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Tong Liu,1 Sheng Yang,1 Yan-ping Cheng,1 Xiao-ling Kong,1 Dan-dan Du,1 Xian Wang,1 Yun-fei Bai,2 Li-hong Yin,1 Yue-pu Pu,1 Ge-yu Liang1 1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210096, People’s Republic of China; 2State Key Laboratory of Bioelectronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People’s Republic of ChinaCorrespondence: Ge-yu LiangSchool of Public Health, Southeast University, No. 87 Dingjiaqiao, Nanjing 210009, People’s Republic of ChinaTel +86-25-83272572Fax +86-25-832-72583Email lianggeyu@163.comPurpose: Gastric cancer (GC) is aggressive cancer with a high mortality rate worldwide. N6-methyladenosine (m6A) RNA methylation is related to tumorigenesis, which is dynamically regulated by m6A modulators (“writer,” “eraser,” and “reader”). We conducted a comprehensive analysis of the m6A genes of GC patients in TCGA datasets to identify the potential diagnostic biomarkers.Materials and Methods: We analyzed the expression profile of m6A genes in the TCGA cohort and constructed a diagnostic-m6A-score (DMS) by the LASSO-logistic model. In addition, by consensus cluster analysis, we identified two different subgroups of GC risk individuals by the expression profile of m6A modulators, revealing that YTHDF1’s expression variation profile in GC diagnosis. We also performed RT-qPCR and WB verification in 17 pairs of GC specimens and paired adjacent non-tumor tissues and GC cell lines, and verified the expression trend of YTHDF1 in five GEO GC datasets. YTHDF1 expression and clinical features of GC patients were assessed by the UALCAN.Results: The DMS with high specificity and sensitivity (AUC = 0.986) is proven to distinguish cancer from normal controls better. Moreover, we found that the expression profile variation of YTHDF1 was significantly associated with the high-risk subtype of GC patients. RT-qPCR and Western blot results are consistent with silicon analysis, revealing that YTHDF1’s potential oncogene role in GC tumor.Conclusion: In conclusion, we developed the m6A gene-based diagnostic signature for GC and found that YTHDF1 was significantly correlated with the high-risk subtype of GC patients, suggesting that YTHDF1 might be a potential target in GC early diagnosis.Keywords: m6A, RNA methylation, diagnostic signature, YTHDF1, gastric cancer

Ding-Yun Feng,1,* Yu-Qi Zhou,1,* Yan-Fang Xing,2,* Chuang-Feng Li,3 Qing Lv,4 Jie Dong,5 Jie Qin,3 Yue-Fei Guo,3 Nan Jiang,6 Chencui Huang,7 Hai-Tao Hu,8 Xing-Hua Guo,9 Jie Chen,10 Liang-Hong Yin,11 Tian-Tuo Zhang,1 Xing Li12 1Department of Respiration, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 2Department of Nephrology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China; 3Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 4Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 5Department of Radiotherapy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 6Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China; 7The Associated Laboratory for AI, Cross-strait TsingHua Research Institute and Huiying Medical Technology, Dongsheng Science and Technology Park, HaiDian District, Beijing 100192, People’s Republic of China; 8Department of Surgery, ChanCheng District Center Hospital, Foshan 528000, People’s Republic of China; 9Department of Rheumatology, The LingNan Hospital of Sun Yat-sen University, Guangzhou 510000, People’s Republic of China; 10Department of Oncology, HengYang City Center Hospital, Hengyang 421001, People’s Republic of China; 11Department of Nephrology, The First Affiliated Hospital of JINAN University, Guangzhou 510630, People’s Republic of China; 12Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China *These authors contributed equally to this work Purpose: The effect of glucocorticoid(s) on connective tissue disease (CTD)-related interstitial lung disease (ILD) is controversial. This multicenter study aimed to identify glucocorticoid-sensitive patients using a radiomics approach. Methods: A total of 416 CTD-ILD patients who began glucocorticoid treatment at the discretion of the attending physician, with or without cyclophosphamide, were included in this study. High doses were defined as pulsed intravenous methylprednisolone, an initial dose of 1 mg/kg/day of prednisolone or 0.8 mg/kg/day of methylprednisolone. Low doses were defined as those less than high doses. Radiomics features were manually extracted from primary lung lesions delineated on computed tomography images, and selected by variance, univariate feature selection, and least absolute shrinkage and selection operator regression model. The prediction models were developed using data from 309 patients from two centers and externally validated in 107 patients from four other hospitals. Results: Treatment response in the training and validation groups was 38.5% and 36.4%, respectively. Eleven radiomics features were selected from 1,029 features with predictive value. Random forest models built for radiomics features to predict treatment response yielded a sensitivity of 0.897. The calibration curve of a nomogram demonstrated good agreement between prediction and observation. Decision curve analysis indicated that glucocorticoid was beneficial if the predicted response rate was 50%–60% for an individual. High doses of glucocorticoids and cyclophosphamide yielded superior efficacy. Conclusion: Radiomics-based predictive models reliably identified glucocorticoid-sensitive CTD-ILD patients. Short-term, high-dose glucocorticoid with cyclophosphamide yielded promising results as a potential therapy. Keywords: radiomics, connective tissue diseases, interstitial lung diseases, glucocorticoid

Li Cui,1 Yu Meng,2 Dan Xu,2 Yanyan Feng,2 Gangyi Chen,3 Bo Hu,2 Guijuan Feng,4 Lianghong Yin2 1Xi'xiang People's Hospital Affiliated to Guangdong Medical College, Shenzhen, People's Republic of China; 2Nephrology Department of the First Hospital Affiliated to Ji'nan University, Guangzhou, People's Republic of China; 3First Hospital of Guangzhou University of Chinese Medicine, 4Assisted Reproductive Centre of the First Hospital Affiliated to Ji'nan University, Guangzhou, People's Republic of China Abstract: The purpose of this study was to compare the metabolic properties of maintenance hemodialysis patients treated with glucose-containing and glucose-free dialysate using metabonomics. Pre- and post-dialysis serum samples from group G (−) using glucose-free dialysate, and group G (+) using glucose-added dialysate (glucose levels were 5.5 mmol/L) were analyzed and tested with high performance liquid chromatography quadrupole time-of-flight mass spectrometry. Orthogonal signal correction–partial least squares discriminate analysis revealed a significant difference in the post-dialysis metabolic properties between samples from the G (−) and G (+) groups, and concentrations of leucine and dihydroxyprostaglandin F2α were higher in the G (+) group than in the G (−) group. However, markers of reactive lipid mobilization and amino acid release, such as bile acids, aspartate, and valine, were lower in the G (+) group than in the G (−) group. There were no significant differences in excitatory neurotransmitters aspartate and phosphorylated anandamide. Use of liquid chromatography-tandem mass spectrometry metabonomics indicated that using glucose-added dialysate was superior to glucose-free dialysate in the protection of the central nervous system of maintenance hemodialysis patients, but had potential risks in stimulating oxidative stress. Keywords: hemodialysis, metabonomics, glucose-added dialysate

