Publications by authors named "Yu Jia"

807 Publications

Multimetal lanthanide phosphonocarboxylate frameworks: structures, colour tuning and near-infrared emission.

Dalton Trans 2021 May 7. Epub 2021 May 7.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200438, China.

A series of isostructural lanthanide phosphonocarboxylate frameworks {(H3O)3[Ln7(pbpdc)6(DMF)4(H2O)3]·4H2O}n (named LnPCF, Ln = Tb, Eu and Gd, H4pbpdc = 4'-phosphono-[1,1'-biphenyl]-3,5-dicarboxylic acid) were solvothermally synthesized and characterized by the single crystal X-ray diffraction technique. By combining lanthanide cations with a phosphonocarboxylate ligand, a heptametallic lanthanide phosphonate [Ln7(PO3)6(COO)12] core was obtained. This core exhibited as a rare highly 18-connected node and was linked by the 3-connected pbpdc4- ligand, forming a (3,18)-connected framework with a novel topology of {43}6{438·676·839}. This LnPCF structure is an ideal platform for accommodating various lanthanide ions. The TbPCF and EuPCF show efficient luminescence emission due to the "antenna effect" and incorporating Gd3+ into the TbPCF results in a drastic luminescence enhancement. Fine colour tuning between green and red can be easily achieved in bimetallic TbxGd1-xPCFs. More significantly, upon combining a few percent of Nd3+ and Gd3+ with Tb3+, the resulting trimetallic Tb0.4Gd0.5Nd0.1PCF shows dual emissions of both visible and near-infrared light.
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http://dx.doi.org/10.1039/d1dt01052bDOI Listing
May 2021

Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer.

Nat Commun 2021 05 5;12(1):2540. Epub 2021 May 5.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.
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http://dx.doi.org/10.1038/s41467-021-22801-0DOI Listing
May 2021

Perfluoroalkyl substances in drinking water sources along the Yangtze River in Jiangsu Province, China: Human health and ecological risk assessment.

Ecotoxicol Environ Saf 2021 Apr 30;218:112289. Epub 2021 Apr 30.

Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing 210042, China; Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Ecology and Environment, Nanjing 210042, China. Electronic address:

Perfluoroalkyl substances (PFASs) in source water is of growing concern for its adverse effects on human health and wildlife as well. The Yangtze River is the vital drinking water source in Jiangsu Province of China, but little attention has been paid on PFASs. The occurrence, spatial distribution and temporal trend of PFASs in 21 water sources along the Jiangsu section of the Yangtze River was investigated with sampling from 2018 to 2020. Moreover, health risk of PFASs was assessed by estimated intake dose and derived tolerable intake dose, while ecological risk was assessed by selected effect concentration and environmental exposure. PFASs concentrations in source water ranged from 12.0 to 128 ng/L, with perfluorooctanoic acid (PFOA) as the dominated congener. Fluorine chemical industry lead to a great increase of perfluorohexanoic acid (PFHxA) in its nearest water source. The estimated daily intake of PFASs through drinking was 0.54 and 0.82 ng/kg bw/day for adults and children. The major health risk was from perfluorooctane sulfonate (PFOS) and PFOA for their toxicity on liver, reproduction, development and immunity, with the maximum hazard quotient of 0.029 and 0.043 for adults and children in the worst scenario. The ecological risks from PFASs on nine species groups ranged from 2.7 × 10 to 5.2. PFOA and Perfluorobutane sulfonate (PFBS) were causing significant risk on wildlife, particularly on worms, mussels, and fish, which may further influence the structure and processes in the foodweb. Overall, PFASs, especially PFOS, PFOA and PFBS, induced considerable risk on human health and aquatic species in some hotspot area. It would be necessary to include them into monitoring in China and develop standards for different protection purposes.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112289DOI Listing
April 2021

Associations between low-density lipoprotein cholesterol and haemorrhagic stroke.

J Geriatr Cardiol 2021 Mar;18(3):204-209

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: To investigate the associations between the blood concentrations of low-density lipoprotein cholesterol (LDL-C) and the clinical features of haemorrhagic stroke.

Methods: This study analysed the data from patients with acute haemorrhagic stroke at a comprehensive stroke centre from 2013 to 2018. Patients were stratified into three groups according to their baseline LDL-C levels: < 70, 70 to < 100 and ≥ 100 mg/dL. We used multivariate logistic regression models to analyse the associations between LDL-C and the risks of having severe neurological deficits (National Institute Health Stroke Scale [NIHSS] scores ≥ 15) and unfavourable outcomes (modified Rankin Scale [mRS] scores>2) at discharge.

Results: Six-hundred and six patients were analysed. Their median age was 58 years. Among the patients, 75 (12%) patients had LDL-C levels < 70 mg/dL, 194 (32%) patients had LDL-C levels between 70 to < 100 mg/dL and the other 337 (56%) patients had LDL-C levels ≥ 100 mg/dL. Patients with higher LDL-C levels were less likely to suffer severe neurological deficits (LDL-C: 70 to < 100 . < 70 mg/dL, adjusted odds ratio [OR]: 0.29, 95% CI: 0.15-0.57; LDL-C: ≥ 100 . < 70 mg/dL, adjusted OR = 0.27, 95% CI: 0.15-0.51) and to have unfavourable outcomes at discharge (LDL-C: 70 to < 100 . < 70 mg/dL, adjusted OR = 0.50, 95% CI: 0.29-0.87 and LDL-C: ≥ 100 . < 70 mg/dL, adjusted OR = 0.46, 95% CI: 0.28-0.78).

Conclusions: An LDL-C level < 70 mg/dL was independently associated with severe neurological deficits of haemorrhagic stroke and may increase the risks of unfavourable outcomes at discharge.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047185PMC
March 2021

Chiral separation and molecular simulation study of six antihistamine agents on a coated cellulose tri-(3,5-dimethylphenycarbamate) column (Chiralcel OD-RH) and its recognition mechanisms.

