Publications by authors named "Gang Li"

4,468 Publications

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High-efficiency quantitative control of mitochondrial transfer based on droplet microfluidics and its application on muscle regeneration.

Sci Adv 2022 Aug 17;8(33):eabp9245. Epub 2022 Aug 17.

Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong SAR, China.

Mitochondrial transfer is a spontaneous process to restore damaged cells in various pathological conditions. The transfer of mitochondria to cell therapy products before their administration can enhance therapeutic outcomes. However, the low efficiency of previously reported methods limits their clinical application. Here, we developed a droplet microfluidics-based mitochondrial transfer technique that can achieve high-efficiency and high-throughput quantitative mitochondrial transfer to single cells. Because mitochondria are essential for muscles, myoblast cells and a muscle injury model were used as a proof-of-concept model to evaluate the proposed technique. In vitro and in vivo experiments demonstrated that C2C12 cells with 31 transferred mitochondria had significant improvements in cellular functions compared to those with 0, 8, and 14 transferred mitochondria and also had better therapeutic effects on muscle regeneration. The proposed technique can considerably promote the clinical application of mitochondrial transfer, with optimized cell function improvements, for the cell therapy of mitochondria-related diseases.
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http://dx.doi.org/10.1126/sciadv.abp9245DOI Listing
August 2022

Pd(ii)-catalyzed -C-H bromination and chlorination of aniline and benzoic acid derivatives.

Chem Sci 2022 Jul 5;13(29):8686-8692. Epub 2022 Jul 5.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences (CAS) 155 West Yang-Qiao Road Fuzhou Fujian 350002 China

The classic electrophilic bromination leads to - and -bromination of anilines due to their electron-rich properties. Herein we report the development of an unprecedented Pd-catalyzed -C-H bromination of aniline derivatives using commercially available -bromophthalimide (NBP), which overcomes the competing /-selectivity of electrophilic bromination of anilines. The addition of acid additives is crucial for the success of this reaction. A broad range of substrates with various substitution patterns can be tolerated in this reaction. Moreover, benzoic acid derivatives bearing complex substitution patterns are also viable with this mild bromination reaction, and -C-H chlorination is also feasible under similar reaction conditions. The ease of the directing group removal and subsequent diverse transformations of the brominated products demonstrate the application potential of this method and promise new opportunities for drug discovery.
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http://dx.doi.org/10.1039/d2sc01834aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337732PMC
July 2022

Exploration of the Shared Gene Signatures between Myocardium and Blood in Sepsis: Evidence from Bioinformatics Analysis.

Biomed Res Int 2022 6;2022:3690893. Epub 2022 Aug 6.

Department of Critical Care Medicine, Hubei Province Hospital of Traditonal Chinese Medicine, 856 Luoyu Street, Wuhan, Hubei 430061, China.

Background: Septic cardiomyopathy is widespread during sepsis and has adverse effects on mortality. Diagnosis of septic cardiomyopathy now mainly depends on transthoracic echocardiogram. Although some laboratory tests such as troponin T and atrial brain natriuretic peptide play a role in the diagnosis, specific blood biochemistry biomarkers are still lacking. In our study, we sought to find potential biological markers from genes and pathways that are covariant in the blood and myocardium of septic patients. Bioinformatics and machine learning methods were applied to achieve our goal. Datasets of myocardium and peripheral blood of patients with sepsis were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected and received functional enrichment analysis. Unsupervised hierarchical clustering analysis was performed to identify the subtypes of sepsis. Random forest, lasso regression, and logistic regression were used for variable screening and model construction. Internal and external validation sets were applied to verify the efficiency of the model in classifying disease and predicting mortality.

Results: By defining significance for genes using Student's -test, we obtained 1,049 genes commonly changed in both myocardium and blood of patients with sepsis. The upregulated genes (LogFC >0) were related to inflammation pathways, and downregulated (LogFC <0) genes were related to mitochondrial and aerobic metabolism. We divided 468 sepsis patients into two groups with different clinical result based on the mortality-related commonly changed genes (104 genes), using unsupervised hierarchical clustering analysis. In our validation datasets, a six-gene model (, , , , , and ) was obtained and proven to perform well in classifying groups and predicting mortality.

Conclusion: We have identified genes that have the potential to become biomarkers for septic cardiomyopathy. Additionally, the pathophysiological changes in the myocardium of patients with sepsis were also reflected in peripheral blood to some extent. The co-occurring pathological processes can affect the prognosis of sepsis.
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http://dx.doi.org/10.1155/2022/3690893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375705PMC
August 2022

Di(2-ethylhexyl) Phthalate Disturbs Cholesterol Metabolism Through Oxidative Stress In Rat Liver.

Environ Toxicol Pharmacol 2022 Aug 12:103958. Epub 2022 Aug 12.

Department of Environmental Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang Province, China 150086. Electronic address:

Di(2-ethylhexyl) phthalate (DEHP) is widely used and has been implicated in hepatotoxicity, although the mechanism is unclear. Here, we investigated the effect of DEHP on hepatic cholesterol metabolism in SD rats exposed to 0 and 300mg/kg/day DEHP for 12 weeks. An RNA-Seq analysis was performed to describe the hepatic responses to long-term DEHP exposure in combination with serological and oxidative stress parameter measurements. DEHP increased the serum levels of total cholesterol (TC), high-density lipoprotein (HDL), and alanine transaminase (ALT). Moreover, DEHP increased the content of malondialdehyde (MDA) and decreased antioxidant enzyme activities in the liver. Transcriptomic results revealed that DEHP dramatically changed the cholesterol metabolism pathway and oxidation-reduction process and depressed gene expression involved in cholesterol efflux and monooxygenase activity. Total antioxidant capacity (T-AOC) positively correlated with Abcg5 and Abcg8. Overall, this study showed the mechanisms underlying hepatotoxicity caused by DEHP, providing new insights into understanding DEHP poisoning.
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http://dx.doi.org/10.1016/j.etap.2022.103958DOI Listing
August 2022

Non-invasive diagnosis and surveillance of bladder cancer with driver and passenger DNA methylation in a prospective cohort study.

