Publications by authors named "Jing Hu"

1,299 Publications

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Long Non-coding RNA Expression Patterns in Stomach Adenocarcinoma Serve as an Indicator of Tumor Mutation Burden and Are Associated With Tumor-Infiltrating Lymphocytes and Microsatellite Instability.

Front Cell Dev Biol 2021 12;9:618313. Epub 2021 Feb 12.

Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

Long non-coding RNAs (lncRNAs) are crucial in controlling important aspects of tumor immunity. However, whether the expression pattern of lncRNAs in stomach adenocarcinoma (STAD) reflects tumor immunity is not fully understood. We screened differentially expressed lncRNAs (DElncRNAs) between high and low tumor mutation burden (TMB) STAD samples. Using the least absolute shrinkage and selection operator method, 33 DElncRNAs were chosen to establish a lncRNA-based signature classifier for predicting TMB levels. The accuracy of the 33-lncRNA-based signature classifier was 0.970 in the training set and 0.950 in the test set, suggesting the expression patterns of the 33 lncRNAs may be an indicator of TMB in STAD. Survival analysis showed that a lower classifier index reflected better prognosis for STAD patients, and the index showed correlation with expression of immune checkpoint molecules (PD1, PDL1, and CTLA4), tumor-infiltrating lymphocytes, and microsatellite instability. In conclusion, STAD samples with different tumor mutation burdens have different lncRNA expression patterns. The 33-lncRNA-based signature classifier index may be an indicator of TMB and is associated expression of immune checkpoints, tumor-infiltrating lymphocytes, and microsatellite instability.
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http://dx.doi.org/10.3389/fcell.2021.618313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907456PMC
February 2021

Characterizing the Leaf Transcriptome of (Ling et C. Shih), a Drought Resistant, Endemic Plant From China.

Front Genet 2021 11;12:625985. Epub 2021 Feb 11.

College of Life and Health Sciences, Northeastern University, Shenyang, China.

(Ling et C. Shih), an endemic plant that is extremely well-adapted to harsh environments. However, little is known about its molecular biology of the plant's resistant traits against stress, or even its molecular biology of overall plant. To investigate the molecular biology of and mechanism of stress adaptation, we performed transcriptome sequencing of its leaves using an Illumina platform. A total of 130,891 unigenes were obtained, and 97,496 (~74.5%) unigenes were annotated in the public protein database. The similarity search indicated that 40,878 and 74,084 unigenes showed significant similarities to known proteins from NCBI non-redundant and Swissprot protein databases, respectively. Of these, 56,213 and 42,005 unigenes were assigned to the Gene Ontology (GO) database and Cluster of Orthologous Groups (COG), respectively, and 38,918 unigenes were mapped into five main categories, including 18 KEGG pathways. Metabolism was the largest category (23,128, 59.4%) among the main KEGG categories, suggesting active metabolic processes in . About 2,459 unigenes were annotated to have a role in defense mechanism or stress tolerance. Transcriptome analysis of revealed the presence of 12,925 microsatellites in 10,524 unigenes and mono, trip, and dinucleotides having higher polymorphism rates. The phylogenetic analysis based on gene among related species confirmed the reliability of the transcriptomic data. This work is the first genetic study of as a new plant resource of stress-tolerant genes. This large number of transcriptome sequences enabled us to comprehensively understand the basic genetics of and discover novel genes that will be helpful in the molecular improvement of chrysanthemums.
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http://dx.doi.org/10.3389/fgene.2021.625985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906282PMC
February 2021

Seaweed farms provide refugia from ocean acidification.

Sci Total Environ 2021 Feb 10;776:145192. Epub 2021 Feb 10.

King Abdullah University of Science and Technology (KAUST), Red Sea Research Center (RSRC), Thuwal 23955-6900, Saudi Arabia.

Seaweed farming has been proposed as a strategy for adaptation to ocean acidification, but evidence is largely lacking. Changes of pH and carbon system parameters in surface waters of three seaweed farms along a latitudinal range in China were compared, on the weeks preceding harvesting, with those of the surrounding seawaters. Results confirmed that seaweed farming is efficient in buffering acidification, with Saccharina japonica showing the highest capacity of 0.10 pH increase within the aquaculture area, followed by Gracilariopsis lemaneiformis (ΔpH = 0.04) and Porphyra haitanensis (ΔpH = 0.03). The ranges of pH variability within seaweed farms spanned 0.14-0.30 unit during the monitoring, showing intense fluctuations which may also help marine organisms adapt to enhanced pH temporal variations in the future ocean. Deficit in pCO in waters in seaweed farms relative to control waters averaged 58.7 ± 15.9 μatm, ranging from 27.3 to 113.9 μatm across farms. However, ΔpH did not significantly differ between day and night. Dissolved oxygen and Ω were also elevated in surface waters at all seaweed farms, which are benefit for the survival of calcifying organisms. Seaweed farming, which unlike natural seaweed forests, is scalable and is not dependent on suitable substrate or light availability, could serve as a low-cost adaptation strategy to ocean acidification and deoxygenation and provide important refugia from ocean acidification.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145192DOI Listing
February 2021

The Expression of TRIM6 Activates the mTORC1 Pathway by Regulating the Ubiquitination of TSC1-TSC2 to Promote Renal Fibrosis.

Front Cell Dev Biol 2020 9;8:616747. Epub 2021 Feb 9.

