Publications by authors named "Qing Li"

3,984 Publications

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Integrated multi-omics profiling of high-grade estrogen receptor-positive, HER2-negative breast cancer.

Mol Oncol 2021 Jun 19. Epub 2021 Jun 19.

Department of Endocrine and Breast Surgery, The First Affiliated hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, 400016, China.

Estrogen-receptor-positive, and human epidermal growth factor receptor 2-negative (ER+HER2-) breast cancer accounts for ~60-70% of all cases of invasive breast carcinoma. High-grade ER+HER2- tumors respond poorly to endocrine therapy. In this study, we systematically analyzed clinical and multi-omics data to find potential strategies for personalized therapy of patients with high-grade ER+HER2- disease. Six different cohorts were analyzed, for which multi-omics data were available. Grade III ER+HER2- cases harbored higher proportions of large tumor size (>5cm), lymph nodes metastasis, chemotherapy use and luminal B subtypes defined by PAM50, as compared with grade I/II tumors. DNA methylation (HM450) data and methylation specific PCR indicated that the cg18629132 locus in the MKI67 promoter was hypermethylated in grade I/II cases and normal tissue, but hypomethylated in grade III cases or triple negative breast cancer (TNBC), resulting in higher expression of MKI67. Mutations in ESR1 and TP53 were detected in post-endocrine-treatment metastatic samples at a higher rate than in treatment-naive tumors in grade III cases. We identified 42 and 20 focal copy number events in non-metastatic and metastatic high-grade ER+HER2- cases, respectively, with either MYC or MDM2 amplification representing an independent prognostic event in grade III cases. Transcriptional profiling within grade III tumors, highlighted ER signaling downregulation and upregulation of immune-related pathways in non-luminal-like tumors defined by PAM50. Recursive partitioning analysis (RPA) was employed to construct a decision tree of an endocrine-resistant subgroup (GATA3-negative and AGR-negative) of two genes that was validated by immunohistochemistry in a Chinese cohort. All together, these data suggest that grade III ER+HER2- tumors have distinct clinical and molecular characteristics compared with low-grade tumors, particularly in cases with non-luminal-like biology. Due to the dismal prognosis in this group, clinical trials are warranted to test the efficacy of potential novel therapies.
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http://dx.doi.org/10.1002/1878-0261.13043DOI Listing
June 2021

Constructing Co-N-C Catalyst via a Double Crosslinking Hydrogel Strategy for Enhanced Oxygen Reduction Catalysis in Fuel Cells.

Small 2021 Jun 17:e2100735. Epub 2021 Jun 17.

State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.

Exploiting platinum-group-metal (PGM)-free electrocatalysts with remarkable activity and stability toward oxygen reduction reaction (ORR) is of significant importance to the large-scale commercialization of proton exchange membrane fuel cells (PEMFCs). Here, a high-performance and anti-Fenton reaction cobalt-nitrogen-carbon (Co-N-C) catalyst is reported via employing double crosslinking (DC) hydrogel strategy, which consists of the chemical crosslinking between acrylic acid (AA) and acrylamide (AM) copolymerization and metal coordinated crosslinking between Co and P(AA-AM) copolymer. The resultant DC hydrogel can benefit the Co dispersion via chelated Co-N/O bonds and relieve metal agglomeration during the subsequent pyrolysis, resulting in the atomically dispersed Co-Nx/C active sites. By optimizing the ratio of AA/AM, the optimal P(AA-AM)(5-1)-Co-N catalyst exhibits a high content of nitrogen doping (12.36 at%) and specific surface area (1397 m g ), significantly larger than that of the PAA-Co-N catalyst (10.59 at%/746 m g ) derived from single crosslinking (SC) hydrogel. The electrochemical measurements reveal that P(AA-AM)(5-1)-Co-N possesses enhanced ORR activity (half-wave potential (E ) ≈0.820 V versus the reversible hydrogen electrode (RHE)) and stability (≈4 mV shift in E after 5000 potential cycles in 0.5 m H SO at 60 ºC) relative to PAA-Co-N, which is higher than most Co-N-C catalysts reported so far.
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http://dx.doi.org/10.1002/smll.202100735DOI Listing
June 2021

infection in the genital tract is associated with inflammation and hypospermia in the infertile male of China.

Asian J Androl 2021 Jun 18. Epub 2021 Jun 18.

Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.

Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted bacterial disease worldwide. However, unlike that in female infertility, the role of CT infection in male infertility remains controversial. The objective of this retrospective study was to explore the impacts of CT infection in the genital tract on sperm quality, sperm acrosin activity, antisperm antibody levels, and inflammation in a large cohort of infertile males in China. A total of 7154 semen samples were collected from infertile male subjects, 416 of whom were CT positive (CT+ group) and 6738 of whom were CT negative (CT- group), in our hospital between January 2016 and December 2018. Routine semen parameters (semen volume, pH, sperm concentration, viability, motility, morphology, etc.), granulocyte elastase levels, antisperm antibody levels, and sperm acrosin activity were compared between the CT+ and CT- groups. Our results showed that CT infection was significantly correlated with an abnormally low semen volume, as well as an increased white blood cell count and granulocyte elastase level (all P < 0.05) in the semen of infertile males; other routine semen parameters were not negatively impacted. The antisperm antibody level and sperm acrosin activity were not affected by CT infection. These findings suggested that CT infection might contribute to inflammation and hypospermia but does not impair sperm viability, motility morphology, and acrosin activity or generate antisperm antibodies in the infertile males of China.
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http://dx.doi.org/10.4103/aja.aja_54_21DOI Listing
June 2021

Chronic Jet Lag Exacerbates Jejunal and Colonic Microenvironment in Mice.

Front Cell Infect Microbiol 2021 1;11:648175. Epub 2021 Jun 1.

Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Institute of Digestive Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Evidence suggests that circadian rhythm disorder is associated with a variety of gastrointestinal diseases, and the circadian rhythm plays a key role in maintaining the homeostasis of intestinal flora. The underlying mechanisms are still not completely identified. This study was aimed to explore whether jet lag-caused circadian disruption influences gut microbiome and its metabolites.

