovirus-mediated HIF-2α overexpression, respectively. In addition, cell apoptosis markers, matrix metalloproteinase (MMP)-1, 3, -9 and -13, and extracellular matrix-related genes were evaluated. Our results demonstrated that IL-1β induced distinct inflammation in chondrocytes. In addition, HIF-2α upregulated in the IL-1β-treated chondrocytes compared to the untreated cells. Interestingly, 10% PRP protected chondrocytes against IL-1β-induced apoptosis and matrix degradation, and meanwhile suppressed the HIF-2α activation. Furthermore, HIF-2α siRNA and HIF-2α overexpression experiments indicated that PRP induced chondroprotection through targeting HIF-2α. Taken together, our findings indicated that PRP attenuates IL-1β-induced chondrocyte apoptosis and inflammation at least partially through inhibiting HIF-2α.
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http://dx.doi.org/10.1016/j.tice.2021.101646DOI Listing
September 2021

Design, synthesis and anti-tumor evaluation of 1,2,4-triazol-3-one derivatives and pyridazinone derivatives as novel CXCR2 antagonists.

Eur J Med Chem 2021 Sep 9;226:113812. Epub 2021 Sep 9.

Department of Chemistry, Tsinghua University, Beijing, 100084, PR China; State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, PR China; Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, PR China; National & Local United Engineering Lab for Personalized Anti-tumor Drugs, Shenzhen Kivita Innovative Drug Discovery Institute, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, PR China. Electronic address:

Chemokine receptor 2 (CXCR2) is the receptor of glutamic acid-leucine-arginine sequence-contained chemokines CXCs (ELR CXCs). In recent years, CXCR2-target treatment strategy has come a long way in cancer therapy. CXCR2 antagonists could block CXCLs/CXCR2 axis, and are widely used in regulating immune cell migration, tumor metastasis, apoptosis and angiogenesis. Herein, two series of new CXCR2 small-molecule inhibitors, including 1,2,4-triazol-3-one derivatives 1-11 and pyridazinone derivatives 12-22 were designed and synthesized based on the proof-to-concept. The pyridazinone derivative 18 exhibited good CXCR2 antagonistic activity (69.4 ± 10.5 %Inh at 10 μM) and demonstrated its significant anticancer metastasis activity in MDA-MB-231 cells and remarkable anti-angiogenesis activity in HUVECs. Furthermore, noteworthy was that 18 exhibited an obvious synergistic effect with Sorafenib in anti-proliferation assay in MDA-MB-231 cells. Moreover, 18 showed a distinct reduction of the phosphorylation levels of both PI3K and AKT proteins in MDA-MB-231 cells, and also affected the expression levels of other PI3K/AKT signaling pathway-associated proteins. The molecular docking studies of 18 with CXCR2 also verified the rationality of our design strategy. All of these results revealed pyridazinone derivative 18 as a promising CXCR2 antagonist for future cancer therapy.
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http://dx.doi.org/10.1016/j.ejmech.2021.113812DOI Listing
September 2021

Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: a randomised, double-blind, controlled, phase 1/2 trial.

Lancet Infect Dis 2021 Sep 15. Epub 2021 Sep 15.

Beijing Institute of Biological Products, Beijing, China.

Background: Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3-17 years.

Methods: A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3-5 years, 6-12 years, or 13-17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 μg, 4 μg, or 8 μg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing.

Findings: Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 μg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=72, 24 for each age cohort [3-5, 6-12, and 13-17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 μg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=180, 60 for each age cohort [3-5, 6-12, and 13-17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3-5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13-17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3-5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13-17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3-5 years cohort, 84·1 to 168·6 in the 6-12 years cohort, and 88·0 to 155·7 in the 13-17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3-5 years cohort, 127 to 184·8 in the 6-12 years cohort, and 150·7 to 199 in the 13-17 years cohort on day 28 after the third vaccination.

Interpretation: The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3-17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 μg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19.

Funding: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00462-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443232PMC
September 2021

miR-151a-3p-rich small extracellular vesicles derived from gastric cancer accelerate liver metastasis via initiating a hepatic stemness-enhancing niche.

Oncogene 2021 Sep 17. Epub 2021 Sep 17.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China.

