Publications by authors named "Chun Zhou"

260 Publications

TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis.

Biochim Biophys Acta Mol Cell Res 2021 May 29;1868(9):119073. Epub 2021 May 29.

Department of Biological Sciences, A320 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260, United States of America; Australian Research Council Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia; Fundación Instituto Leloir and Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA-CONICET), 1405 Buenos Aires, Argentina; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, 4072, Australia. Electronic address:

The Endoplasmic Reticulum (ER) is responsible for the folding and post-translational modification of secretory proteins, as well as for triaging misfolded proteins. During folding, there is a complex yet only partially understood interplay between disulfide bond formation, which is an enzyme catalyzed event in the oxidizing environment of the ER, along with other post-translational modifications (PTMs) and chaperone-supported protein folding. Here, we used the glycoprotein torsinA as a model substrate to explore the impact of ER redox homeostasis on PTMs and protein biogenesis. TorsinA is a AAA+ ATPase with unusual oligomeric properties and controversial functions. The deletion of a C-terminal glutamic acid residue (∆E) is associated with the development of Early-Onset Torsion Dystonia, a severe movement disorder. TorsinA differs from other AAA+ ATPases since it is an ER resident, and as a result of its entry into the ER torsinA contains two N-linked glycans and at least one disulfide bond. The role of these PTMs on torsinA biogenesis and function and the identity of the enzymes that catalyze them are poorly defined. Using a yeast torsinA expression system, we demonstrate that a specific protein disulfide isomerase, Pdi1, affects the folding and N-linked glycosylation of torsinA and torsinA∆E in a redox-dependent manner, suggesting that the acquisition of early torsinA folding intermediates is sensitive to perturbed interactions between Cys residues and the quality control machinery. We also highlight the role of specific Cys residues during torsinA biogenesis and demonstrate that torsinA∆E is more sensitive than torsinA when these Cys residues are mutated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbamcr.2021.119073DOI Listing
May 2021

Occupational Physical Activity and New-Onset Hypertension: A Nationwide Cohort Study in China.

Hypertension 2021 Jul 1;78(1):220-229. Epub 2021 Jun 1.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Clinical Research Center for Kidney Disease, Guangzhou, China (Q.L., Y.Z., P.H., Z.Z., M.L., C.Z., H.L., C.L., X.Q.).

[Figure: see text].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17281DOI Listing
July 2021

Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney Function.

Clin J Am Soc Nephrol 2021 Jun 29;16(6):889-897. Epub 2021 May 29.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China

Background And Objectives: The relationship of depressive symptoms with kidney function remains poorly investigated. We aimed to evaluate the prospective association between depressive symptoms and rapid decline in kidney function in Chinese adults with normal kidney function.

Design, Setting, Participants, & Measurements: A total of 4763 participants with eGFR≥60 ml/min per 1.73 m at baseline were enrolled from the China Health and Retirement Longitudinal Study. Baseline depressive symptoms were determined using a ten-item Center for Epidemiologic Studies Depression scale with a cutoff score of greater than or equal to ten to define high depressive symptoms. The GFR was estimated by a combination of serum creatinine and cystatin C. The primary outcome was rapid decline in kidney function, defined as an annualized decline in eGFR of ≥5 ml/min per 1.73 m. Secondary outcome was defined as an annualized decline in eGFR of ≥5 ml/min per 1.73 m and to a level of <60 ml/min per 1.73 m at the exit visit.

Results: During a median follow-up of 4 years (interquartile range, 3.92-4.00), 260 (6%) participants developed rapid decline in kidney function. Overall, there was a significant positive association between baseline depressive symptoms and rapid decline in kidney function (per five-scores increment; adjusted odds ratio, 1.15; 95% confidence interval, 1.03 to 1.28) after adjustments for major demographic, clinical, or psychosocial covariates. Consistently, compared with participants with low depressive symptoms (total Center for Epidemiologic Studies Depression scale score less than ten), a significantly higher risk of rapid decline in kidney function was found among those with high depressive symptoms (total Center for Epidemiologic Studies Depression scale score greater than or equal to ten; adjusted odds ratio, 1.39; 95% confidence interval, 1.03 to 1.88). Similar results were found for the secondary outcome (per five-scores increment; adjusted odds ratio, 1.26; 95% confidence interval, 1.06 to 1.51).

Conclusions: High depressive symptoms were significantly associated with a higher risk of rapid kidney function decline among Chinese adults with normal kidney function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.18441120DOI Listing
June 2021

Relationship of several serum folate forms with kidney function and albuminuria: Cross-sectional data from the NHANES 2011-2018.

Br J Nutr 2021 May 21:1-33. Epub 2021 May 21.

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510515, China.

We aim to examine the relation of several folate forms (5-methyltetrahydrofolate [5-mTHF], unmetabolized folic acid [UMFA], and MeFox) with kidney function and albuminuria, which remained uncertain. The cross-sectional study was conducted in 18,757 participants from National Health and Nutrition Examination Survey 2011-2018. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m2), microalbuminuria (albumin-to-creatinine ratio of 30-299 mg/g), and macroalbuminuria (albumin-to-creatinine ratio ≥ 300 mg/g).Overall, there were significant inverse associations between serum 5-mTHF and kidney outcomes with significant lower prevalence of reduced eGFR (OR, 0.71; 95%CI: 0.57-0.87) and macroalbuminuria (OR, 0.65; 95%CI: 0.46-0.91) in participants in quartile 3-4 (vs. quartile 1-2; ≥34.0 vs. <34.0nmol/L; both P for trend across quartiles <0.05). In contrast, there were significant positive relationship between serum UMFA and kidney outcomes with significant higher prevalence of reduced eGFR in participants in quartile 2-4 (vs. quartile 1; ≥0.5 vs. <0.5nmol/L; OR, 2.12; 95%CI: 1.45-3.12; P for trend <0.001) and higher prevalence of macroalbuminuria in participants in quartile 4 (vs. quartile 1-3; ≥ 1.0 vs. <1.0 nmol/L; OR, 1.46; 95%CI: 1.06-2.01; P for trend <0.001). However, there was no significant associations of 5-mTHF and UMFA with microalbuminuria. In addition, there were significant positive relationships of serum MeFox with reduced eGFR, microalbuminuria and macroalbuminuria (all P for trend <0.01). In conclusion, higher 5-mTHF level, along with lower UMFA and MeFox level, were associated with lower prevalence of kidney outcomes, which may help counsel future clinical trials and nutritional guidelines regarding the folate supplement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0007114521001665DOI Listing
May 2021

Buried Structure in Block Copolymer Films Revealed by Soft X-ray Reflectivity.