Electrophoresis 2021 Apr 27. Epub 2021 Apr 27.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, P. R. China.

Enantiomeric separation of six antihistamine agents was first systematically investigated on a cellulose-based chiral stationary phase (CSP), that is, cellulose tris-(3,5-dimethyl phenyl carbamate) (Chiralcel OD-RH), under the reversed-phase mode. Orphenadrine, meclizine, terfenadine, dioxopromethazine, and carbinoxamine enantiomers were completely separated under the optimized mobile phase conditions with resolutions of 5.02, 1.93, 1.68, 1.67, and 1.54, respectively. Mequitazine was partially separated with a resolution of 0.77. The influences of type and concentration of buffer salt, the pH of buffer solution, and the type and ratio of organic modifier on the chiral separation were evaluated and optimized. For a better insight into the enantiorecognition mechanisms, molecular docking was carried out via the Autodock software. The lowest binding energy and the optimal conformations of the analytes/CSP complexes were supplied, and the mechanisms of chiral recognition were determined. According to the results, the key interactions for the chiral recognition of these six analytes on CDMPC were π-π interactions, hydrophobic interactions, hydrogen bond interactions, and some special interactions.
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http://dx.doi.org/10.1002/elps.202100033DOI Listing
April 2021

The Peculiar Clinical Symptoms and Treatment of Limbic Encephalitis Associated with AMPA Receptor Antibody.

Eur Neurol 2021 Apr 15:1-6. Epub 2021 Apr 15.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibody-related diseases are very rare in autoimmune neurological diseases. We collected and analyzed the data of 3 patients with peculiar clinical manifestation positive for AMPA2-R antibody in the Department of Neurology, Xuanwu Hospital, Capital Medical University. In our reported case series, 2 patients were male and 1 was female. The initial clinical features of 3 patients were all consistent with an encephalopathy predominantly involving the limbic system. Interestingly, as the disease continues to advance, case 1 presented with limb paralysis, case 2 developed typical cerebellar ataxia, and case 3 had symptoms of autonomic instability. These 3 types of clinical features were very rare in patients with AMPAR-Ab. After immunotherapy, cases 1 and 3 responded well and case 2 was not responsive. During the follow-up, residual memory loss of cases 1 and 3 improved gradually, and they returned to work. To eliminate the influence of the presence of other pathogenic antibodies, we analyzed the available individual clinical information of 37 patients with the single AMPAR-Ab by systematic literature review. A majority of patients had sudden short-term memory loss as the initial symptom and developed limbic encephalitis. Residual memory deficit was the most common symptom after discharge. The combination of at least 2 types of immunotherapy was recommended as the first-line treatment, and patients would benefit from the tumor screening. In addition, compared with the patients positive for single AMPAR-Ab, the patients with both AMPAR-Ab and other antibodies had a higher risk of malignant tumor and might have a poor therapeutic response, which led to a poor prognosis.
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http://dx.doi.org/10.1159/000515592DOI Listing
April 2021

Early risk stratification of acute myocardial infarction using a simple physiological prognostic scoring system: insights from the REACP study.

Eur J Cardiovasc Nurs 2021 Apr;20(2):167-174

Department of Cardiology, West China Hospital, Sichuan University, China.

Background: A more accurate and simpler scoring systems for early risk stratification of acute myocardial infarction at admission can accelerate and improve decision-making.

Aim: To develop and validate a simple physiological prognostic scoring system for early risk stratification in patients with acute myocardial infarction.

Methods: Easily accessible physiological vital signs and demographic characteristics of patients with acute myocardial infarction at the time of presentation in the multicentre Retrospective Evaluation of Acute Chest Pain study were used to develop a multivariate logistic regression model predicting 12 and 24-month mortality. The study population consisted of 2619 patients from seven hospitals and was divided into a 70% sample for model derivation and a 30% sample for model validation. A nomogram was created to enable prospective risk stratification for clinical care.

Results: The simple physiological prognostic scoring system consisted of age, heart rate, body mass index and Killip class. The area under the receiver operating characteristic curve of the simple physiological prognostic scoring system was superior to that of several risk scoring systems in clinical use. Net reclassification improvement, integrated discrimination improvement and decision curve analysis of the derivation set also revealed superior performance to the Global Registry of Acute Coronary Events score, and the Hosmer-Lemeshow test indicated good calibration for predicting mortality in patient with acute myocardial infarction in the validation set (P = 0.612).

Conclusion: This simple physiological prognostic scoring system may be a useful risk stratification tool for early assessment of patients with acute myocardial infarction.
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http://dx.doi.org/10.1177/1474515120952214DOI Listing
April 2021

The role of spontaneous portal-systemic shunts in liver transplantation: case report and literature review.

Ann Palliat Med 2021 Mar 24. Epub 2021 Mar 24.

Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.

We described two liver transplants for patients with end-stage liver disease and spontaneous portal-systemic shunt (SPSS). We ligated the splenorenal shunt (SRS) in the first case but did not ligate it in the second case. Postoperative examination revealed significant differences in portal blood flow velocity, serum ammonia level, liver function and prognosis between two cases. The portal blood flow in the first case was sufficient with decreased serum ammonia and immediate liver graft function. The portal blood flow was insufficient and serum ammonia level was not significantly reduced after operation in the second case probably because SRS was still present after surgery. The first case recovered well after operation and was discharged uneventfully, however, the second patient suffered early allograft dysfunction (EAD) after operation and died of pulmonary infection on postoperative day (POD) 18. Proper management of SPSS in liver transplantation (LT) is important because it can affect the function of liver graft and patient prognosis, so we reviewed the relevant literature and list different types of SPSS and their clinical characteristics. We recommend that SPSS greater than 8 mm in diameter should be ligated in LT with non-small size graft to ensure adequate portal flow and preserved with small size liver graft to avoid portal hypertransfusion and portal hypertension except obviously insufficient portal blood flow.
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http://dx.doi.org/10.21037/apm-20-2431DOI Listing
March 2021

LncRNA SNHG4 sponges miR-200b to inhibit cell apoptosis in diabetic retinopathy.

