Publications by authors named "Wei Wei"

4,006 Publications

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Clinical value of tumor-associated antigens and autoantibody panel combination detection in the early diagnostic of lung cancer.

Cancer Biomark 2021 Jun 19. Epub 2021 Jun 19.

Background: This study aimed to investigate the efficiency of combining tumor-associated antigens (TAAs) and autoantibodies in the diagnosis of lung cancer.

Methods: The serum levels of TAAs and seven autoantibodies (7-AABs) were detected from patients with lung cancer, benign lung disease and healthy controls. The performance of a new panel by combing TAAs and 7-AABs was evaluated for the early diagnosis of lung cancer.

Results: The positive rate of 7-AABs was higher than the single detection of antibody. The positive rate of the combined detection of 7-AABs in lung cancer group (30.2%) was significantly higher than that of healthy controls (16.8%), but had no statistical difference compared with that of benign lung disease group (20.8%). The positive rate of 7-AABs showed a tendency to increase in lung cancer patients with higher tumor-node-metastasis (TNM) stages. For the pathological subtype analysis, the positive rate of 7-AABs was higher in patients with squamous cell carcinoma and small cell lung cancer than that of adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 211 (CYFRA 211) were significantly higher than that of benign lung disease and healthy control groups. An optimal model was established (including 7-AABs, CEA and CYFRA21-1) to distinguish lung cancer from control groups. The performance of this model was superior than that of single markers, with a sensitivity of 52.26% and specificity of 77.46% in the training group. Further assessment was studied in another validation group, with a sensitivity of 44.02% and specificity of 83%.

Conclusions: The diagnostic performance was enhanced by combining 7-AABs, CEA and CYFRA21-1, which has critical value for the screening and early detection of lung cancer.
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http://dx.doi.org/10.3233/CBM-210099DOI Listing
June 2021

Safety and feasibility of umbilical cord blood collection from preterm neonates after delayed cord clamping for the use of improving preterm complications.

Am J Transl Res 2021 15;13(5):4553-4560. Epub 2021 May 15.

The First Affiliated Hospital of Jinan University Guangzhou, China.

Background: Umbilical cord blood (UCB) is a new and convenient source of stem cells reported to be safe and effective in preventing and treating preterm complications. The initial processing step for this therapy involves cord blood collection and isolation of the mononuclear cell (MNC) layer. However, there is limited information regarding the feasibility and safety of cord blood collection in preterm infants, and whether cord blood cell quality and quantity are adequate for treating complications in preterm infants. UCB units from preterm infants are currently discarded due to safety concerns regarding collection and owing to the harvesting of inadequate volumes for banking. This study aimed to investigate the feasibility and safety of UCB collection following delayed cord clamping (DCC) for preventing and treating complications in preterm infants.

Methods And Materials: Singleton preterm infants below 35 weeks gestation were assigned to two cohorts: cord blood collection and non-cord blood collection groups. Mortality and preterm complications in the two groups were compared to evaluate the safety of cord blood collection in preterm infants. The characteristics of the cord blood cells in preterm infants were investigated by comparing the cord blood parameters before and after processing with those of term infants born during the same period.

Results: There were 90 preterm infants and 120 term neonates enrolled in this study. Compared to those of the term group, the preterm neonates had significantly less cord blood volume and fewer cell numbers. Nevertheless, the MNC number in the preterm group was 1.92±1.35×10 per kg, which fulfilled the previously reported targeted cell dose (5×10 cells/kg) suitable for application to improve preterm complications. There was no significant difference regarding complications in the preterm neonates with or without cord blood collection.

Conclusions: The collection of UCB after DCC in preterm infants is feasible and safe. The cell numbers and quality fulfill the criteria for use in improving preterm complications. Cord blood MNCs from preterm neonates should be reconsidered as an ideal source for use in stem cell therapy for preterm complications.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205698PMC
May 2021

Hierarchical Porous RGO/PEDOT/PANI Hybrid for Planar/Linear Supercapacitor with Outstanding Flexibility and Stability.

Nanomicro Lett 2020 Jan 4;12(1):17. Epub 2020 Jan 4.

Shenzhen Key Laboratory of Polymer Science and Technology, College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518060, People's Republic of China.

Many hybrid electrodes for supercapacitors (SCs) are a reckless combination without proper structural design that keeps them from fulfilling their potential. Herein, we design a reduced graphene oxide/poly(3,4-ethylenedioxythiophene)/polyaniline (RGO/PEDOT/PANI) hybrid with hierarchical and porous structure for high-performance SCs, where components fully harness their advantages, forming an interconnected and conductive framework with substantial reactive sites.Thus, this hybrid achieves a high capacitance of 535 F g along with good rate capability and cyclability. The planar SC based on this hybrid deliver an energy density of 26.89 Wh kg at a power density of 800 W kg. The linear SC developed via modifying a cotton yarn with the hybrid exhibits good flexibility and structural stability, which operates normally after arbitrary deformations. This work provides a beneficial reference for developing SCs.
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http://dx.doi.org/10.1007/s40820-019-0342-5DOI Listing
January 2020

Screening potential insect vectors in a museum biorepository reveals undiscovered diversity of plant pathogens in natural areas.

Ecol Evol 2021 Jun 1;11(11):6493-6503. Epub 2021 May 1.

Illinois Natural History Survey Prairie Research Institute University of Illinois Champaign IL USA.

Phytoplasmas (, ), vector-borne obligate bacterial plant parasites, infect nearly 1,000 plant species and unknown numbers of insects, mainly leafhoppers (Hemiptera, Deltocephalinae), which play a key role in transmission and epidemiology. Although the plant-phytoplasma-insect association has been evolving for >300 million years, nearly all known phytoplasmas have been discovered as a result of the damage inflicted by phytoplasma diseases on crops. Few efforts have been made to study phytoplasmas occurring in noneconomically important plants in natural habitats. In this study, a subsample of leafhopper specimens preserved in a large museum biorepository was analyzed to unveil potential new associations. PCR screening for phytoplasmas performed on 227 phloem-feeding leafhoppers collected worldwide from natural habitats revealed the presence of 6 different previously unknown phytoplasma strains. This indicates that museum collections of herbivorous insects represent a rich and largely untapped resource for discovery of new plant pathogens, that natural areas worldwide harbor a diverse but largely undiscovered diversity of phytoplasmas and potential insect vectors, and that independent epidemiological cycles occur in such habitats, posing a potential threat of disease spillover into agricultural systems. Larger-scale future investigations will contribute to a better understanding of phytoplasma genetic diversity, insect host range, and insect-borne phytoplasma transmission and provide an early warning for the emergence of new phytoplasma diseases across global agroecosystems.
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http://dx.doi.org/10.1002/ece3.7502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207438PMC
June 2021

Promotion effects of DEHP on hepatocellular carcinoma models: up-regulation of PD-L1 by activating the JAK2/STAT3 pathway.