Department of Nephrology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Renal fibrosis is considered as the final pathway of all types of kidney diseases, which can lead to the progressive loss of kidney functions and eventually renal failure. The mechanisms behind are diversified, in which the mammalian target of rapamycin (mTOR) pathway is one of the most important regulatory pathways that accounts for the disease. Several processes that are regulated by the mTOR pathway, such as autophagy, epithelial-mesenchymal transition (EMT), and endoplasmic reticulum (ER) stress, are tightly associated with renal fibrosis. In this study, we have reported that the expression of tripartite motif-containing (TRIM) protein 6, a member of TRIM family protein, was highly expressed in renal fibrosis patients and positively correlated with the severity of renal fibrosis. In our established and renal fibrosis models, its expression was upregulated by the Angiotensin II-induced nuclear translocation of nuclear factor-κB (NF-κB) p50 and p65. In HK2 cells, the expression of TRIM6 promoted the ubiquitination of tuberous sclerosis proteins (TSC) 1 and 2, two negative regulators of the mTORC1 pathway. Moreover, the knockdown of TRIM6 was found efficient for alleviating renal fibrosis and inhibiting the downstream processes of EMT and ER in both HK2 cells and 5/6-nephrectomized rats. Clinically, the level of TRIM6, TSC1/2, and NF-κB p50 was found closely related to renal fibrosis. As a result, we have presented the first study on the role of TRIM6 in the mTORC1 pathway in renal fibrosis models and our findings suggested that TRIM6 may be a potential target for the treatment of renal fibrosis.
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http://dx.doi.org/10.3389/fcell.2020.616747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901959PMC
February 2021

Clinical and microbiological characteristics of nosocomial, healthcare-associated, and community-acquired Klebsiella pneumoniae infections in Guangzhou, China.

Antimicrob Resist Infect Control 2021 Feb 25;10(1):41. Epub 2021 Feb 25.

Department of Nosocomial Infection Administration, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.

Background: Klebsiella pneumoniae (K. pneumoniae) is a common pathogen associated with hospital and community-onset infections. This study aimed to compare the clinical and microbiological characteristics of nosocomial, healthcare-associated (HCA), and community-acquired (CA) K. pneumoniae infections.

Methods: Clinical data were extracted from electronic medical records and analyzed retrospectively. Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) production were determined for all identified strains. Carbapenemase and ESBL genes were amplified by PCR. Genotyping of carbapenem-resistant K. pneumoniae (CRKP) and ESBL-producing strains was performed by pulsed-field gel electrophoresis (PFGE).

Results: Of 379 K. pneumoniae infections, 98 (25.9%) were nosocomial, 195 (51.5%) were healthcare-associated, and 86 (22.6%) were community-acquired. Hematological malignancy (OR = 4.467), and hypertension (OR = 2.08) and cerebral vascular disease (OR = 2.486) were associated with nosocomial and HCA infections respectively, when compared to CA infections. Overall, the incidence of antimicrobial resistance for the majority of agents tested was similar between nosocomial and HCA infections (P > 0.05) and both groups had a higher incidence than CA infections (P < 0.05). Moreover, 95.1% (78/82) of CRKP strains were isolated from the nosocomial and HCA groups. The bla was the most prevalent carbapenemase gene among CRKP strains (80.5%, 66/82). ESBL-producing strains were prevalent among nosocomial (40.8%), HCA (35.9%) and CA groups (24.4%). The bla and bla genes were predominant in nosocomial (65.0%) and CA strains (66.7%), respectively. PFGE results showed ESBL-producing and CRKP strains were genetically diverse. Identical PFGE profiles were observed among HCA and nosocomial strains.

Conclusions: Nosocomial and HCA K. pneumoniae infections presented similar clinical features and antimicrobial resistance, and both two types of infections were different to CA infections. CRKP and ESBL-producing strains were disseminated mainly in HCA and nosocomial groups, and showed a clonal diversity. The cross transmission of CRKP was existed among HCA and nosocomial patients. This finding suggests that similar empirical therapy should be considered for patients with nosocomial and HCA K. pneumoniae infections and bacterial resistance surveillance of these infections is necessary.
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http://dx.doi.org/10.1186/s13756-021-00910-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908793PMC
February 2021

Effect of Different-Volume Fluid Resuscitation on Organ Functions in Severe Acute Pancreatitis and Therapeutic Effect of .

Evid Based Complement Alternat Med 2020 14;2020:6408202. Epub 2020 Oct 14.

Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To explore the effect of different-volume fluid resuscitation (FR) on organ functions in severe acute pancreatitis (SAP) and to elucidate the therapeutic effect and mechanism of on organ injuries caused by high-volume FR.

Methods: 1. Clinical study: retrospective analysis of thirty-one patients about the effect of titrated fluid resuscitation protocol (TFR) on the occurrence of acute kidney injury (AKI) secondary to SAP. 2. Experimental study: rats ( = 30) were randomly divided into five groups: sham, model, low-volume FR (1.5 ml/kg/h), high-volume FR (10 ml/kg/h), and combined with high-volume FR (10 ml/kg/h + intraintestinal administration 5 g/kg); serum or plasma indicators and histopathologic scores were compared to explore the effect and mechanism of different fluid volumes and on organ function in SAP.

Results: The occurrence of AKI, fluid volume, and fluid velocity in TFR group was lower than that in the control group. Logistic regression analysis showed that increased Marshall scores and fluid velocity were risk factors for predicting occurrence of AKI in SAP. Low-volume FR decreased the levels of blood urea nitrogen (BUN), serum creatinine (Cr), matrix metalloproteinase (MMP), and pathologic scores of the pancreas and kidney. High-volume FR increased ascites, MMPs, and kidney pathologic scores. decreased the levels of BUN, Cr, MMPs, and pathologic scores of the pancreas and kidney and increased the arterial oxygen saturation.

Conclusion: TFR-associated lower fluid volume and velocity reduced the occurrence of AKI secondary to SAP. High volume might aggravate AKI via increased MMP release leading to endothelial glycocalyx damage and vascular endothelial dysfunction. reduced MMP release, relieved glycocalyx damage, and alleviated the pancreas and kidney injury aggravated by high fluid volume in SAP. Therefore, endothelial glycocalyx protection might be a new strategy in the treatment of SAP.
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http://dx.doi.org/10.1155/2020/6408202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895597PMC
October 2020

Trends and Patterns in Traditional Chinese Medicine Use Among Chinese Population in Late Adulthood: An Eight-Year Repeated Panel Survey.

Am J Chin Med 2021 Feb 20:1-15. Epub 2021 Feb 20.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, P. R. China.