Clin Transl Med 2022 Aug;12(8):e1008

Department of Urology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.

Background: State-of-art non-invasive diagnosis processes for bladder cancer (BLCA) harbour shortcomings such as low sensitivity and specificity, unable to distinguish between high- (HG) and low-grade (LG) tumours, as well as inability to differentiate muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). This study investigates a comprehensive characterization of the entire DNA methylation (DNAm) landscape of BLCA to determine the relevant biomarkers for the non-invasive diagnosis of BLCA.

Methods: A total of 304 samples from 224 donors were enrolled in this multi-centre, prospective cohort study. BLCA-specific DNAm signature discovery was carried out with genome-wide bisulfite sequencing in 32 tumour tissues and 12 normal urine samples. A targeted sequencing assay for BLCA-specific DNAm signatures was developed to categorize tumour tissue against normal urine, or MIBC against NMIBC. Independent validation was performed with targeted sequencing of 259 urine samples in a double-blinded manner to determine the clinical diagnosis and prognosis value of DNAm-based classification models. Functions of genomic region harbouring BLCA-specific DNAm signature were validated with biological assays. Concordances of pathology to urine tumour DNA (circulating tumour DNA [ctDNA]) methylation, genomic mutations or other state-of-the-art diagnosis methods were measured.

Results: Genome-wide DNAm profile could accurately classify LG tumour from HG tumour (LG NMIBC vs. HG NMIBC: p = .038; LG NMIBC vs. HG MIBC, p = .00032; HG NMIBC vs. HG MIBC: p = .82; Student's t-test). Overall, the DNAm profile distinguishes MIBC from NMIBC and normal urine. Targeted-sequencing-based DNAm signature classifiers accurately classify LG NMIBC tissues from HG MIBC and could detect tumours in urine at a limit of detection of less than .5%. In tumour tissues, DNAm accurately classifies pathology, thus outperforming genomic mutation or RNA expression profiles. In the independent validation cohort, pre-surgery urine ctDNA methylation outperforms fluorescence in situ hybridization (FISH) assay to detect HG BLCA (n = 54) with 100% sensitivity (95% CI: 82.5%-100%) and LG BLCA (n = 26) with 62% sensitivity (95% CI: 51.3%-72.7%), both at 100% specificity (non-BLCA: n = 72; 95% CI: 84.1%-100%). Pre-surgery urine ctDNA methylation signature correlates with pathology and predicts recurrence and metastasis. Post-surgery urine ctDNA methylation (n = 61) accurately predicts recurrence-free survival within 180 days, with 100% accuracy.

Conclusion: With the discovery of BLCA-specific DNAm signatures, targeted sequencing of ctDNA methylation outperforms FISH and DNA mutation to detect tumours, predict recurrence and make prognoses.
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http://dx.doi.org/10.1002/ctm2.1008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377153PMC
August 2022

Harmonized neonatal brain MR image segmentation model for cross-site datasets.

Biomed Signal Process Control 2021 Aug 1;69. Epub 2021 Jun 1.

Department of Radiology and BRIC, University of North Carolina at Chapel Hill, NC, USA.

Accurate segmentation of white matter, gray matter and cerebrospinal fluid from neonatal brain MR images is of great importance in characterizing early brain development. Deep-learning-based methods have been successfully applied to neonatal brain MRIs with superior performance if testing subjects were acquired with the same imaging protocols/scanners as training subjects. However, for the testing subjects acquired with different imaging protocols/scanners, they cannot achieve accurate segmentation results due to large appearance/pattern differences between the testing and training subjects. Besides, imaging artifacts, like head motion, which are inevitable during the imaging acquisition process, also pose a challenge for the segmentation methods. To address these issues, in this paper, we propose a harmonized neonatal brain MR image segmentation model that harmonizes testing images acquired by different protocols/scanners into the domain of training images through a cycle-consistent generative adversarial network (CycleGAN). Meanwhile, the artifacts can be largely alleviated during the harmonization. Then, a densely-connected U-Net based segmentation model trained in the domain of training images can be applied robustly for segmenting the harmonized testing images. Comparisons with existing methods illustrate the better performance of the proposed method on neonatal brain MR images from cross-sites, a grand segmentation challenge, as well as images with artifacts.
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http://dx.doi.org/10.1016/j.bspc.2021.102810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9371447PMC
August 2021

Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts.

Research (Wash D C) 2022 19;2022:9826426. Epub 2022 Jul 19.

Department of Cell Biology, Third Military Army Medical University, Chongqing 400038, China.

Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.
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http://dx.doi.org/10.34133/2022/9826426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351587PMC
July 2022

Type-I Heterostructure Based on WS/PtS for High-Performance Photodetectors.

ACS Appl Mater Interfaces 2022 Aug 12. Epub 2022 Aug 12.