Arch Physiol Biochem 2021 Apr 6:1-6. Epub 2021 Apr 6.

Department of Ophthalmology, The First Affiliated Hospital of Bengbu Medical College, Bengbu City, People's Republic of China.

This study aimed to investigate the role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 4 (SNHG4) in diabetic retinopathy (DR). We found that SNHG4 was downregulated in DR. SNHG4 could directly interact with miR-200b, while overexpression of miR-200b did not affect the expression of SNHG4 in human retinal pigment epithelial cells ARPE-19. In contrast, overexpression of SNHG4 led to the upregulation of oxidation resistance 1 (Oxr1), a target of miR-200b. Cell apoptosis analysis showed that overexpression of miR-200b increased the apoptotic rate of ARPE-19 cells under high glucose treatment. Oxr1 and SNHG4 played opposite roles and reduced the effects of overexpression of miR-200b. In conclusion, SNHG4 may sponge miR-200b to inhibit cell apoptosis in DR by upregulating Oxr1.
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http://dx.doi.org/10.1080/13813455.2021.1900873DOI Listing
April 2021

An Antifungal Chitosanase from SH21.

Molecules 2021 Mar 25;26(7). Epub 2021 Mar 25.

Key Laboratory of Agricultural Product Detection and Control of Spoilage Organisms and Pesticides, Beijing Laboratory for Food Quality and Safety, Beijing Engineering Laboratory of Probiotics Key Technology Development, Beijing Engineering Technology Research Center of Food Safety Immune Rapid Detection, Food Science and Engineering College, Beijing University of Agriculture, Beijing 102206, China.

SH21 was observed to produce an antifungal protein that inhibited the growth of . To purify this protein, ammonium sulfate precipitation, gel filtration chromatography, and ion-exchange chromatography were used. The purity of the purified product was 91.33% according to high-performance liquid chromatography results. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed that the molecular weight of the protein is 30.72 kDa. The results of the LC-MS/MS analysis and a subsequent sequence-database search indicated that this protein was a chitosanase, and thus, we named it chitosanase SH21. Scanning and transmission electron microscopy revealed that chitosanase SH21 appeared to inhibit the growth of by causing hyphal ablation, distortion, or abnormalities, and cell-wall depression. The minimum inhibitory concentration of chitosanase SH21 against was 68 µg/mL. Subsequently, the corresponding gene was cloned and sequenced, and sequence analysis indicated an open reading frame of 831 bp. The predicted secondary structure indicated that chitosanase SH21 has a typical a-helix from the glycoside hydrolase (GH) 46 family. The tertiary structure shared 40% similarity with that of N174. This study provides a theoretical basis for a topical cream against fungal infections in agriculture and a selection marker on fungi.
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http://dx.doi.org/10.3390/molecules26071863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036696PMC
March 2021

Mechanism of Resveratrol Dimers Isolated from Grape Inhibiting O Induced DNA Damage by UHPLC-QTOF-MS and UHPLC-QQQ-MS Analyses.

Biomedicines 2021 Mar 8;9(3). Epub 2021 Mar 8.

Xi'an Key Laboratory of Characteristic Fruit Storage and Preservation, Shaanxi Engineering Laboratory for Food Green Processing and Safety Control and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.

Resveratrol dimers have been extensively reported on due to their antioxidative activity. Previous studies revealed that resveratrol dimer has been shown to selectively quench singlet oxygen (O), and could protect DNA from oxidative damage. The mechanism of resveratrol dimers protecting DNA against oxidative damage is still not clear. Therefore, in this project, the reactants and products of resveratrol dimers protecting guanine from oxidative damage were qualitatively monitored and quantitatively analyzed by UHPLC-QTOF-MS and UHPLC-QQQ-MS. Results showed that when guanine and resveratrol dimers were attacked by O, mostly resveratrol dimers were oxidized, which protected guanine from oxidation. Resveratrol dimers' oxidation products were identified and quantified at 467.1134 [M-H] and 467.1118 [M-H], respectively. The resorcinol of resveratrol dimers reacted with singlet oxygen to produce p-benzoquinone, protecting guanine from O damage. Therefore, it is hereby reported for the first time that the resorcinol ring is the characteristic structure in stilbenes inhibiting O induced-DNA damage, which provides a theoretical basis for preventing and treating DNA damage-mediated diseases.
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http://dx.doi.org/10.3390/biomedicines9030271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999633PMC
March 2021

Asymptomatic Hyperuricemia and Metabolically Unhealthy Obesity: A Cross-Sectional Analysis in the Tianning Cohort.

Diabetes Metab Syndr Obes 2021 25;14:1367-1374. Epub 2021 Mar 25.

Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People's Republic of China.

Objective: The relationship between obesity and hyperuricemia has been demonstrated by many studies. However, whether or to what extent metabolic condition influents the association between obesity and hyperuricemia was not clear. Here, we aimed to examine the association between obese-metabolic phenotype and hyperuricemia in a large sample of Chinese adults.

Methods: According to BMI and metabolic syndrome, obese-metabolic phenotype was defined as metabolically unhealthy obesity (MUO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO) and metabolically healthy non-obesity (MHNO)in the Tianning cohort (N=5072). We conducted a cross-sectional analysis between obese-metabolic phenotype and hyperuricemia, followed by a Mendelian Randomization analysis using GWAS summary data to confirm the causality between uric acid and BMI.

Results: The average level of serum UA showed 41.87-higher μmol/L in participants with MHO (β=41.87, <0.001) and 63.18-higher μmol/L in participants with MUO (β=63.18, <0.001), compared to those with MHNO. Compared to participants with MHNO, those with MUO had the highest likelihood to have hyperuricemia (OR=4.56, <0.001), followed by those with MHO (OR=3.32, <0.001). Mendelian randomization analysis indicated that uric acid was more likely to be a consequence of BMI (β=0.059, =6.54×10).