Ad.CMV-CD is a replication incompetent adenoviral vector carrying a cytomegalovirus (CMV)-driven transcription unit of the cytosine deaminase (CD) gene. The CD transcription unit in this vector catalyzes the deamination of the nontoxic pro-drug, 5-fluorocytosine (5-FC), thus converting it to the cytotoxic drug 5-fluorouracil (5-FU). This adenoviral vector prodrug activation system has been proposed for use in selectively sensitizing breast cancer cells, which may contaminate collections of autologous stem cells products from breast cancer patients, to the toxic effects of 5-FC, without damaging the reconstitutive capability of the normal hematopoietic cells. This system could conceivably kill even the nondividing breast cancer cells, because the levels of 5-FU generated by this system are 10 to 30 times that associated with systemic administration of 5-FU. The incorporation of 5-FU into mRNA at these high levels is sufficient to disrupt mRNA processing and protein synthesis so that even nondividing cells die of protein starvation. To test if the CD adenoviral vector sensitizes breast cancer cells to 5-FC, we exposed primary explants of normal human mammary epithelial cells (HMECs) and the established breast cancer cell (BCC) lines MCF-7 and MDA-MB-453 to the Ad.CMV-CD for 90 minutes. This produced a 100-fold sensitization of these epithelial cells to the effects of 48 hours of exposure to 5-FC. We next tested the selectivity of this system for BCC. When peripheral blood mononuclear cells (PBMCs), collected from cancer patients during the recovery phase from conventional dose chemotherapy-induced myelosuppression, were exposed to the Ad.CMV-CD for 90 minutes in serum-free conditions, little or no detectable conversion of 5-FC into 5-FU was seen even after 48 hours of exposure to high doses of 5-FC. In contrast, 70% of 5-FC was converted into the cytotoxic agent 5-FU when MCF-7 breast cancer cells (BCCs) were exposed to the same Ad.CMV-CD vector followed by 5-FC for 48 hours. All of the BCC lines tested were shown to be sensitive to infection by adenoviral vectors when exposed to a recombinant adenoviral vector containing the reporter gene betagalactosidase (Ad.CMV-betagal). In contrast, less than 1% of the CD34-selected cells and their more immature subsets, such as the CD34+CD38- or CD34(+)CD33- subpopulations, were positive for infection by the Ad.CMV-betagal vector, as judged by fluorescence-activated cell sorting (FACS) analysis, when exposed to the adenoviral vector under conditions that did not commit the early hematopoietic precursor cells to maturation. When artificial mixtures of hematopoietic cells and BCCs were exposed for 90 minutes to the Ad.CMV-CD vector and to 5-FC for 10 days or more, a greater than 1 million fold reduction in the number of BCCs, as measured by colony-limiting dilution assays, was observed. To test if the conditions were damaging for the hematopoietic reconstituting cells, marrow cells collected from 5-FU-treated male donor mice were incubated with the cytosine deaminase adenoviral vector and then exposed to 5-FC either for 4 days in vitro before transplantation or for 14 days immediately after transplantation in vivo. There was no significant decrease in the reconstituting capability of the male marrow cells, as measured by their persistence in female irradiated recipients for up to 6 months after transplantation. These observations suggest that adenovirus-mediated gene transfer of the Escherichia coli cytosine deaminase gene followed by exposure to the nontoxic pro-drug 5-FC may be a potential strategy to selectively reduce the level of contaminating BCCs in collections of hematopoietic cells used for autografts in breast cancer patients.

Aims: The limited therapeutic options for diabetic tubulopathy (DT) in early diabetic kidney disease (DKD) reflect the difficulty of targeting renal tubular compartment. While renin-angiotensin-aldosterone system (RAS) inhibitors are commonly utilized in the management of DKD, how intrarenal RAS contributes to diabetic tubular injury is not fully understood. Mitochondrial disruption and reactive oxygen species (ROS) overgeneration have been involved in diabetic tubular injury. Herein, we aim to test the hypothesis that angiotensin-converting enzyme (ACE)-dependent intrarenal angiotensin II (AngII) disrupts tubular mitochondrial membranous homeostasis and causes excessive ROS generation in DT. Results: Mice suffered from renal tubular mitochondrial disruption and ROS overgeneration following high-fat diet/streptozocin-type 2 diabetic induction. Intrarenal AngII generation is ACE-dependent in DT. Local AngII accumulation in renal tissues was achieved by intrarenal artery injection. ACE-dependent intrarenal AngII-treated mice exhibit markedly elevated levels of makers of tubular injury. CTP: Phosphoethanolamine cytidylyltransferase (PCYT2), the primary regulatory enzyme for the biosynthesis of phosphatidylethanolamine, was enriched in renal tubules according to single-cell RNA sequencing. ACE-dependent intrarenal AngII-induced tubular membranous disruption, ROS overgeneration, and PCYT2 downregulation. The diabetic ambiance deteriorated the detrimental effect of ACE-dependent intrarenal AngII on renal tubules. Captopril, the ACE inhibitor (ACEI), showed efficiency in partially ameliorating ACE-dependent intrarenal AngII-induced tubular deterioration pre- and post-diabetic induction. Innovation and Conclusion: This study uncovers a critical role of ACE-dependent intrarenal AngII in mitochondrial membranous disruption, ROS overgeneration, and PCYT2 deficiency in diabetic renal tubules, providing novel insight into DT pathogenesis and ACEI-combined therapeutic targets. Antioxid. Redox Signal. 00, 000-000.

Introduction: Sepsis is the leading contributor to acute kidney injury (AKI), responsible for 45-70% of AKI occurrences. Despite this, septic AKI is a highly multifactorial and complex condition, and our grasp of its pathogenesis is still not fully developed. Consequently, there remains a significant gap in effective diagnostic and therapeutic strategies for septic AKI., Methods: In the in vitro experiments, BUMPT cells were exposed to lipopolysaccharides (LPS). In vivo experiments involved inducing sepsis in mice through administration of LPS injections. Additionally, in certain experiments, either a miR-455-5p mimic or an anti-miR-455-5p LAN was administered to the mice via injections into the tail vein. The mice were then sacrificed 24 h following LPS administration for subsequent analysis., Results: We observed a significant elevation in miR-455-5p levels within renal tubular cells following LPS-induced septic AKI. Our investigation revealed that NF-κB plays a crucial role in the upregulation of miR-455-5p. Inhibition of NF-κB using TPCA-1 prevented the rise in miR-455-5p levels in BUMPT cells (mouse proximal tubular cells from Boston University) cultured in vitro. Chromatin immunoprecipitation assays confirmed that NF-κB directly interacts with the promoter region of the miR-455-5p gene in response to LPS treatment. Functionally, introducing miR-455-5p mimics intensified cell apoptosis, kidney damage, and the production of inflammatory cytokines, while silencing miR-455-5p had protective effects in septic mice. Notably, administering anti-miR-455-5p enhanced SOCS3 expression, whereas miR-455-5p mimics reduced SOCS3 levels following LPS exposure. Furthermore, our luciferase reporter assays demonstrated that SOCS3 is a direct target of miR-455-5p., Conclusion: This study indicates an NF-κB/miR-455-5p/SOCS3 axis which can exacerbate kidney damage by enhancing renal inflammation. This process highlights potential therapeutic targets for managing septic AKI., (© 2024 S. Karger AG, Basel.)

Groundwater nitrate (NO 3 - ) contamination in China has become a serious environmental problem, especially in agricultural production areas, which greatly affects the safety of drinking groundwater and requires urgent attention. In this study, the main sources of groundwater nitrate in China were reviewed, including atmospheric deposition, soil nitrogen, agricultural fertilization, and fecal sewage, among which fecal sewage and agricultural fertilization were the main reasons for the excessive groundwater nitrate. The application of hydrochemical analysis, multivariate statistical analysis, stable isotope tracer method, and microbial source tracking in the source apportionment of groundwater nitrate was summarized. All types of source apportionment methods had certain limitations. It is suggested that a variety of methods should be used to identify the source of groundwater nitrate, and the contribution rate of different pollution sources should be calculated using multivariate statistical analysis and isotope quantitative analysis models. The source apportionment of nitrate pollution has undergone a process from qualitative to quantitative research. At present, the SIAR and MixSIAR models based on δ 15 N-NO 3 - and δ 18 O-NO 3 - have been used widely to analyze the source of nitrate. However, due to the overlap of isotope characteristic values of different input end-members, the difference in δ 15 N-NO 3 - and δ 18 O-NO 3 - values under different spatial and temporal changes, and the influence of isotope fractionation in the process of nitrogen migration and transformation, the results calculated by the model remain uncertain. It is necessary to further optimize the analytical method of the model to obtain the source of nitrate pollution and its contribution rate more accurately to further aid in the scientific management of groundwater resources.