Liver metastasis (LM) severely affects gastric cancer (GC) patients' prognosis. Small extracellular vesicles (sEVs) play key roles in intercellular communication. Specific sEV-miRNAs from several types of cancer were found to induce a premetastatic niche in target organs before tumor cell arrive. However, whether the primary GC affects hepatic microenvironment or the role of sEV-miRNAs in GC-LM is yet unclear. We report that GC-derived sEVs are primarily absorbed by Kupffer cells (KCs). sEV-miR-151a-3p is highly expressed in GC-LM patients' plasma and presents poor prognosis. Treating mice with sEVs-enriched in miR-151a-3p promotes GC-LM, whereas has no influence on the proliferation of GC cells in situ. Mechanistically, sEV-miR-151a-3p inhibits SP3 in KCs. Simultaneously, sEV-miR-151a-3p targets YTHDF3 to decrease the transcriptional inhibitory activity of SP3 by reducing SUMO1 translation in a N6-methyladenosine-dependent manner. These factors contribute to TGF-β1 transactivation in KCs, subsequently activating the SMAD2/3 pathway and enhancing the stem cell-like properties of incoming GC cells. Furthermore, sEV-miR-151a-3p induces miR-151a-3p transcription in KCs to form a positive feedback loop. In summary, our results reveal a previously unidentified regulatory axis initiated by sEV-miR-151a-3p that establishes a hepatic stemness-permissive niche to support GC-LM. sEV-miR-151a-3p could be a promising diagnostic biomarker and preventive treatment candidate for GC-LM.
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http://dx.doi.org/10.1038/s41388-021-02011-0DOI Listing
September 2021

Moderate to severe OSA screening based on support vector machine of the Chinese population faciocervical measurements dataset: a cross-sectional study.

BMJ Open 2021 Sep 17;11(9):e048482. Epub 2021 Sep 17.

Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Objectives: Obstructive sleep apnoea (OSA) has received much attention as a risk factor for perioperative complications and 68.5% of OSA patients remain undiagnosed before surgery. Faciocervical characteristics may screen OSA for Asians due to smaller upper airways compared with Caucasians. Thus, our study aimed to explore a machine-learning model to screen moderate to severe OSA based on faciocervical and anthropometric measurements.

Design: A cross-sectional study.

Setting: Data were collected from the Shanghai Jiao Tong University School of Medicine affiliated Ruijin Hospital between February 2019 and August 2020.

Participants: A total of 481 Chinese participants were included in the study. PRIMARY AND SECONDARY OUTCOME: (1) Identification of moderate to severe OSA with apnoea-hypopnoea index 15 events/hour and (2) Verification of the machine-learning model.

Results: Sex-Age-Body mass index (BMI)-maximum Interincisal distance-ratio of Height to thyrosternum distance-neck Circumference-waist Circumference (SABIHC2) model was set up. The SABIHC2 model could screen moderate to severe OSA with an area under the curve (AUC)=0.832, the sensitivity of 0.916 and specificity of 0.749, and performed better than the STOP-BANG (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference, and male gender) questionnaire, which showed AUC=0.631, the sensitivity of 0.487 and specificity of 0.772. Especially for asymptomatic patients (Epworth Sleepiness Scale <10), the SABIHC2 model demonstrated better predictive ability compared with the STOP-BANG questionnaire, with AUC (0.824 vs 0.530), sensitivity (0.892 vs 0.348) and specificity (0.755 vs 0.809).

Conclusion: The SABIHC2 machine-learning model provides a simple and accurate assessment of moderate to severe OSA in the Chinese population, especially for those without significant daytime sleepiness.
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http://dx.doi.org/10.1136/bmjopen-2020-048482DOI Listing
September 2021

Hierarchical chromatin features reveal the toxin production in Bungarus multicinctus.

Chin Med 2021 Sep 17;16(1):90. Epub 2021 Sep 17.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

Background: Bungarus multicinctus, from which a classical Chinese medicine is produced, is known as the most venomous land snake in the world, but the chromatin organization and transcription factor activity during venom replenishment progress have not been explored yet. This study aimed to determine the roles of chromatin structure in toxin activity via bioinformatics and experimental validation.