Methods: Mice were synchronized with 12-h light/dark cycles (control group) or subjected to daily 8-h advance of the light/dark cycle for every 3 days (jet-lagged group). Four months later, fecal samples and jejunal contents were collected and analyzed by 16S rRNA gene sequencing. In addition, fecal samples were subjected to metabolome analysis with ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

Results: The results of 16s rRNA sequencing showed that chronic jet lag led to decreased microbial abundance, richness, and diversity in both feces and jejunal contents. ANOSIM analysis revealed significant difference between control and jet-lagged groups. As the colonic microbiome, the abundance of Bacteroidetes phylum was significantly decreased and that of Actinobacteria phylum was increased in jet-lagged mice. Jet lag increased the ratio of Firmicutes to Bacteroidetes, an indicator for the imbalance of gut microbiota. Metabolome analysis of fecal samples showed that the levels of tryptophan and its derivatives were decreased in jet-lagged mice. In addition, fecal levels of secondary bile acids changed under jet lag conditions. Correlation analysis identified associations between tryptophan (and its derivatives) levels and colonic microbiota.

Conclusions: This study presents a comprehensive landscape of gut microbiota and its metabolites in mice subjected to chronic jet lag. The results suggest that circadian disruption may lead to changes in fecal and jejunal microbiota and fecal metabolites. Moreover, our results demonstrate a novel interplay between the gut microbiome and metabolome.
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http://dx.doi.org/10.3389/fcimb.2021.648175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204051PMC
June 2021

Vaccinia-related kinase 2 drives pancreatic cancer progression by protecting Plk1 from Chfr-mediated degradation.

Oncogene 2021 Jun 17. Epub 2021 Jun 17.

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

As a key cell cycle regulator, polo-like kinase 1 (Plk1) has been recognized as a crucial factor involved in the progression of pancreatic cancer (PC). However, its regulatory mechanism is poorly understood. Here, we present evidence that Plk1 is a novel substrate of vaccinia-related kinase 2 (VRK2), a serine-threonine kinase that is highly expressed and predicts poor prognosis in PC. VRK2 phosphorylates Plk1 at threonine 210 and protects it from ubiquitin-dependent proteasomal degradation. We showed that mechanistically complement factor H-related protein (CFHR), as a major E3 ligase, promotes Plk1 degradation by ubiquitinating it at lysine 209. Phosphorylation of Plk1 at threonine 210 by VRK2 interferes with the interaction of Chfr with Plk1 and antagonizes Plk1 ubiquitination, thereby stabilizing the Plk1 protein. Taken together, our data reveal a mechanism of Plk1 overexpression in PC and provide evidence for targeting VRK2 as a potential therapeutic strategy.
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http://dx.doi.org/10.1038/s41388-021-01893-4DOI Listing
June 2021

Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA-binding factor RPA.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences and Frontier Science Centre for Immunology and Metabolism, Wuhan University, Wuhan 320072, China;

Single-stranded DNA (ssDNA) covered with the heterotrimeric Replication Protein A (RPA) complex is a central intermediate of DNA replication and repair. How RPA is regulated to ensure the fidelity of DNA replication and repair remains poorly understood. Yeast Rtt105 is an RPA-interacting protein required for RPA nuclear import and efficient ssDNA binding. Here, we describe an important role of Rtt105 in high-fidelity DNA replication and recombination and demonstrate that these functions of Rtt105 primarily depend on its regulation of RPA. The deletion of causes elevated spontaneous DNA mutations with large duplications or deletions mediated by microhomologies. Rtt105 is recruited to DNA double-stranded break (DSB) ends where it promotes RPA assembly and homologous recombination repair by gene conversion or break-induced replication. In contrast, Rtt105 attenuates DSB repair by the mutagenic single-strand annealing or alternative end joining pathway. Thus, Rtt105-mediated regulation of RPA promotes high-fidelity replication and recombination while suppressing repair by deleterious pathways. Finally, we show that the human RPA-interacting protein hRIP-α, a putative functional homolog of Rtt105, also stimulates RPA assembly on ssDNA, suggesting the conservation of an Rtt105-mediated mechanism.
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http://dx.doi.org/10.1073/pnas.2106393118DOI Listing
June 2021

PSP net-based automatic segmentation network model for prostate magnetic resonance imaging.

Comput Methods Programs Biomed 2021 May 29;207:106211. Epub 2021 May 29.

Department of Urology, the Fifth Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 11100, China.

Purpose: Prostate cancer is a common cancer. To improve the accuracy of early diagnosis, we propose a prostate Magnetic Resonance Imaging (MRI) segmentation model based on Pyramid Scene Parsing Network (PSP Net).

Method: A total of 270 prostate MRI images were collected, and the data set was divided. Contrast limited adaptive histogram equalization (CLAHE) was enhanced in this study. We use the prostate MRI segmentation model based on PSP net, and use segmentation accuracy, under segmentation rate, over segmentation rate and receiver operating characteristic (ROC) curve evaluation index to compare the segmentation effect based on FCN and U-Net.

Results: PSP net has the highest segmentation accuracy of 0.9865, over segmentation rate of 0.0023, under segmentation rate of 0.1111, which is less than FCN and U-Net. The ROC curve of PSP net is closest to the upper left corner, AUC is 0.9427, larger than FCN and U-Net.

Conclusion: This paper proves through a large number of experimental results that the prostate MRI automatic segmentation network model based on PSP Net is able to improve the accuracy of segmentation, relieve the workload of doctors, and is worthy of further clinical promotion.
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http://dx.doi.org/10.1016/j.cmpb.2021.106211DOI Listing
May 2021

Analysis, occurrence, and potential sensory significance of tropical fruit aroma thiols, 3-mercaptohexanol and 4-methyl-4-mercapto-2-pentanone, in Chinese Baijiu.