ACS Nano 2021 May 20. Epub 2021 May 20.

Materials Science and Engineering Division, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, Maryland 20899, United States.

Interactions between polymers and surfaces can be used to influence properties including mechanical performance in nanocomposites, the glass transition temperature, and the orientation of thin film block copolymers (BCPs). In this work we investigate how specific interactions between the substrate and BCPs with varying substrate affinity impact the interfacial width between polymer components. The interface width is generally assumed to be a function of the BCP properties and independent of the surface affinity or substrate proximity. Using resonant soft X-ray reflectivity the optical constants of the film can be controlled by changing the incident energy, thereby varying the depth sensitivity of the measurement. Resonant soft X-ray reflectivity measurements were conducted on films of polystyrene--poly(2-vinylpyridine) (PS--P2VP) and PS--poly(methyl methacrylate) (PS--PMMA), where the thickness of the film was varied from half the periodicity () of the BCP to 5.5 . The results of this measurement on the PS--P2VP films show a significant expansion of the interface width immediately adjacent to the surface. This is likely caused by the strong adsorption of P2VP to the substrate, which constrains the mobility of the junction points, preventing them from reaching their equilibrium distribution and expanding the observed interface width. The interface width decays toward equilibrium moving away from the substrate, with the decay rate being a function of film thickness below a critical limit. The PMMA block appears to be more mobile, and the BCP interfaces near the substrate match their equilibrium value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c09907DOI Listing
May 2021

All-inorganic quantum dot LEDs based on phase-stabilized α-CsPbI3 perovskite.

Angew Chem Int Ed Engl 2021 May 12. Epub 2021 May 12.

University of Toronto, ECE, 10 King's College Road, ECE, Galbraith Building, Room GB447, M5S 3G4, Toronto, CANADA.

The all-inorganic nature of CsPbI 3 perovskites offers an avenue to enhance stability in perovskite devices. Concerted research efforts have led to improved stability of the black phase in CsPbI 3 films; however, these strategies - including strain and doping - are based on organic-ligand-capped perovskites, which prevent perovskites from forming the close-packed QD solids necessary to achieve high charge transport and thermal transport. Here we develop an inorganic ligand exchange that leads to CsPbI 3 QD films that unite superior phase stability with increased thermal transport. We demonstrate that the atomic ligand exchanged QD films, once mechanically coupled, exhibit improved phase stability, and we link this to distributing strain across the film. Further, operando measurements of the temperature of LEDs indicate that KI-exchanged QD films exhibit increased thermal transport compared to controls that rely on organic ligands. The LEDs exhibit a maximum EQE of 23% with EL emission centered at 640 nm (FWHM of ~31 nm). These red LEDs provide an operating half lifetime of 10 hours (luminance of 200 cd/m 2 ), an operating stability that is 6x higher than that of control devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202104812DOI Listing
May 2021

Inverse association between dietary vitamin A intake and new-onset hypertension.

Clin Nutr 2021 May 18;40(5):2868-2875. Epub 2021 Apr 18.

Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; National Clinical Research Center for Kidney Disease, Guangzhou, 510515, China; Guangdong Provincial Clinical Research Center for Kidney Disease, Guangzhou, 510515, China; State Key Laboratory of Organ Failure Research, Guangzhou, 510515, China; Guangdong Provincial Institute of Nephrology, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510515, China. Electronic address:

Background & Aims: The prospective relation of dietary vitamin A intake with hypertension remains uncertain. We aimed to investigate the relationship of dietary vitamin A intake with new-onset hypertension and examine possible effect modifiers in general population.

Methods: This prospective cohort study included 12,245 participants who were free of hypertension at baseline from China Health and Nutrition Survey (CHNS). Dietary intake was measured by 3 consecutive 24-h dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or diagnosed by physician or under antihypertensive treatment during the follow-up.

Results: During a median follow-up duration of 6.1 years, a total of 4,304 (35.1%) participants developed new-onset hypertension. Overall, there was an L-shaped relation of total dietary vitamin A intake with new-onset hypertension (P for nonlinearity <0.001). Accordingly, compared with participants with lower vitamin A intake (quartile 1, <227.3 μg RE/day), those with higher vitamin A intake (quartile 2-4, ≥227.3 μg RE/day) had a significantly lower risk of new-onset hypertension (adjusted HR, 0.73; 95%CI: 0.63, 0.78). Similar results were found for plant-derived vitamin A intake (adjusted HR, 0.65; 95% CI, 0.61, 0.70) or animal-derived vitamin A intake (adjusted HR, 0.76; 95% CI, 0.70, 0.82).

Conclusions: There was a L-shaped relation of dietary vitamin A intake with new-onset hypertension in general Chinese adults. Our results emphasized the importance of maintaining relatively higher vitamin A intake levels for the prevention of hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2021.04.004DOI Listing
May 2021

Phase-Matching Quantum Key Distribution with Discrete Phase Randomization.

Entropy (Basel) 2021 Apr 23;23(5). Epub 2021 Apr 23.

Henan Key Laboratory of Quantum Information and Cryptography, SSF IEU, Zhengzhou 450001, China.

The twin-field quantum key distribution (TF-QKD) protocol and its variations have been proposed to overcome the linear Pirandola-Laurenza-Ottaviani-Banchi (PLOB) bound. One variation called phase-matching QKD (PM-QKD) protocol employs discrete phase randomization and the phase post-compensation technique to improve the key rate quadratically. However, the discrete phase randomization opens a loophole to threaten the actual security. In this paper, we first introduce the unambiguous state discrimination (USD) measurement and the photon-number-splitting (PNS) attack against PM-QKD with imperfect phase randomization. Then, we prove the rigorous security of decoy state PM-QKD with discrete phase randomization. Simulation results show that, considering the intrinsic bit error rate and sifting factor, there is an optimal discrete phase randomization value to guarantee security and performance. Furthermore, as the number of discrete phase randomization increases, the key rate of adopting vacuum and one decoy state approaches infinite decoy states, the key rate between discrete phase randomization and continuous phase randomization is almost the same.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e23050508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146613PMC
April 2021

Association of estimated glomerular filtration rate from serum creatinine and cystatin C with new-onset diabetes: a nationwide cohort study in China.