Toxicol Res (Camb) 2021 May 12;10(3):376-388. Epub 2021 Apr 12.

Key Laboratory of Anti-inflammatory and Immune Medicine of Education Ministry, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology of Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China.

Di(2-ethylhexyl) phthalate (DEHP), as an endocrine disruptor, is often used as a plasticizer in various polyvinyl chloride plastic products and medical consumables. Epidemiological studies have shown that long-term large intake of DEHP may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and aggravates the progression of chronic liver injury. However, the effects of DEHP on hepatocellular carcinoma (HCC) are rarely studied. In this study, we sought to determine the effects of DEHP on HCC induced by carbon tetrachloride combined with diethylnitrosamine, and further study its molecular mechanism. It was found that DEHP exposure significantly promotes tumor immune escape and activates signaling pathways involved in related protein expression of tumor immune escape, including PD-L1, JAK2, and STAT3. In addition, the trends observed in the HepG2 cells assay are consistent with vivo conditions. In summary, DEHP may play a tumor-promoting role in HCC mice and IFN-γ stimulated HepG2 cells, which may be related to the JAK2/STAT3 signaling pathway.
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http://dx.doi.org/10.1093/toxres/tfab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201567PMC
May 2021

Ginsenoside Rg1 can restore hematopoietic function by inhibiting Bax translocation-mediated mitochondrial apoptosis in aplastic anemia.

Sci Rep 2021 Jun 17;11(1):12742. Epub 2021 Jun 17.

Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.

The present study investigated, the anti-apoptotic activity of Ginsenoside Rg1 (Rg1) via inhibition of Bax translocation and the subsequent recovery of hematopoietic function. Mitochondrial apoptosis in bone marrow mononuclear cells (BMNCs) was observed in aplastic anemia (AA) patients. To establish a mouse model of AA, BALB/c mice were transplanted with lymph node cells from DBA/2 donor mice via vein injection after treatment with Co60 γ-radiation. After treatment with Rg1 for 14 days, the peripheral blood and Lin-Sca-1 + c-Kit + (LSK) cell counts of the treated group were increased compared with those of the untreated model mice. In in vivo and in vitro tests of LSKs, Rg1 was found to increase mitochondrial number and the ratio of Bcl-2/Bax and to decrease damage to the mitochondrial inner and outer membranes, the mitochondrial Bax level and the protein levels of mitochondrial apoptosis-related proteins AIF and Cyt-C by decreasing the ROS level. Rg1 also improved the concentration-time curve of MAO and COX and levels of ATP, ADP and AMP in an in vitro test. In addition, high levels of Bax mitochondrial translocation could be corrected by Rg1 treatment. Levels of markers of mitochondrial apoptosis in the Rg1-treated group were significantly better than those in the AA model group, implying that Rg1 might improve hematopoietic stem cells and thereby restore hematopoietic function in AA by suppressing the mitochondrial apoptosis mediated by Bax translocation.
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http://dx.doi.org/10.1038/s41598-021-91471-1DOI Listing
June 2021

A phase I study of APX005M and cabiralizumab with/without nivolumab in patients with melanoma, kidney cancer or non-small cell lung cancer resistant to anti-PD-(L)1.

Clin Cancer Res 2021 Jun 17. Epub 2021 Jun 17.

Smilow Cancer Center, Yale School of Medicine.

Purpose: PD-1/PD-L1 inhibitors are approved for multiple tumor types. However, resistance poses substantial clinical challenges.

Methods: We conducted a phase I trial of CD40 agonist APX005M (sotigalimab) and CSF1R inhibitor cabiralizumab with/without nivolumab using a 3+3 dose escalation design (NCT03502330). Patients were enrolled from June 2018-April 2019. Eligibility included biopsy-proven advanced melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) patients who progressed on anti-PD-1/PD-L1. APX005M was dose escalated (0.03, 0.1, or 0.3 mg/kg IV) with a fixed dose of cabiralizumab with/without nivolumab every 2 weeks until disease progression or intolerable toxicity.

Results: Twenty-six patients (12 melanoma, 1 NSCLC, and 13 RCC) were enrolled in six cohorts, 17 on nivolumab-containing regimens. Median duration of follow-up was 21.3 months. The most common TRAEs were asymptomatic elevations of LDH (n=26), CK (n=25), AST (n=25), and ALT (n=19); periorbital edema (n=17), and fatigue (n=13). One DLT (acute respiratory distress syndrome) occurred in Cohort 2. RP2D was APX005M 0.3 mg/kg, cabiralizumab 4 mg/kg, and nivolumab 240 mg q2wk. Median days on treatment was 66 (range 23-443). Median cycles was 4.5 (range 2-21). One patient had unconfirmed partial response (4%), 8 stable disease (31%), 16 disease progression (62%), and 1 unevaluable (4%). Pro-inflammatory cytokines were upregulated 4 hours post-infusion. CD40 and M-CSF increased after therapy.

Conclusions: This first in-human study of patients with anti-PD-1/PD-L1-resistant tumors treated with dual macrophage-polarizing therapy, with or without nivolumab demonstrated safety and pharmacodynamic activity. Optimization of the dosing frequency and sequence of this combination is warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0903DOI Listing
June 2021

Design and Mechanism of a Self-Powered and Disintegration-Reorganization-Regeneration Power Supply with Cold Resistance.

Adv Mater 2021 Jun 17:e2101239. Epub 2021 Jun 17.

Academy for Engineering and Technology, Institute for Electric Light Sources, School of Information Science and Technology, Fudan University, Shanghai, 200433, China.

