Publications by authors named "Xiaohua Wang"

437 Publications

Comparison of Epidermal Gene Expression Profiles in Mice Aged 1 to 20 Months.

Clin Cosmet Investig Dermatol 2022 16;15:69-76. Epub 2022 Jan 16.

Department of Dermatology, Jinan University, Guangzhou City, Guangdong Province, People's Republic of China.

Introduction: Although it is well known that epidermal function changes with aging, the transcriptomic basis and possible signaling pathways for aging-associated functional changes remain largely unknown.

Methods: Here, we employed RNA sequencing techniques to assess epidermal gene expression profiles in the epidermis of mice aged 1, 2, 6, 12 and 20 months.

Results: A total of 132 genes displayed reductions in expression levels with aging, while expression levels of 406 genes increased with aging. Epidermal gene expression was prominently upregulated in 2-month-old vs 1-month-old mice, while more genes were downregulated in 12-month-old mice. Upregulation of genes associated with immune/inflammatory responses was observed in the epidermis of aged mice in comparison to that of young mice, whereas downregulated signaling pathways in the epidermis of aged mice were primarily involved in metabolism, such as fatty acid elongation, glutathione metabolism and biosynthesis of antibiotics. Some signaling pathways, such as chemokine signaling, cytokine/cytokine receptor interaction signaling and IL-17 signaling pathways, were remarkably upregulated in 12-month-old mice. Steroid synthesis, metabolic pathway, thermogenesis and proteasome pathways were steadily downregulated, starting at 2 months old.

Conclusion: These results indicate that the epidermis of aged mice displays an upregulation of genes associated with inflammatory signaling pathways, and downregulation of genes related to metabolic signaling pathways.
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http://dx.doi.org/10.2147/CCID.S346416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778644PMC
January 2022

Deep muscularis propria tumor invasion without lymph node metastasis as a unique subclassification of stage IB gastric cancer: a retrospective study.

BMC Gastroenterol 2022 Jan 21;22(1):30. Epub 2022 Jan 21.

The Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, People's Republic of China.

Background: The prognosis difference based on the depth of tumor muscularis propria invasion in gastric cancer (GC) was still debated, and therapy strategy for stage IB GC patient required further investigation.

Methods: A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in superficial muscularis propria (sMP) group and 195 in deep muscularis propria (dMP) group.

Results: The overall survival (OS) was significantly better for patients in sMP group than for patients in dMP group (P = 0.007). In multivariate analysis, depth of tumor invasion, pN stage, age, primary location, positive expression of p53, elevated maximal LDH, elevated initial CA19-9 and AFP level were independent prognostic factors for OS. The sMP group had a significantly better OS than dMP group (P = 0.014) in pN0 stage. After further stratification, the survival outcomes were not significantly different between deep muscularis propria tumor invasion without lymph node metastasis (dMPN0) group (stage IB) and superficial muscularis propria tumor invasion with stage 1-2 lymph node metastasis (sMPN1-2) group (stage II) (P = 0.100). Patients with adjuvant chemotherapy had a statistically better survival than those without in dMPN0 group (P = 0.045) and dMPN0 patients with adjuvant chemotherapy had better OS than sMPN1-2 patients (P = 0.015). In addition, greater postoperative survival could be observed in sMPN0 patients than dMPN0 patients in p53-positive group (P = 0.002), and similar OS could be seen between dMPN0 patients with p53-positive and T2N1-2 patients (P = 0.872).

Conclusion: As a unique subclassification of stage IB GC, appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53, elevated LDH could be potential factors in identifying the different prognoses for stage IB GC patients.
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http://dx.doi.org/10.1186/s12876-021-02090-zDOI Listing
January 2022

Subhealth Risk Perception Scale: Development and Validation of a New Measure.

Comput Math Methods Med 2022 10;2022:9950890. Epub 2022 Jan 10.

School of Marxism Studies, Anhui Medical University, Hefei, Anhui 230032, China.

Background: To develop an individual's physical subhealth risk perception scale and evaluate its reliability and validity, so as to provide a measurement tool for individual physical health risk.

Methods: A questionnaire on the perception risk of physical subhealth was developed. Using a random sampling method, 785 people in the Anhui provincial physical examination centre were selected as the research participants. Of the questionnaires returned, 770 were valid, giving an effective rate of 98%. Firstly, the Pearson correlation coefficient method was used to study the correlation of 35 items in the initial scale, and then, polychoric factor structure analysis was carried out by using the Pratt matrix to optimize the item structure. The Cronbach' coefficient method was used to test the internal consistency reliability, and a structural equation model was used to explore the construct validity of the scale. The discriminant validity of the scale was obtained by factor analysis. A general linear model was used to analyse the relationship between the clinical manifestations of physical subhealth and the level of risk perception, and the convergent validity of the scale was evaluated.

Results: All the data of 35 items were significantly correlated at the 0.01 level. The correlation coefficients between a1 and a2, a3 and a4, b1 and b2, b2 and b3, c4 and c5, c5 and c6, c6 and c7, c8 and c9, d1 and d2, d2 and d3, e5 and e6, g1 and g2, g2 and g3, and g2 and g4 were greater than 0.6. The items with correlation coefficients greater than 0.6 were reduced by a Pratt matrix. The resulting physical subhealth risk perception scale covers five factors with a total of 18 items. The Cronbach' coefficient of the scale was 0.889, and the Cronbach' coefficients of the five factors F1-F5 were 0.780, 0.825, 0.801, 0.736, and 0.704, respectively. Structural equation model analysis showed that /df = 3.43, < 0.001, RMSEA = 0.08, GFI = 0.88, NFI = 0.84, AGFI = 0.84, and CFI = 0.88. Factor analysis showed that factors F1-F5 had significant correlations ( < 0.01), and the correlation coefficients were less than the corresponding square root value of AVE. Based on the subhealth clinical manifestations of the participants, the general linear model was used to explore the convergent validity of the scale, and the results indicated that the scale passed the convergent validity test.

Conclusions: We propose a physical subhealth risk perception scale amounting to 18 items, which includes five dimensions: health knowledge (2 items), risk perception (5 items), trust selection (4 items), information channel (4 items), and social groups (3 items). The reliability and validity of the physical subhealth risk perception scale are acceptable. Applying the scale into practice has potential to improve the overall public health level.
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http://dx.doi.org/10.1155/2022/9950890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764275PMC
January 2022

rhADAMTS13 reduces oxidative stress by cleaving VWF in ischaemia/reperfusion-induced acute kidney injury.