The Kuaize River is a small typical karst watershed in the source area of the Pearl River as well as an important coal mining area in Eastern Yunnan with a fragile ecological environment. Strengthening the research on the water environment in the region plays an important role in supporting the comprehensive management of the ecological environment and water resources in the source region of the Pearl River. Through the systematic collection of surface water, karst groundwater, and mine water samples, mathematical statistics analysis, correlation analysis, ion ratio analysis, absolute principal component scores multiple linear regression(APCS-MLR), and other methods were used to study the characteristics of hydrochemical evolution and control factors in Kuaize River Basin. The results showed that the average pH value of surface water in Kuaize River Basin was 7.8, which was weakly alkaline. The main cations were Ca 2+ and Na + , showing the characteristics of Ca 2+ >Na + >Mg 2+ >K + . The main anions were HCO 3 - and SO 4 2- , showing the characteristics of HCO 3 - >SO 4 2- >NO 3 - >Cl - . The variation coefficients of Na + , SO 4 2- , and NO 3 - in surface water were high, showing strong spatial variability. The water chemical type of the trunk stream was mainly HCO 3 -Ca, whereas the water chemical type of the tributary was relatively complex, mainly HCO 3 -Ca, HCO 3 -Ca·Na, and HCO 3 ·SO 4 -Ca·Na. The chemical composition of surface water was mainly affected by rock weathering, cation exchange, and human activities. Ca 2+ , Mg 2+ , Na + , and HCO 3 - in surface water mainly came from the weathering of carbonate rock and silicate rock; SO 4 2- mainly came from the oxidation of sulfide, such as pyrite in coal seams; K + , Cl - , and NO 3 - mainly came from domestic sewage and agricultural activities. The APCS-MLR receptor model analysis results showed that the surface water in the Kuaize River Basin was mainly affected by sulfide oxidation, carbonate weathering, weathering of silicate rock in mine water, domestic sewage, agricultural activities, and unknown sources. In general, the contribution rate of human activities such as mining, domestic sewage, and agricultural activities to the surface water reached 47.17%, indicating that human activities were the key driving factor of surface water chemistry in the Kuaize River Basin.

Gaussian graphical model is a strong tool for identifying interactions from metabolomics data based on conditional correlation. However, data may be collected from different stages or subgroups of subjects with heterogeneity or hierarchical structure. There are different integrating strategies of graphical models for multi-group data proposed by data scientists. It is challenging to select the methods for metabolism data analysis. This study aimed to evaluate the performance of several different integrating graphical models for multi-group data and provide support for the choice of strategy for similar characteristic data. We compared the performance of seven methods in estimating graph structures through simulation study. We also applied all the methods in breast cancer metabolomics data grouped by stages to illustrate the real data application. The method of Shaddox et al. achieved the highest average area under the receiver operating characteristic curve and area under the precision-recall curve across most scenarios, and it was the only approach with all indicators ranked at the top. Nevertheless, it also cost the most time in all settings. Stochastic search structure learning tends to result in estimates that focus on the precision of identified edges, while BEAM, hierarchical Bayesian approach and birth-death Markov chain Monte Carlo may identify more potential edges. In the real metabolomics data analysis from three stages of breast cancer patients, results were in line with that in simulation study., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for cytosolic DNA-sensing and the subsequent immune responses. The inappropriate activation of this pathway leads to DNA-induced autoimmune response. Understanding the precise regulation of cGAS-STING pathway is important for developing therapeutics to treat several autoimmune diseases caused by self-DNA., Results: We report that Meloxicam (MXC) inhibits intracellular DNA-, but not RNA-induced immune responses. We find that MXC inhibits the phosphorylation of STING by examining in different cells with various DNA stimulations. We further find that MXC significantly dampens the expression levels of interferon-stimulated genes (ISGs) by using DNA 3' repair exonuclease 1 (TREX1)-deficient cell, an experimental model for self-DNA-induced autoimmune disease. Importantly, we demonstrate that MXC could promote the survival in Trex1 -/- mouse model for Aicardi-Goutières syndrome (AGS)., Conclusions: Our study identified a non-steroidal anti-inflammatory drug, MXC, that exhibits potential effect in treating the autoimmunity caused by self-DNA., (© 2023. The Author(s).)

The skin is the first barrier to maintain the stability of internal environment of the body and resist harmful factors of external environment, and is easily damaged because of various external factors. When full-thickness skin defects reach a certain level, it is difficult for the skin to repair itself, so wound dressings are needed to promote wound healing. Seeking an ideal dressing that can promote wound healing has long been a hot research topic. Chitosan is a unique biopolysaccharide polymer with good biocompatibility, biodegradability, antibacterial activity, and thermal stability, which has great potential in the development and application of wound dressings. Based on the introduction of properties of chitosan, this article reviews the role and mechanism of chitosan-based wound dressings in wound healing, and summarizes the hemostatic effect, antibacterial effect, delivery effect, and tissue regeneration promotion effect of chitosan, aiming to provide a certain reference for the research and development of new chitosan-based wound dressings in the future.

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors originally developed for the treatment of type 2 diabetes are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood., Methods: We generated single-cell transcriptomes of kidneys from rats with 5/6 nephrectomy before and after SGLT2 inhibitors treatment by single-cell RNA sequencing., Findings: Empagliflozin treatment decreased BUN, creatinine and urinary albumin excretion compared to placebo by 39.8%, 34.1%, and 55%, respectively (p < 0.01 in all cases). Renal interstitial fibrosis and glomerulosclerosis was likewise decreased by 51% and 66.8%; respectively (p < 0.05 in all cases). 14 distinct kidney cell clusters could be identified by scRNA-seq. The polarization of M2 macrophages from state 1 (CD206 - CD68 - M2 macrophages) to state 5 (CD206 + CD68 + M2 macrophages) was the main pro-fibrotic process, as CD206 + CD68 + M2 macrophages highly expressed fibrosis-promoting genes and can convert into fibrocytes. Empagliflozin remarkably inhibited the expression of fibrosis-promoting (IFG1 and TREM2) and polarization-associated genes (GPNMB, LGALS3, PRDX5, and CTSB) in CD206 + CD68 + M2 macrophages and attenuated inflammatory signals from CD8 + effector T cells. The inhibitory effect of empagliflozin on CD206 + CD68 + M2 macrophages polarization was mainly achieved by affecting mitophagy and mTOR pathways., Interpretation: We propose that the beneficial effects of empagliflozin on kidney function and morphology in 5/6 nephrectomyiced rats with established CKD are at least partially due to an inhibition of CD206 + CD68 + M2 macrophage polarization by targeting mTOR and mitophagy pathways and attenuating inflammatory signals from CD8 + effector T cells., Fundings: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section., Competing Interests: Conflict of interest statement The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Diabetic kidney disease (DKD) is among the most important causes for chronic kidney disease. Anthocyanins (ANT) are polyphenolic compounds present in various food and play an important role in ameliorating hyperglycemia and insulin sensitivity. However, the effects of ANT in DKD are still poorly understood. This study aimed to investigate the effect of ANT (cyanidin-3-O-glucoside [C3G]) on the renal function of DKD, and whether the anti-DKD effect of ANT is related to metabolic pathways., Methods: To explore the role of ANT in DKD, we performed the examination of blood glucose, renal function, and histopathology. As for the mechanism, we designed the label-free quantification proteomics and nontargeted metabolomics analysis for kidney and serum. Subsequently, we revealed the anti-DKD effect of ANT through the bioinformatic analysis., Results: We showed that the fasting blood glucose level (- 6.1 mmol/L, P = 0.037), perimeter of glomerular lesions (- 24.1 μm, P = 0.030), fibrosis score of glomerular (- 8.8%, P = 0.002), and kidney function (Cystatin C: - 701.4 pg/mL, P = 0.043; urine creatinine: - 701.4 mmol/L, P = 0.032) were significantly alleviated in DKD mice after ANT treatment compared to untreated in the 20th week. Further, proteins and metabolites in the kidneys of DKD mice were observed to be dramatically altered due to changes in amino acid metabolism with ANT treatment; mainly, taurine and hypotaurine metabolism pathway was upregulated (P = 0.0001, t value = 5.97). Furthermore, upregulated tryptophan metabolism (P < 0.0001, t value = 5.94) and tyrosine metabolism (P = 0.0037, t value = 2.91) pathways had effects on serum of DKD mice as responsed ANT regulating., Conclusions: Our results suggested that prevention of the progression of DKD by ANT could be related to the regulation of amino acid metabolism. The use of dietary ANT may be one of the dietary strategies to prevent and treat DKD., (© 2022. The Author(s).)