Up to now, power supplies designed based on the electrochemical reaction principle have had unavoidable defects, in that a complete redox reaction must be formed inside the power supply to operate normally, which makes it unable to be reconstructed and regenerated. Hence, the design and interpretation of this self-powered and disintegration-reorganization-regeneration power supply are generally considered to be almost insurmountable obstacles to haunt both experimenters and theorists. Herein, a self-powered and disintegration-reorganization-regeneration power supply with relatively stable discharge for 8.3 h is realized by the principle of ion-selective diffusion, which regenerates by radical polymerization. Additionally, the mechanism is investigated systematically by molecular dynamics simulation, and this power supply with a variety of self-powered and disintegration-reorganization-regeneration units can discharge continuously at freezing temperatures and variable temperature (0-25 °C). As a hypothetical model, a self-powered and deformable arch bridge with disintegration and reorganization is fabricated. In the future, this power supply is expected to be applied in prosthetic limbs, bionic skins, implantable power supplies, mobile phones, portable computers, wearable devices, etc. Moreover, with the improvement of the stability and discharge life, it could promote major revolutionary breakthroughs in the fields of intelligent industrial automation, smart buildings, intelligent transportation systems, intelligent power systems, etc.
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http://dx.doi.org/10.1002/adma.202101239DOI Listing
June 2021

Extracts as Novel PKM2 Inhibitors for Treatment of Triple Negative Breast Cancer.

Biomed Res Int 2021 26;2021:5514669. Epub 2021 May 26.

The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University (NENU), Changchun, China.

Pyruvate kinase (PK), a key enzyme that determines glycolytic activity, has been known to support the metabolic phenotype of tumor cells, and specific pyruvate kinase isoform M2 (PKM2) has been reported to fulfill divergent biosynthetic and energetic requirements of cancerous cells. PKM2 is overexpressed in several cancer types and is an emerging drug target for cancer during recent years. Therefore, this study was carried out to identify PKM2 inhibitors from natural products for cancer treatment. Based on the objectives of this study, firstly, plant extract library was established. In order to purify protein for the establishment of enzymatic assay system, pET-28a-HmPKM2 plasmid was transformed to BL21 (DE3) cells for protein expression and purification. After the validation of enzymatic assay system, plant extract library was screened for the identification of inhibitors of PKM2 protein. Out of 51 plant extracts screened, four extracts (leaf, seed, and bark) and bark extracts were found to be inhibitors of PKM2. In the current study, (leaf, seed, and bark) extracts were further evaluated dose dependently against PKM2. These extracts showed different degrees of concentration-dependent inhibition against PKM2 at 90-360 g/ml concentrations. We have also investigated the anticancer potential of these extracts against MDA-MB231 cells and generated dose-response curves for the evaluation of IC values. (bark and seed) extracts significantly halted the growth of MDA-MB231 cells with IC values of 108 g/ml and 33 g/ml, respectively. Literature-based phytochemical analysis of was carried out, and -derived 94 compounds were docked against three binding sites of PKM2 for the identification of PKM2 inhibitors. The results of based screening have unveiled various PKM2 modulators; however, further studies are recommended to validate their PKM2 inhibitory potential via biochemical assay. The results of this study provide novel findings for possible mechanism of action of (bark and seed) extracts against TNBC via PKM2 inhibition suggesting that might be of therapeutic interest for the treatment of TNBC.
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http://dx.doi.org/10.1155/2021/5514669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175167PMC
May 2021

Surgical Disparities of Parathyroid Carcinoma: Long-Term Outcomes and Deep Excavation Based on a Large Database.

J Oncol 2021 27;2021:8898926. Epub 2021 May 27.

Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Purpose: Parathyroid carcinoma (PC) is an uncommon endocrine disease, and surgery is considered the only potential cure. PC does not have a mature staging system because of the small number of PC patients. Our aim is to further investigate the prognostic factors associated with PC and explore the optimal extent of resection for PC patients.

Methods: Univariate and multivariate Cox regression analyses were conducted to explore the influence of relevant factors on cancer-specific survival (CSS) and overall survival (OS). Survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. The mortality rates per 1,000 person-years were calculated to evaluate patients' follow-up data. We also performed subgroup analysis based on the extent of resection.

Results: The extent of resection was related to both CSS and OS, whereas race and extent of disease had a significant positive correlation with OS (all < 0.05). Patients who underwent parathyroidectomy had remarkably better CSS and OS than patients who did not undergo definitive treatment.

Conclusion: The extent of resection is related to CSS and OS in patients with PC. No significant difference in prognosis was observed between patients who underwent parathyroidectomy and those who underwent en bloc resection, which may provide useful parameters for the treatment of PC.
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http://dx.doi.org/10.1155/2021/8898926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178016PMC
May 2021

Transforming acidic coiled-coil protein-3: a novel marker for differential diagnosis and prognosis prediction in endocervical adenocarcinoma.

Mol Med 2021 Jun 10;27(1):60. Epub 2021 Jun 10.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.

Background: Endocervical adenocarcinoma (ECA) is further classified as human papillomavirus (HPV)-associated (HPVA) or non-HPVA (NHPVA), per the International Endocervical Adenocarcinoma Criteria and Classification (IECC). HPVA is a glandular tumor with stromal invasion and/or exophytic expansile-type invasion, associated with the typical molecular characteristics of high-risk HPV (HR-HPV) infection. Transforming acidic coiled-coil protein-3 (TACC3),an oncogene that is frequently abnormally expressed,represents a vital biomarker for multiple human malignancies. This study aimed to examine the role of TACC3 in the diagnosis and prognosis of ECA.

Methods: We analyzed 264 patients with ECA who underwent surgical resection, classifying their tumors into HPVA and NHPVA subtypes. The expression levels of TACC3, P16, MLH1, PMS2, MSH2, MSH6 and Ki-67 in tumors were evaluated by tissue microarray using immunohistochemistry (IHC). HPV subtypes were identified in formalin-fixed paraffin-embedded (FFPE) ECA tissues by the polymerase chain reaction (PCR).