Key Laboratory of Materials Physics, Anhui Key Laboratory of Nanomaterials and Nanotechnology, Institute of Solid State Physics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, P. R. China.

van der Waals (vdW) heterodiodes composed of two-dimensional (2D) layered materials led to a new prospect in photoelectron diodes and photovoltaic devices. Existing studies have shown that Type-I heterostructures have great potential to be used as photodetectors; however, the tunneling phenomena in Type-I heterostructures have not been fully revealed. Herein, a highly efficient nn WS/PtS Type-I vdW heterostructure photodiode is constructed. The device shows an ultrahigh reverse rectification ratio of 10 owing to the transmission barrier-induced low reverse current. A unilateral depletion region is formed on WS, which inhibits the recombination of carriers at the interface and makes the external quantum efficiency (EQE) of the device reach 67%. Due to the tunneling mechanism of the device, which allows the co-existence of a large photocurrent and a low dark current, this device achieves a light on/off ratio of over 10. In addition, this band design allows the device to maintain a high detectivity of 4.53 × 10 Jones. Our work provides some new ideas for exploring new high-efficiency photodiodes.
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http://dx.doi.org/10.1021/acsami.2c08827DOI Listing
August 2022

LncRNA MNX1-AS1 contributes to lung adenocarcinoma progression by targeting the miR-34a/SIRT1 axis.

Am J Transl Res 2022 15;14(7):4977-4989. Epub 2022 Jul 15.

Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University Zhengzhou 450008, Henan, China.

LncRNA MNX1-AS1 is known to be involved in progression of several tumor types. However, few studies have investigated the molecular mechanism of MNX1-AS1 in lung adenocarcinoma (LAC). To explore the function of MNX1-AS1 in the pathogenesis of LAC, qRT-PCR was performed to show MNX1-AS1 expression. MNX1-AS1 expression in LAC cells was suppressed by siRNA to detect the biologic behavior. The relationships among miR-34a, MNX1-AS1 and SIRT1 were confirmed by pull-down and dual-luciferase reporter assay. Whether MNX1-AS1 was involved in LAC by targeting miR-34a/SIRT1 axis was verified. MNX1-AS1 was up-regulated in LAC, and over-expression of MNX1-AS1 was significantly associated with lymph node metastasis and poor prognosis. In A549 and H1299 cells, cell proliferation, migration, and invasion were suppressed, the cell cycle was regulated, as well as apoptosis was increased after silencing MNX1-AS1. Mechanistically, MNX1-AS1 served as a ceRNA of miR-34a to down-regulate miR-34a expression. SIRT1 is targeted by miR-34a and its expression is regulated by MNX1-AS1 and miR-34a. Up-regulation of SIRT1 salvaged the effect of silencing MNX1-AS1 on A549 and H1299 cells, to some extent. These results showed that MNX1-AS1 contributes to LAC progression by targeting the miR-34a/SIRT1 axis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360842PMC
July 2022

Shift in subsistence crop dominance from broomcorn millet to foxtail millet around 5500 BP in the western Loess Plateau.

Front Plant Sci 2022 26;13:939340. Epub 2022 Jul 26.

MOE Key Laboratory of Western China's Environmental System, College of Earth & Environmental Sciences, Lanzhou University, Lanzhou, China.

Broomcorn and foxtail millet were the most important crops in northern China during the Neolithic period. Although the significance of broomcorn millet in human subsistence exceeded that of foxtail millet during the early Neolithic, this pattern was reversed by the end of Neolithic period. However, the process underlying this shift remains unclear. The recent excavation of the Gedachuan (GDC) in Zhangjiachuan county has revealed an abundance of relics including millet crop remains from relatively continuous strata of the Yangshao and Qijia cultures, and therefore provides a unique opportunity to examine how and when foxtail millet replaced broomcorn millet as the dominant crop in the western Loess Plateau during the Neolithic period. In this study, we identify 1,738 and 2,686 broomcorn and foxtail millet remains, respectively, from 74 flotation samples, accounting for 38.81% and 59.98% of total plant remains, respectively. Compared with 23 direct dates of carbonized crop grains in GDC, we propose that the weight of foxtail millet in plant subsistence of GDC first exceeded that of broomcorn millet as early as ∼5,500 BP, filling an important gap in the archaeobotanical record from the western Loess Plateau. Further comparative analysis of multidisciplinary data suggests the shift in significance of these two millet crops during the late Neolithic may have been triggered by variations in human settlement intensity and climate change in the western Loess Plateau. The results of this study also suggest that the Banpo Phase of Yangshao Culture survived in the western Loess Plateau as late as ∼5,600 BP.
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http://dx.doi.org/10.3389/fpls.2022.939340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362993PMC
July 2022

HSPB8 Overexpression Ameliorates Cognitive Impairment in Diabetic Mice via Inhibiting NLRP3 Inflammation Activation.

Oxid Med Cell Longev 2022 1;2022:9251835. Epub 2022 Aug 1.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of cognitive impairment. And the underlying mechanism remains unillustrated. HSPB8 is a member of the small heat shock protein family. In this study, we found that the expression of HSPB8 was upregulated in the hippocampus of high - fat diet (HFD) + streptozotocin (STZ) -  induced diabetic mice and N2a cells exposed to high glucose. Overexpression of HSPB8 relieved cognitive decline in DM mice. Mechanically, HSPB8 overexpression in the hippocampus of diabetic mice inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation via dephosphorylating mitochondrial fission-associated protein dynamin-related protein 1 (DRP1) at the phosphorylated site Ser616 (p-Drp1S616). Furthermore, HSPB8 overexpression increased mitochondrial membrane potential (MMP) and reduced oxidative stress. These results indicate a protective effect of HSPB8 in the hippocampus of diabetic mice and N2a cells exposed to high glucose. Overexpression of HSPB8 might be a useful strategy for treating T2DM-related cognitive decline.
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http://dx.doi.org/10.1155/2022/9251835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359860PMC
August 2022

Serum complement C1q level is associated with left ventricular hypertrophy induced by coarctation of the aorta: A retrospective observational study.