Traditional Chinese medicine (TCM), originated from China, is different from Western medicine in theory and practice. This study aimed to document the longitudinal trends and the patterns by demographical characteristics in the prevalence of TCM among the middle-aged and elderly Chinese population. This study used nationally representative longitudinal survey data from the China Health and Retirement Longitudinal Study (CHARLS), covering approximately 20,000 individuals in each panel survey from 2011 to 2018. The questions regarding medication use in the questionnaire was used to identify the TCM users. The prevalence of using TCM for treating chronic diseases among the patients with chronic diseases stabilized between 2011 and 2018, while the prevalence of TCM use for any purpose among the overall population climbed from 19.03% (95% CI 18.37% to 19.69%) in 2011 to 23.91% (95% CI 23.23% to 24.60%) in 2015. Moreover, the prevalence of TCM use for nonchronic conditions among the overall population increased during the same period as well. The TCM users were more likely to be females and city dwellers. The increasing prevalence of TCM use for any purpose among the overall population reflects the increasing influence and potentials of TCM by year. With the expected rising demand in TCM for the following decades in China, more clinical trials on safety and healthcare policy regarding TCM are merited in the future.
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http://dx.doi.org/10.1142/S0192415X21500142DOI Listing
February 2021

Association between body mass index and risk of cardiovascular disease-specific mortality among adults with hypertension in Shanghai, China.

Aging (Albany NY) 2021 Feb 17;13. Epub 2021 Feb 17.

Department of Biostatistics, School of Public Health, Fudan University, Shanghai, People’s Republic of China.

The aim of our study was to examine the association between body mass index (BMI) and the risk of cardiovascular disease (CVD)-specific mortality among Chinese adults with hypertension by sex. This study included 212,394 adult hypertensive patients aged 20-85 years registered in the records of Minhang District during 2007-2018. Cox proportional hazards regression was performed to evaluate the association between BMI and CVD-specific mortality among Chinese adults with hypertension. There were 14,029 deaths over an average of 8.24 years (range, 0.19-11.96 years). The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) across BMI categories (< 18.5 kg/m, 18.5-24.9 kg/m [reference group], 25.0-29.9 kg/m, and ≥ 30 kg/m) for CVD-specific mortality were 1.37 (1.22-1.53), 1.00 (reference), 0.95 (0.90-1.01), and 1.21 (1.04-1.40) in males, and 1.44 (1.31-1.59), 1.00 (reference), 0.96 (0.91-1.01), and 1.04 (0.92-1.17) in females. A U-shaped relationship was observed between BMI and CVD-specific mortality (overall association < 0.001; non-linearity < 0.001). This association was attenuated in old age. This study revealed a U-shaped relationship between BMI and CVD-specific mortality among hypertensive men and women. In older people, overweight and obesity are potential factors that reduce the risk of CVD death.
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http://dx.doi.org/10.18632/aging.202543DOI Listing
February 2021

Randomized controlled trials of Chinese herbal medicine published in English from 2010 to 2019: a bibliometrics study.

Ann Palliat Med 2021 Feb 11. Epub 2021 Feb 11.

Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing, China.

Background: As the use of Chinese herbal medicine (CHM) in the international market increases, the number of clinical studies including randomized controlled trials (RCTs) of CHM which published in international journals has also increased. Using bibliometrics, we systematically and comprehensively analyzed the research status of CHM RCTs published in English during the period of 2010 to 2019.

Methods: Electronic searches in MEDLINE, EMBASE, and Cochrane Library databases were undertaken. CHM RCTs published in English between January 2010 and December 2019 were included. We randomly selected 20% from the eligible articles. Descriptive statistical analysis was carried out by extracting information on general information, characteristics of the study participants, interventions, outcomes, and risk of bias assessment of included RCTs.

Results: Two hundred and twenty-seven CHM RCTs published in English were included in our study. Chinese Journal of Integrative Medicine was the journal which published most of the relevant papers (22.0%). A total of 45,774 participants were included, sample size ranged from 12 to 3,143 (median: 115). The most common disease was the circulatory diseases (n=36, 15.9%). Decoction was the most common dosage form (28.2%), and "CHM vs. placebo" was the most common type of control (36.1%). The median of the total number of outcomes was 4 (range: 1-14), 92 (40.5%) did not clearly specify any primary outcome, 56 (24.7%) did not report any adverse event, 41 (18.1%) and 68 (30.0%) reported traditional Chinese medicine (TCM)- specific outcomes and quality of life, respectively. Eighty-five (37.4%) did not report sufficient information about the random sequence generation process, 100 (44.1%) used the adequate allocation concealment, 92 (40.5%) blinded participants and key study personnel, and 24 (10.6%) blinded outcome assessors.

Conclusions: Our results provided insight into the research status regarding CHM RCTs published in English during the past decade, this study may be helpful in understanding research trends in this field.
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http://dx.doi.org/10.21037/apm-20-1033DOI Listing
February 2021

SNHG3 promotes migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the miR-186-5p/ZEB1 axis.

Am J Transl Res 2021 15;13(2):585-600. Epub 2021 Feb 15.

Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Chongqing Medical University Chongqing 400000, China.

Increasing evidence suggests that the long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. The lncRNA small nucleolar RNA host gene 3 (SNHG3) reportedly acts as an oncogene in hepatocellular carcinoma and colorectal cancer; however, little is known about the biological function and oncogenic mechanisms of SNHG3 in breast cancer. We demonstrated that the expression of SNHG3 was abnormally high in breast cancer tissues and cells, and transgenic expression of SNHG3 promoted the proliferation, migration, and invasion of breast cancer cell lines (MCF-7 and MDA-MB-231). The mean volume of the xenografts from the SNHG3-knockdown MCF-7 cells was lower than that of the control tumor cells. Moreover, the expression of zinc finger E-box binding homeobox 1 (ZEB1) increased after SNHG3 overexpression and . Overexpression of ZEB1 triggered cellular migration and invasion behaviors. Analysis of the mechanism underlying these effects suggested that SNHG3 is an effective sink for miR-186-5p and modulates ZEB1 repression, conferring an additional level to its post-transcriptional regulation. In conclusion, SNHG3 promotes the migration and invasion of breast cancer cells through miR-186-5p/ZEB1 regulation and the induction of the epithelial to mesenchymal transition, indicating that SNHG3 is a potential treatment target for breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868844PMC
February 2021

Dye-free spectrophotometric measurement of nucleic acid-to-protein ratio for cell-selective extracellular vesicle discrimination.