Results: ECA samples showed increased TACC3 expression relative to adjacent non-carcinoma samples. TACC3 expression was higher in HPVA than in NHPA. In the HPVA subtype, high TACC3 expression was significantly correlated with P16-positive, Ki-67-high expression. Furthermore, TACC3 levels were significantly related to tumor histological type (P = 0.006), nerve invasion (P = 0.003), differentiation (P = 0.004), surgical margin (P = 0.012), parametrium invasion (P = 0.040), P16 expression (P < 0.001), and Ki-67 (P = 0.004). Additionally, Kaplan-Meier analysis showed that TACC3 upregulation was associated with poor overall survival (OS, P = 0.001), disease-free survival (DFS, P < 0.001), and recurrence survival (P < 0.001). Multivariate analysis indicated that elevated TACC3 expression served as a marker to independently predict ECA prognosis. ROC curve analyses indicated that TACC3, P16, and HPV subtypes showed similar utility for distinguishing HPVA from NHPVA, with areas under the ROC curves of 0.640, 0.649, and 0.675, respectively. The combination of TACC3 and HPV subtypes improved the diagnostic performance of ECA compared with TACC3, P16, and HPV subtypes alone.

Conclusions: Taken together, our findings identify that TACC3 is a promising complementary biomarker for diagnosis and prognosis for patients with ECA.
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http://dx.doi.org/10.1186/s10020-021-00298-zDOI Listing
June 2021

A facile oxygen vacancy and bandgap control of Bi(OH)SO·HO for achieving enhanced photocatalytic remediation.

J Environ Manage 2021 Jun 12;294:113046. Epub 2021 Jun 12.

Centre for Technology in Water and Wastewater (CTWW), School of Civil and Environmental Engineering, University of Technology Sydney (UTS), Ultimo, NSW, 2007, Australia. Electronic address:

The development of highly efficient photocatalysts is crucial for the remediation of organic pollutants. Herein, we reported a facile synthesis of oxygen vacancy rich Bi(OH)SO·HO photocatalyst by the control of precursor. The samples were characterized by XRD, scanning electron microscope, electron paramagnetic resonance, X-ray photoelectron spectroscopy etc. With more oxygen vacancies introduced, the photocatalytic activity on the degradation of RhB and tetracycline was significantly boosted. Density functional theory calculation was used to further reveal the influence of oxygen vacancy on the band structure of Bi(OH)SO·HO. The results and finding of this work are helpful for the development of sustainable environmental protection.
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http://dx.doi.org/10.1016/j.jenvman.2021.113046DOI Listing
June 2021

3DMol-Net: Learn 3D Molecular Representation using Adaptive Graph Convolutional Network Based on Rotation Invariance.

IEEE J Biomed Health Inform 2021 Jun 14;PP. Epub 2021 Jun 14.

Studying the deep learning-based molecular representation has great significance on predicting molecular property, promoted the development of drug screening and new drug discovery, and improving human well-being for avoiding illnesses. It is essential to learn the characterization of drug for various downstream tasks, such as molecular property prediction. In particular, the 3D structure features of molecules play an important role in biochemical function and activity prediction. The 3D characteristics of molecules largely determine the properties of the drug and the binding characteristics of the target. However, most current methods merely rely on 1D or 2D properties while ignoring the 3D topological structure, thereby degrading the performance of molecular inferring. In this paper, we propose 3DMol-Net to enhance the molecular representation, considering both the topology and rotation invariance (RI) of the 3D molecular structure. Specifically, we construct a molecular graph with soft relations related to the spatial arrangement of the 3D coordinates to learn 3D topology of arbitrary graph structure and employ an adaptive graph convolutional network to predict molecular properties and biochemical activities. Comparing with current graph-based methods, 3DMol-Net demonstrates superior performance in terms of both regression and classification tasks. Further verification of RI and visualization also show better robustness and representation capacity of our model.
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http://dx.doi.org/10.1109/JBHI.2021.3089162DOI Listing
June 2021

A novel multikinase inhibitor SKLB-YTH-60 ameliorates inflammation and fibrosis in bleomycin-induced lung fibrosis mouse models.

Cell Prolif 2021 Jun 14:e13081. Epub 2021 Jun 14.

Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Objectives: Idiopathic pulmonary fibrosis (IPF) is marked by the excessive accumulation of extracellular matrix, which participates in a variety of chronic diseases or injuries and seriously threatens human health. Due to the side effects of clinical drugs, there is still a need to develop novel and less toxic drugs to treat pulmonary fibrosis.

Materials And Methods: SKLB-YTH-60 was developed through computer-aided drug design, de novo synthesis and high-throughput screening. We employed the bleomycin (BLM)-induced lung fibrosis animal models and used TGF-β to induce the epithelial-mesenchymal transition (EMT) of A549 cells in vitro. Meanwhile, the protein expression of collagen I and the α-smooth muscle actin (α-SMA), E-cadherin, p-FGFR1, p-PLCγ, p-Smad2/3 and p-Erk1/2 was detected by western blot.

Results: YTH-60 has obvious anti-proliferative activity on fibroblasts and A549 cells. Moreover, YTH-60 could impair the EMT of A549 cells and suppressed fibrosis by inhibiting FGFR and TGF-β/Smad-dependent pathways. Intraperitoneal administration of preventive YTH-60 could significantly reduce the degree of fibrosis in mice and regulate the imbalance of the immune microenvironment. In addition, we observed that therapeutic YTH-60 treatment attenuated fibrotic changes in mice during the period of fibrosis. Importantly, YTH-60 has shown an acceptable oral bioavailability (F = 17.86%) and appropriate eliminated half-life time (T  = 8.03 hours).

Conclusions: Taken together, these preclinical evaluations suggested that YTH-60 could be a promising drug candidate for treating IPF.
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http://dx.doi.org/10.1111/cpr.13081DOI Listing
June 2021

Improving Chinese Electronic Medical Record Retrieval by Field Weight Assignment, Negation Detection, and Re-ranking.

J Biomed Inform 2021 Jun 8:103836. Epub 2021 Jun 8.

