[Analysis of the Spatiotemporal Distribution of Algal Blooms and Its Driving Factors in Chaohu Lake Based on Multi-source Datasets].

Eutrophication and harmful algae blooms are one of the common ecological and environmental problems faced by freshwater lakes all over the world. As a typical inland freshwater lake, Chaohu Lake exhibits a high level of eutrophication and algae blooms year-round and shows a spatiotemporal difference in different regions of the lake. In order to understand the basic regularity of the development and outbreak of algal blooms in Chaohu Lake, the data from the comprehensive water observation platform and remote sensing were integrated to obtain the spatiotemporal distribution of algal blooms from 2015 to 2020. Then, an evaluation model based on Boosted Regression Trees (BRT) was constructed to quantitatively assess the importance and interactions of various environmental factors on algal blooms at different stages. The results indicated that:① The occurrence of algal blooms in Chaohu Lake exhibited significant seasonal variations, with the cyanobacteria beginning to recover in spring and bring about a light degree of algal blooms in the western and coastal areas of Chaohu Lake. The density of cyanobacteria reached its maximum in summer and autumn, accompanied by moderate and severe degrees of algal bloom outbreaks. ② During the non-outbreak period, the variation in the cyanobacteria density was greatly affected by physical and chemical factors, which explained 80.3% of the variance in the change in cyanobacteria density. The high concentrations of dissolved oxygen content in the water column and the weak alkalinity (7.2-7.6) and appropriate water temperature (about 3℃) provided a favorable environmental condition for the breeding and growth of cyanobacteria. In addition, the onset of algal blooms was closely related to the air temperature steadily passing through the threshold. According to the statistics, the date of first outbreak of algal blooms in Chaohu Lake was 11 days or so after the air temperature steadily remained above 7℃. ③ During the outbreak period, the occurrence of algal blooms was influenced by the combination of cyanobacterial biomass and meteorological conditions such as temperature, wind speed, and sunshine duration. The cumulative contribution ratio of the four factors was as high as 95%, and each factor had an optimal interval conductive to the outbreak of algal blooms. Furthermore, the results of multi-factor interaction analysis indicated a larger probability of the outbreak of algal blooms in Chaohu Lake under the combined effect of high cyanobacteria density, suitable temperature, and the breeze. This study analyzed and revealed the spatiotemporal characteristics and the dominant influencing factors of algal blooms in Chaohu Lake at different stages, which could provide the scientific basis for the prediction, early warning, and disposal of algal blooms under the context of climate change.

Systematic review and network meta-analysis of different non-steroidal anti-inflammatory drugs for juvenile idiopathic arthritis.

BACKGROUND: Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been developed. AIM: To perform a systematic review and network meta-analysis to determine the optimal instructions. METHODS: We searched for randomized controlled trials (RCTs) from PubMed, EMBASE, Google Scholar, CNKI, and Wanfang without restriction for publication date or language at August, 2023. Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis. The surface under the cumulative ranking curve (SUCRA) analysis was used to rank the treatments. P value less than 0.05 was identified as statistically significant. RESULTS: We included 8 RCTs (1127 patients) comparing 8 different instructions including meloxicam (0.125 qd and 0.250 qd), Celecoxib (3 mg/kg bid and 6 mg/kg bid), piroxicam, Naproxen (5.0 mg/kg/d, 7.5 mg/kg/d and 12.5 mg/kg/d), inuprofen (30-40 mg/kg/d), Aspirin (60-80 mg/kg/d, 75 mg/kg/d, and 55 mg/kg/d), Tolmetin (15 mg/kg/d), Rofecoxib, and placebo. There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response. The SUCRA shows that celecoxib (6 mg/kg bid) ranked first (SUCRA, 88.9%), rofecoxib ranked second (SUCRA, 68.1%), Celecoxib (3 mg/kg bid) ranked third (SUCRA, 51.0%). There were no significant differences between any two NSAIDs regarding adverse events. The SUCRA shows that placebo ranked first (SUCRA, 88.2%), piroxicam ranked second (SUCRA, 60.5%), rofecoxib (0.6 mg/kg qd) ranked third (SUCRA, 56.1%), meloxicam (0.125 mg/kg qd) ranked fourth (SUCRA, 56.1%), and rofecoxib (0.3 mg/kg qd) ranked fifth (SUCRA, 56.1%). CONCLUSION: In summary, celecoxib (6 mg/kg bid) was found to be the most effective NSAID for treating JIA. Rofecoxib, piroxicam, and meloxicam may be safer options, but further research is needed to confirm these findings in larger trials with higher quality studies.