BMC Cardiovasc Disord 2022 08 10;22(1):367. Epub 2022 Aug 10.

Beijing Institute of Heart, Lung and Blood Vessel Diseases, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing, 100029, China.

Background: The complement system plays an important role in the development of left ventricular hypertrophy. Complement C1q is an initial component of the classical complement pathway and is related to many inflammatory diseases. We aimed to determine whether there was an association between serum complement C1q and left ventricular hypertrophy induced by coarctation of the aorta (CoA).

Methods: Based on whether CoA was combined with a large ventricular septal defect (VSD) or patent ductus arteriosus (PDA), the patients were divided into a simple CoA group (n = 15) and a complex CoA group (n = 13). Meanwhile, we selected simple large VSD (n = 14) patients and normal children (n = 28) as the control group. The serum complement C1q level was compared using immunity transmission turbidity among different groups.

Results: The preoperative content of C1q in the simple CoA group was significantly lower than that in the complex CoA group and normal group (96.97 ± 20.66 vs. 130.73 ± 35.78, 96.97 ± 20.66 vs. 156.21 ± 29.14, P < 0.05). There was no significant difference in the preoperative content of C1q between the complex CoA group and the large VSD group (P > 0.05). There was a negative correlation between the preoperative complement C1q content and the interventricular septal thickness and left ventricular posterior wall thickness (r = - 0.035, r = - 0.288, P < 0.05). The percentage of postoperative decrease in C1q in children with simple CoA or complex CoA was positively correlated with the time of cardiopulmonary bypass and aortic cross clamp, respectively (r = 0.797, r = 0.622, r = 0.898, r = 0.920, P < 0.05). There was no significant difference in the content of preoperative triglycerides (TG), total cholesterol (TCHO), high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C) among the different groups (P > 0.05). In the simple CoA group and complex CoA group, the preoperative complement C1q, TG, TCHO, HDL-C and LDL-C levels were significantly higher than those after the operation (P < 0.05). There was no significant correlation between preoperative complement C1q and TG, TCHO, HDL-C or LDL-C (P > 0.05).

Conclusions: Complement C1q has an inhibitory effect on the formation of left ventricular hypertrophy, which may not be mediated by regulating lipid metabolism. During cardiac surgery, complement C1q may have a protective effect against myocardial injury.
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http://dx.doi.org/10.1186/s12872-022-02807-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364524PMC
August 2022

Detection of potential pathogen in pancreatic fluid aspiration with metagenomic next-generation sequencing in patients with suspected infected pancreatic necrosis.

Dig Liver Dis 2022 Aug 7. Epub 2022 Aug 7.

Center of Severe Acute Pancreatitis (CSAP), Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; National Institute of Healthcare Data Science, Nanjing University, Nanjing, China. Electronic address:

Background: Timely and accurate microbial diagnosis is important in managing patients with infected pancreatic necrosis (IPN).

Aims: To evaluate the diagnostic performance of Metagenomic next-generation sequencing (mNGS) in patients with suspected IPN.

Methods: The clinical data of 40 patients with suspected IPN who underwent CT-guided pancreatic fluid aspiration were retrospectively analyzed. Microbial culture and mNGS were simultaneously applied to identify the potential pathogens. The diagnostic performance of the mNGS was assessed by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results: The mNGS report can be obtained significantly earlier than culture methods (42 (36-62 h) vs. 60 (42-124 h), P = 0.032). Across all the study samples, seven species of bacteria and two species of fungi were reported accordingly to the culture results, while 22 species of bacteria and two species of fungi were detected by mNGS. The sensitivity, specificity, NPV, and PPV of mNGS were 88.0%, 100%, 83.33%, and 100%, respectively.

Conclusions: The diagnostic accuracy of mNGS in patients with suspected IPN is satisfactory. Moreover, mNGS may broaden the range of identifiable infectious pathogens and provide a more timely diagnosis.
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http://dx.doi.org/10.1016/j.dld.2022.07.014DOI Listing
August 2022

Fast Lasso-type safe screening for Fine-Gray competing risks model with ultrahigh dimensional covariates.

Stat Med 2022 Aug 9. Epub 2022 Aug 9.

Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA.

The Fine-Gray proportional sub-distribution hazards (PSH) model is among the most popular regression model for competing risks time-to-event data. This article develops a fast safe feature elimination method, named PSH-SAFE, for fitting the penalized Fine-Gray PSH model with a Lasso (or adaptive Lasso) penalty. Our PSH-SAFE procedure is straightforward to implement, fast, and scales well to ultrahigh dimensional data. We also show that as a feature screening procedure, PSH-SAFE is safe in a sense that the eliminated features are guaranteed to be inactive features in the original Lasso (or adaptive Lasso) estimator for the penalized PSH model. We evaluate the performance of the PSH-SAFE procedure in terms of computational efficiency, screening efficiency and safety, run-time, and prediction accuracy on multiple simulated datasets and a real bladder cancer data. Our empirical results show that the PSH-SAFE procedure possesses desirable screening efficiency and safety properties and can offer substantially improved computational efficiency as well as similar or better prediction performance in comparison to their baseline competitors.
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http://dx.doi.org/10.1002/sim.9545DOI Listing
August 2022

Dexmedetomidine Ameliorated Cognitive Dysfunction Induced by Intestinal Ischemia Reperfusion in Mice with Possible Relation to the Anti-inflammatory Effect Through the Locus Coeruleus Norepinephrine System.

Neurochem Res 2022 Aug 9. Epub 2022 Aug 9.

Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China.