Academy of Military Medical Sciences, Beijing 100850, China. Electronic address:

The technique of information retrieval has been widely used in electronic medical record (EMR) systems. It's a pity that most existing methods have not considered the structures and language features of Chinese EMRs, which affects the performance of retrieval. To improve accuracy and comprehensiveness, we propose an improved algorithm of Chinese EMR retrieval. First, the weights of fields in Chinese EMRs are assigned based on the corresponding importance in clinical applications. Second, negative relations in EMRs are detected, and the retrieval scores of negative terms are adjusted accordingly. Third, the retrieval results are re-ranked by expansion terms and time information to enhance the recall without decreasing precision. Experiment results show that the improved algorithm increases the precision and recall significantly, which shows that the algorithm takes a full account of the characteristics of Chinese EMRs and fits the needs for clinical applications.
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http://dx.doi.org/10.1016/j.jbi.2021.103836DOI Listing
June 2021

Tumor-to-Gland Volume Ratio versus Tumor-to-Breast Ratio as Measured on CBBCT: Possible Predictors of Breast-Conserving Surgery.

Cancer Manag Res 2021 3;13:4463-4471. Epub 2021 Jun 3.

Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People's Republic of China.

Background: Breast-conserving surgery plus postoperative radiotherapy is the standard surgical treatment mode for early breast cancer. Currently, there are no clear predictive indicators to determine whether a patient can choose breast-conserving surgery, which mainly depends on the surgeon's clinical experience and subjective judgment. Cone-beam breast computed tomography (CBBCT) reconstructs the breast 3D image from three mutually perpendicular angles, helping surgeons to locate and accurately measure the volume of the tumor, mammary gland, and breast. We used CBBCT to retrospectively measure the tumor-to-gland volume ratio and tumor-to-breast volume ratio in breast cancer cases. Then, we analyzed the correlation between the surgical methods and ratios in breast cancer patients.

Methods: We collected 100 patients undergoing breast-conserving surgery as the study group, and 100 patients undergoing mastectomy as the control group. All patients chose the surgical approach after comprehensive consideration of examination results and assessment of patient condition. Patients underwent CBBCT examination before surgery. We retrospectively measured the volume of tumor, mammary glands and breast, then calculated tumor-to-gland and tumor-to-breast volume ratios.

Results: Tumor volume and the ratios of the two groups statistically differed (P < 0.001), while the mammary gland and breast volume did not (P > 0.05). The average tumor-to-gland volume ratio was 4.32% in the study group and 10.74% in the control group, and the average tumor-to-breast volume ratio was 0.74% in the study group and 1.36% in the control group. In breast-conserving surgery, the 95% reference range of tumor-to-gland ratio is (0, 12.90%), and the 95% reference range of tumor-to-breast ratio is (0, 2.17%).

Conclusion: The tumor-to-gland volume ratio and tumor-to-breast volume ratio measured using CBBCT are correlated with the choice of surgical methods (breast-conserving surgery or mastectomy) for breast cancer patients. This can be used as possible predictor of breast-conserving surgery to help surgeons.
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http://dx.doi.org/10.2147/CMAR.S312288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184154PMC
June 2021

Identification of SARS-CoV-2-against aptamer with high neutralization activity by blocking the RBD domain of spike protein 1.

Signal Transduct Target Ther 2021 06 10;6(1):227. Epub 2021 Jun 10.

School of Life Science; Advanced Research Institute of Multidisciplinary Science; Institute of Engineering Medicine; Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing, China.

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http://dx.doi.org/10.1038/s41392-021-00649-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190169PMC
June 2021

Targeting Mutated p53 Dependency in Triple-Negative Breast Cancer Cells Through CDK7 Inhibition.

Front Oncol 2021 24;11:664848. Epub 2021 May 24.

Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.

Background: Cyclin-dependent kinase 7 (CDK7) is crucial for cell cycle progression and gene expression transcriptional regulation, which are often not assessed in cancer developing process. CDK7 inhibitors have emerged as promising drugs for treating diverse cancers, including breast cancer. However, the mechanism behind its anticancer effect has not been well investigated. Here, the possible mechanism of CDK7 inhibitors for treating human triple-negative breast cancer (TNBC) has been studied.

Methods: The effects of CDK7 inhibitors on breast cancer cells have been identified by measuring cell viability (Cell Counting Kit-8) and cell proliferation and calculating colony formation. The short hairpin RNA and short interfering RNA were used for the construction of knockdown cells. To assess the expression of associated proteins, western blot was used.

Results: This study confirmed that, compared to hormone receptor-positive breast cancer cells, TNBC cells were more sensitive to THZ1, a novel CDK7 inhibitor. THZ1 treatment specifically downregulated mutated p53 in a dose- and time-dependent manner in TNBC cells with p53 mutation. Another CDK7 inhibitor, LDC4297, also potently interfered with the expression of mutated p53. Furthermore, endogenous CDK7 expression was positively correlated with the levels of mutated p53 in TNBC cells with p53 mutation. Downregulating mutated p53 expression significantly suppressed the proliferation of TNBC cells with p53 mutation.

Conclusion: Our findings demonstrated that targeting CDK7 was an effective approach for the treatment of TNBC with p53 mutation.
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http://dx.doi.org/10.3389/fonc.2021.664848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183379PMC
May 2021

Immediate Analgesic Effect of Acupuncture in Patients With Primary Dysmenorrhea: A fMRI Study.

Front Neurosci 2021 24;15:647667. Epub 2021 May 24.

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Primary dysmenorrhea (PDM) is a common gynecological disease characterized by lower abdominal pain. Acupuncture is considered a good alternative therapy for PDM. However, the central mechanism of the analgesic effect of acupuncture is largely unknown. In this study, eligible patients were randomized into the real and sham acupuncture groups using a computer-generated, permuted block randomization method. The study cohort comprised 34 patients: 19 in the real acupuncture group and 15 in the sham acupuncture group. The clinical characteristics of the patients during their menstrual period were collected, and imaging scans were performed during the first 3 days of the patients' menstrual period. We analyzed task and resting functional magnetic resonance imaging (fMRI) data to investigate the potential central mechanism of the immediate effect of acupuncture intervention on the intensity of PDM pain. The task fMRI study found that the rostral anterior cingulate cortex (rACC) and right supplemental motor area were activated during real acupuncture. Using the resting-state functional connectivity (FC) method, we found a post- versus pre-treatment change in the FC of the rACC and left precentral gyrus in the comparison of real acupuncture versus sham acupuncture. In addition, the FC of the rACC-left precentral gyrus at baseline was negatively correlated with short-term analgesia, while the change in the FC of the rACC-left precentral gyrus was positively correlated with short-term analgesia after acupuncture treatment. These findings support the importance of rACC-left precentral gyrus resting-state FC in the modulation of the intensity of PDM pain through acupuncture, which may shed light on the central mechanism of acupuncture in the treatment of PDM.
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http://dx.doi.org/10.3389/fnins.2021.647667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180846PMC
May 2021

A High-Resolution Ternary Model Demonstrates How PEGylated 2D Nanomaterial Stimulates Integrin α β on Cell Membrane.