Acta Diabetol 2021 Apr 28. Epub 2021 Apr 28.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Clinical Research Center for Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Aims: The association between estimated glomerular filtration rate (eGFR) and the risk of diabetes remains uncertain. We aimed to examine the association between eGFR based on creatinine (eGFRcr), cystatin C (eGFRcys), or a combination of both (eGFRcr-cys) and new-onset diabetes, using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative cohort study.

Methods: A total of 4,775 participants with pertinent measurements and without diabetes at baseline from CHARLS were included in the final analysis. The eGFR was calculated by creatinine, cystatin C or a combination of both using the Chronic Kidney Disease Epidemiology Collaboration equations. The study outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 126 mg/dL, random glucose ≥ 200 mg/dL, or HbA1c ≥ 6.5% (48 mmol/mol) at the exit visit.

Results: The mean age of the study population was 59.6 years. The mean values for the eGFRcr, eGFRcys, and eGFRcr-cys were 92.4, 78.9 and 85.9 mL/min/1.73m, respectively. Over 4 years of follow-up, 612 (12.8%) participants experienced diabetes. Participants with lower eGFRcr-cys (< 60 mL/min/1.73m) had a significantly higher risk of new-onset diabetes (adjusted OR, 1.46; 95%CI: 1.02, 2.09), compared to those with eGFRcr-cys ≥ 60 mL/min/1.73m. However, there was no significant association between eGFRcr (< 60 vs. ≥ 60 mL/min/1.73m; adjusted OR, 1.27; 95%CI: 0.75, 2.17) or eGFRcys (adjusted OR, 1.04; 95%CI: 0.80, 1.36) and new-onset diabetes.

Conclusions: Lower eGFRcr-cys (< 60 mL/min/1.73m), but not eGFRcr or eGFRcys, was significantly associated with an increased risk of new-onset diabetes in Chinese adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00592-021-01719-5DOI Listing
April 2021

Association of visceral adiposity index with new-onset type 2 diabetes and impaired fasting glucose in hypertensive Chinese adults.

Eat Weight Disord 2021 Apr 12. Epub 2021 Apr 12.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong Provincial Clinical Research Center for Kidney Disease, Guangzhou, 510515, China.

Purpose: Visceral adiposity index (VAI) is a reliable indicator for the distribution and function of adipose tissue in the body. The relation of VAI with new-onset type 2 diabetes and new-onset impaired fasting glucose (IFG) remains uncertain. We aimed to investigate the prospective relation of VAI with new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive adults.

Methods: A total of 14,838 hypertensive adults free of type 2 diabetes at baseline were included from the China Stroke Primary Prevention Trial. The primary outcome was new-onset type 2 diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary outcome was new-onset IFG, defined as fasting glucose < 6.1 mmol/L at baseline, while fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L at the exit visit.

Results: Over a median of 4.5 years' follow-up, 1612 (10.9%) participants developed type 2 diabetes. When VAI was categorized into quartiles, compared with participants in quartile 1-3 (< 2.80), significantly higher risk of new-onset type 2 diabetes (OR 1.30; 95% CI 1.08-1.56) and new-onset IFG (OR 1.28; 95% CI 1.08-1.52) was found in those in quartile 4 (≥ 2.80). Moreover, the positive associations were consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) levels; or with different numbers of abnormal VAI components (all P interactions > 0.05).

Conclusion: Our study suggested a positive relation of VAI with the risk of new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive patients, independent of its components.

Level Of Evidence: Level III, a well-designed cohort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40519-021-01187-4DOI Listing
April 2021

Regulation of Anion Channel LRRC8 Volume-Regulated Anion Channels in Transport of 2'3'-Cyclic GMP-AMP and Cisplatin under Steady State and Inflammation.

J Immunol 2021 May 7;206(9):2061-2074. Epub 2021 Apr 7.

The Center for Microbes, Development and Health, Chinese Academy of Sciences Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China;

The recently identified anion channel LRRC8 volume-regulated anion channels (VRACs) are heteromeric hexamers constituted with the obligate LRRC8A subunit paired with at least one of the accessory LRRC8B to LRRC8E subunits. In addition to transport chloride, taurine, and glutamate, LRRC8 VRACs also transport the anticancer agent cisplatin and STING agonists 2'3'-cyclic GMP-AMP (cGAMP) and cyclic dinucleotides; hence, they are implicated in a variety of physiological and pathological processes, such as cell swelling, stroke, cancer, and viral infection. Although the subunit composition largely determines VRAC substrate specificity, the opening of various VRAC pores under physiological and pathological settings remains enigmatic. In this study, we demonstrated that VRACs comprising LRRC8A and LRRC8E (LRRC8A/E-containing VRACs), specialized in cGAMP transport, can be opened by a protein component present in serum under resting condition. Serum depletion ablated the tonic activity of LRRC8A/E-containing VRACs, decreasing cGAMP transport in various human and murine cells. Also, heating or proteinase K treatment abolished the ability of serum to activate VRAC. Genetic analyses revealed a crucial role for cGAMP synthase (cGAS) in serum/TNF-promoted VRAC activation. Notably, the presence of cGAS on the plasma membrane, rather than its DNA-binding or enzymatic activity, enabled VRAC activation. Moreover, phospholipid PIP2 seemed to be instrumental in the membrane localization of cGAS and its association with VRACs. Corroborating a role for LRRC8A/D-containing VRACs in cisplatin transport, serum and TNF markedly potentiated cisplatin uptake and killing of cancer cells derived from human or mouse. Together, these observations provide new insights into the complex regulation of VRAC activation and suggest a novel approach to enhance the efficacy of cGAMP and cisplatin in treating infection and cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2000989DOI Listing
May 2021

Prediction Scores for Any-Stage and Stage-3 Acute Kidney Injury After Adult Cardiac Surgery in a Chinese Population.