Food Chem 2021 May 28;363:130232. Epub 2021 May 28.

Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China; Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China.

Fruity notes are important to the flavor of Baijiu (Chinese Liquor) and are considered to originate from ester compounds; however, little is known about the other chemicals that contribute to the fruity aroma. In this study, the sensory impacts of two tropical fruit aroma thiols, 3-mercaptohexanol (3MH) and 4-methyl-4-mercapto-2-pentanone (4MP), in Chinese Light-, Strong- and Soy sauce flavor type Baijiu were systemically subjected to a sensory evaluation, qualitative and quantitative analysis, and multivariate statistical analyses. The flavor dilution factors of 3MH and 4MP were 9-729. The contents of 3MH and 4MP were the highest (p < 0.001) in Strong- and Soy sauce aroma-type Baijiu, respectively. According to their odor activity values (OAVs), 3MH (OAV: 1-22) and 4MP (OAV: 1-9) are important to the aroma of Baijiu. Notably, 4MP was identified for the first time in Baijiu, and the multivariate statistical analysis demonstrated that 3MH and 4MP could be used to differentiate Baijiu.
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http://dx.doi.org/10.1016/j.foodchem.2021.130232DOI Listing
May 2021

degradation, biocompatibility and antibacterial properties of pure zinc: assessing the potential of Zn as a guided bone regeneration membrane.

J Mater Chem B 2021 Jun 15. Epub 2021 Jun 15.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.

Membrane exposure is a common complication after the guided bone regeneration (GBR) procedure and has a detrimental influence on the bone regeneration outcomes, while the commercially available GBR membranes show limited exposure tolerance. Recently, zinc (Zn) has been suggested as a promising material to be used as a barrier membrane in GBR therapy for bone augmentation. In this study, the degradation behavior in artificial saliva solution, cytotoxicity and antibacterial activity of pure Zn were investigated to explore its degradation and associated biocompatibility in the case of premature membrane exposure. The results indicated that the degradation rate of Zn in artificial saliva solution was about 31.42 μm year-1 after 28 days of immersion. The corrosion products on the Zn surface were mainly composed of Zn3(PO4)2, Ca3(PO4)2, CaHPO4, Zn5(CO3)2(OH)6 and ZnO. Besides, Zn presented an acceptable in vitro HGF cytocompatibility and a high antibacterial activity against Porphyromonas gingivalis. The preliminary results demonstrate that pure Zn exhibits appropriate degradation behavior, adequate cell compatibility and favorable antibacterial properties in the oral environment and is thus believed to sustain profitable function when membrane exposure occurs. The results provided new insights for understanding the exposure tolerance of Zn based membranes and are beneficial to their clinical applications.
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http://dx.doi.org/10.1039/d1tb00596kDOI Listing
June 2021

Mitochondrial Targeting of Herbal Medicine in Chronic Kidney Disease.

Front Pharmacol 2021 26;12:632388. Epub 2021 May 26.

Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.

Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of nephrons and an eventual decline in glomerular filtration rate. CKD increases mortality and has a significant impact on the quality of life and the economy, which is becoming a major public health issue worldwide. Since current conventional-medicine treatment options for CKD are not satisfactory, many patients seek complementary and alternative medicine treatments including Traditional Chinese Medicine. Herbal medicine is often used to relieve symptoms of renal diseases in the clinic. The kidney is abundant in the number of mitochondria, which provide enough energy for renal function and metabolism. In recent years, a vital role for mitochondrial dysfunction has been suggested in CKD. Mitochondria have become a new target for the treatment of diseases. A growing number of studies have demonstrated herbal medicine could restore mitochondrial function and alleviate renal injury both and . In this review, we sum up the therapeutic effect of herbal medicine in CKD via targeting mitochondrial function. This implies future strategies in preventing CKD.
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http://dx.doi.org/10.3389/fphar.2021.632388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188236PMC
May 2021

Enantioselective metabolism of phenylpyrazole insecticides by rat liver microsomal CYP3A1, CYP2E1 and CYP2D2.

Pestic Biochem Physiol 2021 Jul 11;176:104861. Epub 2021 May 11.

College of Resources and Environment, Anhui Agricultural University, Key Laboratory of Agri-food Safety of Anhui Province, Hefei 230036, China. Electronic address:

The stereoselective difference of chiral pesticide enantiomers is an important factor of risk evaluation and the subject has received wide attention. In the present work, enantioselective metabolism of chiral phenylpyrazole insecticides including fipronil, ethiprole and flufiprole in rat liver microsomes was investigated in vitro. The result showed remarkable enantioselectivity for fipronil and ethiprole with the EF values of 0.11-0.58. The metabolite fipronil-sulfone was formed with the degradation of fipronil. R-Ethiprole to S-ethiprole transformation was observed, but not S-ethiprole to R-ethiprole. No enantioselective metabolism was observed for flufiprole with the EF values of 0.49-0.51. The enzymatic assays showed that the inhibition ratio of R-fipronil and S-ethiprole was 1.5-2.1times that of the corresponding enantiomers on CYP2E1 and CYP2D2 activity, leading to the enantioselective metabolism. The result of the homology modeling and molecular docking further revealed that S-fipronil (-7.56 kcal mol) and R-ethiprole (-6.45 kcal mol) performed better binding with CYP2E1 and CYP2D2, respectively. The results provided useful data for the risk evaluation of chiral phenylpyrazole insecticides on ecological safety and human health.
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http://dx.doi.org/10.1016/j.pestbp.2021.104861DOI Listing
July 2021

Identification of key genes in the tumor microenvironment of lung adenocarcinoma.

Med Oncol 2021 Jun 12;38(7):83. Epub 2021 Jun 12.

Key Laboratory of Medical Imaging and Artifical Intelligence of Hunan Province, 423000, Chenzhou, P. R. China.