Conclusion: MUO, in comparison with MHO, was significantly associated with hyperuricemia in Chinese adults.
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http://dx.doi.org/10.2147/DMSO.S301363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006809PMC
March 2021

Patients With Short PFS to EGFR-TKIs Predicted Better Response to Subsequent Anti-PD-1/PD-L1 Based Immunotherapy in EGFR Common Mutation NSCLC.

Front Oncol 2021 11;11:639947. Epub 2021 Mar 11.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Background: Despite disappointing outcomes from immuno-monotherapy, studies reported that NSCLC patients with EGFR mutation may possibly benefit from combined immunotherapy. Whether the response to prior EGFR-TKI has association with the outcomes of subsequent immunotherapy remains unclear.

Patients And Methods: Advanced NSCLC patients with resistance to EGFR-TKIs and received ICI treatment from January 2016 to June 2019 were retrospectively analyzed. Single cell sequencing and flow cytometry were conducted to explore the difference of cell components in tumor microenvironments (TME). A 1:3 matched case-control study was conducted to compare the clinical effects of combined immunotherapy with standard chemotherapy as second-line treatment.

Results: Fifty-eight patients treated with anti-PD-1/PD-L1 based immunotherapy behind EGFR-TKI treatment were enrolled. Correlation analysis showed TKI-PFS had a significantly negative association with corresponding IO-PFS (r = -0.35, p = 0.006). TKI-PFS cutoff 10 months had the most significant predictive function for posterior immunotherapy and was validated to be an independent predictor by uni- and multivariate analyses. Kaplan-Meier analysis showed that patients with TKI-PFS less than 10 months had significantly prolonged IO-PFS and higher ORR than those with long (median PFS, 15.1 3.8 months; HR, 0.26, p = 0.0002; ORR, 31.8 10%, p = 0.04). Single cell RNA-seq revealed that the cell components were varied among patients after treatment with EGFR-TKI. Patients with short TKI-PFS demonstrated a relatively higher proportion of CD8 effector cells and lower ratio of M2 like macrophage to M1 like macrophages, which was validated by flow cytometry. Case-control study demonstrated that combined immunotherapy achieved significantly longer PFS (HR, 0.51, 95% CI: 0.31-0.85, p = 0.02), longer OS (HR, 0.48, 95% CI: 0.26-0.89, p = 0.05) and higher ORR (33.3 10.0%, p = 0.02) than traditional chemotherapy for patients with short TKI-PFS.

Conclusion: Patients with short TKI-PFS conferred better response to immunotherapy than those with long. The status of TME were different among those two populations. Combined ICI treatment could promisingly be a better choice than classical chemotherapy in second-line setting for patients with short TKI-PFS and no T790M mutation. Underlying mechanisms need to be further explored.
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http://dx.doi.org/10.3389/fonc.2021.639947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991800PMC
March 2021

Single-Cell Sequencing, an Advanced Technology in Lung Cancer Research.

Onco Targets Ther 2021 16;14:1895-1909. Epub 2021 Mar 16.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China.

Single-cell sequencing (SCS) which has an unprecedentedly high resolution is an advanced technique for cancer research. Lung cancer still has a high mortality and morbidity. For further understanding the lung cancer, SCS is also been applied to lung cancer research to investigate its heterogeneity, metastasis, drug resistance, tumor microenvironment and many other issues. In this review, we summarized lung cancer research using SCS and their research achievements.
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http://dx.doi.org/10.2147/OTT.S295102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981160PMC
March 2021

Prevalence of congenital microcephaly and its risk factors in an area at risk of Zika outbreaks.

BMC Pregnancy Childbirth 2021 Mar 17;21(1):214. Epub 2021 Mar 17.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.

Background: Prevalence of neonatal microcephaly in populations without Zika-epidemics is sparse. The study aimed to report baseline prevalence of congenital microcephaly and its relationship with prenatal factors in an area at risk of Zika outbreak.

Methods: This study included singletons born after 24 gestational weeks in 2017-2018 at four hospitals in Guangzhou, China. Microcephaly was defined as a head circumference at birth >3SD below the mean for sex and gestational age. Prevalence of microcephaly was estimated by binomial exact method. Multivariable logistic regression was used to examine the associations of microcephaly with prenatal factors. The population attributable fraction (PAF) for associated risk factors was calculated.

Results: Of 46,610 live births included, 154 (3.3, 95% CI 2.8-3.9 per 1000 live births) microcephalies were identified. Maternal hepatitis B virus carriers (HBV, OR 1.80, 95% CI 1.05-3.10) and primipara (OR 2.68, 95% CI 1.89-3.81) had higher risk of having a microcephalic baby. Higher prevalence of microcephaly was observed in women who had premature labor (OR 1.98, 95% CI 1.17-3.34) and had a baby with fetal growth restriction (OR 16.38, 95% CI 11.81-22.71). Four identified factors (HBV, primiparity, preterm labor, and fetal growth restriction) contributed to 66.4% of the risk of microcephaly.

Conclusions: The prevalence of microcephaly in Guangzhou was higher than expected. This study identified four prenatal risk factors that, together, contributed to two-thirds of the increased risk of microcephaly. This is the first reported association between maternal HBV carrier status and microcephaly.
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http://dx.doi.org/10.1186/s12884-021-03705-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972338PMC
March 2021

Bloom helicase explicitly unwinds 3'-tailed G4DNA structure in prostate cancer cells.

Int J Biol Macromol 2021 Mar 13;180:578-589. Epub 2021 Mar 13.