Adv Sci (Weinh) 2021 06 23;8(11):e2004506. Epub 2021 Mar 23.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, No. 1 Bei-Er-Tiao, Zhong-Guan-Cun, Haidian District, Beijing, 100190, P. R. China.

Bio-nano interfaces are integral to all applications of nanomaterials in biomedicine. In addition to peptide-ligand-functionalized nanomaterials, passivation on 2D nanomaterials has emerged as a new regulatory factor for integrin activation. However, the mechanisms underlying such ligand-independent processes are poorly understood. Here, using graphene oxide passivated with polyethylene glycol (GO-PEG) as a test bed, a ternary simulation model is constructed that also includes a membrane and both subunits of integrin α β to characterize GO-PEG-mediated integrin activation on the cell membrane in a ligand-independent manner. Combined with the experimental findings, production simulations of the ternary model show a three-phase mechanotransduction process in the vertical interaction mode. Specifically, GO-PEG first induces lipid aggregation-mediated integrin proximity, followed by transmembrane domain rotation and separation, leading to the extension and activation of extracellular domains. Thus, this study presents a complete picture of the interaction between passivated 2D nanomaterials and cell membranes to mediate integrin activation, and provides insights into the potential de novo design and rational use of novel desirable nanomaterials at diverse bio-nano interfaces.
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http://dx.doi.org/10.1002/advs.202004506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188183PMC
June 2021

Predicting Risk of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: CSTAR Cohort Study.

Arthritis Rheumatol 2021 Jun 9. Epub 2021 Jun 9.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objectives: Pulmonary arterial hypertension is a life-threatening complication of systemic lupus erythematosus. However, there is no algorithm to identify those at high risk. We aimed to develop a prediction model for pulmonary arterial hypertension in lupus patients that provides individualized risk estimates.

Methods: A multicenter, longitudinal cohort study was undertaken from January 2003 to January 2020. The study collected data on 3,624 consecutively evaluated patients diagnosed with lupus. The diagnosis of pulmonary arterial hypertension was confirmed by right heart catheterization. Cox proportional hazards regression and least absolute shrinkage and selection operator were used to fit the model. Model discrimination, calibration, and decision curve analysis were assessed for validation.

Results: Ninety-two lupus patients developed pulmonary arterial hypertension (2.54%) at a median follow-up of 4.84 years (interquartile range, 2.42-8.84). The final prediction model included five clinical variables (acute/subacute cutaneous lupus, arthritis, renal disorder, thrombocytopenia, and interstitial lung disease) and three autoantibodies (anti-RNP, anti-Ro/SSA and anti-La/SSB). A 10-year pulmonary arterial hypertension probability-predictive nomogram was established. The model was internally validated by C statistic (0.78), the Brier score (0.03), and a satisfactory calibration curve. According to the net benefit and predicted probability thresholds, we recommend annual screening in high-risk (> 4.62 %) lupus patients.

Conclusion: We developed a risk stratification model using routine clinical assessments. This new tool may effectively predict the future risk of pulmonary arterial hypertension in patients with systemic lupus erythematosus.
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http://dx.doi.org/10.1002/art.41740DOI Listing
June 2021

Outcomes and Nephrotoxicity Associated with Vancomycin Treatment in Patients 80 Years and Older.

Clin Interv Aging 2021 1;16:1023-1035. Epub 2021 Jun 1.

Department of Internal Medicine and Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.

Purpose: This retrospective observational study investigated the efficacy and safety of vancomycin to treat patients aged 80 years and older. In particular, the associations between vancomycin trough concentration (VTC) and treatment outcomes or nephrotoxicity were explored.

Patients And Methods: Patients aged ≥80 years had received ≥3 vancomycin treatments and ≥1 detection of VTC. Treatment outcomes were defined as success or failure. Nephrotoxicity was considered an increase in serum creatinine ≥ 44.2 mmol/L, or 50% above baseline, for ≥2 consecutive days. Univariate and multivariate analyses were performed to identify risk factors for treatment failure and nephrotoxicity.

Results: Of 349 patients, 120 (34.4%) experienced treatment failure. For patients with VTCs at <10, 10-15, 15-20, and ≥20 µg/mL, the clinical response rates were, respectively, 77.8, 77.0, 80.5, and 61.0%; the 30-day mortality rates were 2.8, 15.0, 15.3, and 37.8%; and the rates of persistent bacteremia were 16.7, 12.4, 11.9, and 11.0%. The multivariate analysis indicated that blood urea nitrogen ≥11 g/dL and heart failure were independently associated with treatment failure; but not VTC ( = 0.004, 0.016, 0.828, respectively). During vancomycin treatment, 42 (12.0%) patients experienced nephrotoxicity with recovery time 7.5 ± 4.5 days. Fewer than half of patients with nephrotoxicity recovered after suspending vancomycin application. The variables found independently associated with increased nephrotoxicity were: VTC ≥15 µg/mL; treatment duration ≥15 d; and concomitant aminoglycosides administration ( = 0.024, 0.035, 0.029).

Conclusion: In patients aged 80 years and older, elevated VTC level was not associated with favorable treatment outcomes. Patients with VTC ≥20 µg/mL appear to suggest a worsened prognosis compared with lower VTCs. The risk of nephrotoxicity increases with elevated VTC, longer treatment time, and concomitant aminoglycoside administration.
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http://dx.doi.org/10.2147/CIA.S308878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179733PMC
June 2021

Low-Temperature Synthesis of Single Palladium Atoms Supported on Defective Hexagonal Boron Nitride Nanosheet for Chemoselective Hydrogenation of Cinnamaldehyde.

ACS Nano 2021 Jun 8. Epub 2021 Jun 8.