Biosens Bioelectron 2021 Feb 9;179:113058. Epub 2021 Feb 9.

Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, LA, 70112, USA. Electronic address:

Extracellular vesicles (EVs) can represent a novel source of disease biomarkers, and are under intensive study for their clinical potential. Most EV-based cancer diagnostic studies have focused on establishing EV assays that detect increased expression of a single cancer-associated marker or marker signatures based on multiplex detection of these biomarkers. EV biomarker readouts can be obscured by high background signal leading to false positives, and may markedly differ between analyses due to variation in sample purity during EV isolation. This can obstruct the comparisons among studies and lead to conflicting conclusions. This work reports that the nucleic acid to protein UV absorption ratio of an EV is a cell-specific EV characteristic. This EV collective attribute can be measured at low-cost to discriminate EVs derived from malignant and non-malignant cells rather than employing single markers that may be cancer- or subtype-specific. Our work also highlighted the application for accessing purity in EV preparations irrelevant to EV yield. It can be employed to distinguish from patients with and without malignant disease upon analysis of EVs isolated from their serum samples.
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http://dx.doi.org/10.1016/j.bios.2021.113058DOI Listing
February 2021

LncRNA NEAT1 Promotes High Glucose-Induced Mesangial Cell Hypertrophy by Targeting miR-222-3p/CDKN1B Axis.

Front Mol Biosci 2020 27;7:627827. Epub 2021 Jan 27.

Department of Nephrology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Glomerular hypertrophy is an early morphological alteration in diabetic nephropathy. Cyclin-Dependent Kinases have been shown to be required for high glucose (HG)-induced hypertrophy; however, the upstream regulators of CDKN1B in glomerular hypertrophy remain unclear. Herein we describe a novel pathway in which Long noncoding RNA (lncRNA) NEAT1 regulates the progression of mesangial cell hypertrophy via a competing endogenous RNA (ceRNA) mechanism. Real-time PCR was performed to detect the relative NEAT1 and miR-222-3p expressions and further confirmed the relationship between NEAT1 and miR-222-3p. Cell cycle was evaluated by flow cytometry. The related mechanisms were explored by Western blot, RNA immunoprecipitation and chromatin immunoprecipitation assay. We show that NEAT1 forms double stranded RNA (dsRNA) with miR-222-3p, thus limiting miR-222-3p's binding with CDKN1B. This release of CDKN1B mRNA leads to elevated CDKN1B protein expression, resulting in hypertrophy. In addition, we demonstrated that STAT3 which is activated by HG induces the transcription of NEAT1 by binding to its promoter. Our findings underscore an unexpected role of lncRNAs on gene regulation and introduce a new mode of proliferation regulation in mesangial cells.
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http://dx.doi.org/10.3389/fmolb.2020.627827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872960PMC
January 2021

A Nomogram Model Involving Immunohistochemical Markers for Predicting the Recurrence of Stage I-II Endometrial Cancer.

Front Oncol 2020 22;10:586081. Epub 2021 Jan 22.

Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: The purpose of this study was to establish a nomogram combining classical parameters and immunohistochemical markers to predict the recurrence of patients with stage I-II endometrial cancer (EC).

Methods: 419 patients with stage I-II endometrial cancer who received primary surgical treatment at the First Affiliated Hospital of Chongqing Medical University were involved in this study as a training cohort. Univariate and multivariate Cox regression analysis of screening prognostic factors were performed in the training cohort to develop a nomogram model, which was further validated in 248 patients (validation cohort) from the Second Affiliated Hospital of Chongqing Medical University. The calibration curve was used for internal and external verification of the model, and the C-index was used for comparison among different models.

Results: There were 51 recurrent cases in the training cohort while 31 cases in the validation cohort. Univariate analysis showed that age, histological type, histological grade, myometrial invasion, cervical stromal invasion, postoperative adjuvant treatment, and four immunohistochemical makers (Ki67, estrogen receptor, progesterone receptor, P53) were the related factors for recurrence of EC. Multivariate analysis demonstrated that histological type (P = 0.029), myometrial invasion (P = 0.003), cervical stromal invasion (P = 0.001), Ki67 (P < 0.001), ER (P = 0.009) and P53 expression (P = 0.041) were statistically correlated with recurrence of EC. Recurrence-free survival was better predicted by the proposed nomogram with a C-index of 0.832 (95% CI, 0.752-0.912) in the training cohort, and the validation set confirmed the finding with a C-index of 0.861 (95% CI, 0.755-0.967).

Conclusion: The nomogram model combining classical parameters and immunohistochemical markers can better predict the recurrence in patients with FIGO stage I-II EC.
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http://dx.doi.org/10.3389/fonc.2020.586081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874072PMC
January 2021

A mechanistic study on removal efficiency of four antibiotics by animal and plant origin precursors-derived biochars.

Sci Total Environ 2021 Jan 30;772:145468. Epub 2021 Jan 30.

Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. Electronic address:

Extensive research has been performed on the utilization of biochar for pollutant removal via sorption. Additionally, the relationship between sorption strength of organic pollutants by organic matter and nanomaterials and their sorption site energy distribution has been studied. However, the linkage between removal efficiency of organic pollutants and the sorption site energy distribution on biochars is unknown. As a first attempt to address this knowledge gap, three biochars were derived from two plant-origin precursors (corn straw-CS; birch sawdust-BS) and one animal-origin precursor (meat and bone meal-MBM) at 500 °C (CS-500, BS-500, and MBM-500). In addition, two biochars were prepared with CS at 300 and 800 °C (CS-300 and CS-800) to examine the relationship between their site energy distribution and removal efficiency of antibiotics including sulfadiazine (SDZ), sulfamethoxazole (SMX), tetracycline (TC) and ciprofloxacin (CFX) by these materials. Our findings showed that the antibiotic-biochar interactions can be well interpreted with site energy distribution and XPS analysis results. Polar interactions between CS-300, CS-500, and CS-800 and SDZ and SMX occurring at the high-energy sites dominated their removal. However, TC and CFX removal by these biochars was driven by their polar interactions occurring at high-energy sites and π-π interactions at low-energy sites. The π-π stacking mechanism tended to dominate their removal with increasing charring temperature. Abundance of polar functionalities on CS-500, BS-500, and MBM-500 and TC removal efficiency of these materials consistently followed an order of MBM-500 > CS-500 > BS-500, highlighting importance of precursors for making biochars and polar interactions in its removal.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145468DOI Listing
January 2021

A novel immunochemotherapy based on targeting of cyclooxygenase and induction of immunogenic cell death.

Biomaterials 2021 Mar 4;270:120708. Epub 2021 Feb 4.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15261, USA; University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA. Electronic address:

Cyclooxygenase (COX) plays a crucial role in the "inflammogenesis of cancer", which leads to tumor progression, metastasis, and immunotherapy resistance. Therefore, reducing "inflammogenesis" by COX inhibition may be a key perspective for cancer therapy. However, the role of tumor-derived COX in the actions of COX inhibitors remains incompletely understood. In this study, applying "old drug new tricks" to repurpose 5-aminosalicylic acid (5-ASA), a COX inhibitor, we examined the effect of 5-ASA, alone or in combination with doxorubicin (DOX), in several cancer cell lines with different levels of COX expression. To facilitate the evaluation of the combination effect on tumors in vivo, a new micellar carrier based on PEG-b-PNHS polymer-conjugated 5-ASA (PASA) was developed to enhance codelivery of 5-ASA and DOX. Folate was also introduced to the polymer (folate-PEG-NH-conjugated PASA (FASA)) to further improve delivery to tumors via targeting both tumor cells and tumor macrophages. An unprecedented high DOX loading capacity of 42.28% was achieved through various mechanisms of carrier/drug interactions. FASA was highly effective in targeting to and in inhibiting the growth of both 4T1.2 and CT26 tumors in BALB/c mice. However, FASA was more effective in CT26 tumor that has a high level of COX expression. Codelivery of DOX via PASA and FASA led to a further improvement in antitumor activity. Mechanistic studies suggest that inhibition of COX in vivo led to a more active tumor immune microenvironment. Interestingly, treatment with FASA led to upregulation of PD-1 on T cells, likely due to repressing the inhibitory effect of prostaglandin E2 (PGE) on PD-1 expression on T cells. Combination of FASA/DOX with anti-PD-1 antibody led to a drastic improvement in the overall antitumor activity including regression of some established tumors at a suboptimal dose of FASA/DOX. Our data suggest that FASA/DOX may represent a new and effective immunochemotherapy for various types of cancers, particularly those cancers with high levels of COX expression.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910750PMC
March 2021

Inhibition of cell proliferation and radioresistance by miR-383-5p through targeting RNA binding protein motif (RBM3) in nasopharyngeal carcinoma.

Ann Transl Med 2021 Jan;9(2):123

Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi'an, China.

Background: RNA binding protein motif (RBM3) is associated with radioresistance in nasopharyngeal carcinoma (NPC), and miR-383-5p was predicted to target the 3'-untranslated region (3'UTR) of RBM3 messenger RNA (mRNA). Our study aimed to investigate the role and the mechanisms of miR-383-5p targeting RBM3 in NPC cell proliferation and radioresistance (RR).

Methods: The expression of miR-383-5p was detected by Real-time quantitative PCR (qRT-PCR) between RS (Radiosensitivity) and RR (Radioresistance) NPC patient- tissue specimens and cell lines. Cell Counting Kit-8 (CCK-8) and Clonogenic survival assay were applied to analyze the effect of miR-383-5p on NPC cell proliferation and radioresistance. Possible downstream target of miR-383-5p in NPC cells, RBM3was evaluated by luciferase assay and qRT-PCR. miR-383-5p inhibited NPC cell proliferation and radioresistance through RBM3 by rescue experiments. The effect of miR-383-5p on radiation-induced apoptosis was explored through Flow cytometric analysis and Western blotting. Western blotting was analyzed the molecular of RBM3-mediated Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) signaling pathways.

Results: The expression of miR-383-5p was decreased in radioresistant NPC tissues and cells. miR-383-5p inhibited cell proliferation and radioresistance in CNE1/IR cells. We also observed that therapeutic administration of a miR-383-5p agomir dramatically sensitized NPC xenografts to radiation in a mouse model. Conversely, in the same xenograft model, administration of a miR-383-5p antagomir dramatically increased NPC resistance to radiation. miR-383-5p targeted the 3'UTR of RBM3. miR-383-5p inhibited NPC cell proliferation and radioresistance through RBM3. Finally, we found that miR-383-5p increased radiation-induced apoptosis, activated JNK signaling, and inhibited ERK signaling.

Conclusions: Our study revealed that miR-383-5p targeted the 3'UTR of RBM3 and contributed to the efficacy of NPC radiation therapy by altering the RBM3-mediated JNK and ERK signaling pathways.
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http://dx.doi.org/10.21037/atm-20-6881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867938PMC
January 2021

[Analysis on international demand investigation for technical specification of acupuncture- moxibustionthe and its general rules of drafting].

Zhongguo Zhen Jiu 2021 Jan;41(1):89-93

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.