In order to serve the water resources management of the Xiaohuangni River basin, this study explored the hydrochemical composition characteristics and ion sources of surface water in the basin. Samples of main stream and tributary river water and mine water were systematically collected. By means of a Piper diagram, Gibbs diagram, ion ratio coefficient, and mathematical statistical analysis, we analyzed the hydrochemical composition, spatial distribution characteristics, and main control factors of the Xiaohuangni River and evaluated the solute contribution rates of different sources. The results showed that the pH of the Xiaohuangni River basin ranged between 7.17 to 9.14, with an average of 8.00, which is generally considered weakly alkaline. Additionally, the total dissolved solids ranged between 154 mg·L -1 to 460 mg·L -1 , with an average of 257.39 mg·L -1 , which was equivalent to that of the main stream of the Xijiang River. The dominant cation was Ca 2+ , accounting for 69% of the total cations; the dominant anions were HCO 3 - and SO 4 2- , accounting for 65% and 30% of the total anions, respectively. The main chemical type of the main stream was HCO 3 -Ca. Affected by mining activities, the tributaries transitioned from HCO 3 -Ca to HCO 3 ·SO 4 -Ca and HCO 3 ·SO 4 -Ca·Na type. River water solute was mainly controlled by the weathering of carbonate rock and silicate rock, with the participation of sulfuric and carbonic acid. The contribution rate of carbonate weathering to river water solute was 63%, and that of silicate weathering was 16.33%. Meanwhile, human activities contributed markedly to the dissolved solutes of the Xiaohuangni River basin, in which the contribution rate of mining activities was 13.4%, and the contribution rate of agricultural activities and domestic sewage was 4%.

Objectives: Shellfish waste is a primary source for making N-acetyl-D-glucosamine. Thus, establishing a high-efficiency and low-cost bioconversion method to produce N-acetyl-D-glucosamine directly from shellfish waste was promising., Results: A mutant C81 was obtained from Chitinolyticbacter meiyuanensis SYBC-H1 via 60 Co-γ irradiation. This mutant C81 showed the highest chitinase activity of 9.8 U/mL that was 85% higher than the parent strain. The mutant C81 exhibted improved antioxidant activities, including total antioxidant capacity, superoxide radical ability, and hydroxyl radical scavenging ability, compared to that of the parent strain. Four out of nine organic solvents increased the chitinase activity by 1.9%, 6.8%, 11.7%, and 15.8%, corresponding to methylbenzene, n-heptane, petroleum ether, and n-hexane, respectively. The biphase system composed of aqueous and hexane presented a five-fold reduction of cell viability compared to the control. Using a continuous fermentation bioconversion process, 4.2 g/L GlcNAc was produced from crayfish shell powder with a yield of 80% of the chitin content., Conclusions: This study demonstrated that the mutant C81 is suitable for converting crayfish shell powder into GlcNAc in an aqueous-organic system., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA., (© 2021 The Authors.)

A series of arylgold(III) complexes of tridentate diphenylpyridine ligand incorporated with fluorene and its heterocyclic spiro derivatives, spiro[fluorene-9,9'-xanthene] and spiro[acridine-9,9'-fluorene], as auxiliary ligands has been prepared. This class of complexes exhibits high decomposition temperatures of up to 387 °C, excellent film morphologies in solid-state thin films with a root-mean-square roughness smaller than 0.20 nm, as well as high photoluminescence quantum yields of up to 0.72 in solid-state thin films. Solution-processed organic light-emitting devices (OLEDs) fabricated from this series of complexes as dopants show intense electroluminescence in the sky-blue region with maximum external quantum efficiencies of 10.0%. Taking advantage of their high thermal stability, vacuum-deposited OLEDs have also been fabricated and satisfactory operational lifetimes of ∼300 h have been recorded.

Objective: Carnitine-acylcarnitine Translocase (CACT) deficiency (OMIM 212138) and carnitine palmitoyl transferase 2 (CPT2) deficiency (OMIM 60065050) are rare inherited disorders of mitochondrial long chain fatty acid oxidation. The aim of our study is to review the clinical, biochemical and molecular characteristics in children diagnosed with CACT and CPT2 deficiencies in Malaysia., Design and Methods: This is a retrospective study. We reviewed medical records of six patients diagnosed with CACT and CPT2 deficiencies. They were identified from a selective high-risk screening of 50,579 patients from January 2010 until Jun 2020., Results: All six patients had either elevation of the long chain acylcarnitines and/or an elevated (C16 + C18:1)/C2 acylcarnitine ratio. SLC25A20 gene sequencing of patient 1 and 6 showed a homozygous splice site mutation at c.199-10 T > G in intron 2. Two novel mutations at c.109C > T p. (Arg37*) in exon 2 and at c.706C > T p. (Arg236*) in exon 7 of SLC25A20 gene were found in patient 2. Patient 3 and 4 (siblings) exhibited a compound heterozygous mutation at c.638A > G p. (Asp213Gly) and novel mutation c.1073 T > G p. (Leu358Arg) in exon 4 of CPT2 gene. A significant combined prevalence at 0.01% of CACT and CPT2 deficiencies was found in the symptomatic Malaysian patients., Conclusions: The use of the (C16 + C18:1)/C2 acylcarnitine ratio in dried blood spot in our experience improves the diagnostic specificity for CACT/CPT2 deficiencies over long chain acylcarnitine (C16 and C18:1) alone. DNA sequencing for both genes aids in confirming the diagnosis., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dioscin, one natural product, has various pharmacological actions. However, its effects on methotrexate (MTX)-induced hepatorenal damages still remain unknown. In the present study, the data manifested that dioscin restored the viabilities of L-02 and NRK-52E cells, reduced ALT, AST, Cr, BUN levels, and ameliorated histopathological changes of liver and kidney. Besides, dioscin decreased ROS levels in cells, and adjusted SOD, MDA, GSH and GSH-Px levels in rats. Dioscin reduced the expression levels of miR-145-5p which directly targeted Sirt5, and then regulated the expression levels of SOD1, Nrf2, Gst, Keap1, HO-1, GCLC and NQO1. MiR-145-5p mimic in cells deteriorated ROS levels and decreased Sirt5 expression to accentuate oxidative stress by regulating the expression levels of SOD1, Nrf2, Keap1, which were all reversed by dioscin. Moreover, MTX-induced hepatorenal damage were worsened in mice by Sirt5 siRNA or miR-145-5p agomir, which were also alleviated by dioscin. Dioscin relieved MTX-induced hepatorenal damages through regulating miR-145-5p-medicated oxidative stress, which should be considered as one effective drug to treat the disorder in future., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Alport syndrome (AS) is an inherited kidney disease caused by defects in type IV collagen, which is characterized by hematuria, progressive nephritis or end-stage renal disease (ESRD), hearing loss, and occasionally ocular lesions. Approximately 80% of AS cases are caused by X-linked mutations in the COL4A5 gene. This study explored novel deletion and missense mutations in COL4A5 responsible for renal disorder in two Han Chinese families. In pedigree 1, the five male patients all had ESRD at a young age, while the affected female members only presented with microscopic hematuria. Whole exome sequencing and Sanger sequencing identified a novel frameshift deletion mutation (c.422&#95;428del, p.Leu142Valfs∗11) in exon 7 of COL4A5 . In pedigree 2, the 16-year-old male proband had elevated serum creatinine (309  μ mol/L) without extrarenal manifestations, while his mother only manifested with hematuria. A missense mutation (c.476G>T, p.Gly159Val) was found in exon 9 of the COL4A5 gene. Neither of these mutations was present in the Exome Variant Server of the NHLBI-ESP database, nor was it found in the ExAC or 1000 Genomes databases. Through the literature review, it was found that male Chinese patients with X-linked AS carried COL4A5 deletion or missense mutations had a more severe phenotype than female patients, particularly in proteinuria and impaired renal function. Compared to male patients with missense mutations, patients in whom deletion mutations were found were more likely to progress to ESRD (15.4% vs. 36.0%, P = 0.041). This study identified two novel COL4A5 mutations in Chinese families with X-linked AS, expanded the mutational spectrum of the COL4A5 gene, and presented findings that are significant for the screening and genetic diagnosis of AS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wen-yu Gong et al.)