The tumor microenvironment plays an important role in tumor development and progression, but the role of immune and stromal cells in this environment has not been sufficiently studied. In this study, we aimed to identify key genes associated with the microenvironment of lung adenocarcinoma (LUAD). Raw data for stromal and immune cells in malignant tumors were downloaded from The Cancer Genome Atlas (TCGA). These expression data were used to identify the differentially expressed genes (DEGs) in tissue samples of LUAD with high and low immune scores. A protein-protein interaction (PPI) network based on genes with significant differential expression was constructed. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to functionally annotate putative hub genes. These genes were assessed via Kaplan Meier analysis to determine their correlation with overall survival. In total, we identified 216 DEGs which were correlated with immune and stromal scores, including 30 hub genes which were identified based on the PPI network. Further analysis suggested that the expression levels of 10 of these genes were significantly correlated with overall survival of LUAD patients. These key hub genes included CCR2, CCR5, CD53, CYBB, HCK, IRF8, LCP2, PLEK, PTPRC, and TLR7. Moreover, the expression level of CCR2 was found to have strong prognostic value for LUAD patients. Additionally, high expression of CYBB was also correlated with better survival of patients with LUAD. The results of this study open several new avenues to explore in the treatment of LUAD.
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http://dx.doi.org/10.1007/s12032-021-01529-3DOI Listing
June 2021

Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress.

Nat Struct Mol Biol 2021 Jun 10;28(6):487-500. Epub 2021 Jun 10.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Both the BIR-like pathway and ICL repair share almost identical molecular mechanisms of 53BP1-BRCA1-controlled signaling response, SLX4- and FAN1-mediated fork cleavage and POLD3-dependent DNA synthesis, suggesting that the FA pathway is intrinsically one of the BIR-like pathways. Replication stress not only triggers BMF in FA-deficient mice, but also specifically induces monosomy 7, which is associated with progression to AML in patients with FA, in FA-deficient cells.
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http://dx.doi.org/10.1038/s41594-021-00602-9DOI Listing
June 2021

Leukocyte kinetics during the early stage acts as a prognostic marker in patients with septic shock in intensive care unit.

Medicine (Baltimore) 2021 Jun;100(23):e26288

Department of Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing, China.

Abstract: The leukocytes play an important role in immune function during sepsis. We performed a retrospective study to investigate if leukocytes kinetics was associated with survival in critically ill patients with septic shock in intensive care unit (ICU).Patients with septic shock from January 1, 2014 to June 30, 2018 in our ICU were included. We extracted the demographic, clinical and laboratory data, comorbidities from our clinical database. The number of white blood cell, neutrophil and lymphocyte on day 1 and day 3 after diagnosis were collected and neutrophil to lymphocyte ratios (NLR) were calculated. Our primary outcome was 28-day mortality. Univariate and multivariate logistic regression models and cox proportional risk model were used to analyze the association between the leukocytes kinetics during first 3 days after ICU admission and the day-28 mortality.A total of 1245 septic shock patients with a 28-day mortality of 35.02% were included into analysis. There were no significant difference of lymphocyte number (0.83 ± 0.02 vs 0.80 ± 0.04, P = .552) between survival and non-survivals on day 1. However, the lymphocyte counts was significantly lower (0.95 ± 0.03 vs 0.85 ± 0.04, P = .024) on the third day. Both multivariate logistic and Cox regression analysis showed that lymphocyte counts on day 3 were associated with day-28 mortality. Moreover, Kaplan-Meier survival analysis revealed that increasing in lymphocyte counts and decreasing WBC, neutrophils and NLR during the first 3 days after diagnosis were associated with longer survival.Leukocytes kinetics during the first 3 days is a valuable prognostic marker in patients with septic shock in the ICU.
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http://dx.doi.org/10.1097/MD.0000000000026288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202536PMC
June 2021

Hierarchical Porous Graphene Bubbles as Host Materials for Advanced Lithium Sulfur Battery Cathode.

Front Chem 2021 24;9:653476. Epub 2021 May 24.

Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.

The serious shuttle effect, low conductivity, and large volume expansion have been regarded as persistent obstacles for lithium sulfur (Li-S) batteries in its practical application. Carbon materials, such as graphene, are considered as promising cathode hosts to alleviate those critical defects and be possibly coupled with other reinforcement methods to further improve the battery performance. However, the open structure of graphene and the weak interaction with sulfur species restrict its further development for hosting sulfur. Herein, a rational geometrical design of hierarchical porous graphene-like bubbles (PGBs) as a cathode host of the Li-S system was prepared by employing magnesium oxide (MgO) nanoparticles as templates for carbonization, potassium hydroxide (KOH) as activation agent, and car tal pitch as a carbon source. The synthesized PGBs owns a very thin carbon layer around 5 nm that can be comparable to graphite nanosheets. Its high content of mesoporous and interconnected curved structure can effectively entrap sulfur species and impose restrictions on their diffusion and shuttle effect, leading to a much stable electrochemical performance. The reversible capacity of [email protected] 0.3 C still can be maintained at 831 mAh g after 100 cycles and 512 mAh g after 500 cycles.
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http://dx.doi.org/10.3389/fchem.2021.653476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181144PMC
May 2021

Transcription shapes DNA replication initiation to preserve genome integrity.

Genome Biol 2021 Jun 9;22(1):176. Epub 2021 Jun 9.

The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Genome Editing Research Center, Peking University, Beijing, 100871, China.

Background: Early DNA replication occurs within actively transcribed chromatin compartments in mammalian cells, raising the immediate question of how early DNA replication coordinates with transcription to avoid collisions and DNA damage.

Results: We develop a high-throughput nucleoside analog incorporation sequencing assay and identify thousands of early replication initiation zones in both mouse and human cells. The identified early replication initiation zones fall in open chromatin compartments and are mutually exclusive with transcription elongation. Of note, early replication initiation zones are mainly located in non-transcribed regions adjacent to transcribed regions. Mechanistically, we find that RNA polymerase II actively redistributes the chromatin-bound mini-chromosome maintenance complex (MCM), but not the origin recognition complex (ORC), to actively restrict early DNA replication initiation outside of transcribed regions. In support of this finding, we detect apparent MCM accumulation and DNA replication initiation in transcribed regions due to anchoring of nuclease-dead Cas9 at transcribed genes, which stalls RNA polymerase II. Finally, we find that the orchestration of early DNA replication initiation by transcription efficiently prevents gross DNA damage.