Acta Physiol (Oxf) 2022 Jan 6:e13778. Epub 2022 Jan 6.

Kidney Disease Center of the First Affiliated Hospital and Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.

Aims: Acute kidney injury (AKI), a major health burden, lacks effective therapy. Anti-inflammatory actions of a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 (ADAMTS13) may provide a new treatment option for AKI. Along with inflammation, oxidative stress is critical for AKI development, yet the impact of ADAMTS13 on oxidative stress in AKI remains to be fully elucidated.

Methods: We assess recombinant human ADAMTS13 (rhADAMTS13) actions on oxidative stress in a murine ischaemia/reperfusion (IR) model. Antioxidant stress-enzyme activities, renal morphology, kidney function markers and vascular function of isolated afferent arterioles are quantified.

Results: rhADAMTS13 provided after IR, reduces blood urea nitrogen (BUN) by 33% and serum creatinine (Scr) by 73% in 24 hours post-IR. rhADAMTS13 reduces BUN (40.03 ± 20.34 mmol/L vs 72.35 ± 18.74 mmol/L, P < .01), Scr (75.67 ± 51.19 μmol/L vs 176.17 ± 55.38 μmol/L, P < .01) and proteinuria by 41% in 48 hours post-IR as well. Moreover, rhADAMTS13 administration decreases malondialdehyde (MDA) and increases the activity of antioxidant stress enzymes, and attenuates reactive oxygen species production. rhADAMTS13 also upregulates nuclear factor-erythroid-2-related factor 2/haem oxygenase-1, enhances antioxidant enzymes activity and alleviates endothelial dysfunction. Finally, treatment with rhADAMTS13 mitigates severe functional and morphological injury present in IR mice. Extracellular signal-regulated kinase (ERK) phosphorylation is limited by rhADAMTS13 and PPARγ expression is partly restored in ischaemic kidneys. Co-administration of von Willebrand factor (VWF) impairs rhADAMTS13's antioxidant capacity and its protective role in IR.

Conclusion: rhADAMTS13 alleviates renal IR injury through antioxidant effects by cleaving VWF.
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http://dx.doi.org/10.1111/apha.13778DOI Listing
January 2022

Optimal regenerative repair of large segmental bone defect in a goat model with osteoinductive calcium phosphate bioceramic implants.

Bioact Mater 2022 May 23;11:240-253. Epub 2021 Sep 23.

National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China.

So far, how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic. In this study, a strategy of combining osteoinductive biphasic calcium phosphate (BCP) bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects (3.0 cm in length) in goat femur model. The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa, and total porosity of 84%. The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs). The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage, promoting the osteogenic process both guided and induced by the BCP scaffolds. At 9 months postoperatively, good integration between the implants and host bone was observed, and a large amount of newborn bones formed, accompanying with the degradation of the material. At 18 months postoperatively, almost the complete new bone substitution in the defect area was achieved. The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery. Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects. The current study could provide an effective method to treat the clinical large segmental bone defects.
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http://dx.doi.org/10.1016/j.bioactmat.2021.09.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668427PMC
May 2022

Alternating therapeutic plasma exchange (TPE) with double plasma molecular adsorption system (DPMAS) for the treatment of fulminant hepatic failure (FHF).

Clin Case Rep 2021 Dec 13;9(12):e05220. Epub 2021 Dec 13.

Department of Nephrology Center of Nephrology and Urology The Seventh Affiliated Hospital Sun Yat-sen University Shenzhen China.

Alternating therapeutic plasma exchange with double plasma molecular adsorption system can rapidly remove bilirubin and ammonia and supplement the essential substance from the blood, which could be used as an effective treatment for fulminant hepatic failure.
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http://dx.doi.org/10.1002/ccr3.5220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667290PMC
December 2021

BI-1 ameliorates myocardial injury by activating the mitochondrial unfolded protein response and FUNDC1-related mitophagy in cardiorenal syndrome type 3.

Cell Signal 2022 Mar 16;91:110218. Epub 2021 Dec 16.

Department of Vascular Medicine, Peking University Shougang Hospital, Beijing 100144, China. Electronic address:

It has been suggested that mitochondrial dysfunction underlies the myocardial injury seen following cardiorenal syndrome type 3 (CRS-3). Both mitophagy and the mitochondrial unfolded protein response (UPR) are protective programs that preserve mitochondrial homeostasis. Here, we explored whether Bax inhibitor-1 (BI-1) overexpression attenuates CRS-3-related myocardial injury through activation of mitophagy and the UPR in cardiomyocytes. Following CRS-3 induction via renal ischemia-reperfusion injury, BI-1 transgenic (BI1) mice showed greater preservation of myocardial integrity and relaxation function and less cardiomyocyte apoptosis than wild-type (WT) mice. Moreover, BI-1 overexpression attenuated CRS-3-mediated myocardial inflammation, as indicated by decreased MCP-1 and IL-6 expression and normalized ATP production in cardiomyocytes. After CRS-3 induction, mitophagy was inhibited in cardiomyocytes from WT mice, as indicated by both decreased Fundc1 transcription and mt-Keima fluorescence, and modest activation of the UPR, denoted by a slight increase in Atf6 mRNA levels. By contrast, activation of mitophagy and marked UPR upregulation were observed in cardiac tissue from BI1 mice. shRNA-mediated silencing of Fundc1 or Atf6 greatly impaired mitochondrial metabolism and survival in cultured cardiomyocytes overexpressing BI-1. Thus, upregulation of BI-1 expression aimed at activating mitophagy and the UPR may represent a useful therapeutic approach for the treatment of CRS-3.
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http://dx.doi.org/10.1016/j.cellsig.2021.110218DOI Listing
March 2022

Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells.

Front Pharmacol 2021 16;12:727920. Epub 2021 Nov 16.

Department of Nephrology, Center of Nephrology and Urology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.

Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs and . Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.
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http://dx.doi.org/10.3389/fphar.2021.727920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636678PMC
November 2021

Transplanted Human Oligodendrocyte Progenitor Cells Restore Neurobehavioral Deficits in a Rat Model of Preterm White Matter Injury.