J Cardiothorac Vasc Anesth 2021 Feb 22. Epub 2021 Feb 22.

Department of Cardiopulmonary Bypass, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Objectives: This study was performed to internally derive and then validate risk score systems using preoperative and intraoperative variables to predict the occurrence of any-stage (stage 1, 2, 3) and stage-3 acute kidney injury (AKI) within seven days of cardiac surgery.

Design: Single-center, retrospective, observational study.

Setting: Single, large, tertiary care center.

Participants: Adult patients undergoing open cardiac surgery between January 1, 2012, and January 1, 2019.

Measurements And Main Results: The clinical data were divided into the following two groups: a derivation cohort (n = 43,799) and a validation cohort (n = 14,600). AKI was defined using the Kidney Disease: Improving Global Outcomes criteria. Multivariate logistic regression analysis was used to develop the prediction models. The overall prevalence of any-stage AKI and stage-3 AKI after cardiac surgery were 34.3% and 1.7%, respectively. The discriminatory ability of the any-stage AKI prediction model measured with the area under the curve (AUC) was acceptable (AUC = 0.69, 95% confidence interval 0.68-0.69), and the calibration measured with the Hosmer-Lemeshow test was good (p = 0.95). The AUC for the stage-3 AKI prediction model was 0.84 (95% confidence interval 0.83-0.85), and the Hosmer-Lemeshow test also indicated a good calibration (p = 0.73).

Conclusions: This research study, which used preoperative and intraoperative variables, derived and internally validated two predictive scoring systems for any-stage AKI and stage-3 AKI as defined by modified Kidney Disease: Improving Global Outcomes criteria using a very large cohort of Chinese cardiac surgical patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.jvca.2021.02.047DOI Listing
February 2021

MicroRNA-32-5p inhibits epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting SMAD family 3.

J Cancer 2021 22;12(8):2258-2267. Epub 2021 Feb 22.

Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University; Gulou, Nanjing 210029, P.R. China.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated death worldwide. MicroRNA (miRNA)-32-5p is as an important cancer-associated miRNA in different types cancer. To date, the role of miR-32-5p in the migration and invasion of NSCLC remains unknown. In the present study, a Transwell assay was performed to investigate the role of miR-32-5p in lung adenocarcinoma. miR-32-5p expression level was determined via reverse transcription-quantitative PCR in 24 pairs of NSCLC and adjacent normal tissues. SMAD family member 3 (SMAD3) was considered as a novel target gene by luciferase reporter assay and western blot in NSCLC. The present study demonstrated that miR-32-5p is frequently downregulated in NSCLC tissues. The overexpression of miR-32-5p resulted in the inhibition of migratory and invasive abilities in NSCLC cells. Thus, SMAD3 was identified as a target of miR-32-5p, and its expression was negatively correlated with miR-32-5p expression in clinical NSCLC tissues. Overall, these findings indicate that miR-32-5p serves as a tumor suppressor by targeting SMAD3. Thus, miR-32-5p may be a potential therapeutic target for the treatment of lung adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.48387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974882PMC
February 2021

A mobile technology-based cooperative learning platform for undergraduate biology courses in common college classrooms.

Biochem Mol Biol Educ 2021 May 10;49(3):427-440. Epub 2021 Mar 10.

Center for Teaching and Learning, Mercy College, Dobbs Ferry, New York, USA.

As a high-impact educational practice, cooperative learning uses a structured group study to promote students' active learning. Currently, it lacks economical yet effective tools to facilitate the interactive nature of structured cooperative learning in regular classrooms. Here, we have established a mobile technology-based cooperative learning (MBCL) platform that comprises the 2018 iPad, Apple Pencil, LiveBoard, Google Forms, and Google Drive. We tested the MBCL platform in multiple undergraduate biology courses. During semester-long MBCL studies, the students engaged in cooperative learning to discuss a real-life issue or chapter-based contents. With the MBCL platform, the students' group study processes were shown on shared, visible electronic whiteboards that were updated in real-time, generating visible thinking and instant, interactive communication. The instructor was able to guide the students promptly to conduct knowledge integration and knowledge synthesis using tables and diagrams. The deep learning outcome was evident in the examples and quantitative analyses of students' whiteboard study results and team presentations. Thus, integrating innovative mobile technologies into high-impact teaching practices, exemplified by the MBCL platform, promotes deep learning in higher education.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmb.21496DOI Listing
May 2021

Superselective Vesical Artery Embolization for Intractable Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in 26 Patients.

Cardiovasc Intervent Radiol 2021 Jun 19;44(6):943-951. Epub 2021 Feb 19.

Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China.

Purpose: To evaluate the safety and efficacy of superselective vesical artery embolization (SVAE) in the treatment of intractable hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT).

Methods: From January 2010 to December 2018, 26 patients with hematologic malignancy who underwent SVAE for treatment of intractable HC following HSCT were retrospectively reviewed. SVAE was performed with 300-500 μm gelatin-sponge particles initially. Technical success was defined as achieving bilateral SVAE for all the prominent vesical arteries. Therapeutic efficacy was defined as: Complete response (CR): macroscopic hematuria completely disappeared on more than 2 consecutive days after SVAE; Partial response (PR): macroscopic hematuria reduced after SVAE or briefly disappeared after SVAE but reappeared soon within 2 days; No response: no response to SVAE or hematuria aggravated after SVAE; Recurrence: macroscopic hematuria relapsed on follow-up after achieving an initial CR. Adverse events were also registered.

Results: There was a mean follow-up of 11.4 months (range, 0.5-83.7). The mean interval for the onset of HC after HSCT was 39.7 ± 19.0 days, and mean duration of hematuria before embolization was 14.9 ± 15.7 days. SVAE was technically successful in all patients. After embolization, macroscopic hematuria regressed within 48 h for all patients. The mean urine erythrocyte counts dropped from 14,213.2 ± 20,999.0/uL before SVAE to 6072.9 ± 12,720.7/uL on 3d after SVAE (P = 0.002) and 3720.2 ± 8988.9/uL on 7 d after SVAE (P = 0.001), respectively. Hematuria completely disappeared prior to discharge in 23 (88.5%) patients (including 20 with one embolization and 3 with 2 embolizations) and remainder 3 patients had PR. No major procedure-related complications were noted, except for post-embolization syndrome in 8 patients, which resolved with symptomatic treatment. On follow-up monthly, hematuria recurrence was seen in 4/23 patients (17.4%) and was managed conservatively in 2 patients and with repeat embolization in the remainder 2 patients.