Discovery of novel diaryl substituted isoquinolin-1(2H)-one derivatives as hypoxia-inducible factor-1 signaling inhibitors for the treatment of rheumatoid arthritis.

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50 = 0.55 µM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy.

[Repair effect of different doses of human umbilical cord mesenchymal stem cells on white matter injury in neonatal rats]. / 不同剂量人脐带间å è´¨å¹²ç»†èƒžç§»æ¤å¯¹æ–°ç”Ÿå¤§é¼ è„‘ç™½è´¨æŸä¼¤çš„ä¿®å¤ä½œç”¨.

OBJECTIVES: To compare the repair effects of different doses of human umbilical cord mesenchymal stem cells (hUC-MSCs) on white matter injury (WMI) in neonatal rats. METHODS: Two-day-old Sprague-Dawley neonatal rats were randomly divided into five groups: sham operation group, WMI group, and hUC-MSCs groups (low dose, medium dose, and high dose), with 24 rats in each group. Twenty-four hours after successful establishment of the neonatal rat white matter injury model, the WMI group was injected with sterile PBS via the lateral ventricle, while the hUC-MSCs groups received injections of hUC-MSCs at different doses. At 14 and 21 days post-modeling, hematoxylin and eosin staining was used to observe pathological changes in the tissues around the lateral ventricles. Real-time quantitative polymerase chain reaction was used to detect the quantitative expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) mRNA in the brain tissue. Immunohistochemistry was employed to observe the expression levels of GFAP and neuron-specific nuclear protein (NeuN) in the tissues around the lateral ventricles. TUNEL staining was used to observe cell apoptosis in the tissues around the lateral ventricles. At 21 days post-modeling, the Morris water maze test was used to observe the spatial learning and memory capabilities of the neonatal rats. RESULTS: At 14 and 21 days post-modeling, numerous cells with nuclear shrinkage and rupture, as well as disordered arrangement of nerve fibers, were observed in the tissues around the lateral ventricles of the WMI group and the low dose group. Compared with the WMI group, the medium and high dose groups showed alleviated pathological changes; the arrangement of nerve fibers in the medium dose group was relatively more orderly compared with the high dose group. Compared with the WMI group, there was no significant difference in the expression levels of MBP and GFAP mRNA in the low dose group (P>0.05), while the expression levels of MBP mRNA increased and GFAP mRNA decreased in the medium and high dose groups. The expression level of MBP mRNA in the medium dose group was higher than that in the high dose group, and the expression level of GFAP mRNA in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the protein expression of GFAP and NeuN in the low dose group (P>0.05), while the expression of NeuN protein increased and GFAP protein decreased in the medium and high dose groups. The expression of NeuN protein in the medium dose group was higher than that in the high dose group, and the expression of GFAP protein in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the number of apoptotic cells in the low dose group (P>0.05), while the number of apoptotic cells in the medium and high dose groups was less than that in the WMI group, and the number of apoptotic cells in the medium dose group was less than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the escape latency time in the low dose group (P>0.05); starting from the third day of the latency period, the escape latency time in the medium dose group was less than that in the WMI group (P<0.05). The medium and high dose groups crossed the platform more times than the WMI group (P<0.05). CONCLUSIONS: Low dose hUC-MSCs may yield unsatisfactory repair effects on WMI in neonatal rats, while medium and high doses of hUC-MSCs have significant repair effects, with the medium dose demonstrating superior efficacy.

Analysis of airway structural parameters in Han Chinese adults: a prospective cross-sectional study.