Front Neurol 2021 10;12:749244. Epub 2021 Nov 10.

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

Preterm white matter injury (PWMI) is a common brain injury and a leading cause of life-long neurological deficits in premature infants; however, no effective treatment is available yet. This study aimed to investigate the fate and effectiveness of transplanted human oligodendrocyte progenitor cells (hOPCs) in a rat model of PWMI. Hypoxia-ischemia was induced in rats at postnatal day 3, and hOPCs (6 × 10 cells/5 μL) were intracerebroventricularly transplanted at postnatal day 7. Neurobehavior was assessed 12 weeks post-transplant using the CatWalk test and Morris water maze test. Histological analyses, as well as immunohistochemical and transmission electron microscopy, were performed after transcardial perfusion. Transplanted hOPCs survived for 13 weeks in PWMI brains. They were widely distributed in the injured white matter, and migrated along the corpus callosum to the contralateral hemisphere. Notably, 82.77 ± 3.27% of transplanted cells differentiated into mature oligodendrocytes, which produced myelin around the axons. Transplantation of hOPCs increased the fluorescence intensity of myelin basic protein and the thickness of myelin sheaths as observed in immunostaining and transmission electron microscopy, while it reduced white matter atrophy at the level of gross morphology. With regard to neurobehavior, the CatWalk test revealed improved locomotor function and inter-paw coordination after transplantation, and the cognitive functions of hOPC-transplanted rats were restored as revealed by the Morris water maze test. Myelin restoration through the transplantation of hOPCs led to neurobehavioral improvements in PWMI rats, suggesting that transplanting hOPCs may provide an effective and promising therapeutic strategy in children with PWMI.
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http://dx.doi.org/10.3389/fneur.2021.749244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631304PMC
November 2021

Comparative analysis of physiological, agronomic and transcriptional responses to drought stress in wheat local varieties from Mongolia and Northern China.

Plant Physiol Biochem 2022 Jan 17;170:23-35. Epub 2021 Nov 17.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China. Electronic address:

Drought is one of the major abiotic stresses that threaten wheat production worldwide, especially in the Mongolian Plateau and adjacent regions. This study aims to find local wheat varieties with high yields and drought resistance at various developmental stages based on agronomic traits and drought resistance indices analysis and explore the underlining molecular mechanisms by transcriptome analysis. Our results revealed that drought stress started at the seedling stage has a greater impact on crop yields. Four types of drought responses were found among the tested varieties. Type 1 and type 2 show low tolerance to drought stress despite high or low yield in control condition, type 3 exhibits high yield under control condition but dropped significantly after drought, and type 4 displays relatively high and stable yields under control and drought conditions. Transcriptome analysis performed with the representative varieties of the four types revealed GO terms and KEGG pathways enriched among drought-triggered differential expressed genes (DEGs). A network containing 18 modules was constructed using weighted gene co-expression analysis (WGCNA). Ten modules were significantly correlated to yield by module-trait correlation, and 3 modules showed Darkhan 144 specific gene expression patterns. C2H2 zinc finger factor-recognized motifs were identified from the promoters of genes in these modules. qRT-PCR confirmed several key DEGs with specific expression patterns and physiological measurements validated the relatively low oxidative damage and high antioxidant capacity in the drought tolerant variety Dankhan 144. These findings provide an important basis for local agriculture and breeding of drought-tolerant high yield wheat varieties.
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http://dx.doi.org/10.1016/j.plaphy.2021.11.026DOI Listing
January 2022

Estimating the burden and modeling mitigation strategies of pork-related hepatitis E virus foodborne transmission in representative European countries.

One Health 2021 Dec 18;13:100350. Epub 2021 Nov 18.

Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, China.

Hepatitis E virus (HEV) is an emerging zoonotic pathogen posing global health burden, and the concerns in Europe are tremendously growing. Pigs serve as a main reservoir, contributing to pork-related foodborne transmission. In this study, we aim to specifically simulate this foodborne transmission route and to assess potential interventions. We firstly established a dose-response relationship between the risk of transmission to human and the amount of ingested viruses. We further estimated the incidence of HEV infection specifically attributed to pork-related foodborne transmission in four representative European countries. Finally, we demonstrated a proof-of-concept of mitigating HEV transmission by implementing vaccination in human and pig populations. Our modeling approach bears essential implications for better understanding the transmission of pork-related foodborne HEV and for developing mitigation strategies.
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http://dx.doi.org/10.1016/j.onehlt.2021.100350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606544PMC
December 2021

Effect of limb rotation on radiographic alignment measurement in mal-aligned knees.

Biomed Eng Online 2021 Nov 27;20(1):119. Epub 2021 Nov 27.

Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, People's Republic of China.

Purpose: Long-leg-radiography (LLR) is commonly used for the measurement of lower limb alignment. However, limb rotations during radiography may interfere with the alignment measurement. This study examines the effect of limb rotation on the accuracy of measurements based on the mechanical and anatomical axes of the femur and tibia, with variations in knee flexion and coronal deformity.

Methods: Forty-five lower limbs of 30 patients were scanned with CT. Virtual LLRs simulating five rotational positions (neutral, ± 10[Formula: see text], and ± 20[Formula: see text] internal rotation) were generated from the CT images. Changes in the hip-knee-ankle angle (HKA) and the femorotibial angle (FTA) were measured on each image with respect to neutral values. These changes were related to knee flexion and coronal deformity under both weight- and non-weight-bearing conditions.

Results: The measurement errors of the HKA and FTA derived from limb rotation were up to 4.84 ± 0.66[Formula: see text] and 7.35 ± 0.88[Formula: see text], respectively, and were correlated with knee flexion (p < 0.001) and severe coronal deformity (p < 0.001). Compared with the non-weight-bearing position, the coronal deformity measured in the weight-bearing condition was 2.62[Formula: see text] greater, the correlation coefficients between the coronal deformity and the deviation ranges of HKA and FTA were also greater.