Conclusion: For fragile patients with hematologic malignancy, SVAE is safe and effective to treat HC following HSCT, even though repeat embolization may be required to achieve a sustained complete remission of the hematuria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00270-021-02786-5DOI Listing
June 2021

Neutrophil counts and the risk of first stroke in general hypertensive adults.

Hypertens Res 2021 Feb 9. Epub 2021 Feb 9.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

We aimed to investigate the association between neutrophil counts and first stroke and examine possible effect modifiers among treated hypertensive adults. This is a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). A total of 11,878 hypertensive adults with data on neutrophil counts at baseline were included in the current study. The primary outcome was first stroke. During a median follow-up of 4.5 years, 414 (3.5%) participants experienced a first stroke, including 358 with ischemic stroke, 55 with hemorrhagic stroke and one with uncertain type of stroke. Compared with participants in quartile 1 (<2.9 × 10/L) of neutrophil counts, those in the upper quartiles (quartile 2-4 [≥2.9 × 10/L]) had a significantly higher risk of first stroke (HR, 1.35; 95% CI: 1.02, 1.78) or first ischemic stroke (HR, 1.38; 95% CI: 1.02, 1.86). Moreover, a strong positive association between neutrophil counts and first ischemic stroke was found in participants with total homocysteine (tHcy) levels <15 μmol/L (HR, 1.74; 95% CI: 1.17, 2.58; vs. ≥15 μmol/L; HR, 0.91; 95% CI: 0.57, 1.46, P interaction = 0.042) at baseline or time-averaged mean arterial pressure (MAP) ≥102 mmHg (median) (HR, 1.92; 95% CI: 1.27, 2.89; vs. <102 mmHg; HR, 0.89; 95% CI: 0.57, 1.41, P interaction = 0.015) during the treatment period. However, no such association between neutrophil counts and first hemorrhagic stroke was found. In summary, high baseline neutrophil counts were associated with an increased risk of first ischemic stroke among hypertensive patients, especially in those with low tHcy at baseline or high time-averaged MAP during the treatment period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41440-021-00625-1DOI Listing
February 2021

induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway.

Oncol Lett 2021 Feb 4;21(2):165. Epub 2021 Jan 4.

Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

() is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of -associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in -infected Mongolian gerbil gastric tissues and cells co-cultured with by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with infection. Furthermore, infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with . Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without . The levels of p-AKT and p-GSK3β were increased in -infected Mongolian gerbils. In conclusion, the present study demonstrated that infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2021.12426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798028PMC
February 2021

Relationship of several serum folate forms with the risk of mortality: A prospective cohort study.

Clin Nutr 2021 Jan 27. Epub 2021 Jan 27.

Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510515, China. Electronic address:

Objective: We aim to examine the relation of several folate forms (5-methyltetrahydrofolate [5-mTHF], unmetabolized folic acid [UMFA], non-methyl folate, and MeFox [pyrazino-s-triazine derivative of 4α-hydroxy-5-methyltetrahydrofolate]) with the risk of mortality.

Methods: Using data from National Health and Nutrition Examination Survey 2011-2014, a total of 10,661 people with folate forms data were recruited. Death information was obtained from the National Death Index until 2015. Cox proportional hazards regression models were developed to evaluate the relationship between folate forms and mortality.

Results: During 2.99 years of follow-up, 344 (2.6%) deaths occurred. Overall, significantly higher risks of all-cause mortality were found in participants with higher level of serum 5-mTHF (≥51.3 nmol/L [quartile 4] vs. 23.9-51.3 nmol/L [quartile 2-3]; HR, 1.61; 95% CI: 1.03-2.53), UMFA (≥1.1 nmol/L [quartile 4] vs. <1.1 nmol/L [quartile 1-3]; HR, 1.55; 95% CI: 1.15-2.09), non-methyl folate (≥1.7 nmol/L [quartile 4] vs. 1.2-1.7 nmol/L [quartile 3]; HR, 1.62; 95% CI: 1.06-2.48), or MeFox (≥2.5 nmol/L [quartile 4] vs. <2.5 nmol/L [quartile 1-3]; HR, 1.54; 95% CI: 1.11-2.12). In addition, there was an increased risk of all-cause mortality for those with low level of serum 5-mTHF (<23.9 nmol/L [quartile 1] vs. 23.9-51.3 nmol/L [quartile 2-3]; HR, 1.66; 95% CI: 1.12-2.47). Most importantly, none of any folate forms significantly modified the association between other folate forms and mortality (all P for interactions >0.05).

Conclusion: Higher levels of serum folate forms (5-mTHF, UMFA, non-methyl folate, and MeFox) were associated with higher risk of mortality while 5-mTHF insufficiency also showed a negative impact on mortality. Our findings emphasized the importance of monitoring the folate forms concentrations and may help counsel future related clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2021.01.025DOI Listing
January 2021

Dietary Carbohydrate Intake and New-Onset Hypertension: A Nationwide Cohort Study in China.

Hypertension 2021 Feb 8:HYPERTENSIONAHA12016751. Epub 2021 Feb 8.

From the Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, China (Q.L., C.L., Y.Z., P.H., Z.Z., M.L., C.Z., Z.Y., Q.W., H.L., X.Q.).