State Key Laboratory of Functions And Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Science, Guiyang 550014, PR China; Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang 550025, PR China. Electronic address:

G-quadruplex DNA (G4DNA) structure, which widely exists in the chromosomal telomeric regions and oncogenic promoter regions, plays a pivotal role in extending telomeric DNA with the help of telomerase in human cells. Bloom (BLM) helicase, a crucial member of the family of genome surveillance proteins, plays an essential role in DNA metabolic and repair pathways, including DNA replication, repair, transcription, recombination during chromosome segregation, and assuring telomere stability. The unwinding of G4DNA requires the participation of DNA helicase, which is crucial for maintaining chromosomal stability in cancer cells. Using fluorescence polarization and the electrophoretic mobility shift assay (EMSA), this study aimed to investigate the DNA-binding and unwinding properties of BLM helicase, cloned and purified from prostate cancer cells, toward G4DNA. The results revealed that BLM helicase derived from prostate cancer cells could bind and unwind G4DNA. The molecular affinity of bond between G4DNA and the helicase was dependent on the single-stranded DNA (ssDNA) terminals in G4DNA; the helicase was effectively bound to the G4DNA when the helicase monomer sufficiently covered approximately 10 nucleotides at the 3' or 5' ssDNA tail of G4DNA. For the unwinding of G4DNA, there was an apparent requirement of a 3' ssDNA tail and ATP; a G4DNA with only a 3' ssDNA tail was identified to be the most suitable substrate to be unwound by BLM helicase and required 3' ssDNA tails of at least 10 nt in length for efficient unwinding. Besides, BLM helicase was loosely bound and partly unwound the blunt-ended G4DNA. Although further mechanistic studies are warranted, the experimental results presented in this study are beneficial to further our understanding of the functional implication of BLM helicase in prostate cancer cells.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.060DOI Listing
March 2021

Stacking-Engineered Heterostructures in Transition Metal Dichalcogenides.

Adv Mater 2021 Apr 14;33(16):e2005735. Epub 2021 Mar 14.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (Nanjing Tech), 30 South Puzhu Road, Nanjing, 211800, China.

The layer-by-layer assembly of 2D transition metal dichalcogenide monolayer blocks to form a 3D stack, with a precisely chosen sequence/angle, is the newest development for these materials. In this way, one can create "van der Waals heterostructures (HSs)," opening up a new realm of materials engineering and novel devices with designed functionalities. Herein, a detailed systematic review of transition metal dichalcogenide stacking-engineered heterostructures, from controllable fabrication to typical characterization, and stacking-correlated physical behaviors is presented. Furthermore, recent advances in stacking design, such as stacking sequence, twist angles, and moiré superlattice heterojunctions, are also comprehensively summarized. Finally, the remaining challenges and possible strategies for using stacking engineering to tune the properties of 2D materials are also outlined.
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http://dx.doi.org/10.1002/adma.202005735DOI Listing
April 2021

Curative efficacy might be an early predictor of prognosis in patients with small cell lung cancer treated with 2 cycles of platinum-based first-line chemotherapy.

J Thorac Dis 2021 Feb;13(2):1205-1214

Department of Hematology, Xiangtan Central Hospital, Xiangtan, China.

Background: Platinum-based chemotherapy remains the essential therapy for small cell lung cancer (SCLC). Here, we conducted a statistical analysis to explore whether the curative efficacy of 2-cycle platinum-based chemotherapy can predict the survival of patients with SCLC.

Methods: Fifty-six SCLC patients who had each received 2 cycles of platinum-based chemotherapy were enrolled. The curative efficacy of the chemotherapy was evaluated, mainly by chest computed tomography, and the treatment response was categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients were continuously followed up for progression-free survival (PFS) and overall survival. The 55 patients were separated into 2 groups by the curative efficacy of the 2-cycle first-line platinum-based chemotherapy. All statistical analyses were performed with SPSS software (version 17.0; SPSS, Inc.; Chicago, IL, USA).

Results: Patients who responded to 2-cycle chemotherapy (partial response, PR) had significantly better survival than others who did not (stable disease, SD or progressive disease, PD). The median progression-free survival (mPFS) in the PR group was 6.330 months, which was significantly longer than the 2.870 months seen in SD+PD group (95% CI: 4.631-8.029 0.000-5.790, P=0.022). The median overall survival (mOS) was 10.870 months in the PR group, which was remarkably longer than the 8.970 months observed in the SD+PD group (95% CI: 9.546-12.194 6.517-11.423, P=0.028). Curative efficacy had no correlation with clinical features.

Conclusions: The curative efficacy of 2-cycle first-line platinum-based chemotherapy was significantly correlated with PFS and OS, and showed prognostic value in SCLC patients. Patients who were sensitive to chemotherapy had superior survival to those who were chemotherapy insensitive.
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http://dx.doi.org/10.21037/jtd-21-216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947513PMC
February 2021

Protective effects of berberine in a rat model of polycystic ovary syndrome mediated via the PI3K/AKT pathway.

J Obstet Gynaecol Res 2021 May 11;47(5):1789-1803. Epub 2021 Mar 11.

Department of Reproductive Medicine, Zhejiang Provincial Integrated Chinese and Western Medicine Hospital, HangZhou City, China.

Background: Ber, a Chinese herbal monomer has been reported to exhibit an array of pharmacological activities related to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). In the present study, we aimed to elucidate the effect of berberine (Ber) on a rat model of PCOS mediated via the PI3K/AKT signaling pathway.

Methods: A PCOS animal model was induced with the administration of letrozole, and animals were then randomized into untreated or Ber and metformin hydrochloride treated groups. After administration, fasting blood glucose, HOMA-IR, fasting insulin (FINS) values, and the serum hormone levels were measured in PCOS rats. The ovarian tissues were stained with hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) for pathological and apoptosis examination. Moreover, the effect of Ber on the proliferation and apoptosis of granulosa cells was detected by CCK-8 assays and flow cytometry. The influence of Ber on granulosa cells was confirmed by blockade of the PI3K/AKT pathway. In addition, the modulatory effect of the blockade of the PI3K/AKT pathway on the expression of related proteins was demonstrated via western blotting.

Results: We found that Ber was able to restore the serum hormone levels and improve IR in a PCOS rat model. The morphological lesions and apoptosis of the ovary were also restored by the Ber treatment. Blockade of the PI3K/AKT pathway attenuated the influences of Ber on the proliferation and apoptosis of granulosa cells.