Conclusions: Flexion and severe coronal deformity have a significant influence on the measurement error of lower limb alignment. Errors can be amplified in the weight-bearing condition compared with the non-weight-bearing condition. When using HKA and FTA to represent the mechanical axis and the anatomical axis on LLR, limb rotation impacts the anatomic axis more than the mechanical axis in patients with severe deformities. Considering LLR as the gold standard image modality, attention should be paid to the measurement of knee alignment. Especially for the possible errors derived from weight-bearing long-leg radiographs of patients with severe knee deformities.
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http://dx.doi.org/10.1186/s12938-021-00956-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626971PMC
November 2021

Association between Dietary Fiber Intake and Incidence of Depression and Anxiety in Patients with Essential Hypertension.

Nutrients 2021 Nov 20;13(11). Epub 2021 Nov 20.

School of Nursing, Medical College, Soochow University, Suzhou 215006, China.

(1) Background: Our previous study found that the dietary fiber supplement in patients with hypertension increased SCFA-producers, Bififidobacterium and Spirillum in the gut microbiota, which may be associated with improvement of depression and anxiety through the gut-brain axis. However, only a few studies have explored the association between dietary fiber intake (DFI) and the incidence of depression and anxiety in hypertensive patients. (2) Methods: A cross-sectional survey was conducted in one comprehensive hospital and one community clinic aimed at understanding the status of DFI and the association between DFI and incidences of depression and anxiety in hypertensive patients. Levels of DFI were obtained through a two-24 h diet recall. According to the levels of DFI from low to high, the participants were divided into Q1, Q2, Q3 and Q4 groups. The Reported Outcomes Measurement Information System short form v1.0-Depression 8b and Anxiety 8a were used to assess patients' levels of depression and anxiety. (3) Results: A total of 459 hypertensive patients were recruited and the daily DFI was 10.4 g. The incidences of hypertension combined with depression and anxiety were 19.6% and 18.5%, respectively. Regression analysis showed statistically significant associations between DFI and depression (B = -0.346, = 0.001) and anxiety score (B = -0.565, < 0.001). In logistic regression, after the covariates were adjusted, DFI was associated with the incidence of depression in Q3 (OR 2.641, 95% CI 1.050-6.640) and with that of anxiety in Q1 (OR 2.757, 95% CI 1.035-7.346), compared with Q4. (4) Conclusions: A higher consumption of DF was a protective factor for depression and anxiety in hypertensive patients.
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http://dx.doi.org/10.3390/nu13114159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623764PMC
November 2021

miR‑30a‑5p induces the adipogenic differentiation of bone marrow mesenchymal stem cells by targeting FAM13A/Wnt/β‑catenin signaling in aplastic anemia.

Mol Med Rep 2022 01 25;25(1). Epub 2021 Nov 25.

Department of Blood Transfusion, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222061, P.R. China.

Aplastic anemia (AA) is a bone marrow failure syndrome with high morbidity and mortality. Bone marrow (BM)‑mesenchymal stem cells (MSCs) are the main components of the BM microenvironment, and dysregulation of BM‑MSC adipogenic differentiation is a pathologic hallmark of AA. MicroRNAs (miRNAs/miRs) are crucial regulators of multiple pathological processes such as AA. However, the role of miR‑30a‑5p in the modulation of BM‑MSC adipogenic differentiation in AA remains unclear. The present study aimed to explore the effect of miR‑30a‑5p on AA BM‑MSC adipogenic differentiation and the underlying mechanism. The levels of miR‑30a‑5p expression and family with sequence similarity 13, member A (FAM13A) mRNA expression in BM‑MSCs were quantified using reverse transcription‑quantitative (RT‑q) PCR. The mRNA expression levels of adipogenesis‑associated factors [fatty acid‑binding protein 4 (FABP4), lipoprotein lipase (LPL), perilipin‑1 (PLIN1), peroxisome proliferator‑activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)] were analyzed using RT‑qPCR. Lipid droplet accumulation was evaluated using Oil Red O staining in BM‑MSCs. The interaction between miR‑30a‑5p and the FAM13A 3'‑untranslated region was identified by TargetScan, and a dual‑luciferase reporter assay was used to confirm the interaction. The expression levels of FAM13A and Wnt/β‑catenin pathway‑related proteins were examined via western blotting. The results showed that miR‑30a‑5p expression levels were significantly elevated in BM‑MSCs from patients with AA compared with those in control subjects (iron deficiency anemia). miR‑30a‑5p expression levels were also significantly increased in adipose‑induced BM‑MSCs in a time‑dependent manner. miR‑30a‑5p significantly promoted AA BM‑MSC adipogenic differentiation, and significantly enhanced the mRNA expression levels of FABP4, LPL, PLIN1, PPARγ and C/EBPα as well as lipid droplet accumulation. miR‑30a‑5p was also demonstrated to target FAM13A in AA BM‑MSCs. FAM13A significantly reduced BM‑MSC adipogenic differentiation by activating the Wnt/β‑catenin signaling pathway. In conclusion, miR‑30a‑5p was demonstrated to serve a role in AA BM‑MSC adipogenic differentiation by targeting the FAM13A/Wnt/β‑catenin signaling pathway. These findings suggest that miR‑30a‑5p may be a therapeutic target for AA.
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http://dx.doi.org/10.3892/mmr.2021.12543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630822PMC
January 2022

Fusion of KATZ measure and space projection to fast probe potential lncRNA-disease associations in bipartite graphs.

PLoS One 2021 22;16(11):e0260329. Epub 2021 Nov 22.

Pharmacy School, Guilin Medical University, Guilin, China.

It is well known that numerous long noncoding RNAs (lncRNAs) closely relate to the physiological and pathological processes of human diseases and can serves as potential biomarkers. Therefore, lncRNA-disease associations that are identified by computational methods as the targeted candidates reduce the cost of biological experiments focusing on deep study furtherly. However, inaccurate construction of similarity networks and inadequate numbers of observed known lncRNA-disease associations, such inherent problems make many mature computational methods that have been developed for many years still exit some limitations. It motivates us to explore a new computational method that was fused with KATZ measure and space projection to fast probing potential lncRNA-disease associations (namely KATZSP). KATZSP is comprised of following key steps: combining all the global information with which to change Boolean network of known lncRNA-disease associations into the weighted networks; changing the similarities calculation into counting the number of walks that connect lncRNA nodes and disease nodes in bipartite graphs; obtaining the space projection scores to refine the primary prediction scores. The process to fuse KATZ measure and space projection was simplified and uncomplicated with needing only one attenuation factor. The leave-one-out cross validation (LOOCV) experimental results showed that, compared with other state-of-the-art methods (NCPLDA, LDAI-ISPS and IIRWR), KATZSP had a higher predictive accuracy shown with area-under-the-curve (AUC) value on the three datasets built, while KATZSP well worked on inferring potential associations related to new lncRNAs (or isolated diseases). The results from real cases study (such as pancreas cancer, lung cancer and colorectal cancer) further confirmed that KATZSP is capable of superior predictive ability to be applied as a guide for traditional biological experiments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260329PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608294PMC
January 2022

Upcycle hazard against other hazard: Toxic fluorides from plasma fluoropolymer etching turn novel microbial disinfectants.