Cognitive impairment is a common central nervous system complication that occurs following surgery or organs damage outside the nervous system. Neuroinflammation plays a key role in the molecular mechanisms of cognitive impairment. Dexmedetomidine alleviates neuroinflammation and reduces cognitive dysfunction incidence; however, the mechanism by which dexmedetomidine alleviates cognitive dysfunction remains unclear. This study evaluated the effect of dexmedetomidine on attenuation of early cognitive impairment induced by intestinal ischemia-reperfusion in mice and examined whether the locus coeruleus norepinephrine (LCNE) system participates in the anti-inflammatory effect of dexmedetomidine. The superior mesenteric artery was clamped for 45 min to induce intestinal ischemia reperfusion injury. Dexmedetomidine alone or combined with DSP-4, a selective locus coeruleus noradrenergic neurotoxin, was used for pretreatment. Postoperative cognition was assessed using the Morris water maze. Serum and hippocampal levels of IL-1β, TNF-α, norepinephrine (NE), and malondialdehyde (MDA) were assessed by enzyme-linked immunosorbent assay. Immunofluorescence, immunohistochemistry, and hematoxylin and eosin staining were used to evaluate the expression of tyrosine hydroxylase (TH) in the locus coeruleus, hippocampal microglia, and intestinal injury. Pretreatment with dexmedetomidine alleviated intestinal injury and decreased the serum and hippocampal levels of NE, IL-1β, TNF-α, and MDA at 24 h after intestinal ischemia reperfusion, decreased TH-positive neurons in the locus coeruleus, and ameliorated cognitive impairment. Similarly, DSP-4 pre-treatment alleviated neuroinflammation and improved cognitive function. Furthermore, α2-adrenergic receptor antagonist atipamezole or yohimbine administration diminished the neuroprotective effects and improved cognitive function with dexmedetomidine. Therefore, dexmedetomidine attenuated early cognitive dysfunction induced by intestinal ischemia-reperfusion injury in mice, which may be related to its anti-inflammatory effects through the LCNE system.
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http://dx.doi.org/10.1007/s11064-022-03706-wDOI Listing
August 2022

Mapping developmental regionalization and patterns of cortical surface area from 29 post-menstrual weeks to 2 years of age.

Proc Natl Acad Sci U S A 2022 Aug 8;119(33):e2121748119. Epub 2022 Aug 8.

Department of Radiology and Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.

Surface area of the human cerebral cortex expands extremely dynamically and regionally heterogeneously from the third trimester of pregnancy to 2 y of age, reflecting the spatial heterogeneity of the underlying microstructural and functional development of the cerebral cortex. However, little is known about the developmental patterns and regionalization of cortical surface area during this critical stage, due to the lack of high-quality imaging data and accurate computational tools for pediatric brain MRI data. To fill this critical knowledge gap, by leveraging 1,037 high-quality MRI scans with the age between 29 post-menstrual weeks and 24 mo from 735 pediatric subjects in two complementary datasets, i.e., the Baby Connectome Project (BCP) and the developing Human Connectome Project (dHCP), and state-of-the-art dedicated image-processing tools, we unprecedentedly parcellate the cerebral cortex into a set of distinct subdivisions purely according to the developmental patterns of the cortical surface. Our discovered developmentally distinct subdivisions correspond well to structurally and functionally meaningful regions and reveal spatially contiguous, hierarchical, and bilaterally symmetric patterns of early cortical surface expansion. We also show that high-order association subdivisions, where cortical folds emerge later during prenatal stages, undergo more dramatic cortical surface expansion during infancy, compared with the central regions, especially the sensorimotor and insula cortices, thus forming a distinct central-pole division in early cortical surface expansion. These results provide an important reference for exploring and understanding dynamic early brain development in health and disease.
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http://dx.doi.org/10.1073/pnas.2121748119DOI Listing
August 2022

Subpromille Measurements and Calculations of CO (3-0) Overtone Line Intensities.

Phys Rev Lett 2022 Jul;129(4):043002

Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT, United Kingdom.

Intensities of lines in the near-infrared second overtone band (3-0) of ^{12}C^{16}O are measured and calculated to an unprecedented degree of precision and accuracy. Agreement between theory and experiment to better than 1‰ is demonstrated by results from two laboratories involving two independent absorption- and dispersion-based cavity-enhanced techniques. Similarly, independent Fourier transform spectroscopy measurements of stronger lines in this band yield mutual agreement and consistency with theory at the 1‰ level. This set of highly accurate intensities can provide an intrinsic reference for reducing biases in future measurements of spectroscopic peak areas.
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http://dx.doi.org/10.1103/PhysRevLett.129.043002DOI Listing
July 2022

Non-structure protein ORF1ab (NSP8) in SARS-CoV-2 contains potential γδT cell epitopes.

Front Microbiol 2022 22;13:936272. Epub 2022 Jul 22.

Institute of Basic Medical Science, Hubei University of Medicine, Shiyan, China.

Upon activation by the pathogen through T-cell receptors (TCRs), γδT cells suppress the pathogenic replication and thus play important roles against viral infections. Targeting SARS-CoV-2 γδT cells provides alternative therapeutic strategies. However, little is known about the recognition of SARS-CoV-2 antigens by γδT cells. We discovered a specific Vγ9/δ2 CDR3 by analyzing γδT cells derived from the patients infected by SARS-CoV-2. Using a cell model exogenously expressing γδ-TCR established, we further screened the structural motifs within the CDR3 responsible for binding to γδ-TCR. Importantly, these sequences were mapped to NSP8, a non-structural protein in SARS-CoV-2. Our results suggest that NSP8 mediates the recognition by γδT cells and thus could serve as a potential target for vaccines.
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http://dx.doi.org/10.3389/fmicb.2022.936272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354780PMC
July 2022

Soil mesofauna alter the balance between stochastic and deterministic processes in the plastisphere during microbial succession.