The electronic questionnaire was adopted to survey the international demand on - ( for short) to explore the potential problems during the application and provide the evidence for the development of international standard of . A total of 102 valid questionnaires were collected from 18 countries and regions. The priority of the demand for international standard on the technical specification of acupuncture-moxibustion is filiform needle, moxibustion, electroacupuncture, cupping, auricular acupuncture, scalp acupuncture and scraping. One hundred experts (98.04%) at home and abroad believe the necessity of the international standard development of . The awareness rate of the existing national standard of is 71.57% and the foreign experts think that its expression may be "unclear" and the domestic experts think it may be "lack of practicability". The domestic experts hope to highlight the commonness in the scope of the international standard of and the foreign experts hope to retain more individuality. Regarding the specific questions during the technique manipulations of acupuncture-moxibustion, there are the big differences in "relevant terminology" "preoperative preparation" and "adverse reaction and contraindications" at home and abroad. In order to improve the international compatibility and applicability, it is necessary to give full consideration to the needs of different countries in the development of international standard of and balance as far as possible between refining "common problems" and satisfying "individual needs".
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http://dx.doi.org/10.13703/j.0255-2930.20200601-k0002DOI Listing
January 2021

[Analysis on international demand investigation for technical specification of acupuncture- moxibustionthe and its general rules of drafting].

Zhongguo Zhen Jiu 2021 Jan;41(1):89-93

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.

The electronic questionnaire was adopted to survey the international demand on - ( for short) to explore the potential problems during the application and provide the evidence for the development of international standard of . A total of 102 valid questionnaires were collected from 18 countries and regions. The priority of the demand for international standard on the technical specification of acupuncture-moxibustion is filiform needle, moxibustion, electroacupuncture, cupping, auricular acupuncture, scalp acupuncture and scraping. One hundred experts (98.04%) at home and abroad believe the necessity of the international standard development of . The awareness rate of the existing national standard of is 71.57% and the foreign experts think that its expression may be "unclear" and the domestic experts think it may be "lack of practicability". The domestic experts hope to highlight the commonness in the scope of the international standard of and the foreign experts hope to retain more individuality. Regarding the specific questions during the technique manipulations of acupuncture-moxibustion, there are the big differences in "relevant terminology" "preoperative preparation" and "adverse reaction and contraindications" at home and abroad. In order to improve the international compatibility and applicability, it is necessary to give full consideration to the needs of different countries in the development of international standard of and balance as far as possible between refining "common problems" and satisfying "individual needs".
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http://dx.doi.org/10.13703/j.0255-2930.20200601-k0002DOI Listing
January 2021

Stability Assessment of a Polymeric Brominated Flame Retardant in Polystyrene Foams under Application-Relevant Conditions.

Environ Sci Technol 2021 Feb 7. Epub 2021 Feb 7.

Polyurethanes, Dow, Derbyshire SK22 1BR, United Kingdom.

The flame retardant (FR) BLUEDGE polymeric flame retardant (PFR) has been in use since 2011 and was developed as a replacement FR for hexabromocyclododecane in polystyrene (PS)-based insulation foams. To better understand the degradation behavior of the PFR used within PS foams, we examined the degradation of PFR under application-relevant conditions. Thermo-oxidative and photolytic pathways represent the most relevant degradation pathways. Separately, both the thermal and oxidative degradations of PFR at ambient conditions were shown to be negligible based on kinetic models of thermogravimetric analysis data obtained at elevated temperatures; the models predict that it would take 100 years to degrade 1% of PFR at 50 °C and 1000 years at 20 °C. Photodegradation was shown to degrade PFR after accelerated ultraviolet (UV) aging/exposure. UV radiation did not significantly penetrate the foam insulation (<2000 μm); the degradation process took place primarily at the surface. The molecular weight of the polymer changed with degradation, but there was minimal loss of bromine from the foam with degradation. The data from the liquid chromatography-mass spectrometry analysis focused primarily on several small-molecule polar products formed, which included two brominated species. These species were predicted using computer-based modeling to be biodegradable, to not be persistent in the environment, and to exhibit a low toxicity to aquatic organisms.
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http://dx.doi.org/10.1021/acs.est.0c04325DOI Listing
February 2021

Diarylheptanoid-chalcone hybrids with PTP1B and α-glucosidase dual inhibition from Alpinia katsumadai.

Bioorg Chem 2021 Mar 27;108:104683. Epub 2021 Jan 27.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, People's Republic of China. Electronic address:

The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A-A (1-16), together with 13 known analogues (17-29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which compounds 1-3, 5-7, 11-14, 21-25, and 27 showed PTP1B/TCPTP selective inhibition with IC values ranging from 22.0 to 96.7 μM, which were 2-10 times more active than sodium orthovanadate (IC, 215.7 μM). All compounds exhibited obvious inhibition against α-glucosidase with IC values of 2.9-29.5 μM, indicating 6-59 times more active than acarbose (IC, 170.9 μM). Study of enzyme kinetics indicated compounds 1, 3, and 12 were PTP1B and α-glucosidase mixed-type inhibitors with K values of 13.1, 12.9, 21.6 μM, and 4.9, 7.4, 3.4 μM, respectively.
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http://dx.doi.org/10.1016/j.bioorg.2021.104683DOI Listing
March 2021

Analyzing the potential therapeutic mechanism of Huashi Baidu Decoction on severe COVID-19 through integrating network pharmacological methods.

J Tradit Complement Med 2021 Mar 18;11(2):180-187. Epub 2021 Jan 18.

Department of Biology, School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.

Background And Aim: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods.

Experimental Procedure: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of "Chinese materia medica-active compounds-therapeutic target proteins" was built, then key Chinese materia medica and main active compounds were selected.

Results And Conclusion: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO_BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19.

Taxonomy Classification By Evise: Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine.
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http://dx.doi.org/10.1016/j.jtcme.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834580PMC
March 2021

Screening and identifying hepatobiliary diseases through deep learning using ocular images: a prospective, multicentre study.

Lancet Digit Health 2021 Feb;3(2):e88-e97

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China; Centre for Precision Medicine, Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images.

Methods: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score.

Findings: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification.

Interpretation: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool.