J Hazard Mater 2022 02 2;424(Pt D):127658. Epub 2021 Nov 2.

State Key Laboratory of Electrical Insulation and Power Equipment, Center for Plasma Biomedicine, Xi'an Jiaotong University, Xi'an 710049, PR China.

The release of toxic fluoride byproducts is a seemingly unavoidable artifact of surface engineering, causing severe environmental and human health problems. Here we propose and implement a new "upcycle hazard against other hazard" concept in the case study of cold atmospheric plasma surface modification of fluoropolymers such as polytetrafluorethylene (PTFE). Capitalizing on the excellent controllability, precision and energy efficiency of the plasma surface processing, complemented with the recently discovered ability of plasmas to activate water to produce a potent electrochemical disinfectant, referred to as the plasma-activated water (PAW), we demonstrate a radically new solution to capture the hazardous gaseous fluorides into the PAW and use the as-fluorinated PAW (F-PAW) as a very effective antimicrobial disinfectant. A customized surface discharge reactor is developed to evaluate the effects of fluorides released from the plasma etching of PTFE on the chemistries in gas-phase plasmas and F-PAW, as well as the antibacterial effect of F-PAW. The results show that gaseous fluorides, including COF, CFCOF, and SiF are produced in gas-phase plasmas, and the dissolution of thus-generated fluorides into PAW has a strong effect on inactivating catalase and destroying the oxidation resistance of bacterial cells. As a result, the antibacterial effect of PAW-fluorides against the methicillin-resistant Staphylococcus aureus (MRSA) is enhanced by > 5 log reductions, suggesting that otherwise hazardous fluorides from the plasma processing of PTFE can be used to enhance the microbial disinfection efficiency of PAW. The demonstrated approach opens new avenues for sustainable hazard valorization exemplified by converting toxic fluoride-etching products into potent antimicrobial and potentially anti-viral disinfectants.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127658DOI Listing
February 2022

Early-pregnancy maternal heart rate is related to gestational diabetes mellitus (GDM).

Eur J Obstet Gynecol Reprod Biol 2022 Jan 10;268:31-36. Epub 2021 Nov 10.

Nursing Department, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Objective: The study examined the association between resting heart rate (RHR) of early pregnancy and risk of gestational diabetes mellitus (GDM) in Chinese population.

Methods: As retrospective study, medical data of 15,092 pregnant women gave birth in 2019 was collected and analyzed. The pregnant women's age, educational level, pre-pregnancy body weight, height, parity, family history of diabetes, lipid profile, blood pressure and RHR were recorded during 11 ∼ 13 weeks. Multivariate logistic regression analysis was used to estimate the association between maternal characteristics and RHR and GDM. And we further evaluated the predictive roll of RHR in different sub-groups defined by their body mass index (BMI), age, fasting plasma glucose (FPG), total cholesterol and triglyceride.

Results: 2313 women (15.33%) were diagnosed as GDM according to 75 g OGTT. According to the quartile value of RHR, the subjects were divided into four groups. Risk of GDM increased significantly as RHR increased. In the fully adjusted model, ORs(95%CI) for the lowest vs highest quartiles of heart rate were 1(as reference), 1.14(0.97 ∼ 1.33), 1.25(1.05 ∼ 1.40), 1.41(1.21 ∼ 1.62), respectively. In the subgroup's analysis, we found the relationship between RHR and risk of GDM was evident in women with low and normal BMI; with normal fasting plasma; and normal serum lipid level.

Conclusion: The current study shows early-pregnancy maternal RHR is associated with potential risk of developing GDM.
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http://dx.doi.org/10.1016/j.ejogrb.2021.11.007DOI Listing
January 2022

Trimethylamine N-oxide promotes hyperoxaluria-induced calcium oxalate deposition and kidney injury by activating autophagy.

Free Radic Biol Med 2022 Feb 10;179:288-300. Epub 2021 Nov 10.

Department of Physiology, School of Basic Medical Sciences, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 10117, Germany. Electronic address:

Calcium oxalate (CaOx) is the most common component of kidney stones. Oxidative stress, inflammation and autophagy-induced cell death are the major causes of CaOx crystal deposition and CaOx crystal deposition can further lead to kidney injury. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, plays an important role in the pathogenesis of many diseases, such as atherosclerosis, diabetes and chronic kidney disease, but the effect of TMAO on hyperoxaluria-induced CaOx crystal deposition and kidney injury remains unknown. We hypothesize that TMAO aggravates CaOx crystal deposition via promoting CaOx-mediated cell death. C57Bl/6 mice were given high-oxalate diet as a model of hyperoxaluria. TMAO was provided via drinking water. Serum TMAO levels increased 15 days after CaOx treatment (6.30 ± 0.17 μmol/L vs. 34.65 ± 8.95 μmol/L). High-oxalate diet induced inflammation, CaOx deposition and kidney injury, which TMAO aggravated. In accordance, TMAO intensified high-oxalate diet induced oxidative stress, autophagy and apoptosis. Moreover, TMAO enhanced CaOx crystal adhesion to HK-2 cells and reduced cell viability (from 88.9 ± 1.6% to 75.0 ± 2.7%). Protein kinase R-like endoplasmic reticulum kinase (PERK) may mediate these TMAO effects, as TMAO promoted PERK phosphorylation. Consistently, PERK knockdown alleviated TMAO-evoked CaOx-autophagy, apoptosis and oxidative stress in HK-2 cells. In conclusion, TMAO can aggravate hyperoxaluria-induced kidney injury by triggering the PERK/ROS pathway, which enhances autophagy, apoptosis and inflammation, and facilitates CaOx crystal deposition in renal tubular cells.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.11.010DOI Listing
February 2022

Healthy values and domestication of sand rice (), a comparative view against .