Sci Total Environ 2022 Aug 3;849:157820. Epub 2022 Aug 3.

Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen 361021, China; Ningbo Urban Environment Observation and Research Station, Chinese Academy of Sciences, 88 Zhongke Road, NingBo 315800, China. Electronic address:

Plastic debris, as a novel substrate, provides an avenue for enriching microbial growth. Although the structure of the aquatic plastisphere microbial community is well-characterised, linkages between microbial community assembly and species co-existence in the soil plastisphere vary and remain poorly understood, particularly when soil fauna is involved. This study investigated the soil plastisphere community, including bacteria, fungi, and protists, focusing on microbial succession and community assembly processes impacted by soil mesofauna. Certain soil plastisphere microbial taxa thrived at particular time points (e.g. Actinobacteria at 60 d), indicating the irreplaceable role of microplastic selection for time-sensitive taxa. Additionally, the biodiversity of keystone ecological clusters in the soil plastisphere was significantly associated with incubation time. Furthermore, the slopes of bacterial and fungal time-decay curves in soil plastisphere were steeper when treated with soil mesofauna than without soil mesofauna, whereas protist time-decay curves (total and abundant taxa) exhibited the opposite trend. Soil mesofauna increased the relative importance of determinacy in the soil plastisphere bacterial assembly process, while enhancing the stochasticity of fungal and protistan community assemblages. The study demonstrates the complex assembly patterns of soil plastisphere microbial communities, emphasising the importance of interactions between the plastisphere and local soil fauna from an ecological perspective.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157820DOI Listing
August 2022

Prevalence and risk factors analysis for low back pain among occupational groups in key industries of China.

BMC Public Health 2022 08 5;22(1):1493. Epub 2022 Aug 5.

National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP.

Methods: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors.

Results: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors.

Conclusion: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.
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http://dx.doi.org/10.1186/s12889-022-13730-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354373PMC
August 2022

Plasma metagenomic next-generation sequencing of microbial cell-free DNA detects pathogens in patients with suspected infected pancreatic necrosis.

BMC Infect Dis 2022 Aug 5;22(1):675. Epub 2022 Aug 5.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Background: Infected pancreatic necrosis (IPN) is a life-threatening complication of acute pancreatitis (AP). Timely diagnosis of IPN could facilitate appropriate treatment, but there is a lack of reliable non-invasive screening tests. In this study, we aimed to evaluate the diagnostic value of plasma metagenomic next-generation sequencing (mNGS) based on circulating microbial cell-free DNA in patients with suspected IPN.

Methods: From October 2020 to October 2021, 44 suspected IPN patients who underwent plasma mNGS were reviewed. Confirmatory diagnosis of IPN within two weeks after the index blood sampling was considered the reference standard. The confirmation of IPN relied on the microbiological results of drains obtained from the necrotic collections. The distribution of the pathogens identified by plasma mNGS was analyzed. Positive percent agreement (PPA) and negative percent agreement (NPA) were evaluated based on the conformity between the overall mNGS results and culture results of IPN drains. In addition, the clinical outcomes were compared between mNGS positive and negative patients.

Results: Across all the study samples, thirteen species of bacteria and five species of fungi were detected by mNGS. The positivity rate of plasma mNGS was 54.55% (24/44). Of the 24 mNGS positive cases, twenty (83.33%, 95% CI, 68.42-98.24%) were consistent with the culture results of IPN drains. The PPA and NPA of plasma mNGS for IPN were 80.0% (20/25; 95% CI, 64.32-95.68%) and 89.47% (17/19; 95% CI, 75.67-100%), respectively. Compared with the mNGS negative group, patients in the positive group had more new-onset septic shock [12 (50.0%) vs. 4 (20.0%), p = 0.039].

Conclusion: IPN relevant pathogens can be identified by plasma mNGS, potentially facilitating appropriate treatment. The clinical application of mNGS in this cohort appears feasible.
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http://dx.doi.org/10.1186/s12879-022-07662-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356476PMC
August 2022

Thermodynamic and kinetic studies on harmful algal blooms harvesting by novel etherified cationic straw flocculant.

Bioresour Technol 2022 Aug 2;361:127737. Epub 2022 Aug 2.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin, Heilongjiang Province 150090, China.

Harmful algal blooms (HABs) are growing threats that cause tens of billion dollars economic loss annually. Aiming at efficient disposal of HABs, a cheap and eco-friendly cationic straw was developed by etherification of wheat straw, which replaced hydroxyl groups on cellulose by quaternary ammonium groups. It endowed the cationic straw with high positive charge and achieved 93.92% of harvesting efficiency by enhancing HABs cells aggregation via charge neutralization. Different from inorganic salts-based flocculants, HABs harvesting by the cationic straw is a spontaneous and exothermic process with negative ΔG° and ΔH° under all adsorption conditions. Thermodynamics and kinetics analysis elucidated that HABs adsorption process by cationic straw were mainly driven by physical forces. Together, cationic straw preparation and HABs harvesting processes were comprehensively optimized with orthogonal experiments. The work may inspire cost-effective HABs disposal and fill knowledge gaps of process nature for HABs harvesting.
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http://dx.doi.org/10.1016/j.biortech.2022.127737DOI Listing
August 2022

Foxp2 inhibits Th9 cell differentiation and attenuates allergic airway inflammation in a mouse model of ovalbumin-induced asthma.

Int Immunopharmacol 2022 Aug 2;111:109060. Epub 2022 Aug 2.