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the production of multiple autoimmune antibodies and potentially involves any organ or tissue with a broad range of clinical manifestations. Conventional therapy still utilizes glucocorticoids and immunosuppressants. However, some patients show inadequate responses to glucocorticoids and immunosuppression, which may induce secondary immune dysfunction and severe infection as well as lead to an increased tumor risk. The lack of in vitro models has hampered progress in understanding and treating SLE. Patient-derived induced pluripotent stem cells (iPSCs) may provide a unique opportunity for modeling in vitro diseases as well as a platform for drug screening in individual patients. We isolated peripheral blood mononuclear cells from blood to explore the establishment of an in vitro model platform for SLE and directly purified CD34+ cells and seeded them for expansion. CD34+ cells were forced to express seven pluripotency factors, OCT4, SOX2, NANOG, LIN28, c-MYC, KLF4, and SV40LT, through transduction in lentiviral vectors. The morphological characteristics of induced pluripotent stem-like cells, such as prominent nucleoli and a high nucleus-to-cytoplasm ratio, were observed. The pluripotency of established SLE patient-derived iPSCs was confirmed by the expression of embryonic stem cell (ESC) markers and the ability of cells to differentiate into multiple cell lines. SLE patient-derived iPSCs exhibited human ESC properties, including morphology; growth characteristics; expression of pluripotency, genes, and surface markers; and teratoma formation. In conclusion, we generated SLE patient-derived iPSCs and validated their pluripotency. This study is a first but critical step that can provide a model platform for research aimed at understanding the SLE mechanism, which may lead to the discovery of new targets or compounds for the treatment of this disease.

The article "Suppression of microRNA-101 attenuates hypoxia-induced myocardial H9c2 cell injury by targeting DIMT1-Sp1/survivin pathway, by Z.-X. Guo, F.-Z. Zhou, W. Song, L.-L. Yu, W.-J. Yan, L.-H. Yin, H. Sang, H.-Y. Zhang, published in Eur Rev Med Pharmacol Sci 2018; 22 (20): 6965-6976-DOI: 10.26355/eurrev&#95;201810&#95;16167-PMID: 30402863" has been withdrawn from the authors due to some inaccuracies. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16167.

MiR-23a-5p is involved in the occurrence and development of some serious diseases, but its effects on intestinal ischemia-reperfusion (II/R) injury is unclear. In this research, the hypoxia/reoxygenation (H/R) model on IEC-6 cells and II/R model in mice were used. The data showed that the ROS level in model group was significantly increased compared with control group. The level of intestinal MPO was increased and serum SOD was decreased in mice compared with sham group. Moreover, the expression levels of miR-23a-5p in model groups were obviously increased in vitro and in vivo, while the expression levels of PPARα, FOXO3α, PGC-1α, Nrf2, CAT, NQO1, HO-1 and SOD2 were significantly decreased. The double luciferase reporter gene assay showed that there was binding site between miR-23a-5p and PPARα. When miR-23a-5p was inhibited or PPARα gene was overexpressed, H/R-caused cell damage was alleviated and ROS level was decreased compared with NC group. PPARα expression level was increased, accompanied by the increased levels of FOXO3α, PGC-1α, Nrf2, CAT, NQO1, HO-1 and SOD2. After enhancing miR-23a-5p expression or silencing PPARα gene, H/R-caused cell damage was further aggravated compared with NC group, and ROS level was increased associated with the decreased levels of FOXO3α, PGC-1α, Nrf2, CAT, NQO1, HO-1 and SOD2. Our study demonstrated that miR-23a-5p exacerbated II/R injury by promoting oxidative stress via targeting PPARα, which should be considered as one new drug target to treat II/R injury., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Elevated parathyroid hormone (PTH) concentrations were reported to be associated with chronic renal allograft failure. However, measurements of PTH are challenging, because PTH can occur either as non-oxidized (n-ox) or oxidized (ox) PTH. Only n-ox PTH is a PTH receptor agonist. The intact PTH (iPTH) concentrations measured routinely in clinical practice, however, equals non-oxidized PTH (n-oxPTH) plus oxidized PTH (oxPTH). In CKD patients, the majority of the circulating PTH is oxidized. We measured iPTH, oxPTH and n-oxPTH at study entry in 600 kidney transplant recipients (KTRs). They were followed for graft loss for 3 years. Graft loss was defined as need for initiation of renal replacement therapy. Thirty-eight patients had graft loss during the 3 years follow-up. OxPTH correlated very well with iPTH (R 2  = 0.997, p < 0.0001), whereas the correlation between n-oxPTH and iPTH was much weaker (R 2  = 0.762, p < 0.0001). Compared to KTRs without graft loss, KTRs with graft loss had significantly higher levels of iPTH, oxPTH, and n-oxPTH (p < 0.0001 in all cases). After adjusting for confounding factors in cox proportional hazards analysis, only n-oxPTH, but not oxPTH neither iPTH, was significantly associated with graft loss (Hazard ratio (HR): 1.02, 95% CI: 1.01-1.03, p = 1.84 × 10 -3 ). The very close correlation between oxPTH and iPTH measurements suggests that conventional iPTH measurements most likely describe oxidative stress rather than PTH bioactivity. Only non-oxidized PTH but not oxidized PTH nor intact PTH is associated with graft loss in stable kidney transplant recipients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To compare the epidemiological characteristics of COVID-19 in Guangzhou and Wenzhou, and evaluate the effectiveness of their prevention and control measures. Methods: Data of COVID-19 cases reported in Guangzhou and Wenzhou as of February 29, 2020 were collected. The incidence curves of COVID-19 in two cities were constructed. The real time reproduction number ( R(t) ) of COVID-19 in two cities was calculated respectively. Results: A total of 346 and 465 confirmed COVID-19 cases were analysed in Guangzhou and Wenzhou, respectively. In two cities, most cases were aged 30-59 years (Guangzhou: 54.9%; Wenzhou: 70.3%). The incidence curve peaked on 27 January, 2020 in Guangzhou and on 26 January, 2020 in Wenzhou, then began to decline in both cities. The peaks of imported COVID-19 cases from Hubei occurred earlier than the peak of COVID-19 incidences in two cities, and the peak of imported cases from Hubei occurred earlier in Wenzhou than in Guangzhou. In early epidemic phase, imported cases were predominant in both cities, then the number of local cases increased and gradually took the dominance in Wenzhou. In Guangzhou, the imported cases was still predominant. Despite the different epidemic pattern, the R(t) and the number of COVID-19 cases declined after strict prevention and control measures were taken in Guangzhou and in Wenzhou. Conclusion: The time and scale specific differences of imported COVID-19 resulted in different epidemic patterns in two cities, but the spread of the disease were effectively controlled after taking strict prevention and control measures.

Ankylosing spondylitis (AS) is a chronic immune-mediated disease. Various immune cells play an essential role in the AS pathogenesis. However, the specific pathogenesis of AS has not been well understood. Proteomic profiles of peripheral blood mononuclear cells (PBMCs) were applied to reveal the specific pathogenesis of AS. Quantitative proteomic analyses were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based methods to investigate the protein profiling of PBMCs from new-onset AS patients ( n = 9) and healthy controls ( n = 9). We identified 782 differentially expressed proteins (DEPs) and 527 differentially phosphorylated proteins (DPPs) between AS patients and healthy controls. The subcellular location of DEPs and DPPs showed that most of the DEPs were from the cytoplasm ( n = 296, 38%), were extracellular ( n = 141, 18%), and from the nucleus ( n = 114, 15%); most of the DPPs were from the cytoplasm ( n = 37, 34%), nucleus ( n = 35, 32%), and plasma membrane ( n = 10, 9%). We further identified 89 proteins with both expression and phosphorylation differences. The functional annotation of the 89 differentially expressed and phosphorylated proteins enriched in the antigen processing and presentation pathway. Four DEPs with six phosphorylated positions were found in the antigen processing and presentation pathway. The differentially expressed and phosphorylated proteins may be helpful to uncover the pathogenesis of AS. The six AS-specific proteins may serve as candidate markers for AS diagnosis and new treatment targets., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