Crit Rev Food Sci Nutr 2021 Nov 10:1-22. Epub 2021 Nov 10.

Key Laboratory of Stress Physiology and Ecology in Cold and Arid Regions, Gansu Province, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou, P.R, China.

Sand rice () is prized for its well-balanced nutritional properties, broad adaptability in Central Asia and highly therapeutic potentials. It has been considered as a potential climate-resilient crop. Its seed has comparable metabolite profile with and is rich in proteins, essential amino acids, minerals, polyunsaturated fatty acids, and phenolics, but low in carbohydrates. Phenolics like protocatechuic acid and quercetins have been characterized with biological functions on regulation of lipid and glucose metabolism in addition to anti-inflammatory and antioxidant activities. Sand rice is thus an important source for developing functional and nutraceutical products. Though historical consumption has been over 1300 years, sand rice has undergone few agronomic improvements until recently. Breeding by individual selection has been performed and yield of the best genotype can reach up to 1295.5 kg/ha. Furthermore, chemical mutagenesis has been used to modify the undesirable traits and a case study of a dwarf line (), which showed the Green Revolution-like phenotypes, is presented. Utilization of both breeding methodologies will accelerate its domestication process. As a novel crop, sand rice research is rather limited compared with quinoa. More scientific input is urgently required if the nutritional and commercial potentials are to be fully realized.
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http://dx.doi.org/10.1080/10408398.2021.1999202DOI Listing
November 2021

Follow-up of two newborns with c.158G>A (p.Arg53His) mutation in gene and assessment of the site function.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Aug;50(4):444-453

3. Medical Genetics and Prenatal Diagnosis of Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610041, China.

: To investigate the clinical significance of c.158G>A mutation.: The blood phenylalanine (Phe) was continuously monitored in 2 unrelated newborns with suspected hyperphenylalaninimia (HPA) carrying c.158G>A mutation. The cross-species conservation of the mutant amino acid was analyzed using T-Coffee. Swiss-Model software was used to construct a 3D protein structure and the impact of candidate mutations on the secondary structure of the protein product was analyzed. The population carrying rate of the p.Arg53His mutation was analyzed by literature searching. Allelic phenotype values (APV) and genotypic phenotype values (GPV) were used to predict the phenotype associated with the mutation. Two mutations of gene were detected in each newborn: c.611A>G(p.Tyr204Cys), c.158G>A(p.Arg53His) and c.1238G>C(p.Arg413Pro), c.158G>A(p.Arg53His). Two children tolerated normal diet and plasma Phe levels were within the normal range during follow-up. The mother of case 2 was homozygous with p.Arg53His mutation under the condition of long-term normal diet, and the blood Phe concentration and Phe/Tyr were all within the normal range. The mutant amino acids were not highly conserved among the 13 different species. The 3D structural model showed that p.Arg53His mutation reduced the hydrogen bond from 2 to 1 between the 53rd and 49th amino acids of PAH. The allele frequency of p.Arg53His was 0.015 08 in HPA patients and 0.001 621 in normal population, while the prevalence of p.Arg53His allele was highest in the East Asian normal population (0.013 73). The APV and GPV system predicted that the mutation was related to mild HPA(MHP) type. : The different compound heterozygous mutations of p.Arg53His lead to clinical phenotype varieties. The reduction of enzyme activity caused by the mutation of p.Arg53His is not sufficient to cause symptoms of phenylketonuria, so the mutation may be "likely benign".
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http://dx.doi.org/10.3724/zdxbyxb-2021-0256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714477PMC
August 2021

Plant Sterol Clustering Correlates with Membrane Microdomains as Revealed by Optical and Computational Microscopy.

Membranes (Basel) 2021 Sep 29;11(10). Epub 2021 Sep 29.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.

Local inhomogeneities in lipid composition play a crucial role in the regulation of signal transduction and membrane traffic. This is particularly the case for plant plasma membrane, which is enriched in specific lipids, such as free and conjugated forms of phytosterols and typical phytosphingolipids. Nevertheless, most evidence for microdomains in cells remains indirect, and the nature of membrane inhomogeneities has been difficult to characterize. We used a new push-pull pyrene probe and fluorescence lifetime imaging microscopy (FLIM) combined with all-atom multiscale molecular dynamics simulations to provide a detailed view on the interaction between phospholipids and phytosterol and the effect of modulating cellular phytosterols on membrane-associated microdomains and phase separation formation. Our understanding of the organization principles of biomembranes is limited mainly by the challenge to measure distributions and interactions of lipids and proteins within the complex environment of living cells. Comparing phospholipids/phytosterol compositions typical of liquid-disordered (Ld) and liquid-ordered (Lo) domains, we furthermore show that phytosterols play crucial roles in membrane homeostasis. The simulation work highlights how state-of-the-art modeling alleviates some of the prior concerns and how unrefuted discoveries can be made through a computational microscope. Altogether, our results support the role of phytosterols in the lateral structuring of the PM of plant cells and suggest that they are key compounds for the formation of plant PM microdomains and the lipid-ordered phase.
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http://dx.doi.org/10.3390/membranes11100747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539253PMC
September 2021

High STK40 Expression as an Independent Prognostic Biomarker and Correlated with Immune Infiltrates in Low-Grade Gliomas.

Int J Gen Med 2021 5;14:6389-6400. Epub 2021 Oct 5.

Department of Neurology, The Third People's Hospital of Huai'an, Huai'an, Jiangsu, 223001, People's Republic of China.

Background: Expression of STK40 is observed in some cancer types, while its role in low-grade gliomas (LGG) is unclear. The present study aimed to demonstrate the relationship between STK40 and LGG based on The Cancer Genome Atlas (TCGA) database and bioinformatics analysis.

Methods: Kruskal-Wallis test, Wilcoxon sign-rank test, and logistic regression were used to evaluate the relationship between clinicopathological features and STK40 expression. Kaplan-Meier method and Cox regression analysis were used to evaluate prognostic factors. Gene set enrichment analysis (GSEA) and immuno-infiltration analysis were used to determine the significant involvement of STK40 in function.