Department of Respiratory Medicine, Children's Hospital of Soochow University, Suzhou 215003, China. Electronic address:

This study aimed to explore the effects of forkhead box P2 gene (Foxp2) on T-helper 9 (Th9) differentiation in asthmatic mice. An in vivo asthmatic mouse model was induced with ovalbumin (OVA). An in vitro model was established by culturing CD4 T cells with TGF-β, IL-4, and anti-IFN-γ. ELISA, flow cytometry, qRT-PCR and Western blot were performed to examine IL-9 secretion, Th9 cell number, and Th9 cell transcription factor expression, respectively. Pathological changes in lung tissues and airway mucus secretion were assessed with HE and PAS glycogen staining. Anti-IL-9 mAb reversed the elevation in Th9 cells and IL-9 expression in lung tissues and bronchoalveolar lavage fluid (BALF) of asthmatic mice. Foxp2 was downregulated in BALF and lung tissue of asthmatic mice and Th9 cells. Overexpression of Foxp2 inhibited Th9 cell differentiation in vitro and improved airway inflammation in vivo. Our study suggests that overexpression of Foxp2 attenuates allergic asthma by inhibiting Th9 cell differentiation.
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http://dx.doi.org/10.1016/j.intimp.2022.109060DOI Listing
August 2022

Intestinal stents: Structure, functionalization and advanced engineering innovation.

Biomater Adv 2022 Jun 29;137:212810. Epub 2022 Apr 29.

Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA. Electronic address:

Intestinal stents are a palliative treatment option that solves many shortcomings of traditional surgeries for cancer-induced intestinal obstructions. The present review provides an overview of the incidence, clinical manifestations and limitations in the treatment of intestinal cancers. The paper also discusses material property requirements, indications, complications and the future of stent-assisted therapy. The advantages and disadvantages of different materials and processing techniques for intestinal stents are reviewed along with new stent treatment combinations for colorectal cancer. Challenges that require further cooperative studies are also detailed. The future development of intestinal stents will depend on innovation in material designs as well as the utilization of multi-functional strategies and innovative engineering solutions.
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http://dx.doi.org/10.1016/j.bioadv.2022.212810DOI Listing
June 2022

Establishment of a patient-derived organoid model and living biobank for nasopharyngeal carcinoma.

Ann Transl Med 2022 May;10(9):526

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital of the Southern Medical University, Guangzhou, China.

Background: Recurrent nasopharyngeal carcinoma (NPC) remains a major challenge for clinicians and scientists. Tumor organoid is a revelational disease model that highly resembled the heterogeneity and histopathological characteristics of original tumors. This study aimed to optimize the modeling process of patient-derived NPC organoids (NPCOs), and establish a living-biobank of NPCs to study the mechanism and explore the more effective treatment of the disease.

Methods: Sixty-two fresh NPC tissue samples and 15 normal mucosa samples were collected for 3-dimensional (3D) organoid culture. The organoids were confirmed using hematoxylin and eosin assays. The expression levels of , and Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were detected by immunohistochemistry (IHC) and in situ hybridization (ISH). Recurrent NPCOs were frozen in liquid nitrogen for 6 months and then resuscitated and passaged.

Results: We identified a novel two-step enzymatic strategy for the treatment of NPC and nasal mucosa specimens and an optimal medium for culturing NPCOs and nasal mucosa organoids (NMOs). Organoid cultures were generated from 34 primary NPC samples, 28 recurrent NPC samples, and 15 normal mucosa samples. The success rates for primary NPCO, recurrent NPCO, and NMO formation were 47.06%, 81.25%, and 86.5%, respectively. All the NPCOs were positive and negative. Recurrent NPCOs had higher expressions of stem cell markers, including , and . Additionally, recurrent NPCOs could be cultured to passage 4 and frozen and revived repeatedly, while primary NPCOs were challenging to culture.

Conclusions: In summary, we successfully established a living biobank using the NPCO model, which has enormous potential in basic and clinical research on NPC.
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http://dx.doi.org/10.21037/atm-22-1076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347035PMC
May 2022

Fintech, Bank Risk-Taking, and Risk-Warning for Commercial Banks in the Era of Digital Technology.

Front Psychol 2022 13;13:934053. Epub 2022 Jul 13.

Graduate School, Jungwon University, Cheongju, South Korea.

Fintech risks commercial banks in three ways, particularly operational efficiency, financial innovation, and risk management. Based on the data of 37 Chinese-listed commercial banks from 2011 to 2020, the study empirically analyzes the impact of fintech on bank risk-taking, and the intermediary effects of the three channels, such as operational efficiency, financial innovation, and risk management. The results show that fintech can effectively reduce the risk of banks. The results of heterogeneity analysis revealed that fintech strongly affects the risk-taking of state-owned banks but not obviously for rural commercial banks. Financial efficiency, financial innovation, and risk management indirectly affect the risk-taking of banks that contributed 8.51, 7.18, and 5.77%, respectively. We also constructed the commercial bank risk-warning index. Based on the quarterly data of banks from 2011 to 2020, we empirically tested the early warning effect of the bank risk-warning index. The results showed that when the signal month is set to 12 months, the bank risk-warning index can have a warning effect in this period.
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http://dx.doi.org/10.3389/fpsyg.2022.934053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345119PMC
July 2022

Diagnostic Accuracy of Deep Learning and Radiomics in Lung Cancer Staging: A Systematic Review and Meta-Analysis.

Front Public Health 2022 18;10:938113. Epub 2022 Jul 18.

Department of Cardiology, The 3rd Affiliated Hospital of Chengdu Medical College, Pidu District People's Hospital, Chengdu, China.

Background: Artificial intelligence has far surpassed previous related technologies in image recognition and is increasingly used in medical image analysis. We aimed to explore the diagnostic accuracy of the models based on deep learning or radiomics for lung cancer staging.