The association between carbohydrate intake and the risk of hypertension remains uncertain. We aimed to evaluate the prospective relations of the amount and type of carbohydrate intake with new-onset hypertension. A total of 12 177 adults who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was measured by 3 consecutive 24-hour dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or diagnosed by physician or under antihypertensive treatment during the follow-up. A total of 4269 subjects developed hypertension during 95 157 person-years of follow-up. Overall, there was a U-shaped association between the percentage energy consumed from total carbohydrate (mean, 56.7%; SD, 10.7) and new-onset hypertension ( for nonlinearity <0.001), with the lowest risk observed at 50% to 55% carbohydrate intake. The increased risks were mainly found in those with lower intake of high-quality carbohydrate (mean, 6.4%; SD, 5.6) or higher intake of low-quality carbohydrate (mean, 47.0%; SD, 13.0). Moreover, there was an inverse association between the plant-based low-carbohydrate scores for low-quality carbohydrate and new-onset hypertension. However, there was a U-shaped association between the animal-based low-carbohydrate scores for low-quality carbohydrate and new-onset hypertension ( for nonlinearity <0.001). In summary, both high and low percentages of carbohydrate diets were associated with increased risk of new-onset hypertension, with minimal risk at 50% to 55% carbohydrate intake. Our findings support the intake of high-quality carbohydrate, and the substitution of plant-based products for low-quality carbohydrate for prevention of hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16751DOI Listing
February 2021

Targeted inhibition of ATP5B gene prevents bone erosion in collagen-induced arthritis by inhibiting osteoclastogenesis.

Pharmacol Res 2021 Mar 27;165:105458. Epub 2021 Jan 27.

SMU-KI United Medical Inflammatory Center, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Bone resorption by osteoclasts is an energy consuming activity, which depends on mitochondrial ATP. ATP5B, a mitochondrial ATP synthase beta subunit, is a catalytic core involved in producing ATP. Here, we investigated the contribution of ATP5B in osteoclast differentiation and joint destruction. ATP5B (LV-ATP5B) targeting or non-targeting (LV-NC) siRNA containing lentivirus particles were transduced into bone marrow macrophage derived osteoclasts or locally administered to arthritic mouse joints. Inhibition of ATP5B reduced the expression of osteoclast related genes and proteins, suppressed bone resorption by significantly impairing F-actin formation and decreased the levels of adhesion-associated proteins. In addition, ATP5B deficiency caused osteoclast mitochondrial dysfunction and, impaired the secretion of vacuole protons and MMP9. Importantly, inhibition of ATP5B expression, protected arthritis mice from joint destructions although serum levels of inflammatory mediators (TNF-α, IL-1β) and IgG2α antibodies were unaffected. These results demonstrate an essential function of ATP5B in osteoclast differentiation and bone resorption, and suggest it as a potential therapeutic target for protecting bones in RA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105458DOI Listing
March 2021

Single transition metal anchored CN sheets as an efficient catalyst for CO oxidation: a first-principles study.

Phys Chem Chem Phys 2021 Jan;23(3):1868-1873

School of Physical Science and Technology, Ningbo University, Ningbo, P. R. China.

Single-atom catalysts (SACs) often exhibit superb catalytic activity due to their high atom utilization. By comparing the adsorption energies of O2 and CO adsorbed on [email protected], we expect that Co and Ni anchored at the cavity of C9N4 exhibit a higher catalytic activity for CO oxidation. For the entire reaction, the Eley-Rideal, New Eley-Rideal, Ter-molecular Eley-Rideal and Langmuir-Hinshelwood mechanisms are all taken into account. Depending on the reaction mechanisms, the catalysts [email protected] and [email protected] show excellent activity, with a kinetic energy barrier ranging from 0.19 eV to 0.54 eV for the former, while the corresponding energy barrier is 0.26 eV to 0.44 eV for the latter. The superior stability and activity of Co/[email protected] can efficiently oxidize the large amounts of CO caused by inadequate combustion of coal and natural gas resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cp05306fDOI Listing
January 2021

Evaluation of Dietary Niacin and New-Onset Hypertension Among Chinese Adults.

JAMA Netw Open 2021 01 4;4(1):e2031669. Epub 2021 Jan 4.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Importance: The relationship of dietary niacin intake with the risk of hypertension remains unknown.

Objective: To determine the prospective association between dietary niacin intake and new-onset hypertension, and examine factors that may modify the association among Chinese adults.

Design, Setting, And Participants: This nationwide cohort study of 12 243 Chinese adults used dietary intake data from 7 rounds of the China Health and Nutrition Survey. Dietary intake was measured by 3 consecutive 24-hour dietary recalls from participants in combination with a weighing inventory taken over the same 3 days at the household level. Statistical analysis was conducted from May 2020 to August 2020.

Exposures: Dietary intake.

Main Outcomes And Measures: The study outcome was new-onset hypertension, defined as systolic blood pressure 140 mm Hg or greater and/or diastolic blood pressure 90 mm Hg or greater, diagnosis by physician, or current antihypertensive treatment during the follow-up.

Results: The mean (SD) age of the study population was 41.2 (14.2) years, and 5728 (46.8%) of participants were men. The mean (SD) dietary niacin intake level was 14.8 (4.1) mg/d. A total of 4306 participants developed new-onset hypertension during a median (interquartile range) follow-up duration of 6.1 (3.6-11.3) years. When dietary niacin was assessed in quartiles, the lowest risk of new-onset hypertension was found in participants in quartile 3 (14.3 to <16.7 mg/d; adjusted hazard ratio, 0.83; 95% CI, 0.75-0.90) compared with those in quartile 1 (<12.4 mg/d). Consistently in the threshold analysis, for every 1 mg/d increase in dietary niacin, there was a 2% decrease in new-onset hypertension (adjusted HR, 0.98; 95% CI, 0.96-1.00) in those with dietary niacin intake less than 15.6 mg/d, and a 3% increase in new-onset hypertension (adjusted HR, 1.03; 95% CI, 1.02-1.04) in participants with dietary niacin 15.6 mg/d or greater. Based on these results, there was a J-shaped association between dietary niacin intake and new-onset hypertension in the general population of Chinese adults, with an inflection point at 15.6 mg/d and a minimal risk at 14.3 to 16.7 mg/d (quartile 3) of dietary niacin intake.

Conclusions And Relevance: The results of this study provide some evidence for maintaining the optimal dietary niacin intake levels for the primary prevention of hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.31669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788463PMC
January 2021

Identifying Key Genes for Nasopharyngeal Carcinoma by Prioritized Consensus Differentially Expressed Genes Caused by Aberrant Methylation.

J Cancer 2021 1;12(3):874-884. Epub 2021 Jan 1.