Conclusion: RNA polymerase II redistributes MCM complexes, but not the ORC, to prevent early DNA replication from initiating within transcribed regions. This RNA polymerase II-driven MCM redistribution spatially separates transcription and early DNA replication events and avoids the transcription-replication initiation collision, thereby providing a critical regulatory mechanism to preserve genome stability.
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http://dx.doi.org/10.1186/s13059-021-02390-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188667PMC
June 2021

Local Structures of Soft Carbon and Electrochemical Performance of Potassium-Ion Batteries.

ACS Appl Mater Interfaces 2021 Jun 9. Epub 2021 Jun 9.

State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.

Due to climate variation and global warming, utilization of renewable energy becomes increasingly imperative. Rechargeable potassium-ion batteries (PIBs) have lately attracted much attention due to their earth-abundance and cost-effectiveness. Because soft carbon materials are cheap, abundant, and safe, extensive feasible research studies have indicated that they could become promising anode materials for PIBs. In spite of gaining achievements, fundamental questions regarding effects of the basic structure unit inside soft carbon on potassium storage potential have not been sufficiently addressed yet. Here, a series of soft carbon pyrolyzed from 900 to 2900 °C were systematically and quantitatively characterized by combining Raman spectroscopy, near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, X-ray pair distribution function analysis, and advanced evaluation of wide-angle X-ray scattering data. All these characterizations reveal structural details of soft carbon with increasing pyrolysis temperature. Our results show that the potassium storage behavior, especially the potential plateau is closely correlated to non-uniformity in interlayer distance and defect concentration in soft carbon, which is further confirmed by reverse Monte Carlo (RMC) modeling and density functional theory calculation. On the basis of these results, optimizing strategies are discussed to design an advanced soft carbon anode. This work provides significant insights into the structure engineering of soft carbon for high-performance rechargeable PIBs.
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http://dx.doi.org/10.1021/acsami.1c06303DOI Listing
June 2021

REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway.

Commun Biol 2021 Jun 7;4(1):688. Epub 2021 Jun 7.

Department of Pathology, McGill University and the Research Institute of McGill University Health Centre, Montreal, QC, Canada.

Persistent acinar to ductal metaplasia (ADM) is a recently recognized precursor of pancreatic ductal adenocarcinoma (PDAC). Here we show that the ADM area of human pancreas tissue adjacent to PDAC expresses significantly higher levels of regenerating protein 3A (REG3A). Exogenous REG3A and its mouse homolog REG3B induce ADM in the 3D culture of primary human and murine acinar cells, respectively. Both Reg3b transgenic mice and REG3B-treated mice with caerulein-induced pancreatitis develop and sustain ADM. Two out of five Reg3b transgenic mice with caerulein-induced pancreatitis show progression from ADM to pancreatic intraepithelial neoplasia (PanIN). Both in vitro and in vivo ADM models demonstrate activation of the RAS-RAF-MEK-ERK signaling pathway. Exostosin-like glycosyltransferase 3 (EXTL3) functions as the receptor for REG3B and mediates the activation of downstream signaling proteins. Our data indicates that REG3A/REG3B promotes persistent ADM through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway. Targeting REG3A/REG3B, its receptor EXTL3, or other downstream molecules could interrupt the ADM process and prevent early PDAC carcinogenesis.
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http://dx.doi.org/10.1038/s42003-021-02193-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184755PMC
June 2021

Magnetic field-mediated Janus particles with sustained driving capability for severe bleeding control in perforating and inflected wounds.

Bioact Mater 2021 Dec 18;6(12):4625-4639. Epub 2021 May 18.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, 400715, China.

Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge. Therefore, we present a novel hemostatic strategy based on magnetic field-mediated guidance. The biphasic Janus magnetic particle ([email protected]) comprised aggregates of α-FeO nanoparticles (FeO NPs) as the motion actuator, negatively modified microporous starch (MSS) as the base hemostatic substrate, and thrombin as the loaded hemostatic drug. Before application, the particles were first wrapped using NaHCO and then doped with protonated tranexamic acid (TXA-NH), which ensured their high self-dispersibility in liquids. During application, the particles promptly self-diffused in blood by bubble propulsion and travelled to deep bleeding sites against reverse rushing blood flow under magnetic guidance. tests confirmed the superior hemostatic performance of the particles in perforating and inflected wounds ("V"-shaped femoral artery and "J"-shaped liver bleeding models). The present strategy, for the first time, extends the range of magnetically guided drug carriers to address the challenges in the hemorrhage control of perforating and inflected wounds.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141897PMC
December 2021

Recent advances in black phosphorus-based electrochemical sensors: A review.

Anal Chim Acta 2021 Jul 8;1170:338480. Epub 2021 Apr 8.

Hunan Key Laboratory of Biomedical Nanomaterials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou, 412007, China.

Since the discovery of liquid-phase-exfoliated black phosphorus (BP) as a field-effect transistor in 2014, BP, with its 2D layered structure, has attracted significant attention, owing to its anisotropic electroconductivity, tunable direct bandgap, extraordinary surface activity, moderate switching ratio, high hole mobility, good biocompatibility, and biodegradability. Several pioneering research efforts have explored the application of BP in different types of electrochemical sensors. This review summarizes the latest synthesis methods, protection strategies, and electrochemical sensing applications of BP and its derivatives. The typical synthesis methods for BP-based crystals, nanosheets, and quantum dots are discussed in detail; the degradation of BP under ambient conditions is introduced; and state-of-the-art protection methodologies for enhancing BP stability are explored. Various electrochemical sensing applications, including chemically modified electrodes, electrochemiluminescence sensors, enzyme electrodes, electrochemical aptasensors, electrochemical immunosensors, and ion-selective electrodes are discussed in detail, along with the mechanisms of BP functionalization, sensing strategies, and sensing properties. Finally, the major challenges in this field are outlined and future research avenues for BP-based electrochemical sensors are highlighted.
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http://dx.doi.org/10.1016/j.aca.2021.338480DOI Listing
July 2021

Preoperative combi-elastography for the prediction of early recurrence after curative resection of hepatocellular carcinoma.