Joint International Research Laboratory of Advanced Chemical Catalytic Materials & Surface Science, College of Chemistry and Chemical Engineering, Northeast Petroleum University, Daqing, 163318, PR China.

Metal-support interactions are of great importance in determining the support-activity in heterogeneous catalysis. Here we report a low-temperature synthetic strategy to create atomically dispersed palladium atoms anchored on defective hexagonal boron nitride (h-BN) nanosheet. Density functional theory (DFT) calculations suggest that the nitrogen-containing B vacancy can provide stable anchoring sites for palladium atoms. The presence of single palladium atoms was confirmed by spherical aberration correction electron microscopy and extended X-ray absorption fine structure measurement. This catalyst showed exceptional efficiency in chemoselective hydrogenation of cinnamaldehyde, along with excellent recyclability, sintering-resistant ability, and scalability. We anticipate this synthetic approach for the synthesis of high-quality SACs based on h-BN support is amenable to large-scale production of bench-stable catalysts with maximum atom efficiency for industrial applications.
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http://dx.doi.org/10.1021/acsnano.1c02094DOI Listing
June 2021

Single-cell profiling of D-2-hydroxyglutarate using surface-immobilized resazurin analogs.

Biosens Bioelectron 2021 May 29;190:113368. Epub 2021 May 29.

Department of Chemistry, University of California, Riverside, Riverside, CA, 92521, USA. Electronic address:

D-2-hydroxyglutarate (D2HG) is over-produced as an oncometabolite due to mutations in isocitrate dehydrogenases (IDHs). Accumulation of D2HG can cause the dysfunction of many enzymes and genome-wide epigenetic alterations, which can promote oncogenesis. Quantification of D2HG at single-cell resolution can help understand the phenotypic signatures of IDH-mutant cancers and identify effective therapeutics. In this study, we developed an analytical method to detect D2HG levels in single cancer cells by adapting cascade enzymatic reactions on a resazurin-based fluorescence reporter. The resazurin probe was immobilized to the sensing surface via biotin-streptavidin interaction. This surface chemistry was rationally optimized to translate the D2HG levels to sensitive fluorescence readouts efficiently. This D2HG assay demonstrated good selectivity and high sensitivity toward D2HG, and it was compatible with the previously developed single-cell barcode chip (SCBC) technology. Using the SCBC platform, we performed simultaneous single-cell profiling of D2HG, glucose uptake, and critical oncogenic signaling proteins in single IDH-mutant glioma cells. The results unveiled the complex interplays between metabolic and oncogenic signaling and led to the identification of effective combination targeted therapy against these IDH-mutant glioma cells.
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http://dx.doi.org/10.1016/j.bios.2021.113368DOI Listing
May 2021

Spatially displaced excitation contributes to the encoding of interrupted motion by a retinal direction-selective circuit.

Elife 2021 Jun 7;10. Epub 2021 Jun 7.

Committee on Neurobiology Graduate Program, The University of Chicago, Chicago, United States.

Spatially distributed excitation and inhibition collectively shape a visual neuron's receptive field (RF) properties. In the direction-selective circuit of the mammalian retina, the role of strong null-direction inhibition of On-Off direction-selective ganglion cells (On-Off DSGCs) on their direction selectivity is well-studied. However, how excitatory inputs influence the On-Off DSGC's visual response is underexplored. Here, we report that On-Off DSGCs have a spatially displaced glutamatergic receptive field along their horizontal preferred-null motion axes. This displaced receptive field contributes to DSGC null-direction spiking during interrupted motion trajectories. Theoretical analyses indicate that population responses during interrupted motion may help populations of On-Off DSGCs signal the spatial location of moving objects in complex, naturalistic visual environments. Our study highlights that the direction-selective circuit exploits separate sets of mechanisms under different stimulus conditions, and these mechanisms may help encode multiple visual features.
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http://dx.doi.org/10.7554/eLife.68181DOI Listing
June 2021

Promotion of Differentiating Bone Marrow Mesenchymal Stromal Cells (BMSCs) into Cardiomyocytes via HCN2 and HCN4 Cotransfection.

Biomed Res Int 2021 13;2021:5529276. Epub 2021 May 13.

Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, China.

Aim: Investigation of the influences HCN2 and HCN4 has on bone marrow mesenchymal stromal cells (BMSCs) on cardiomyocyte differentiation.

Methods: Miniature adult pigs were used for bone marrow extraction and isolation of BMSCs. The identification of these BMSCs was done by using flow cytometry for the detection of expressed surface antigens CD45, CD11B, CD44, and CD90. Using HCN2 and HCN4 genes cotransfected into BMSCs as group HCN2+HCN4 while myocardial induction solution was used to induced BMSC differentiation in the BMSC induction group. Myocardial marker proteins -actin and cTnT were detected by immunofluorescence staining, while -actin, cTnT, and Desmin myocardial marker proteins expressed were detected by Western blot. The whole-cell patch-clamp technique was used to identify and detect cellular HCN2 channels, HCN4 channel current activation curve, and the inhibitory effect of CsCl on heterologous expression currents.

Results: Flow cytometry results showed that CD45 and CD11B were expressed negatively while CD90 and CD44 were positive. Post HCN2 and HCN4 gene transfection, immunofluorescence staining, and Western blot showed significantly increased HCN2, HCN4, -actin, and cTnT expressed in group HCN2+HCN4 were, which could be compared to the expression levels in the BMSC-induced group. The HCN2+HCN4 group was able to document cell membrane channel ion currents that were similar to If properties.

Conclusion: HCN2 and HCN4 overexpression can considerably enhance the MSC ability to differentiate into cardiomyocytes in vitro and restore the ionic current.
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http://dx.doi.org/10.1155/2021/5529276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140823PMC
May 2021

Efficacy of combined angiotensin II receptor blocker with tripterygium glycosides on diabetic nephropathy: A protocol for meta-analysis.

Medicine (Baltimore) 2021 Jun;100(22):e25991

Department of Clinical Laboratory, Zhang Ye People's Hospital Affiliated to Hexi University, Zhangye City, Gansu, China.