Results: High STK40 expression in LGG was associated with WHO grade (P<0.001), IDH status (P<0.001), primary therapy outcome (P=0.027), 1p/19q codeletion (P<0.001) and histological type (P<0.001). High STK40 expression predicted a poorer overall survival (OS) (HR: 3.07; 95% CI: 2.09-4.51; P<0.001), progression-free survival (PFS) (HR:2.11; 95% CI: 1.59-2.81; P<0.001) and disease specific survival (DSS) (HR: 3.27; 95% CI: 2.17-4.92; P<0.001). STK40 expression (HR: 2.284; 95% CI: 1.125-4.637; P=0.022) was independently correlated with OS in LGG patients. GSEA demonstrated that pathways including cell cycle mitotic, neutrophil degranulation, signaling by Rho GTPases, signaling by interleukins, M phase, PI3K-Akt signaling pathway and naba secreted factors were differentially enriched in STK40 high expression phenotype. Immune infiltration analysis showed that STK40 expression was correlated with some types of immune infiltrating cells.

Conclusion: STK40 expression was significantly correlated with poor survival and immune infiltration in LGG, and it may be a promising prognostic biomarker in LGG.
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http://dx.doi.org/10.2147/IJGM.S335821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502031PMC
October 2021

Hand-assisted laparoscopic versus open surgery for radical gastrectomy in the treatment of advanced distal gastric cancer: long-term overall and disease-free survival (final results of a single-center study).

J Int Med Res 2021 Sep;49(9):3000605211047700

Department of Information, West War Zone General Hospital of Chinese People's Liberation Army, Chengdu, Sichuan Province 610083, China.

Objective: To compare the surgical effects and long-term efficacy of hand-assisted laparoscopic surgery (HALS) and open surgery (OS) in radical gastrectomy for advanced distal gastric cancer.

Methods: One hundred twenty-four patients who were admitted to the Department of Gastrointestinal Surgery of the West War Zone General Hospital from May 2008 to April 2012 were randomly divided into a HALS group (n = 62) and an OS group (n = 62). After surgery, 113 patients were followed up for 5 and 8 years, and 11 patients were lost to follow-up. The 5- and 8-year overall survival and disease-free survival rates of the two groups were compared and analyzed.

Results: The 5- and 8-year overall survival rates were 31.90% and 18.40% in the HALS group and 32.50% and 18.60% in the OS group, respectively. The 5- and 8-year disease-free survival rates were 21.50% and 13.00% in the HALS group and 21.90% and 13.10% in the OS group, respectively. No significant differences were found.

Conclusion: Hand-assisted laparoscopic radical gastrectomy for advanced distal gastric cancer has the advantages of less severe trauma, less intraoperative blood loss, more rapid postoperative recovery, and equivalent long-term efficacy compared with OS.
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http://dx.doi.org/10.1177/03000605211047700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489768PMC
September 2021

Aged and young mice differentially respond to tape-stripping in epidermal gene expression.

Exp Dermatol 2021 Sep 29. Epub 2021 Sep 29.

Dermatology Hospital, Southern Medical University, Guangdong, China.

Disruption of epidermal permeability barrier induces an increase in proinflammatory cytokine expression and release, stimulation of epidermal lipid and DNA synthesis, and expression of antimicrobial peptides. Although alterations in epidermal function in the aged skin are known, whether the epidermal transcriptomic responses to barrier disruption differ between aged and young mice remains unknown. Here, we performed RNA sequencing of the epidermis in 2-month- vs. 20-month-old mice following barrier disruption with repeated tape-stripping. At baseline condition, the epidermis of 20-month-old mice displayed an upregulation of inflammation-associated genes and down-regulation of epidermal structure- and development-related genes in comparison to 2-month-old mice. Barrier disruption upregulated expression levels of 327 genes and downregulated 209 genes in 2-month-old mice. In 20-month-old mice, the numbers of upregulated and down-regulated genes were 537 and 299, respectively. In comparison to young mice, the prominently upregulated genes in the 20-month-old mice were associated with the IL-17 signalling pathway, while downregulated genes were mainly involved in the cytokine-cytokine receptor interaction pathway. These results indicate that inflammation-associated signalling pathways are upregulated, while epidermal structure- and development-related genes are downregulated in the epidermis of aged mice, with further aggravation following barrier disruption, suggesting the importance of improving epidermal function in the elderly.
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http://dx.doi.org/10.1111/exd.14463DOI Listing
September 2021

Multicomponent SF decomposition product sensing with a gas-sensing microchip.

Microsyst Nanoeng 2021 1;7:18. Epub 2021 Mar 1.

State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, 710049 Xi'an, China.

A difficult issue restricting the development of gas sensors is multicomponent recognition. Herein, a gas-sensing (GS) microchip loaded with three gas-sensitive materials was fabricated via a micromachining technique. Then, a portable gas detection system was built to collect the signals of the chip under various decomposition products of sulfur hexafluoride (SF). Through a stacked denoising autoencoder (SDAE), a total of five high-level features could be extracted from the original signals. Combined with machine learning algorithms, the accurate classification of 47 simulants was realized, and 5-fold cross-validation proved the reliability. To investigate the generalization ability, 30 sets of examinations for testing unknown gases were performed. The results indicated that SDAE-based models exhibit better generalization performance than PCA-based models, regardless of the magnitude of noise. In addition, hypothesis testing was introduced to check the significant differences of various models, and the bagging-based back propagation neural network with SDAE exhibits superior performance at 95% confidence.
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http://dx.doi.org/10.1038/s41378-021-00246-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433328PMC
March 2021

Sleep profile and the risk of cardiovascular events in patients undergoing percutaneous coronary intervention.

Psychol Health Med 2021 Sep 26:1-13. Epub 2021 Sep 26.

Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, China.