Clin Imaging 2021 May 31;79:173-178. Epub 2021 May 31.

Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China. Electronic address:

Purpose: To estimate the prognostic value of preoperative combi-elastography for early recurrence (ER) of hepatocellular carcinoma (HCC) after radical resection.

Methods: A total of 94 HCC patients undergoing hepatectomy from January to August 2019 were included. The combined elastography (ARIETTA 850, Hitachi Healthcare) was used for real-time tissue elastography and shear wave measurement analysis. Six elastography related indicators were calculated. The patients were randomly divided into a training and a validation group in a 7:3 ratio and prediction model was assessed about discrimination capability by using area under the receiver operating curve. Univariate and multivariate analyses were performed to determine the prognostic value of clinicopathological factors, laboratory tests, and elastography for HCC ER.

Results: The Vs, E, F, and A indexes were significantly higher in patients with ER than in those without ER (P = 0.002, P = 0.002, P < 0.001, and P < 0.001, respectively). Multivariate logistic regression analysis indicated that microvascular invasion (MVI, odds ratio [OR] = 3.964, 95% confidence interval [CI] = 1.326-11.845; P = 0.010) and the F index (OR = 9.533, 95%CI = 1.921-47.296; P = 0.006) were independent predictors of ER in HCC. A ER prediction model based on laboratory tests, MVI and F index were moderate [area under curves (AUCs) in training and validation cohort were 0.829(95%CI: 0.723-0.935; P < 0.001) and 0.846 (95%CI: 0.699-0.994; P = 0.002), respectively].

Conclusion: Preoperative combi-elastography analysis could be used as a potential prognostic tool for HCC ER and assist in clinical decision-making.
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http://dx.doi.org/10.1016/j.clinimag.2021.05.020DOI Listing
May 2021

A case study of glycogen storage disease type Ia presenting with multiple hepatocellular adenomas: an analysis by gadolinium ethoxybenzyl-diethylenetriamine-pentaacetic acid magnetic resonance imaging.

Quant Imaging Med Surg 2021 Jun;11(6):2785-2791

Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Glycogen storage disease type Ia (GSD Ia) is a rare disease caused by a deficiency of hepatic glucose-6-phosphatase (G6Pase). Here, we report a 17-year-old Chinese boy with GSD Ia. Clinical manifestations of the patient included hepatomegaly, growth retardation, doll face, and biochemical abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia. The computed tomography (CT) and gadolinium ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI) revealed multiple masses in the left and right hemiliver. These masses presented as different dynamic enhanced patterns in the Gd-EOB-DTPA MRI. In addition, a large amount of glycogen deposit was detected in the liver tissue biopsy. Liver puncture confirmed that the masses were hepatocellular adenomas (HCAs). Genetic analyses confirmed the presence of liver metabolic disease, and the final clinical diagnostic was GSD Ia. The patient's clinical manifestations were significantly improved following regular treatment with raw corn starch for 9 months. Unfortunately, it was suspected that parts of the adenoma had undergone malignant transformation.
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http://dx.doi.org/10.21037/qims-20-746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107322PMC
June 2021

GPC5 suppresses lung cancer progression and metastasis via intracellular CTDSP1/AhR/ARNT signaling axis and extracellular exosome secretion.

Oncogene 2021 Jun 2. Epub 2021 Jun 2.

Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.

Lung cancer is the leading cause of cancer-related death worldwide. Glypican-5 (GPC5) is a member of heparan sulfate proteoglycans, and its biological importance in initiation and progression of lung cancer remains controversial. In the present study, we revealed that GPC5 transcriptionally enhanced the expression of CTDSP1 (miR-26b host gene) via AhR-ARNT pathway, and such up-regulation of CTDSP1 intracellularly contributed to the inhibited proliferation of lung cancer cells. Moreover, exosomes derived from GPC5-overexpressing human lung cancer cells (GPC5-OE-derived exosomes) had an extracellular repressive effect on human lymphatic endothelial cells (hLECs), leading to decreased tube formation and migration. Comparison between GPC5-WT- and GPC5-OE-derived exosomes showed that miR-26b (embedded within introns of CTDSP1 gene) was significantly up-regulated in GPC5-OE-derived exosomes and critical to the influence on hLECs. On the mechanism, we demonstrated that miR-26b transferred into hLECs directly targeted to PTK2 3'-UTR and led to PTK2 down-regulation, resulting in defects in tube formation and migration of hLECs. By uncovering the regulation network among GPC5, miR-26b, miR-26b host gene (CTDSP1), and target gene (PTK2), our findings demonstrated that GPC5 functioned as a tumor suppressor in human lung cancer.
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http://dx.doi.org/10.1038/s41388-021-01837-yDOI Listing
June 2021

Propionibacterium acnes overabundance in gastric cancer promote M2 polarization of macrophages via a TLR4/PI3K/Akt signaling.

Gastric Cancer 2021 Jun 2. Epub 2021 Jun 2.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.

Objective: Eradication of Helicobacter pylori (H. pylori) could not completely prevent the progression of gastric cancer (GC), suggesting that non-H. pylori bacteria may participate in the carcinogenesis of GC. The dysbiosis of microbiota in the stomach of GC has gradually been investigated, while the detailed mechanism that promotes GC in this process has not been elucidated. We aimed to identify a non-H. pylori bacteria that contribute to GC.