Background: Several studies have reported good results for angiotensin II receptor blockers (ARB) combined with tripterygium glycosides (TGs) in the treatment of diabetic nephropathy (DN). However, because a small number of cases were included in each study, the statistical power was limited. Therefore, we performed a protocol for meta-analysis to further evaluate the clinical efficacy and safety of combined ARB and TGs in treatment of DN.

Methods: The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, Science Direct up to April 2021. Outcome measures were 24-h urinary total protein, urinary albumin excretion rate, serum creatinine, blood urea nitrogen, albumin, hemoglobin A1c, β2-microglobulin and serum glutamic pyruvic transaminase. The risk of bias assessment of the included studies was performed by two authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). We performed meta-analysis using STATA 11.0.

Results: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.

Conclusion: The findings will provide helpful evidence for the application of combined ARB and TGs in the treatment of DN.

Osf Registration Number: 10.17605/OSF.IO/ARGE3.
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http://dx.doi.org/10.1097/MD.0000000000025991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183734PMC
June 2021

Essential hypertension in patients exposed to high-arsenic exposed areas in western China: Genetic susceptibility and urinary arsenic metabolism characteristics.

J Trace Elem Med Biol 2021 Sep 21;67:126778. Epub 2021 May 21.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province & Ministry of Health, Harbin, 150081, China(1). Electronic address:

Objective: To clarify the urinary arsenic metabolism characteristics in individuals with essential hypertension and to analyze the relationship between lipid metabolism gene polymorphisms and susceptibility to essential hypertension in individuals in high-arsenic areas in western China.

Methods: A case-control study was conducted and involved individuals exposed to high arsenic levels (in this study, the arsenic content in the pressurized well water was 0-510.2 μg/L, and that in the mechanical well water was 167 μg/L) in two adjacent high-arsenic areas in Shanxi Province and the Inner Mongolia Autonomous Region, China. A total of 699 samples were collected, including 192 case samples (patients with hypertension) and 507 control samples (no hypertension). Blood pressure measurement data obtained from an epidemiological survey were used to determine whether the subjects had hypertension, and a logistic regression model was used to analyze the association between lipid metabolism gene polymorphisms and hypertension susceptibility. Blood and urine samples were collected based on epidemiological methods, single nucleotide polymorphisms (SNPs) were genotyped using a SNPscan™ multiple SNP typing kit, and urinary arsenic concentrations were determined using the hydride generation atomic fluorescence method (HG-AFS).

Results: ADIPOQ/rs266729 was the dominant genetic model [(GC + GG) vs CC = 0.686:1, 95 % CI = 0.478-0.983], and FABP2/rs1799883 was the recessive genetic model [TT vs (CC + TC) = 1.690:1, 95 % CI = 1.014-2.816]. The distribution of the urinary arsenic secondary methylation ratio (SMR) [dimethylated arsenic (DMA)/monomethylated arsenic (MMA)] was different between hypertensive patients and controls.

Conclusion: ADIPOQ/rs266729 and FABP2/rs1799883 polymorphisms affect susceptibility to essential hypertension in individuals exposed to high levels of arsenic; there was a clear difference in the urinary arsenic metabolism pattern between hypertensive patients and controls.
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http://dx.doi.org/10.1016/j.jtemb.2021.126778DOI Listing
September 2021

Alisol A 24-acetate protects against brain microvascular endothelial cells injury through inhibiting miR-92a-3p/tight junctions axis.

Aging (Albany NY) 2021 Jun 4;13(11):15353-15365. Epub 2021 Jun 4.

The Affiliated Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou 350003, China.

Blood brain barrier (BBB) dysfunction developed with aging is related to brain microvascular endothelial cells (BMECs) injury and losses of tight junctions (TJs). In the present study, we found that Alisol A 24-acetate (AA), a natural compound frequently used as treatment against vascular diseases was essential for BMECs injury and TJs degradation. Our experimental results showed that AA enhanced cell viability and increased zonula occludens-1 (ZO-1), claudin-5, and occludin expression in the oxygen-glucose deprivation (OGD)-induced BMECs. The exploration of the underlying mechanism revealed that AA restrained miR-92a-3p, a noncoding RNA involved in endothelial cells senescence and TJs impairment. To test the role of the miR-92a-3p in BMECs, the cells were transfected with miR-92a-3p mimics and inhibitor. The results showed that miR-92a-3p mimics inhibited cell viability and elevated lactate dehydrogenase (LDH) levels as well as suppressed ZO-1, claudin-5 and occludin expression, while the miR-92a-3p inhibitor reversed the above results. These findings were similar to the therapeutic effects of AA in the OGD-induced BMECs. Bioinformatics analysis and dual-luciferase assay confirmed ZO-1 and occludin were the target genes of miR-92a-3p mediated AA protective roles. In summary, the data demonstrated that AA protected against BMECs damage and TJs loss through the inhibition of miR-92a-3p expression. This provided evidence for AA application in aging-associated BBB protection.
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http://dx.doi.org/10.18632/aging.203094DOI Listing
June 2021

is a strong candidate gene in regulation of pork water-holding capacity.

Arch Anim Breed 2021 23;64(1):109-118. Epub 2021 Mar 23.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, PR China.

The UBX domain containing protein 1-like gene () promotes the degradation of myofibrillar proteins during meat maturation, which affects meat water-holding capacity (WHC). This study aims to identify functional mutations in promoter region, which affects the transcription activity and therefore the WHC. Firstly, we confirmed that the expression level was positively associated with WHC. Individuals with high and low WHC ( per group) were selected from 168 Duroc   Large White   Yorkshire (D   L   Y) crossbred pigs. The promoter region was comparatively sequenced using DNA pools from these two groups, and a mutation ca. 379T   G was revealed that had reverse allele distribution. The single nucleotide polymorphism (SNP) was then genotyped in the abovementioned population. TT genotype individuals exhibited higher mRNA level and higher WHC compared with GG genotype ones. Further luciferase assay confirmed that TT genotype promoter had higher activity. Moreover, the degradation of cytoskeletal framework proteins of muscle cells like , , , and was higher in TT genotype individuals than GG ones. In conclusion, we identified a SNP in the gene promoter that contributes to WHC improvement and pork quality. And is a strong candidate gene in regulation of pork WHC.
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http://dx.doi.org/10.5194/aab-64-109-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162240PMC
March 2021