School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy. Large-scale genetics or epigenetics studies of NPC have been relatively scarce and sporadic, and there are no effective targeted drugs for NPC. Integrative analysis of multiple different omics profiles has been proved to be an effective approach to shed new light on cancer. We developed a pipeline to aggregate consensus differentially expressed genes (DEGs) from multiple expression datasets from different platforms. Integrated bioinformatics analysis of DNA methylation and gene expression was used to prioritize key genes in NPC. We explored the biological and clinical importance of key genes, combining differential co-expression analysis, network analysis of protein-protein and microRNA (miRNA)-target interactions, and pan-cancer survival analysis. We obtained 668 upregulated and 594 downregulated consensus DEGs, which enriched in the PI3K-AKT, NF-κB and immune-related pathways. In NPC, 98% of 3364 differentially methylated sites were hypermethylated. Actively expressed EBV gene was positively correlated with over-expressed genes coding DNA methyltransferase and Polycomb group proteins, suggesting that EBV infection may have an important role in the hypermethylation of NPC. Through integrated analysis of DNA methylation and mRNA and miRNA expression profiles, we prioritized 56 hypermethylated downregulated genes, including 7 tumor suppressor genes, and constructed a miRNA-target regulation network consisting of 12 hypermethylated miRNAs and 25 upregulated oncogenes. The promoter hypermethylation of causing its downregulation was validated by experimental results and higher expression was associated with longer overall survival in head-neck squamous cell carcinoma, suggesting the potential of as a promising disease biomarker for NPC. Our integrative analysis provides reliable key genes for candidate biomarkers for diagnosis and prognosis in NPC. Based on the combined evidence of promoter hypermethylation, expression up-regulation, and association with overall survival, genes such as , , , , and could be promising novel diagnostic biomarkers, and miRNAs including , , and could be candidate prognosis biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.49392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778547PMC
January 2021

Deep-Blue Perovskite Single-Mode Lasing through Efficient Vapor-Assisted Chlorination.

Adv Mater 2021 Feb 22;33(5):e2006697. Epub 2020 Dec 22.

The Edward S. Rogers Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, M5S 3G4, Canada.

Metal halide perovskites have emerged as promising candidates for solution-processed laser gain materials, with impressive performance in the green and red spectral regions. Despite exciting progress, deep-blue-an important wavelength for laser applications-remains underexplored; indeed, cavity integration and single-mode lasing from large-bandgap perovskites have yet to be achieved. Here, a vapor-assisted chlorination strategy that enables synthesis of low-dimensional CsPbCl  thin films exhibiting deep-blue emission is reported. Using this approach,  high-quality perovskite thin films having a low surface roughness (RMS ≈ 1.3 nm) and efficient charge transfer properties are achieved. These enable us to document low-threshold amplified spontaneous emission. Levering the high quality of the gain medium,  vertical-cavity surface-emitting lasers with a low lasing threshold of 6.5 µJ cm  are fabricated. This report of deep-blue perovskite single-mode lasing showcases the prospect of increasing the range of deep-blue laser sources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202006697DOI Listing
February 2021

Interaction of neutrophil counts and folic acid treatment on new-onset proteinuria in hypertensive patients.

Br J Nutr 2020 Dec 14:1-8. Epub 2020 Dec 14.

National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou510515, People's Republic of China.

We aimed to examine whether baseline neutrophil counts affected the risk of new-onset proteinuria in hypertensive patients, and, if so, whether folic acid treatment is particularly effective in proteinuria prevention in such a setting. A total of 8208 eligible participants without proteinuria at baseline were analysed from the renal substudy of the China Stroke Primary Prevention Trial. Participants were randomised to receive a double-blind daily treatment of 10 mg of enalapril and 0·8 mg of folic acid (n 4101) or 10 mg of enalapril only (n 4107). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. The mean age of the participants was 59·5 (sd, 7·4) years, 3088 (37·6 %) of the participants were male. The median treatment duration was 4·4 years. In the enalapril-only group, a significantly higher risk of new-onset proteinuria was found among participants with higher neutrophil counts (quintile 5; ≥4·8 × 109/l, OR 1·44; 95 % CI 1·00, 2·06), compared with those in quintiles 1-4. For those with enalapril and folic acid treatment, compared with the enalapril-only group, the new-onset proteinuria risk was reduced from 5·2 to 2·8 % (OR 0·49; 95 % CI 0·29, 0·82) among participants with higher neutrophil counts (≥4·8 × 109/l), whereas there was no significant effect among those with neutrophil counts <4·8 × 109/l. In summary, among hypertensive patients, those with higher neutrophil counts had increased risk of new-onset proteinuria, and this risk was reduced by 51 % with folic acid treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S000711452000505XDOI Listing
December 2020

Exploiting Ca signaling in T cells to advance cancer immunotherapy.

Semin Immunol 2020 06 30;49:101434. Epub 2020 Nov 30.

Bone Marrow Transplantation Center of the First Affiliated Hospital, Department of Cell Biology, Zhejiang University School of Medicine, Zhejiang, China. Electronic address:

Decades of basic research has established the importance of Ca to various T cell functions, such as cytotoxicity, proliferation, differentiation and cytokine secretion. We now have a good understanding of how proximal TCR signaling initiates Ca influx and how this influx subsequently changes transcriptional activities in T cells. As chimeric antigen receptor (CAR)-T therapy has achieved great clinical success, is it possible to harness Ca signaling to further advance CAR-T research? How is CAR signaling different from TCR signaling? How can functional CARs be identified in a high-throughput way? Quantification of various Ca signals downstream of CAR/TCR activation might help answer these questions. Here we first summarized recent studies that used Ca dye, genetically-encoded Ca indicators (GECI) or transcriptional activity reporters to understand CAR activation in vitro and in vivo. We next reviewed several proof-of-concept reports that manipulate Ca signaling by light or ultrasound to achieve precise spatiotemporal control of T cell functions. These efforts, though preliminary, opened up new avenues to solve the on-target/off-tumor problem of therapeutic T cells. Other modalities to regulate Ca signaling, such as radio wave and electrical pulse, were also discussed. Thus, monitoring or manipulating Ca signaling in T cells provides us many opportunities to advance cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.smim.2020.101434DOI Listing
June 2020

Relationship of Weight Change Patterns From Young to Middle Adulthood With Incident Cardiovascular Diseases.