Methods: Studies were systematically reviewed using literature searches from PubMed, EMBASE, Web of Science, and Wanfang Database, according to PRISMA guidelines. Studies about the diagnostic accuracy of radiomics and deep learning, including the identifications of lung cancer, tumor types, malignant lung nodules and lymph node metastase, were included. After identifying the articles, the methodological quality was assessed using the QUADAS-2 checklist. We extracted the characteristic of each study; the sensitivity, specificity, and AUROC for lung cancer diagnosis were summarized for subgroup analysis.

Results: The systematic review identified 19 eligible studies, of which 14 used radiomics models and 5 used deep learning models. The pooled AUROC of 7 studies to determine whether patients had lung cancer was 0.83 (95% CI 0.78-0.88). The pooled AUROC of 9 studies to determine whether patients had NSCLC was 0.78 (95% CI 0.73-0.83). The pooled AUROC of the 6 studies that determined patients had malignant lung nodules was 0.79 (95% CI 0.77-0.82). The pooled AUROC of the other 6 studies that determined whether patients had lymph node metastases was 0.74 (95% CI 0.66-0.82).

Conclusion: The models based on deep learning or radiomics have the potential to improve diagnostic accuracy for lung cancer staging.

Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0167/, identifier: INPLASY202230167.
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http://dx.doi.org/10.3389/fpubh.2022.938113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339706PMC
August 2022

Prevalence of Metabolic Syndrome and Risk Factors Among Chinese Adults: Results from a Population-Based Study - Beijing, China, 2017-2018.

China CDC Wkly 2022 Jul;4(29):640-645

Institute of Reproductive and Child Health / Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.

What Is Already Known About This Topic?: Metabolic syndrome (MetS) is one of the most easily available health indicative markers for cardiovascular diseases, and it has become a major public health problem worldwide due to increasing urbanization and aging populations. The prevalence of MetS increased dramatically in China, however, there are no records of MetS defined by the 2017 Chinese Diabetes Society for Beijing by far.

What Is Added By This Report?: In this study, the data of 24,412 participants aged 18-74 years from a large population-based study in Beijing was collected. The overall prevalence of MetS among Beijing residents was 24.5%. The prevalence was 35.2% in males and 15.4% in females.

What Are The Implications For Public Health Practice?: Effective public health strategies should target males, people with older age, lower education, higher body mass index, smokers, those who drink alcohol, those who are unemployed or retired, and those who live in rural areas on MetS prevention and control.
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http://dx.doi.org/10.46234/ccdcw2022.138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339350PMC
July 2022

Comparative evaluation of thermal and emission performances for improved commercial coal-fired stoves in China.

RSC Adv 2022 Jul 20;12(32):20886-20896. Epub 2022 Jul 20.

Bioenergy and Environmental Science and Technology Laboratory, College of Engineering, China Agricultural University Beijing 100083 China.

The extensive use of traditional cooking stoves to meet daily cooking and heating requirements has highlighted the serious problem of indoor and outdoor air pollution. This study evaluates seven improved coal-fired space-heating and cooking stoves and compares them with a widely used stove of an older design, selected as a baseline reference. The seven stoves were selected from a range of candidate improved stoves submitted by manufacturers for testing as part of the air quality improvement in the Hebei Clean Air Project, Hebei Province, China. Stove performance was evaluated when burning raw coal and coal briquettes during the high and low power stages respectively. All seven improved cooking stoves surpassed the baseline stove in combined heating and cooking thermal and emission performance. Among the improved cooking stoves, Model 2-TL was found to have the highest average thermal efficiency, 87.2 ± 0.5%, when burning coal briquettes at high and low power. The lowest emission of PM was 0.94 ± 0.5 mg MJ , CO 0.55 ± 0.28 g MJ , and CO/CO 1.1 ± 0.6%, respectively. It is concluded that the use of these improved heating and cooking stoves should be promoted for daily cooking and heating requirements. This strategy will not only save fuel to the benefit of the household, but widespread adoption could contribute to significant reductions of CO and PM emissions in Hebei Province.
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http://dx.doi.org/10.1039/d2ra03364jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297129PMC
July 2022

Nerve implants with bioactive interfaces enhance neurite outgrowth and nerve regeneration in vivo.

Colloids Surf B Biointerfaces 2022 Jul 27;218:112731. Epub 2022 Jul 27.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address:

Nerve implants functionalized with growth factors and stem cells are critical to promote neurite outgrowth, regulate neurodifferentiation, and facilitate nerve regeneration. In this study, human umbilical cord mesenchymal stem cells (hUCMSCs) and 3,4-hydroxyphenalyalanine (DOPA)-containing insulin-like growth factor 1 (DOPA-IGF-1) were simultaneously applied to enhance the bioactivity of poly(lactide-co-glycolide) (PLGA) substrates which will be potentially utilized as nerve implants. In vitro and in vivo evaluations indicated that hUCMSCs and DOPA-IGF-1 could synergistically regulate neurite outgrowth of PC12 cells, improve intravital recovery of motor functions, and promote conduction of nerve electrical signals in vivo. The enhanced functional and structural nerve regeneration of injured spinal cord might be mainly attributable to the synergistically enhanced biofunctionality of hUCMSCs and DOPA-IGF-1/PLGA on the bioactive interfaces. Findings from this study demonstrate the potential of hUCMSC-seeded, DOPA-IGF-1-modified PLGA implants as promising candidates for promoting axonal regeneration and motor functional recovery in spinal cord injury treatment.
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http://dx.doi.org/10.1016/j.colsurfb.2022.112731DOI Listing
July 2022
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