Methods: Chromosome conformation capture (Hi-C) analysis was used to examine interactions among chromosomes and identify different scales of chromatin during envenomation in B. multicinctus. Correlations between epigenetic modifications and chromatin structure were verified through ChIP-seq analysis. RNA-seq was used to validate the influence of variation in chromatin structure and gene expression levels on venom production and regulation.

Results: Our results suggested that intra-chromosomal interactions are more intense than inter-chromosomal interactions among the control group, 3-day group of venom glands and muscles. Through this, we found that compartmental transition was correlated with chromatin interactions. Interestingly, the up-regulated genes in more compartmental switch regions reflect the function of toxin activity. Topologically associated domain (TAD) boundaries enriched with histone modifications are associated with different distributions of genes and the expression levels. Toxin-coding genes in the same loop are highly expressed, implying that the importance of epigenetic regulation during envenomination. On a smaller scale, the epigenetic markers affect transcriptional regulation by controlling the recruitment/inhibition of transcription initiation complexes.

Conclusions: Chromatin structure and epigenetic modifications could play a vital status role in the mechanisms of venom regulation in B. multicinctus.
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http://dx.doi.org/10.1186/s13020-021-00502-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447776PMC
September 2021

The role of Escherichia coli type III secretion system 2 chaperone protein ygeG in pathogenesis of avian pathogenic Escherichia coli.

Res Vet Sci 2021 Sep 10;140:203-211. Epub 2021 Sep 10.

Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, PR China. Electronic address:

The Escherichia coli type III secretion system 2 (ETT2) is present in most E. coli strains, carries a 29.9-kb ETT2 pathogenicity island (PAI) and is involved in the virulence of avian pathogenic Escherichia coli (APEC). A chaperone protein is essential for the bacterial secretion system, but the function of the ETT2 chaperone protein has not been determined. This study showed that ygeG had sequence homology with the identified bacterial chaperone protein and it possessed tetratri-copeptide repeats (TPR) containing protein. To investigate the role of ygeG in the ETT2 of APEC, ygeG mutant and complemented strains were constructed and characterized. Inactivation of ygeG had no effect on APEC growth, but significantly promoted biofilm formation, and the adherence to and invasion of DF-1 cells, especially the survival abilities in specific-pathogen-free (SPF) chicken sera serum. Analysis of the role of ygeG in chicken infection models revealed that the deletion of ygeG increased bacterial virulence. RNA Sequencing (RNA-Seq) analyses comparing the APEC wild type and the ygeG mutant indicated that multiple genes encoding biofilm formation, outer membrane proteins, fimbrial genes and virulence effector protein genes were regulated by ygeG. These results revealed the role of ygeG as a chaperone protein that affected the virulence and pathogenicity of APEC.
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http://dx.doi.org/10.1016/j.rvsc.2021.09.011DOI Listing
September 2021

Tylosin toxicity in the alga Raphidocelis subcapitata revealed by integrated analyses of transcriptome and metabolome: Photosynthesis and DNA replication-coupled repair.

Aquat Toxicol 2021 Sep 9;239:105964. Epub 2021 Sep 9.

Shaanxi Key Laboratory of Earth Surface System and Environmental Carrying Capacity, College of Urban and Environmental Sciences, Northwest University, Xi'an 710127, China; State Key Laboratory of Marine Pollution and Department of Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR, China. Electronic address:

Tylosin (TYN) is widely used in veterinary prophylactic as a macrolide and frequently detected in the surface water. Previous studies showed that exposure to TYN caused suppression of chlorophyll biosynthesis and inhibition of photosynthesis at the physiological level, associated with reduced growth performances in algae, but the molecular mechanisms remain unknown, especially at environmental exposure levels. The present study elucidated the underlying molecular mechanism(s) of TYN toxicity in a model green alga Raphidocelis subcapitata using approaches of transcriptomics and metabolomics. Following a 7-day exposure, algal growth performances were reduced by 26.3% and 58.3% in the 3 (an environmentally realistic level) and 400 μg L TYN treatment group, respectively. A total of 577 (99) and 5438 (180) differentially expressed genes (differentially accumulated metabolites) were identified in algae treated with 3 and 400 μg L TYN, respectively. Signaling pathways including photosynthesis - antenna protein, porphyrin and chlorophyll metabolism, carbon fixation in photosynthetic organisms, and DNA replication were altered in the 400 μg L TYN treatment, while photosynthesis and DNA replication were the shared pathways in both TYN treatments. The metabolomic data further suggest that molecular pathways related to photosynthesis, DNA replication-coupled repair and energy metabolism were impaired. Photosynthesis was identified as the most sensitive target of TYN toxicity in R. subcapitata, in contrast to protein synthesis inhibition caused by TYN in bacteria. This study provides novel mechanistic information of TYN toxicity in R. subcapitata.
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http://dx.doi.org/10.1016/j.aquatox.2021.105964DOI Listing
September 2021