Conclusion: The beneficial effects of Ber on PCOS included alterations of the serum hormone levels, recovery of morphological lesions in the ovary, improvement of insulin resistance, and cell viability and inhibition of apoptosis, which were all mediated through the PI3K/AKT pathway.
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http://dx.doi.org/10.1111/jog.14730DOI Listing
May 2021

Identification and analysis of olfactory genes in Dioryctria abietella based on the antennal transcriptome.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Feb 15;38:100814. Epub 2021 Feb 15.

Key Laboratory for Sustainable Forest Ecosysttem Management of Ministry of Education, College of Forestry, Northeast Forestry University, Harbin 150040, Heilongjiang, People's Republic of China. Electronic address:

The coneworm Dioryctria abietella (Lepidoptera: Pyralidae) is an economy devastating pest that infests many valuable conifer species in the Holarctic regions, such as Pinus koraiensis Siebold and Zucc. The chemosensory system plays a crucial role in the mating, foraging, and ovipositing of this pest, and therefore it is desirable to identify chemosensory molecules for pest control. However, little is known at molecular level about the olfactory mechanisms in D. abietella. In the present study, we first established antennal transcriptomes of D. abietella and identified 132 putative chemosensory genes, including 15 odorant-binding proteins, 18 chemosensory proteins, 65 odorant receptors, 5 sensory neuron membrane proteins, 24 ionotropic receptors, and 5 gustatory receptors. In addition, phylogenetic trees were constructed for chemosensory genes to investigate the orthologs between D. abietella and other species of insects. Furthermore, we also compared the patterns of motifs between OBPs and CSPs using MEME. Additionally, we observed that most of DabiOBPs and DabiCSPs had the antenna-biased expression by quantitative real-time PCR (RT-qPCR), and there was a higher expression of DabiPBP1 and DabiPBP2 in male antennae than in female antennae. The binding sites of DabiPBPs (DabiPBP1, DabiPBP2) and DabiPRs (DabiOR19, DabiOR31) to the sex pheromone were predicted well by three-dimensional docking structure modelling and molecular docking. Our finding supplied a foundation for further research on the binding process of OBPs or CSPs and sensing process of ORs, SNMPs, IRs or GRs in D. abietella.
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http://dx.doi.org/10.1016/j.cbd.2021.100814DOI Listing
February 2021

Biological Behavior and Lipid Metabolism of Colon Cancer Cells are Regulated by a Combination of Sterol Regulatory Element-Binding Protein 1 and ATP Citrate Lyase.

Onco Targets Ther 2021 1;14:1531-1542. Epub 2021 Mar 1.

Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.

Purpose: To research the effects of ATP citrate lyase (ACLY) and Sterol-regulatory element binding protein 1 (SREBP1) on the biology and lipid metabolism of colorectal cancer cells.

Methods: Colorectal cancer cells Caco-2 and Lovo were transfected with or gene knockdown lentiviruses. Four groups were set: knockdown, knockdown group, empty vector-transfected (negative control), and untreated cells (blank control). Cell proliferation was measured using CCK-8, colony formation, and EdU labeling assays. Apoptosis was detected using Annexin V-APC/7- AAD and JC-1 assay. Transwell migration and wound healing assays analyzed cell migration and invasion. A triglyceride test kit and oil red O stain assessed cell lipid production. Key factors related to lipid metabolism were detected.

Results: and promoted cell proliferation at 48 and 120 h, but there was no significant difference in Caco-2 cells at 24 h, at which point the effect of was more important. 's effect on cell proliferation was more obvious at 120 h. Colony formation assays in Caco-2 showed similar results to the CCK-8 assay at 120 h, but knockdown had no effect in Lovo cells. EDU assays showed that or facilitated DNA reproduction in the two cell lines, in which was more significant. Knockdown of the two genes showed significant differences in Lovo cells. However, knockdown promoted apoptosis to a greater extent than knockdown in Caco-2 cells. In addition, and enhanced migration, invasion, and lipid production in both cell lines. Knockdown of or reduced lipid metabolism pathway gene expression in the two cell lines.

Conclusion: Knockdown of and genes inhibit the proliferation, migration, and invasion of colorectal cancer cells, while promoting their apoptosis. Our results identified potential new targets to treat colorectal cancer via lipid synthesis modulation in cancer cells.
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http://dx.doi.org/10.2147/OTT.S282906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935446PMC
March 2021

The Association of Socioeconomic Status with the Burden of Cataract-related Blindness and the Effect of Ultraviolet Radiation Exposure: An Ecological Study.

Biomed Environ Sci 2021 Feb;34(2):101-109

Department of Environmental Health, School of Public Health, China Medical University, Shenyang 110122, Liaoning, China.

Objective: To assess the association of socioeconomic status with the burden of cataract blindness in terms of year lived with disability (YLD) rates and to determine whether ultraviolet radiation (UVR) levels modify the effect of socioeconomic status on this health burden.

Methods: National and subnational age-standardized YLD rates associated with cataract-related blindness were derived from the Global Burden of Disease (GBD) study 2017. The human development index (HDI) from the Human Development Report was used as a measure of socioeconomic status. Estimated ground-level UVR exposure was obtained from the Ozone Monitoring Instrument (OMI) dataset of the National Aeronautics and Space Administration (NASA).

Results: Across 185 countries, socioeconomic status was inversely associated with the burden of cataract blindness. Countries with a very high HDI had an 84% lower age-standardized YLD rate [95% confidence interval ( ): 60%-93%, < 0.001] than countries with a low HDI; for high-HDI countries, the proportion was 76% (95% : 53%-88%, < 0.001), and for medium-HDI countries, the proportion was 48% (95% : 15%-68%, = 0.010; for trend < 0.001). The interaction analysis showed that UVR exposure played an interactive role in the association between socioeconomic status and cataract blindness burden ( value for interaction = 0.047).