Funding: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S2589-7500(20)30288-0DOI Listing
February 2021

Drip fertigation with straw incorporation significantly reduces NO emission and N leaching while maintaining high vegetable yields in solar greenhouse production.

Environ Pollut 2021 Jan 18;273:116521. Epub 2021 Jan 18.

Institute for Meteorology and Climate Research (IMK-IFU), Karlsruhe Institute of Technology, Garmisch-Partenkirchen, 82467, Germany; State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing, 100029, China.

Approximately 1/3 of vegetables in China are produced in solar greenhouses. Most farmers use conventional irrigation with over fertilisation (CIF), thereby applying approximately 2000 kg N ha fertiliser over two cropping seasons per year. Here, we tested the effect of drip irrigation with reduced fertilisation (DIF) combined with straw incorporation on reducing NO emissions and nitrogen leaching from solar greenhouse vegetable production systems. Over three consecutive tomato cropping seasons, NO emissions and nitrogen leaching were monitored in high temporal resolution, thereby producing a unique dataset. Compared to CIF, the realised drip fertigation scheme reduces NO emission and nitrogen leaching of nitrate and dissolved organic nitrogen by approximately a factor of 5-10 (NO-DIF: 10.3, CIF: 47.5 kg N ha yr; N leaching-DIF: 83.6, CIF: 863 kg N ha yr). Straw incorporation in CIF, though advantageous for soil health, resulted in pollution swapping as soil NO emissions increased while NO leaching losses decreased. On the contrary, no significant negative environmental N effects of straw incorporation were found for DIF. As crop productivity was not affected by straw incorporation, neither for CIF nor for DIF, our study provides a sound basis for policy advice to recommend farmers to adopt drip fertigation combined with straw application. Wide scale adoption of this technique will result in reductions of environment N losses, alleviate major soil degradation signs, including soil acidity, nutrient imbalance and deterioration of soil microbial community structure, while allowing to maintaining high yields of vegetables in solar greenhouse production systems.
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http://dx.doi.org/10.1016/j.envpol.2021.116521DOI Listing
January 2021

Dissecting the Invasion-Associated Long Non-coding RNAs Using Single-Cell RNA-Seq Data of Glioblastoma.

Front Genet 2020 11;11:633455. Epub 2021 Jan 11.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Glioblastoma (GBM) is characterized by rapid and lethal infiltration of brain tissue, which is the primary cause of treatment failure and deaths for GBM. Therefore, understanding the molecular mechanisms of tumor cell invasion is crucial for the treatment of GBM. In this study, we dissected the single-cell RNA-seq data of 3345 cells from four patients and identified dysregulated genes including long non-coding RNAs (lncRNAs), which were involved in the development and progression of GBM. Based on co-expression network analysis, we identified a module (M1) that significantly overlapped with the largest number of dysregulated genes and was confirmed to be associated with GBM invasion by integrating EMT signature, experiment-validated invasive marker and pseudotime trajectory analysis. Further, we denoted invasion-associated lncRNAs which showed significant correlations with M1 and revealed their gradually increased expression levels along the tumor cell invasion trajectory, such as VIM-AS1, WWTR1-AS1, and NEAT1. We also observed the contribution of higher expression of these lncRNAs to poorer survival of GBM patients. These results were mostly recaptured in another validation data of 7930 single cells from 28 GBM patients. Our findings identified lncRNAs that played critical roles in regulating or controlling cell invasion and migration of GBM and provided new insights into the molecular mechanisms underlying GBM invasion as well as potential targets for the treatment of GBM.
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http://dx.doi.org/10.3389/fgene.2020.633455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831882PMC
January 2021

The response of microbial community structure and sediment properties to anthropogenic activities in Caohai wetland sediments.

Ecotoxicol Environ Saf 2021 Mar 19;211:111936. Epub 2021 Jan 19.

College of Resource and Environmental Engineering, Guizhou University, Guiyang 550003, PR China; Guizhou Academy of Sciences, Guiyang 550009, PR China. Electronic address:

This study aimed to investigate the response of sediment microbial communities (including bacteria and archaeal groups) in Caohai Lake to anthropogenic activities. The sediment samples were collected from the regions with high anthropogenic interference and low anthropogenic interference. Their physicochemical properties and enzyme activities were analyzed, and the bacterial and archaeal communities were investigated using high-throughput sequencing technology. The results showed that the physicochemical characters changed by anthropogenic activities were the important factors that influenced enzyme activities, alpha diversity, key functional taxa, and community structure. And the impact of anthropogenic activities on microbial communities might follow a non-linear pattern. Furthermore, few significant differences of alpha indices between the high and low disturbed areas, but clear differences of microbial community composition analysis and beta-diversity analysis were observed. The hypothesis was proved that the intensity of anthropogenic impacts in Caohai had not reached the potential thresholds. The best distinguish biomarkers between the two areas and the most related key nodes among the network did not always have a high microbial abundance. The anthropogenic activities might influence the microbial community by affecting a small number of the key taxon in the ecological network. These findings provided a valuable understanding of how sediment microorganisms respond to anthropogenic activities in Caohai Lake.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111936DOI Listing
March 2021

Pharmacological and genetic perturbation establish SIRT5 as a promising target in breast cancer.

Oncogene 2021 Jan 21. Epub 2021 Jan 21.

Department of Biomedical Sciences, Cornell University, Ithaca, NY, 14853, USA.