INTRODUCTION: Establishing reference ranges for central airway parameters and exploring their influencing factors in Han Chinese non-smoking adults. METHODS: This prospective cross-sectional study was conducted on Han Chinese non-smoking adults who underwent chest CT scans at the Tongzhou Campus of Dongzhimen Hospital Affiliated with the Beijing University of Chinese Medicine between September 2022 and November 2022. The SYNAPSE 3D image analysis software was utilized, enabling the extraction of critical parameters such as central airway length, airway wall thickness (AWT), airway lumen area (ALA), and subcarinal angle (SCA). Pearson's correlation coefficient analysis and multiple linear regression analysis methods were employed to evaluate the relationship between central airway parameters and age, sex, weight, and height. RESULTS: The study encompassed 888 Han Chinese non-smoking adults, comprising 456 females and 432 males. Significant sex differences were noted in central airway length, AWT, and ALA, with measurements in males exceeding those in females (p < 0.01) with no significant difference in SCA. Correlation analyses unveiled relationships between central airway parameters and age, sex, weight, and height. During multiple linear regression analyses, no conclusive evidence emerged to demonstrate the independent or combined explanatory or predictive capacity of the aforementioned variables for central airway length and SCA. Although sex has a significant impact on AWT and ALA, its capability in explanation or prediction remains limited. The conclusions drawn from the primary analysis receive reinforcement from the outcomes of sensitivity analyses. CONCLUSION: Establishing the distribution range of central airway parameters in non-smoking Han Chinese adults. It observed significant sex differences in these parameters, except for the SCA. However, the study found that the predictive or explanatory power of age, sex, weight, and height for central airway parameters was either limited or non-significant.

Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population.

BACKGROUND: The coronavirus disease 2019 (COVID-19) continues to spread worldwide. Integrated Chinese and Western medicine have had some successes in treating COVID-19. OBJECTIVE: This study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas (3-drugs-3-formulas) in patients with COVID-19. SEARCH STRATEGY: Relevant studies were identified from 12 electronic databases searched from their establishment to April 7, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs), non-RCTs and cohort studies that evaluated the effects of 3-drugs-3-formulas for COVID-19. The treatment group was treated with one of the 3-drugs-3-formulas plus conventional treatment. The control group was treated with conventional treatment. DATA EXTRACTION AND ANALYSIS: Two evaluators screened and selected literature independently, then extracted basic information and assessed risk of bias. The treatment outcome measures were duration of main symptoms, hospitalization time, aggravation rate and mortality. RevMan 5.4 was used to analyze the pooled results reported as mean difference (MD) with 95% confidence interval (CI) for continuous data and risk ratio (RR) with 95% CI for dichotomous data. RESULTS: Forty-one studies with a total of 13,260 participants were identified. Our analysis suggests that compared with conventional treatment, the combination of 3-drugs-3-formulas might shorten duration of fever (MD = -1.39; 95% CI: -2.19 to -0.59; P < 0.05), cough (MD = -1.57; 95% CI: -2.16 to -0.98; P < 0.05) and fatigue (MD = -1.36; 95% CI: -2.21 to -0.51; P < 0.05), decrease length of hospital stay (MD = -2.62; 95% CI -3.52 to -1.72; P < 0.05), the time for nucleic acid conversion (MD = -2.92; 95% CI: -4.26 to -1.59; P < 0.05), aggravation rate (RR = 0.49; 95% CI: 0.38 to 0.64; P < 0.05) and mortality (RR = 0.34; 95% CI: 0.19 to 0.62; P < 0.05), and increase the recovery rate of chest computerized tomography manifestations (RR = 1.22; 95% CI: 1.14 to 1.3; P < 0.05) and total effectiveness (RR = 1.24; 95% CI: 1.09 to 1.42; P < 0.05). CONCLUSION: The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19. No severe adverse events related to 3-drugs-3-formulas were observed. Hence, 3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients. Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula. Please cite this article as: You LZ, Dai QQ, Zhong XY, Yu DD, Cui HR, Kong YF, Zhao MZ, Zhang XY, Xu QQ, Guan ZY, Wei XX, Zhang XC, Han SJ, Liu WJ, Chen Z, Zhang XY, Zhao C, Jin YH, Shang HC. Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population. J Integr Med. 2023; 21(5): 441-454.