Conclusion: Long-term high-UVR exposure amplifies the association of poor socioeconomic status with the burden of cataract-related blindness. The findings emphasize the need for strengthening UVR exposure protection interventions in developing countries with high-UVR exposure.
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http://dx.doi.org/10.3967/bes2021.015DOI Listing
February 2021

Aurora-A kinase oncogenic signaling mediates TGF-β-induced triple-negative breast cancer plasticity and chemoresistance.

Oncogene 2021 Apr 5;40(14):2509-2523. Epub 2021 Mar 5.

Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA.

Triple-negative breast cancer (TNBCs) account for 15-20% of all breast cancers and represent the most aggressive subtype of this malignancy. Early tumor relapse and progression are linked to the enrichment of a sub-fraction of cancer cells, termed breast tumor-initiating cells (BTICs), that undergo epithelial to mesenchymal transition (EMT) and typically exhibit a basal-like CD44/CD24 and/or ALDH1 phenotype with critical cancer stem-like features such as high self-renewal capacity and intrinsic (de novo) resistance to standard of care chemotherapy. One of the major mechanisms responsible for the intrinsic drug resistance of BTICs is their high ALDH1 activity leading to inhibition of chemotherapy-induced apoptosis. In this study, we demonstrated that aurora-A kinase (AURKA) is required to mediate TGF-β-induced expression of the SNAI1 gene, enrichment of ALDH1 BTICs, self-renewal capacity, and chemoresistance in TNBC experimental models. Significantly, the combination of docetaxel (DTX) with dual TGF-β and AURKA pharmacologic targeting impaired tumor relapse and the emergence of distant metastasis. We also showed in unique chemoresistant TNBC cells isolated from patient-derived TNBC brain metastasis that dual TGF-β and AURKA pharmacologic targeting reversed cancer plasticity and enhanced the sensitivity of TNBC cells to DTX-based-chemotherapy. Taken together, these findings reveal for the first time the critical role of AURKA oncogenic signaling in mediating TGF-β-induced TNBC plasticity, chemoresistance, and tumor progression.
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http://dx.doi.org/10.1038/s41388-021-01711-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032554PMC
April 2021

A ΔE = 0.63 V Bifunctional Oxygen Electrocatalyst Enables High-Rate and Long-Cycling Zinc-Air Batteries.

Adv Mater 2021 Apr 3;33(15):e2008606. Epub 2021 Mar 3.

Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology, Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China.

Rechargeable zinc-air batteries constitute promising next-generation energy storage devices due to their intrinsic safety, low cost, and feasibility to realize high cycling current density and long cycling lifespan. Nevertheless, their cathodic reactions involving oxygen reduction and oxygen evolution are highly sluggish in kinetics, requiring high-performance noble-metal-free bifunctional electrocatalysts that exceed the current noble-metal-based benchmarks. Herein, a noble-metal-free bifunctional electrocatalyst is fabricated, which demonstrates ultrahigh bifunctional activity and renders excellent performance in rechargeable zinc-air batteries. Concretely, atomic Co-N-C and NiFe layered double hydroxides (LDHs) are respectively selected as oxygen reduction and evolution active sites and are further rationally integrated to afford the resultant CoNC@LDH composite electrocatalyst. The CoNC@LDH electrocatalyst exhibits remarkable bifunctional activity delivering an indicator ΔE of 0.63 V, far exceeding the noble-metal-based Pt/C+Ir/C benchmark (ΔE = 0.77 V) and most reported electrocatalysts. Correspondingly, ultralong lifespan (over 3600 cycles at 10 mA cm ) and excellent rate performances (cycling current density at 100 mA cm ) are achieved in rechargeable zinc-air batteries. This work highlights the current advances of bifunctional oxygen electrocatalysis and endows high-rate and long-cycling rechargeable zinc-air batteries for efficient sustainable energy storage.
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http://dx.doi.org/10.1002/adma.202008606DOI Listing
April 2021

Prognostic Value of the Nutritional Risk Screening 2002 Scale in Patients With Acute Myocardial Infarction: Insights From the Retrospective Multicenter Study for Early Evaluation of Acute Chest Pain.

J Cardiovasc Nurs 2021 Feb 16. Epub 2021 Feb 16.

Fanghui Li, MBBS Doctor, Department of Emergency Medicine; Staff, Disaster Medical Center; and Doctor, Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China. Dongze Li, MBBS, PhD Doctor, Department of Emergency Medicine; and Staff, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Jing Yu, MBBS Staff, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China. Yu Jia, MBBS, PhD Doctor, Department of Emergency Medicine; and Staff, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Ying Jiang, MBBS Doctor, Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China. Xiaoli Chen, RN, MSc Nurse, Department of Emergency Medicine; and Staff, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Yongli Gao, RN Nurse, Department of Emergency Medicine; and Committee Member, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Lei Ye, RN, MSc Nurse, Department of Emergency Medicine; and Staff, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Zhi Wan, MD Doctor, Department of Emergency Medicine; and Committee Member, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Yu Cao, MD Doctor, Department of Emergency Medicine; and Committee Member, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Zhi Zeng, MD Doctor, Department of Emergency Medicine; and Committee Member, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Rui Zeng, MD Doctor, Department of Emergency Medicine; Committee Member, Disaster Medical Center; and Doctor, Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.

Background: The Nutritional Risk Screening 2002 (NRS-2002) scale is a rapid and effective screening instrument that assesses nutritional risk among hospitalized patients.

Objective: The present study aimed to explore the prognostic value of the NRS-2002 scale in acute myocardial infarction (AMI) considering its uncertain role in this particular condition.

Methods: Patients with AMI included in the Retrospective Multicenter Study for Early Evaluation of Acute Chest Pain were investigated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to analyze the association between NRS-2002 and mortality in patients with AMI. The primary and secondary endpoints were all-cause and cardiac mortality during the follow-up period.