SIRT5 is a member of the sirtuin family of NAD-dependent protein lysine deacylases implicated in a variety of physiological processes. SIRT5 removes negatively charged malonyl, succinyl, and glutaryl groups from lysine residues and thereby regulates multiple enzymes involved in cellular metabolism and other biological processes. SIRT5 is overexpressed in human breast cancers and other malignancies, but little is known about the therapeutic potential of SIRT5 inhibition for treating cancer. Here we report that genetic SIRT5 disruption in breast cancer cell lines and mouse models caused increased succinylation of IDH2 and other metabolic enzymes, increased oxidative stress, and impaired transformation and tumorigenesis. We, therefore, developed potent, selective, and cell-permeable small-molecule SIRT5 inhibitors. SIRT5 inhibition suppressed the transformed properties of cultured breast cancer cells and significantly reduced mammary tumor growth in vivo, in both genetically engineered and xenotransplant mouse models. Considering that Sirt5 knockout mice are generally normal, with only mild phenotypes observed, these data establish SIRT5 as a promising target for treating breast cancer. The new SIRT5 inhibitors provide useful probes for future investigations of SIRT5 and an avenue for targeting SIRT5 as a therapeutic strategy.
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http://dx.doi.org/10.1038/s41388-020-01637-wDOI Listing
January 2021

Effects of Bisphosphonates on Osteoporosis Induced by Duchenne Muscular Dystrophy: A Prospective Study.

Endocr Pract 2020 Dec;26(12):1477-1485

From the (1)Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, and the. Electronic address:

Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD.

Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated.

Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group (P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline).

Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol.

Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid.
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http://dx.doi.org/10.4158/EP-2020-0073DOI Listing
December 2020

Koopman analysis in oscillator synchronization.

Authors:
Jing Hu Yueheng Lan

Phys Rev E 2020 Dec;102(6-1):062216

School of Science, Beijing University of Posts and Telecommunications, Beijing 100876, China.

Synchronization is an important dynamical phenomenon in coupled nonlinear systems, which has been studied extensively in recent years. However, analysis focused on individual orbits seems hard to extend to complex systems, while a global statistical approach is overly cursory. Koopman operator technique seems to balance well the two approaches. In this paper we extend Koopman analysis to the study of synchronization of coupled oscillators by extracting important eigenvalues and eigenfunctions from the observed time series. A renormalization group analysis is designed to derive an analytic approximation of the eigenfunction in the case of weak coupling that dominates the oscillation. For moderate or strong couplings, numerical computation further confirms the importance of the average frequencies and the associated eigenfunctions. The synchronization transition points could be located with quite high accuracy by checking the correlation of neighboring eigenfunctions at different coupling strengths, which is readily applied to other nonlinear systems.
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http://dx.doi.org/10.1103/PhysRevE.102.062216DOI Listing
December 2020

Assessing the Relationship Between Monoallelic PRKN Mutations and Parkinson's Risk.

Hum Mol Genet 2021 Jan 15. Epub 2021 Jan 15.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK and UCL Movement Disorders Centre, UCL Queen Square Institute of Neurology.

Biallelic PRKN (Parkin) mutations cause autosomal recessive Parkinson's (PD); however, the role of monoallelic PRKN mutations as a risk factor for PD remains unclear. We investigated the role of single heterozygous PRKN mutations in three large independent case-control cohorts totalling 10 858 PD cases and 8328 controls. Overall, after exclusion of biallelic carriers, single PRKN mutations were more common in PD than controls conferring a > 1.5-fold increase in risk of PD (P = 0.035), with meta-analysis (19 574 PD cases and 468 488 controls) confirming increased risk (OR = 1.65, P = 3.69E-07). Carriers were shown to have significantly younger ages at onset compared to non-carriers (NeuroX: 56.4 vs. 61.4 years; Exome: 38.5 vs. 43.1 years). Stratifying by mutation type, we provide preliminary evidence for a more pathogenic risk profile for single PRKN copy number variant (CNV) carriers compared to single nucleotide variant carriers. Studies that did not assess biallelic PRKN mutations or consist of predominantly early-onset cases may be biasing these estimates, and removal of these resulted in a loss of association (OR = 1.23, P = 0.614; n = 4). Importantly, when we looked for additional CNVs in 30% of PD cases with apparent monoallellic PRKN mutations we found that 44% had biallelic mutations suggesting that previous estimates may be influenced by cryptic biallelic mutation status. While this study supports the association of single PRKN mutations with PD, it highlights confounding effects therefore caution is needed when interpreting current risk estimates. Together, we demonstrate that comprehensive assessment of biallelic mutation status is essential when elucidating PD risk associated with monoallelic PRKN mutations.
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http://dx.doi.org/10.1093/hmg/ddaa273DOI Listing
January 2021

Phosphorus sorption - Desorption behaviors in the sediments cultured with Hydrilla verticillata and Scripus triqueter as revealed by phosphorus fraction and dissolved organic matter.

Chemosphere 2021 Jan 4;271:129549. Epub 2021 Jan 4.

College of Resource and Environmental Engineering, Guizhou University, Guiyang, 550003, PR China; Guizhou Academy of Sciences, Guiyang, 550001, PR China; School of Environment and Energy, South China University of Technology, Guangzhou, 510006, PR China. Electronic address:

The migration of sediment phosphorus (P) could be affected by the existence of aquatic plants. To explore the effects of aquatic plants on the P sorption-desorption behaviors in the sediments, sediment in Caohai wetland was collected and cultured with the submerged plant (Hydrilla verticillata) and emerged plant (Scripus triqueter). Then the sorption and desorption experiments were performed, and physicochemical properties, P fractions, and dissolved organic matter (DOM) characteristics were evaluated. Results showed that the treated sediments exhibited similar P sorption kinetic process fitted well with the two-compartment first-order model. Nevertheless, H. verticillata cultured sediment could be well described by the modified Langmuir isotherm model, while S. triqueter cultured sediment fitted the modified Freundlich equations well. The obvious changing P fractions in cultured sediments were BD-P and NaOH-SRP during sorption. H. verticillata and S. triqueter displayed different sorption-desorption behaviors by altering BD-P, humification index, fluorescence intensity, and PARAFAC component contents in sediments. Compared to raw sediment, H. verticillata presented higher P sorption and lower P release from sediments by decreasing BD-P and increasing DOM (fulvic acid-like and humic-like components) content, while S. triqueter showed adverse P sorption and release effects by reducing DOM components. The growth of submerged plants was suggested to make a positive influence on the high efficiency of P retention capacity and low release risk.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129549DOI Listing
January 2021