Design: GC tissues and adjacent normal tissues were collected to identify bacteria that significantly increased in GC tissues by 16S rRNA gene sequencing and fluorescence in situ hybridization (FISH) analysis. CCK8, wound healing assay, and trans-well assay were performed to analyze the tumor-promoting effect of this bacteria. Next, we detailed the mechanism for tumor-promoting effect of the bacteria by immunofluorescence, RT-qPCR, and western-blotting analysis.

Results: Comparing the microbial community from GC tissues and adjacent normal tissues, we found that Propionibacterium acnes (P. acnes) significantly increased in GC tissues, especially in H. pylori-negative tissues. We further found that the abundance of P. acnes correlated with TNM stages of GC patients. Interestingly, condition medium (CM) from P. acnes-primed macrophages promoted migration of GC cells, while P. acnes only could not. We next proved that P. acnes triggers M2 polarization of macrophages via TLR4/PI3K/Akt signaling.

Conclusions: Together, our finding identified that P. acnes could be a possible agent for the progression of GC besides H. pylori. M2 polarization of macrophages could be promoted by P. acnes via TLR4/PI3K/Akt signaling, thus triggers the progression of GC.
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http://dx.doi.org/10.1007/s10120-021-01202-8DOI Listing
June 2021

Generation of GCaMP6s-Expressing Zebrafish to Monitor Spatiotemporal Dynamics of Calcium Signaling Elicited by Heat Stress.

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China.

The ability of organisms to quickly sense and transduce signals of environmental stresses is critical for their survival. Ca is a versatile intracellular messenger involved in sensing a wide variety of stresses and regulating the subsequent cellular responses. So far, our understanding for calcium signaling was mostly obtained from ex vivo tissues and cultured cell lines, and the in vivo spatiotemporal dynamics of stress-triggered calcium signaling in a vertebrate remains to be characterized. Here, we describe the generation and characterization of a transgenic zebrafish line with ubiquitous expression of GCaMP6s, a genetically encoded calcium indicator (GECI). We developed a method to investigate the spatiotemporal patterns of Ca events induced by heat stress. Exposure to heat stress elicited immediate and transient calcium signaling in developing zebrafish. Cells extensively distributed in the integument of the head and body trunk were the first batch of responders and different cell populations demonstrated distinct response patterns upon heat stress. Activity of the heat stress-induced calcium signaling peaked at 30 s and swiftly decreased to near the basal level at 120 s after the beginning of exposure. Inhibition of the heat-induced calcium signaling by LaCl and capsazepine and treatment with the inhibitors for CaMKII (Ca²/calmodulin-dependent protein kinase II) and HSF1 (Heat shock factor 1) all significantly depressed the enhanced heat shock response (HSR). Together, we delineated the spatiotemporal dynamics of heat-induced calcium signaling and confirmed functions of the Ca-CaMKII-HSF1 pathway in regulating the HSR in zebrafish.
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http://dx.doi.org/10.3390/ijms22115551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197303PMC
May 2021

The Association of Lumbar Disc Herniation with Lumbar Volumetric Bone Mineral Density in a Cross-Sectional Chinese Study.

Diagnostics (Basel) 2021 May 24;11(6). Epub 2021 May 24.

School of Medical Technology, Shaanxi University of Chinese Medicine, Xianyang 712083, China.

Little is known about the effect of lumbar intervertebral disc herniation (LDH) on lumbar bone mineral density (BMD), and few previous studies have used quantitative computed tomography (QCT) to assess whether the staging of LDH correlates with lumbar vertebral trabecular volumetric bone mineral density (Trab.vBMD). To explore the relationship between lumbar Trab.vBMD and LDH, seven hundred and fifty-four healthy participants aged 20-60 years were enrolled in the study from an ongoing study on the degeneration of the spine and knee between June 2014 and 2017. QCT was used to measure L2-4 Trab.vBMD and lumbar spine magnetic resonance images (MRI) were performed to assess the incidence of disc herniation. After 9 exclusions, a total of 322 men and 423 women remained. The men and women were divided into younger (age 20-39 years) and older (age 40-60 years) groups and further into those without LDH, with a single LDH segment, and with ≥2 segments. Covariance analysis was used to adjust for the effects of age, BMI, waistline, and hipline on the relationship between Trab.vBMD and LDH. Forty-one younger men (25.0%) and 59 older men (37.3%) had at least one LDH segment. Amongst the women, the numbers were 46 (22.5%) and 80 (36.4%), respectively. Although there were differences in the characteristics data between men and women, the difference in Trab.vBMD between those without LDH and those with single and ≥2 segments was not statistically significant ( > 0.05). These results remained not statistically significant after further adjusting for covariates ( > 0.05). No associations between lumbar disc herniation and vertebral trabecular volumetric bone mineral density were observed in either men or women.
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http://dx.doi.org/10.3390/diagnostics11060938DOI Listing
May 2021

Effects of - and spp.-Based Potential Probiotics on the Growth Performance, Intestinal Morphology, Immune Responses, and Caecal Microbiota in Broilers.

Antibiotics (Basel) 2021 May 24;10(6). Epub 2021 May 24.

Key Laboratory of Applied Technology on Green-Eco-Health Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A & F University, Hangzhou 311300, China.

We aimed to investigate the effects of -, -, and -based potential probiotics on the growth performance, intestinal morphology, immune responses, and caecal short chain fatty acids (SCFAs) and microbial structure in broiler chickens. Three treatment groups containing a total of 1200 one-day-old AA broilers were included: birds fed with a basal diet only (Con), birds fed with added 10 probiotics cfu/kg (ProL), and birds fed with added 10 probiotics cfu/kg (ProH). The dietary probiotics significantly improved the final and average body weights and serum immunoglobulins A, M, and Y. The probiotics also enhanced the ileal morphology and improved the caecal acetate, butyrate, and propionate contents. Furthermore, 16S rRNA sequencing revealed that dietary compound probiotics modulated the caecal microflora composition as follows: (1) all birds shared 2794 observed taxonomic units; (2) treatment groups were well separated in the PCA and PCoA analysis; (3) the relative abundance of , _UCG-014, , , [_coprostanoligenes_group], []_torques_group, and significantly varied between treatments. The compound probiotics improved the growth performance, serum immune responses, the ratio of ileal villus height to crypt depth, and major caecal SCFAs in broiler chickens. The dietary -, -, and -based probiotics improved overall broiler health and would benefit the poultry industry.
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http://dx.doi.org/10.3390/antibiotics10060624DOI Listing
May 2021

Physical Activity, Sleep, and Sedentary Behavior among Successful Long-Term Weight Loss Maintainers: Findings from a U.S. National Study.