Constructing NiS/NiSe heteroboxes with phase boundaries for Sodium-Ion batteries.

J Colloid Interface Sci 2021 Sep 6;607(Pt 1):752-759. Epub 2021 Sep 6.

College of Chemistry and Materials Science, Sichuan Normal University, Chengdu, 610066, PR China. Electronic address:

Reasonable design and synthesis of anode materials with high capacity, excellent rate capability and good cycling stability is vital for the pragmatic application of sodium-ion batteries (SIBs). Transition metal chalcogenides possess immense potential on account of their distinguished redox reversibility and high theoretical specific capacity. Herein, the hollow metal sulfide/metal selenide (NiS/NiSe) heteroboxes with rich phase boundaries have been manufactured as anode for SIBs. The lattice distortion and charge redistribution at the phase boundary of the as-prepared NiS/NiSe heteroboxes can expose more active sites, which is profitable to the adsorption of Na and accelerate the sodium storage kinetics process, and the unique hollow porous structure is conducive to buffering the volume expansion and can facilitate the penetration of electrolyte during the repeated Na de-intercalation process. By virtue of these advantages, the NiS/NiSe heteroboxes delivers a good rate capability, where the average capacity at 10 A g in comparison with 0.1 A g is 64.3%. Otherwise, it exhibits an ultralong reversible capacity of 292 mA h g after 2000 cycles at 10 A g with only 0.0125% average capacity decay per cycle. The rational construction of phase boundary with unique structure in this article has guiding significance for the manufacture of progressive SIBs anode materials.
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http://dx.doi.org/10.1016/j.jcis.2021.09.015DOI Listing
September 2021

AMPK S-sulfuration contributes to HS donors-induced AMPK phosphorylation and autophagy activation in dopaminergic cells.

Neurochem Int 2021 Sep 14;150:105187. Epub 2021 Sep 14.

Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, China. Electronic address:

Hydrogen sulfide (HS) serves as a neuromodulator and regulator of neuroinflammation. It is reported to be therapeutic for Parkinson's disease (PD) animal and cellular models. However, whether it affects α-synuclein accumulation in dopaminergic cells, the key pathological feature in PD, is poorly understood. In this study we reported that exogenous HS donors NaHS and GYY4137 (GYY) enhanced the autophagy activity, as indicated by the increases of autophagy marker LC3-II expression and LC3 dots formation even during lysosome inhibition in dopaminergic cell lines and HEK293 cells. The enhancement of HS donors on autophagic flux was mediated by adenosine 5'-monophosphate-activated protein kinase (AMPK)-dependent mammalian target of rapamycin (mTOR) inhibition, as HS donors activated AMPK but reduced the mTOR activity and HS donors-induced LC3-II increase was diminished by mTOR activator. Moreover, point mutation of Cys302 into alanine (C302A) in AMPKα2 subunit abolished the AMPK activation and mTOR inhibition, as well as autophagic flux increase elicited by NaHS. Interestingly, NaHS triggered AMPK S-sulfuration, which was not observed in AMPK C302A-transfected cells. Further, NaHS was able to attenuate α-synuclein accumulation in a cellular model induced by dopamine oxidized metabolite 3, 4-dihydroxyphenylacetaldehyde (DOPAL), and this effect was interfered by autophagy inhibitor wortmannin and also eliminated in AMPK Cys302A-transfected cells. In sum, the findings identified a role of Cys302 S-sulfuration in AMPK activation induced by exogenous HS and demonstrated that HS donors could enhance the autophagic flux via AMPK-mTOR signaling and thus reduce α-synuclein accumulation in vitro.
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http://dx.doi.org/10.1016/j.neuint.2021.105187DOI Listing
September 2021
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