A significant proportion of patients with coronary artery disease (CAD) who undergo percutaneous coronary intervention (PCI) suffer from physical and mental disorders which lead to the decline of sleep profile. Sleep disorders are highly prevalent in these patients. But the effect of sleep on the outcomes of post-PCI patients remains unclear. We aim to examine the individual and joint effects of sleep quality and sleep duration on the risk of adverse cardiovascular events in post-PCI patients. We included 314 participants who were diagnosed with a first CAD and underwent PCI with drug-eluting stents and followed up for a mean duration of 341 days to assess major adverse cardiovascular events (MACEs). Sleep quality, based on the Pittsburgh Sleep Quality Index, was categorized as good (a score of ≤7) or poor (>7). Sleep duration was categorized into three classes: ≤ 5, 6-8 (reference group) and ≥ 9 hours per day. The log-rank test and the Cox regression model were used for data analysis. MACEs occurred in 26 (8.3%) patients. Subjects whose sleep duration was ≤ 5 hours per day had a shorter time to MACEs than those whose sleep duration was 6-8 hours (p = 0.036). A significantly increased risk for MACEs was observed for participants with a ≤ 5 hours sleep duration (HR = 2.18, 95% CI = 1.02-4.64) after adjustment for demographic and clinical confounders. Associations between long sleep duration (≥ 9 hours), sleep quality, or their joint effect and MACEs were not found. This suggests the importance of considering sleep loss when developing strategies to improve health outcomes of PCI patients. And further researches are needed to examine the effects of different aspects of sleep quality on the prognosis of PCI patients and explore the reasons that lead to the decline of sleep profile.
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http://dx.doi.org/10.1080/13548506.2021.1985148DOI Listing
September 2021

Extracellular lipopeptide bacillomycin L regulates serial expression of genes for modulating multicellular behavior in Bacillus velezensis Bs916.

Appl Microbiol Biotechnol 2021 Sep 3;105(18):6853-6870. Epub 2021 Sep 3.

Jiangsu Provincial Key Construction Laboratory of Probiotics Preparation, Huaiyin Institute of Technology, Huai'an, 223003, China.

In wild strains of Bacillus, a handful of extracellular natural products act as signals that can regulate multicellular behavior, but relatively little is known about molecular mechanisms' detail. We proposed a previously unreported molecular mechanism for triggering multicellularity in B. velezensis Bs916 by an endogenous cyclic lipopeptide, bacillomycin L. The genome-wide effect on gene expression was caused by the disruption of bacillomycin L gene cluster, and 100 µg/mL bacillomycin L was revealed by quantitative transcriptomics. A total of 878 differentially expressed genes among Bs916, Δbl, and Δbl + 100BL were identified and grouped into 9 functional categories. The transcription levels of 40 candidate genes were further evaluated by RT-qPCR analysis. The expression of eight candidate genes regulated by bacillomycin L in a dose-dependent manner was revealed by LacZ fusion experiment. Although the addition of bacillomycin L could not completely restore the expression levels of the differentially regulated genes in △bl, our results strongly suggest that bacillomycin L acts as a tuning signal of swarming motility and complex biofilm formation by indirectly regulating the expression levels of some two-component systems (TCSs) connector genes, particularly including several Raps that potentially regulate the phosphorylation levels of three major regulators ComA, DegU, and Spo0A.Key points• Proposed model for bacillomycin L regulation in B. velezensis Bs916.• Bacillomycin L can act as an extracellular signal to regulate the phosphorylation levels of three major regulators, ComA, DegU, and Spo0A and control the multicellular processes of vegetative growth, competent, motility, matrix production, sporulation, and autolysis.
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http://dx.doi.org/10.1007/s00253-021-11524-3DOI Listing
September 2021

Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II-induced hypertension.

Redox Biol 2021 10 25;46:102115. Epub 2021 Aug 25.

Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China. Electronic address:

Gut microbiota produce Trimethylamine N-oxide (TMAO) by metabolizing dietary phosphatidylcholine, choline, l-carnitine and betaine. TMAO is implicated in the pathogenesis of chronic kidney disease (CKD), diabetes, obesity and atherosclerosis. We test, whether TMAO augments angiotensin II (Ang II)-induced vasoconstriction and hence promotes Ang II-induced hypertension. Plasma TMAO levels were indeed elevated in hypertensive patients, thus the potential pathways by which TMAO mediates these effects were explored. Ang II (400 ng/kgmin) was chronically infused for 14 days via osmotic minipumps in C57Bl/6 mice. TMAO (1%) or antibiotics were given via drinking water. Vasoconstriction of renal afferent arterioles and mesenteric arteries were assessed by microperfusion and wire myograph, respectively. In Ang II-induced hypertensive mice, TMAO elevated systolic blood pressure and caused vasoconstriction, which was alleviated by antibiotics. TMAO enhanced the Ang II-induced acute pressor responses (12.2 ± 1.9 versus 20.6 ± 1.4 mmHg; P < 0.05) and vasoconstriction (32.3 ± 2.6 versus 55.9 ± 7.0%, P < 0.001). Ang II-induced intracellular Ca release in afferent arterioles (147 ± 7 versus 234 ± 26%; P < 0.001) and mouse vascular smooth muscle cells (VSMC, 123 ± 3 versus 157 ± 9%; P < 0.001) increased by TMAO treatment. Preincubation of VSMC with TMAO activated the PERK/ROS/CaMKII/PLCβ3 pathway. Pharmacological inhibition of PERK, ROS, CaMKII and PLCβ3 impaired the effect of TMAO on Ca release. Thus, TMAO facilitates Ang II-induced vasoconstriction, thereby promoting Ang II-induced hypertension, which involves the PERK/ROS/CaMKII/PLCβ3 axis.
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http://dx.doi.org/10.1016/j.redox.2021.102115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408632PMC
October 2021

Newborn screening with targeted sequencing: a multicenter investigation and a pilot clinical study in China.

J Genet Genomics 2021 Aug 30. Epub 2021 Aug 30.

Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing 100045, China; MOE Key Laboratory of Major Diseases in Children, Beijing 100045, China; Rare Disease Center, National Center for Children's Health, Beijing 100045, China; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address:

Different newborn screening (NBS) programs have been practiced in many countries since the 1960s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing (NESTS) program to screen 11,484 babies in 8 Women and Children's hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85% (902/11,484). With 45.89% (414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07% (50/414), estimating an average of 0.95% (7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.
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http://dx.doi.org/10.1016/j.jgg.2021.08.008DOI Listing
August 2021

Double knockout of vitamin D receptor and its coactivator mediator complex subunit 1 unexpectedly enhances epidermal permeability barrier function in mice.

Biochim Biophys Acta Mol Cell Res 2021 11 26;1868(12):119131. Epub 2021 Aug 26.

Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin 300070, China; Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbamcr.2021.119131DOI Listing
November 2021
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