Int J Environ Res Public Health 2021 May 22;18(11). Epub 2021 May 22.

The Cooper Institute, Dallas, TX 75230, USA.

Despite adults' desire to reduce body mass (weight) for numerous health benefits, few are able to successfully lose at least 5% of their starting weight. There is evidence on the independent associations of physical activity, sedentary behaviors, and sleep with weight loss; however, this study provided insight on the combined effects of these behaviors on long-term body weight loss success. Hence, the purpose of this cross-sectional study was to evaluate the joint relations of sleep, physical activity, and sedentary behaviors with successful long-term weight loss. Data are from the 2005-2006 wave of the National Health and Examination Survey (NHANES). Physical activity and sedentary behavior were measured with an accelerometer, whereas sleep time was self-reported. Physical activity and sleep were dichotomized into meeting guidelines (active/not active, ideal sleep/short sleep), and sedentary time was categorized into prolonged sedentary time (4th quartile) compared to low sedentary time (1st-3rd quartiles). The dichotomized behaviors were combined to form 12 unique behavioral combinations. Two-step multivariable regression models were used to determine the associations between the behavioral combinations with (1) long-term weight loss success (≥5% body mass reduction for ≥12-months) and (2) the amount of body mass reduction among those who were successful. After adjustment for relevant factors, there were no significant associations between any of the independent body weight loss behaviors (physical activity, sedentary time, and sleep) and successful long-term weight loss. However, after combining the behaviors, those who were active (≥150 min MVPA weekly), regardless of their sedentary time, were significantly ( < 0.05) more likely to have long-term weight loss success compared to the inactive and sedentary referent group. These results should be confirmed in longitudinal analyses, including investigation of characteristics of waking (type, domain, and context) and sleep (quality metrics) behaviors for their association with long-term weight loss success.
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http://dx.doi.org/10.3390/ijerph18115557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196944PMC
May 2021

MiR-133a-3p attenuates resistance of non-small cell lung cancer cells to gefitinib by targeting SPAG5.

J Clin Lab Anal 2021 May 31:e23853. Epub 2021 May 31.

Clinical Laboratory of Tianjin Chest Hospital, Tianjin, China.

Background: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), clinically used to treat patients with non-small cell lung cancer driven by EGFR mutations. Unfortunately, EGFR-TKI resistance has become a clinical problem for the effective treatment of NSCLC patients. The purpose of this study was to explore the effect and mechanism of miR-133a-3p on the gefitinib sensitivity of NSCLC cells.

Methods: The gefitinib-resistant PC9 (PC9/GR) cells were established through repeated long-term exposure to gefitinib for half a year. Then, PC9/GR cells were transfected with miR-133a-3p mimics and PC9 cells were transfected with miR-133a-3p inhibitors to increase or decrease the expression of miR-133a-3p. CCK-8 assay, colony formation assay, and caspase-3 activity assay were employed to detect cell resistance to gefitinib. Quantitative real-time PCR and Western blotting were used to evaluate the levels of miR-133a-3p, SPAG5, and other related genes. Starbase database was used to predict the target gene of miR-133a-3p and the prognosis of NSCLC patients. Target gene of miR-133a-3p was verified through dual-luciferase reporter gene assay.

Results: MiR-133a-3p was significantly downregulated in gefitinib-resistant cell line PC9/GR vs. gefitinib-sensitive cell line PC9. Overexpression of miR-133a-3p increased the sensitivity of NSCLC cells to gefitinib and vice versa. Furthermore, SPAG5 is an important target gene of miR-133a-3p, and SPAG5 can reverse miR-133a-3p-mediated gefitinib sensitivity of NSCLC cells.

Conclusions: These findings indicated that miR-133a-3p/SPAG5 axis played a vital role in acquired resistance to gefitinib in NSCLC cells, and miR-133a-3p may represent a potential therapeutic strategy for the treatment of human NSCLC.
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http://dx.doi.org/10.1002/jcla.23853DOI Listing
May 2021

Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination.

Adv Sci (Weinh) 2021 May 30:e2100753. Epub 2021 May 30.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences and the Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China.

Histone acetylation is a key histone post-translational modification that shapes chromatin structure, dynamics, and function. Bromodomain (BRD) proteins, the readers of acetyl-lysines, are located in the center of the histone acetylation-signaling network. How they regulate DNA repair and genome stability remains poorly understood. Here, a conserved function of the yeast Bromodomain Factor 1 (Bdf1) and its human counterpart TAF1 is reported in promoting DNA double-stranded break repair by homologous recombination (HR). Depletion of either yeast BDF1 or human TAF1, or disruption of their BRDs impairs DNA end resection, Replication Protein A (RPA) and Rad51 loading, and HR repair, causing genome instability and hypersensitivity to DNA damage. Mechanistically, it is shown that Bdf1 preferentially binds the DNA damage-induced histone H4 acetylation (H4Ac) via the BRD motifs, leading to its chromatin recruitment. Meanwhile, Bdf1 physically interacts with RPA, and this interaction facilitates RPA loading in the chromatin context and the subsequent HR repair. Similarly, TAF1 also interacts with H4Ac or RPA. Thus, Bdf1 and TAF1 appear to share a conserved mechanism in linking the HR repair to chromatin acetylation in preserving genome integrity.
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http://dx.doi.org/10.1002/advs.202100753DOI Listing
May 2021