Results: A total of 2307 patients were enrolled, among whom 246 (10.7%) died within a median follow-up duration of 10.67 (8.04-14.33) months. Kaplan-Meier analysis revealed that patients with an NRS-2002 score of 3 or higher had poorer cumulative survival than those with an NRS-2002 score lower than 3 (P < .001). In the multivariate Cox regression analysis, patients with an NRS-2002 score of 3 or higher had more than double the risk for all-cause mortality (hazard ratio, 2.25; 95% confidence interval, 1.50-3.40; P < .001) and twice the risk for cardiac-related mortality (hazard ratio, 2.01; 95% confidence interval, 1.29-3.13; P = .002) than did patients with lower scores.

Conclusions: Our results showed that the NRS-2002 screening instrument was an independent prognostic predictor for both all-cause and cardiac mortality in patients with AMI. Nutritional risk assessment based on the NRS-2002 scale may provide useful prognostic information of early nutritional risk stratification in patients with AMI.
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http://dx.doi.org/10.1097/JCN.0000000000000786DOI Listing
February 2021

Sustained low-dose prophylactic early erythropoietin for improvement of neurological outcomes in preterm infants:A systematic review and meta-analysis.

J Affect Disord 2021 03 12;282:1187-1192. Epub 2021 Jan 12.

Department of Psychiatry, Renmin Hospital of Wuhan University, Hubei Zhang Road (formerly Ziyang Road), Wuchang District No. 99, Jiefang Road 238, Wuhan, Hubei province, China. Electronic address:

The aim of this meta-analysis was conducted to assess the effects of different doses of prophylactic rhEPO on neurodevelopmental outcomes and provide reference for rational drug use. The primary outcome was the number of infants with a Mental Developmental Index (MDI) <70 on the Bayley Scales of Infant Development. Five RCTs, comprising 2282 infants, were included in this meta-analysis. Overall, prophylactic rhEPO administration reduced the incidence of infants with an MDI <70, with an odds ratio (95% confidence interval) of 0.55 (0.38-0.79), P <0.05. The low-dose rhEPO subgroup was superior to the placebo subgroup, with an OR (95% CI) of 0.47 (0.25-0.87), P <0.05. However, high-dose rhEPO subgroup had no significant impact on MDI <70 in infants <28 weeks' gestational age. The definitions of the secondary outcome showed that there was no significant effect of rhEPO on cerebral palsy. For neonatal complications, although four studies showed that there were no differences in the pooled results of BPD and ICH events between rhEPO treatment and placebo, the ICH events were significantly lower in the low-dose rhEPO (OR 0.36; 95% CI 0.23-0.59). In addition, in the pooled results of NEC and ROP events, there were significant differences between the two groups (OR 0.63; 95% CI 0.43-0.93) (OR 0.80; 95% CI 0.65-0.98). And the NEC events were significantly lower in the low-dose rhEPO (OR 0.45; 95% CI 0.27-0.73). Sustained low-dose prophylactic early erythropoietin might be more superior than high-dose for improvement of neurological outcomes and several neonatal complications in preterm infants.
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http://dx.doi.org/10.1016/j.jad.2021.01.018DOI Listing
March 2021

HP1c regulates development and gut homeostasis by suppressing Notch signaling through Su(H).

EMBO Rep 2021 Apr 17;22(4):e51298. Epub 2021 Feb 17.

Gene Regulatory Lab, School of Medicine, Tsinghua University, Beijing, China.

Notch signaling and epigenetic factors are known to play critical roles in regulating tissue homeostasis in most multicellular organisms, but how Notch signaling coordinates with epigenetic modulators to control differentiation remains poorly understood. Here, we identify heterochromatin protein 1c (HP1c) as an essential epigenetic regulator of gut homeostasis in Drosophila. Specifically, we observe that HP1c loss-of-function phenotypes resemble those observed after Notch signaling perturbation and that HP1c interacts genetically with components of the Notch pathway. HP1c represses the transcription of Notch target genes by directly interacting with Suppressor of Hairless (Su(H)), the key transcription factor of Notch signaling. Moreover, phenotypes caused by depletion of HP1c in Drosophila can be rescued by expressing human HP1γ, suggesting that HP1γ functions similar to HP1c in Drosophila. Taken together, our findings reveal an essential role of HP1c in normal development and gut homeostasis by suppressing Notch signaling.
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http://dx.doi.org/10.15252/embr.202051298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024896PMC
April 2021

Exercise intervention for the risk of falls in older adults: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(5):e24548

Department of Emergency Medicine, Laboratory of Emergency Medicine, West China Hospital, and Disaster Medical Center.

Background: Falls can easily lead to serious injury and even death in the older adults. Many exercise interventions, such as balance, flexibility, and endurance training have been shown to reduce the incidence of falls in this population. However, which mode of exercise is most beneficial for them remains unanswered.

Methods: We will search the following databases as data sources: PUBMED, EMBASE, Cochrane Library, Wanfang, China knowledge Network (CNKI), Clinical Trials Database, and Science Network. Data extraction will be performed by two independent reviewers, who will discuss and resolve any differences, with the consensus of a third author. The RCTs will be selected according to prespecified inclusion criteria. The main outcome is the occurrence of a fall, and the secondary outcomes are the adverse consequences of a fall and a fall risk assessment index. If the heterogeneity test shows slight or no statistical heterogeneity, a fixed effect model will be used for data synthesis; otherwise, a random effect model will be used. We will develop a unified data extraction table including a number of parameters. The Cochrane cooperative bias risk tool will be used to evaluate the methodological quality of the selected RCTs. RevMan Manager v5.3 software and STATA v16.0 software will be used for data analysis. If enough randomized controlled trials (more than 10) are identified and selected.

Conclusion: This protocol will be applied to synthesize the existing evidence so as to identify the most effective exercise program to prevent falls in the elderly.

Inplasy Registration Number: INPLASY2020110008.
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http://dx.doi.org/10.1097/MD.0000000000024548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870243PMC
February 2021