MiR-142-3p as one key molecule in oncogenesis and inflammation plays crucial roles in hepatic fibrosis, hepatocellular carcinoma and other liver disease. However, there have no literatures to report its effects on hepatic ischemia-reperfusion (HI/R) injury. In the present work, hypoxia reoxygenation (H/R) models on AML12 and HepG2 cells, and ischemia/reperfusion model in mice were established. The methods of real-time PCR, dual luciferase reporter, mimic, inhibitor, agomir, antagomir and siRNA transfection assays were used. The expression levels of miR-142-3p were decreased in model groups in vitro and in vivo compared with control group or Sham group, which directly targeted MARCKS to regulate its expression. Then, MARCKS activated p38/JNK signal, up-regulated NF-κB expression to accelerate inflammation, and inhibited PI3K/AKT signal to promote apoptosis. Moreover, miR-142-3p mimic in vitro and agomir in vivo lowered the expression levels of MARCKS, thereby alleviating apoptosis and inflammation to relieve HI/R injury. Furthermore, miR-142- 3p inhibitor in vitro and antagomir in vivo up-regulated the expression levels of MARCKS to aggravate HI/R damage via promoting inflammation and apoptosis. Consistently, MARCKS siRNA markedly inhibited HI/R injury by restraining apoptosis and inflamm- ation in mice. MiR-142-3p played a considerable part in adjusting HI/R injury by targeting MARCKS, and miR-142-3p/MARCKS should be a new therapeutic target for HI/R injury., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early warning. Methods: Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk index. Results: A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei province. Conclusions: Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.

Renal ischemia-reperfusion (RI/R) injury with high morbidity and mortality is one common clinical disease. Development of drug targets to treat the disorder is critical important. MiR-27a-3p plays important roles in regulating oxidative stress. However, its effects on RI/R injury have not been reported. In this paper, hypoxia/reoxygenation (H/R) models on NRK-52E and HK-2 cells, and RI/R model in C57BL/6 mice were established. The results showed that H/R in vitro decreased cell viability and increased ROS levels in cells, and RI/R caused renal injury and oxidative damage in mice. The expression levels of miR-27a-3p were up-regulated based on real-time PCR and FISH assays in model groups compared with control groups, which directly targeted Grb2 based on dual luciferase reporter assay and co-transfaction test. In addition, miR-27a- 3p markedly reduced Grb2 expression to down-regulate the expression levels of p-PI3K, p-AKT, Nrf2, HO-1, and up-regulate Keap1 expression in model groups. MiR-27a-3p mimics in vitro enhanced H/R-caused oxidative stress via increasing ROS levels and decreasing Grb2 expression to down-regulate PI3K-AKT signal. In contrary, miR-27a-3p inhibitor in vitro significantly reduced H/R-caused oxidative damage via decreasing ROS levels and increasing Grb2 expression to up-regulate PI3K-AKT signal. In vivo, miR-27a- 3p agomir exacerbated RI/R-caused renal damage by decreasing SOD level and increasing Cr, BUN, MDA levels via suppressing Grb2 expression to down-regulate PI3K- AKT signal. However, miR-27a -3p antagomir alleviated RI/R-caused oxidative damage via increasing Grb2 expression to up-regulate PI3k-AKT signal. Grb2siRNA in mice further enhanced RI/R-caused renal injury by increasing Cr, BUN, MDA levels and decreasing SOD level via inhibiting the expression levels of Grb2, Nrf2, HO-1, and increasing Keap1 expression. Our data showed that miR-27a-3p aggravated RI/R injury by promoting oxidative stress via targeting Grb2, which should be considered as one new drug target to treat RI/R injury., Competing Interests: Declaration of Competing Interest In this paper, the authors asserted that they had no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Maternal smoking during pregnancy affects fetal neurological development. Metabolomic studies in the general population suggest that smoking is associated with characteristic metabolic alterations. We investigated the association between the maternal smoking status, the fetal metabolome and head circumference at birth, as a surrogate parameter of brain development. 320 mother/newborn pairs of the Berlin Birth Cohort were investigated. Anthropometric parameters, including head circumference, of newborns of smoking mothers, former smoking mothers, and never smoking mothers were compared to assess the impact of maternal smoking behavior. Associations between maternal smoking behavior and 163 cord blood metabolites and associations between newborn head circumference and concentrations of smoking behavior related metabolites were analysed. Male newborns of smoking mothers had a reduced head circumference when compared with newborns from former smoking and never smoking mothers (p < 0.05). Using linear regression models corrected for established confounding factors, maternal smoking during pregnancy showed an independent association with head circumference (95% CI: -0.75～-0.41 cm, p = 2.45×10 -11 ). In a stepwise linear regression model corrected for known confounding factors of brain growth lyso-phosphatidylcholine 20:3 (95% CI: 6.68～39.88 cm, p = 4.62×10 -4 ) was associated with head circumference in male offspring only. None of the metabolites were associated with head circumference of female newborns. In conclusion, maternal smoking during pregnancy impacted on male offspring's development including brain development. The smoking related metabolite lyso-phosphatidylcholine 20:3 was associated with head circumference of male offspring., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the exported risk of COVID-19 from Hubei Province and the imported risk in various provinces across China. Methods: Data of reported COVID-19 cases and Baidu Migration Indexin all provinces of the country as of February 14, 2020 were collected. The correlation analysis between cumulative number of reported cases and the migration index from Hubei was performed, and the imported risks from Hubei to different provinces across China were further evaluated. Results: A total of 49 970 confirmed cases were reported nationwide, of which 37 884 were in Hubei Province. The average daily migration index from Hubei to other provinces was 312.09, Wuhan and other cities in Hubei were 117.95 and 194.16, respectively. The cumulative COVID-19 cases of provinces was positively correlated with the migration index derived from Hubei Province, also in Wuhan and other cities in Hubei, with correlation coefficients of 0.84, 0.84, and 0.81. In linear model, population migration from Hubei Province, Wuhan and other cities in Hubei account for 71.2%, 70.1%, and 66.3% of the variation, respectively. The period of high exported risk from Hubei occurred before January 27, of which the risks before January 23 mainly came from Wuhan, and then mainly from other cities in Hubei. Hunan Province, Henan Province and Guangdong Province ranked the top three in terms of cumulative imported risk (the cumulative risk indices were 58.61, 54.75 and 49.62 respectively). Conclusion: The epidemic in each province was mainly caused by the importation of Hubei Province. Taking measures such as restricting the migration of population in Hubei Province and strengthening quarantine measures for immigrants from Hubei Province may greatly reduce the risk of continued spread of the epidemic.

Background: Our previous study revealed that microRNA-125a-5p plays a crucial role in regulating hepatic glycolipid metabolism by targeting STAT3 in type 2 diabetes mellitus (T2DM). Dioscin, a major active ingredient in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in T2DM has not been reported., Purpose: The aim of this study was to investigate the effect of dioscin on T2DM and elucidate its potential mechanism., Methods: The effect of dioscin on glycolipid metabolic disorder in insulin-induced HepG2 cells, palmitic acid-induced AML12 cells, high-fat diet- and streptozotocin- induced T2DM rats, and spontaneous T2DM KK-Ay mice were evaluated. Then, the possible mechanisms of dioscin were comprehensively evaluated., Results: Dioscin markedly alleviated the dysregulation of glycolipid metabolism in T2DM by reducing hyperglycemia and hyperlipidemia, improving insulin resistance, increasing hepatic glycogen content, and attenuating lipid accumulation. When the mechanism was investigated, dioscin was found to markedly elevate miR-125a-5p level and decrease STAT3 expression. Consequently, dioscin increased phosphorylation levels of STAT3, PI3K, AKT, GSK-3β, and FoxO1 and decreased gene levels of PEPCK, G6Pase, SREBP-1c, FAS, ACC, and SCD1, leading to an increase in glycogen synthesis and a decrease in gluconeogenesis and lipogenesis. The effects of dioscin on regulating miR-125a-5p/STAT3 pathway were verified by miR-125a-5p overexpression and STAT3 overexpression., Conclusions: Dioscin showed potent anti-T2DM activity by improving the inhibitory effect of miR-125a-5p on STAT3 signaling to alleviate glycolipid metabolic disorder of T2DM., Competing Interests: Declaration of Competing Interest All authors have no competing interests to declare, financial or otherwise., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Accumulating evidence implies that N6-methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation-relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan-Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase-like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up-trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α-smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC., (© 2019 Wiley Periodicals, Inc.)