J Clin Endocrinol Metab 2021 Jan;106(2):e812-e823

Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.

Context: The effect of weight change patterns on cardiovascular diseases (CVD) remains uncertain.

Objective: We aim to examine the relation of weight change patterns and absolute weight change from young adulthood to midlife with incident CVD.

Design: Retrospective cohort study.

Setting: National Health and Nutrition Examination Survey 1999-2016.

Participants: A total of 20 715 US adults aged 40 through 79 with recalled weight at young adulthood (25 years) and midlife (10 years before baseline).

Main Outcome Measure: CVD status was determined by self-report of a prior diagnosis, and age at diagnosis was used to establish time of CVD onset. CVD events was defined as the first occurrence of a congestive heart failure, coronary heart disease, angina pectoris, heart attack, or stroke.

Results: After 9.76 years of follow-up, compared with participants who remained at normal weight, those in maximum overweight, changing from nonobese to obese, changing from obese to nonobese, maintaining obesity between young and middle adulthood had a 39% (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.19-1.62), 93% (HR, 1.93; 95% CI, 1.64-2.28), 125% (HR, 2.25; 95% CI, 1.29-3.94), and 132% (HR, 2.32; 95% CI, 1.68-3.20) higher risk of CVD, respectively. In addition, compared with weight change within 2.5 kg, weight gain ≥ 10.0 kg was associated with higher risk of CVD.

Conclusions: Both nonobese to obese, obese to nonobese, and stable obese from young to middle adulthood were associated with increased risks of CVD. The findings emphasize the importance of maintaining normal weight throughout the adulthood for preventing CVD in later life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa823DOI Listing
January 2021

Inverse Association Between Riboflavin Intake and New-Onset Hypertension: A Nationwide Cohort Study in China.

Hypertension 2020 12 2;76(6):1709-1716. Epub 2020 Nov 2.

From the Division of Nephrology, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, China (M.L., C.Z., Z.Z., P.H., Y.Z., H.L., C.L., X.Q.).

The prospective relation of dietary riboflavin intake with hypertension remains uncertain. We aimed to investigate the relationship of dietary riboflavin intake with new-onset hypertension and examine possible effect modifiers in general population. A total of 12 245 participants who were free of hypertension at baseline from China Health and Nutrition Survey were included. Dietary intake was measured by 3 consecutive 24-hour dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or diagnosed by physician or under antihypertensive treatment during the follow-up. A total of 4303 (35.1%) subjects developed hypertension during 95 573 person-years of follow-up. Overall, there was a nonlinear, inverse association between total, plant-based, or animal-based riboflavin intake and new-onset hypertension (all for nonlinearity, <0.001). The risk of new-onset hypertension was increased only in participants with relatively lower riboflavin intake. Accordingly, a significantly lower risk of new-onset hypertension was found in participants in quartiles 2 to 4 of total riboflavin intake (hazard ratio, 0.74 [95% CI, 0.68-0.80]), plant-derived riboflavin intake (hazard ratio, 0.77 [95% CI, 0.71-0.84]), or animal-derived riboflavin intake (hazard ratio, 0.70 [95% CI, 0.65-0.77]), compared with those in quartile 1. In addition, the association between total riboflavin intake and new-onset hypertension was particularly evident in those with lower dietary sodium/potassium intake ratio ( interaction, <0.001). In summary, there was an inverse association between riboflavin intake and new-onset hypertension in general Chinese adults. Our results emphasized the importance of maintaining relatively higher riboflavin intake levels for the prevention of hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16211DOI Listing
December 2020

Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults.

Cardiovasc Diabetol 2020 10 24;19(1):186. Epub 2020 Oct 24.

Division of Nephrology, Nanfang Hospital, Southern Medical UniversityNational Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510515, China.

Background: The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.

Methods: A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG < 6.1 mmol/L at baseline and ≥ 6.1 but < 7.0 mmol/L at the exit visit.

Results: Over a median of 4.5 years follow-up, 1549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95% CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95% CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) < 10 μmol/L (adjusted OR, 1.24; 95% CI: 1.10, 1.40 vs. ≥ 10 μmol/L: adjusted OR, 1.03; 95% CI: 0.96, 1.10; P-interaction = 0.007) or FG ≥ 5.9 mmol/L (adjusted OR, 1.16; 95% CI: 1.07, 1.27 vs. < 5.9 mmol/L: adjusted OR, 1.00; 95% CI: 0.93, 1.08; P-interaction = 0.009) CONCLUSIONS: In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels. Clinical Trial Registration-URL Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-020-01161-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585682PMC
October 2020

Mechanism of strand exchange from RecA-DNA synaptic and D-loop structures.

Nature 2020 10 14;586(7831):801-806. Epub 2020 Oct 14.

Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

The strand-exchange reaction is central to homologous recombination. It is catalysed by the RecA family of ATPases, which form a helical filament with single-stranded DNA (ssDNA) and ATP. This filament binds to a donor double-stranded DNA (dsDNA) to form synaptic filaments, which search for homology and then catalyse the exchange of the complementary strand, forming either a new heteroduplex or-if homology is limited-a D-loop. How synaptic filaments form, search for homology and catalyse strand exchange is poorly understood. Here we report the cryo-electron microscopy analysis of synaptic mini-filaments with both non-complementary and partially complementary dsDNA, and structures of RecA-D-loop complexes containing a 10- or a 12-base-pair heteroduplex. The C-terminal domain of RecA binds to dsDNA and directs it to the RecA L2 loop, which inserts into and opens up the duplex. The opening propagates through RecA sequestering the homologous strand at a secondary DNA-binding site, which frees the complementary strand to sample pairing with the ssDNA. At each RecA step, there is a roughly 20% probability that duplex opening will terminate and the as-yet-unopened dsDNA portion will bind to another C-terminal domain. Homology suppresses this process, through the cooperation of heteroduplex pairing with the binding of ssDNA to the secondary site, to extend dsDNA opening. This mechanism locally limits the length of ssDNA sampled for pairing if homology is not encountered, and could allow for the formation of multiple, widely separated synapses on the donor dsDNA, which would increase the likelihood of encountering homology. These findings provide key mechanistic insights into homologous recombination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2820-9DOI Listing
October 2020