With the development of China's economy, the field of stomatology has also made considerable progress. With the increase of people's demand for dental medical support, it is urgent to cultivate stomatological professionals with a more international perspective and international communication and competition in the field of production, teaching and research. Through literature search, this paper addressed the significance and role of English teaching in stomatology, explored the characteristics and advantages of different teaching modes, in order to provide ideas on how to carry out English teaching in stomatology more effectively.

Platelet-rich plasma and platelet-rich fibrin (PRF) are widely used in the field of stomatology. Advance-ments in preparation techniques and basic research have enabled the use of PRF derivatives in oral clinical applications. The evolution, preparation techniques, biological properties, and medical research progress of PRF derivatives are reviewed in this paper.

Bipolar cyclometalated dendritic alkynylgold(iii) complexes that exhibit excellent film morphologies in solid-state thin films have been designed and synthesized. Together with their high luminescence quantum yields, high performance solution-processable organic light-emitting devices have been realized, maintaining high external quantum efficiencies of >12% for dendrimers up to the second generation.

Background: Recent scientific evidence has suggested that microRNAs (miRNAs) play an important role in papillary thyroid cancer (PTC). In the current study, we aim to identify a miRNA-related signature as the sensitive and novel prognostic biomarkers., Methods: We performed a comprehensive analysis of the data downloaded from the Cancer Genome Atlas (TCGA) database. The association between survival outcome and miRNA was assessed by the univariate and multivariate Cox proportional hazards model. The risk score model was built to evaluate the predicting value of miRNA signature. The potential biofunctions and transcription factors of target miRNAs were investigated through bioinformatic analysis. The result was verified by the quantitative real-time polymerase chain reaction (qRT-PCR) in 32 pairs of PTC and adjacent nontumor tissues. In addition, the results were verified by other cohorts from gene expression omnibus (GEO) as detected by microarrays., Results: A total of 1030 miRNAs were identified from the TCGA database. Thirty-six key intersection miRNAs were obtained. The associations between clinical features and key miRNAs were evaluated. Eventually, a two-miRNA signature (hsa-miR-181a-2-3p and hsa-miR-138-1-3p) was identified. The power of the miRNA prognostic signature was effective. In total, we identified 202 genes that were associated with 2 miRNAs above, and the top 10 enriched transcript factors that highly related with the target miRNAs were explored. The qRT-PCR and GEO data validation were consistent with bioinformatics results., Conclusions: A tumor-specific miRNA signature was identified, and the joint prognostic power was evaluated, which may be potential biomarkers for prognosis of PTC., Impact: The two-miRNA signature could become the potential prognostic indicator of PTC in the future., (© 2018 Wiley Periodicals, Inc.)

Background: The serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China., Methods: We recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR)., Results: We found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis., Conclusions: The present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.

Herein, we aimed to develop a strategy to assess quality consistency of a drug product, with a focus on two typical cases of injection. Multi-variable analysis using a sequencing combination of factor analysis, one-way analysis of variance and cluster analysis identified all potential Critical Quality Attributes (CQAs) for each manufacturing process, which were identified from the attributes of quality standard (QAs) using supervised (cefazolin sodium pentahydrate, α-CEZ-Na) or unsupervised (cephathiamidine, CETD) analysis. All CQAs from QAs were applied to set up an integrated index, quality consistency attribute (QCA), to evaluate product quality consistency in a specific aspect. Meanwhile, real-time analysis by chemometrics-assisted near-infrared spectroscopy (NIR) was used to obtain useful information corresponding to the CQAs from the process attributes (PAs) of some of the critical processes. The quantitative results of characteristic signals of NIR by multiple linear regression was defined as the process consistency attribute (PrCA), and was used to assess the product quality consistency in another aspect. Therefore, either values of QCA or PrCA displayed sensitivity to changes in product quality, allowing us to establish a strategy with strong practicality, comprehensiveness and visualization to demonstrate the quality consistency of a specific product. Such strategy is not only conducive to the improvement of quality standards, but to the retrospective investigation of manufacturing processes which ultimately allowed maintenance of product consistency.

Objective: To investigate the effects of hydrophilic treatment on the surface morphology and surface properties of pure titanium and titanium-zirconium alloy implants, and to provide reference for the studies of implant surface modification. Methods: The pure titanium group, the hydrophilic pure titanium group, the titanium zirconium alloy group and the hydrophilic titanium-zirconium alloy group were prepared by sandblasting and acid-etching or hydrophilic sandblasting and acid-etching, (11 specimens in each group). The surface morphology and surface properties of four types of titanium specimens were analyzed by surface contact angle meter, scanning electron microscope (SEM), optical profilometer, atomic force microscope (AFM) and Raman spectrometer. Results: The surface contact angles of hydrophilic pure titanium and hydrophilic titanium-zirconium alloy were 1.6°±0.3° and 1.5°±0.2°, and the surface contact angles of pure titanium and titanium-zirconium alloy were 101.4°±4.6° and 96.2°±3.0°, respectively. SEM showed that the nano-protrusions on the surface of pure titanium and titanium-zirconium alloys were less or even absent, while the nano-protrusions on the surface of hydrophilic pure titanium and hydrophilic titanium-zirconium alloys were relatively more; the nano-protrusions on the surface of hydrophilic pure titanium surface were small and dense relatively, but the nano-protrusions of the hydrophilic titanium-zirconium alloy had large diameters and were dispersed relatively. The optical profiler and AFM showed that the surface roughness of hydrophilic pure titanium and hydrophilic titanium-zirconium alloy was significantly higher than that of pure titanium and titanium-zirconium alloy ( P< 0.05). Raman spectroscopy showed that only the amorphous TiO(2) was present on the surface of the pure titanium group, while the rutile TiO(2) characteristic peak was observed in the other three groups, but the lateral inhomogeneity was observed. After Raman shift 610 cm(-1), the Raman spectra of four groups were similar. Conclusions: Hydrophilic sandblasting and acid-etching treatment can improve the surface hydrophilicity and surface roughness of pure titanium and titanium zirconium alloy, and improve the surface properties of pure titanium and titanium zirconium alloy implants.

Due to the surge in type 2 diabetes mellitus (T2DM), treatments for chronic metabolic dysregulations with fewer side-effects are sought. Lycii Cortex (LyC), a traditional Chinese Medicine (TCM) herb has a long history of being widely prescribed to treat T2DM as alternative medicine; however, the bioactive molecules and working mechanism remained unknown. Previous studies revealed kukoamine B (KB) as a major and featured compound for LyC with bioactivities for anti-oxidation and acute inflammation, which may be related to anti-diabetes properties. This study aims to understand the efficacy and the mode of action of KB in the diabetic (db/db) mouse model using a metabolomics approach. Parallel comparison was conducted using the first-line anti-diabetic drugs, metformin and rosligtazone, as positive controls. The db/db mice were treated with KB (50 mg kg -1 day -1 ) for 9 weeks. Bodyweight and fasting blood glucose were monitored every 5 and 7 days, respectively. Metabolomics and high-throughput molecular approaches, including lipidomics, targeted metabolomics (Biocrates p180), and cytokine profiling were applied to measure the alteration of serum metabolites and inflammatory biomarkers between different treatments vs. control (db/db mice treated with vehicle). After 9 weeks of treatment, KB lowered blood glucose, without the adverse effects of bodyweight gain and hepatomegaly shown after rosiglitazone treatment. Lipidomics analysis revealed that KB reduced levels of circulating triglycerides, cholesterol, phosphatidylethanolamine, and increased levels of phosphatidylcholines. KB also increased acylcarnitines, and reduced systemic inflammation (cytokine array). Pathway analysis suggested that KB may regulate nuclear transcription factors (e.g., NF-κB and/or PPAR) to reduce inflammation and facilitate a shift toward metabolic and inflammatory homeostasis. Comparison of KB with first-line drugs suggests that rosiglitazone may over-regulate lipid metabolism and anti-inflammatory responses, which may be associated with adverse side effects, while metformin had less impact on lipid and anti-inflammation profiles. Our research from holistic and systemic views supports the conclusion that KB is the bioactive compound of LyC for managing T2DM, and suggests KB as a nutraceutical or a pharmaceutical candidate for T2D treatment. In addition, our research provides insights related to metformin and rosiglitazone action, beyond lowering blood glucose.

Free vitamin D is the biologically active form of vitamin D. Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. The goal of our current study was to investigate the relation between blood concentrations of free 25-hydroxyvitamin D with cardiovascular events in end-stage chronic kidney disease patients on hemodialysis, because this is unknown so far. We measured free vitamin D levels in 117 stable consecutive prevalent patients in September as a surrogate of vitamin D exposure during the past 6 months, and recorded the number of cardiovascular events during the previous 6 months defined as hospitalization due to heart failure, episodes of acute coronary syndrome, and stroke. Fourteen events occurred during the observation period. In patients without any cardiovascular events the free vitamin D levels were significantly higher as compared to those with cardiovascular events (patients without events: 5.68 [4.37-9.27] pg/mL; patients with events: 4.74 [3.46-5.37] pg/mL, p = 0.015). This finding remained stable after multiple regression analysis considering confounding factors such as age, time on dialysis, preexisting diabetes, hypertension, and coronary heart disease. In conclusion, our study shows that free vitamin D serum concentrations are independently associated with major cardiovascular events in chronic kidney disease patients on dialysis., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background: Uremic encephalopathy (UE), a toxic metabolic encephalopathy, is an uncommon complication resulting from endogenous uremic toxins in patients with severe renal failure. UE syndrome can range from mild inattention to coma. The imaging findings of UE include cortical or subcortical involvement, basal ganglia involvement and white matter involvement. The basal ganglia type is uncommon, although previous cases have reported that Asian patients with diabetes mellitus (DM) are usually affected., Case Presentation: A 32 year-old woman with a history of non-diabetic hemodialysis for 3 years suffered from severe involuntary movement, and brain magnetic resonance imaging showed symmetrical T2-weighted imaging (T2WI) and T2/fluid-attenuated inversion recovery (T2FLAIR) hyperintense nonhemorrhagic lesions in the bilateral basal ganglia. She was diagnosed with UE as syndrome of bilateral basal ganglia lesions, due to a combined effect of uremic toxins and hyperthyroidism. After treatment with high frequency and high flux dialysis, hyperbaric oxygen therapy and declining parathyroid hormone, the patient achieved complete remission with normal body movement and was discharged., Conclusion: UE with basal ganglia involvement is uncommon, although generally seen in Asian patients with DM. Our case reported a hemodialysis patient that had non-diabetic UE with typical bilateral basal ganglia lesions, presenting with involuntary movement.

Objective: MicroRNAs (miRNAs) are small single-stranded RNAs in eukaryotic cells, which play important regulatory roles in the pathogenesis of various diseases. We aimed to investigate the effects of miRNA-101 (miR-101) on hypoxia-induced myocardial infarction (MI) cell injury model (myocardial H9c2 cell injury model). The possible target gene of miR-101 was also analyzed., Materials and Methods: H9c2 cells were exposed to hypoxia treatment. Cell viability, migration, invasion, apoptosis and the expression of miR-101 were detected using CCK-8 assay, transwell assay, flow cytometer analysis, Western blotting and qRT-PCR, respectively. Then, the effects of miR-101 overexpression or suppression on the cell injury induced by hypoxia were assessed. Dual luciferase reporter assay was used to analyze the possible target gene of miR-101. Finally, the effects of dimethyladenosine transferase 1 homolog (DIMT1), the possible target gene of miR-101, on H9c2 cell injury were investigated., Results: Hypoxia significantly induced H9c2 cell injury. miR-101 was up-regulated after hypoxia induction. Hypoxia-induced cell injury was significantly reversed by miR-101 suppression and exacerbated by miR-101 overexpression. DIMT1 was a direct target gene of miR-101. Knockdown of DIMT1 markedly inhibited the protective effects of miR-101 suppression on hypoxia-induced cell injury by suppressing specific protein 1 (Sp1)/Survivin pathway., Conclusions: We verified the critical roles of miR-101 in regulating myocardial cell injury induced by hypoxia. DIMT1-mediated the Sp1/Survivin pathway was also involved in this process. Our findings replenished the understanding of the regulatory roles of miRNAs in hypoxia-induced MI cell injury and provided new molecular target for therapy and diagnosis of MI.

Clear cell renal cell carcinoma (ccRCC) is the main subtype of malignant kidney cancer. Long non‑coding RNA (lncRNA) serves a key role in predicting survival in patients with cancer. The present study aimed to develop an lncRNA‑related signature of prognostic values for patients with ccRCC. RNA sequencing data of 454 patients were analyzed from The Cancer Genome Atlas (TCGA). To identify the differentially expressed lncRNAs, the patients from four groups classified by tumor stages were compared. The association between survival outcome and lncRNA expression profile was assessed by the univariate and multivariate Cox proportional hazards model. Survival was analyzed using the log‑rank test, and functions of target lncRNAs were investigated through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Finally, 19 lncRNAs were identified as significantly associated with overall survival (OS) time. These lncRNAs were gathered as a signal prognostic signature, which may be a potential biomarker for the prognosis of ccRCC. The risk score was built to evaluate the predictive value of the lncRNA signature. There was a significant positive correlation between ccRCC patients with the low‑risk score and OS time (P<0.001). Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to verify the result in 17 pairs of ccRCC and adjacent non‑tumor tissues. Functional enrichment analysis revealed that these lncRNAs were associated with several molecular pathways of the tumor. The RT‑qPCR validation was consistent with the TCGA bioinformatics results. In conclusion, a tumor‑specific lncRNA signature of 19 lncRNAs was identified and the joint prognostic power was evaluated in the present study, and this signature was determined to be a potential biomarker for the prognosis of ccRCC.

Abnormal regulation of long non-coding RNAs (lncRNAs) appears to be a primary feature of numerous types of human cancer. However, the association between the dysregulation of lncRNAs and functional alterations in gastric cancer (GC) remains unclear. In previous studies, we applied microarray and bioinformatics analyses to screen for key lncRNAs from the tumor tissues and matched adjacent non-tumor tissues of 10 patients with GC. There were seven key lncRNAs demonstrated to be significantly different between carcinoma tissues and adjacent non-tumor tissues. In the present study, the expression of these seven selected lncRNAs were validated in 82 patients with GC to further investigate the association between lncRNAs and GC clinical characterization. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results demonstrated that RP5-919F19 , MCPH1 antisense RNA 1 ( CTD-2541M15 ) and urothelial carcinoma-associated 1 ( UCA1 ) exhibited consistent upregulation in cancer compared with adjacent non-tumor tissues, whereas AP000459, LOC101928316 , tumor suppressor candidate 8 ( LINC01071 ) and maternally expressed 3 ( MEG3 ) showed consistent downregulation. The results from the microarray and RT-qPCR experiments achieved 100% agreement. A correlation analysis indicated that RP5-919F19, LOC101928316 and MEG3 were significantly associated with tumor differentiation degree, RP5-919F19, UCA1 and MEG3 were significantly associated with lymph node metastasis, and RP5-919F19, CTD-2541M15 and UCA1 were significantly associated with tumor-node-metastasis stage (P<0.05). In addition, it was identified that the differential expression of LINC01071 and LOC101928316 significantly correlated with the age and gender of the GC patients, respectively (P<0.05). The results suggest that the lncRNAs RP5-919F19, LOC101928316, CTD-2541M15, UCA1 and MEG3 are closely associated with the invasion and metastasis of GC, which reveals these indicators as potential specificity biomarkers for the diagnosis, prognosis and classification of GC. Thus, these lncRNAs merit further study as novel candidate biomarkers for the clinical diagnosis of GC and as potential targets for therapy.