Network pharmacology and molecular docking prediction, combined with experimental validation to explore the potential mechanism of Qishen Yiqi pills against HF-related cognitive dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Qishen Yiqi Pills (QSYQ) is a classical herbal formula for treating heart failure (HF) and has potential efficacy in improving cognitive function. The latter is one of the most common complications in patients with HF. However, there is no study on treating HF-related cognitive dysfunction by QSYQ. AIMS OF THE STUDY: The study aims to investigate the effect and mechanism of QSYQ on treating post-HF cognitive dysfunction based on network pharmacology and experimental validation. MATERIALS AND METHODS: Network pharmacology analysis and molecular docking was used to explore endogenous targets of QSYQ in treating cognitive impairment. Ligation of the anterior descending branch of the left coronary artery and sleep deprivation (SD) were used to induce HF-related cognitive dysfunction in rats. The efficacy and potential signal targets of QSYQ were then verified by functional evaluation, pathological staining, and molecular biology experiments. RESULTS: 384 common targets were identified by intersecting QSYQ 'compound targets' and 'cognitive dysfunction' disease targets. KEGG analysis showed these targets were enriched to the cAMP signal, and four marks responsible for regulating the cAMP signal were successfully docked with core compounds of QSYQ. Animal experiments demonstrated that QSYQ significantly ameliorated cardiac function and cognitive function in rats suffering from HF and SD, inhibited the reduction of cAMP and BDNF content, reversed the upregulation of PDE4 and downregulation of CREB, suppressed the loss of neurons, and restored the expression of synaptic protein PSD95 in the hippocampus. CONCLUSION: This study clarified that QSYQ could improve HF-related cognitive dysfunction by modulating cAMP-CREB-BDNF signals. It provides a rich basis for the potential mechanism of QSYQ in the treatment of heart failure with cognitive dysfunction.

Highly Stereoselective Diels-Alder Reactions Catalyzed by Diboronate Complexes.

A highly enantioselective catalytic system for exo-Diels-Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDB). Activated by various Lewis or Brønsted acids, BPDB can catalyze highly stereoselective asymmetric exo-Diels-Alder reactions of monocarbonyl-based dienophiles. When 1,2-dicarbonyl-based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels-Alder reactions. BPDB can be prepared as crystalline solids on a large scale and are stable under ambient condition. Single-crystal X-ray analysis of the structure for acid-activated BPDB indicated that its activation involves cleavage of a labile B←N bond.

Highly sensitive and selective serotonin (5-HT) electrochemical sensor based on ultrafine Fe3O4 nanoparticles anchored on carbon spheres.

Neurotransmitter serotonin (5-HT) is involved in various physiological and pathological processes. Therefore, its highly sensitive and selective detection in human serum is of great significance for early diagnosis of disease. In this work, employing iron phthalocyanine as Fe source, ultrafine Fe3O4 nanoparticles anchored on carbon spheres (Fe3O4/CSs) have been prepared, which exhibits an excellent electrochemical sensing performance toward 5-HT. With carbonecous spheres turned into conductive carbon spheres under the heat treatment in N2 atmosphere, iron phthalocyanine absorbed on their surfaces are simultaneously pyrolysised and oxidized, and finally transformed into ultrafine Fe3O4 nanoparticles. Electrochemical results demonstrate a high sensitivity (5.503 µA µM-1) and a low detection limit (4 nM) toward 5-HT for as-prepared Fe3O4/CSs. In combination with the morphology and physicochemical property of Fe3O4/CSs, the enhanced sensing mechanism toward 5-HT is disscussed. In addition, the developed electrochemical sensor also displays a good sensing stability and an anti-interferent ability. Further applied in real human serum samples, a satisfactory recovery rate is achieved. Promisingly, the developed electrochemical sensor can be employed for the determination of 5-HT in actual samples.

A multitask classification framework based on vision transformer for predicting molecular expressions of glioma.

PURPOSE: The purpose of this study is to develop a Vision Transformer model with multitask classification framework that is appropriate for predicting four molecular expressions of glioma simultaneously based on MR imaging. MATERIALS AND METHODS: A total of 188 glioma (grades II-IV) patients with an immunohistochemical diagnosis of IDH, MGMT, Ki67 and P53 expression were enrolled in our study. A Vision Transformer (ViT) model, including three independent networks based on T2WI, T1CWI and T2 + T1CWI (T2-net, T1C-net and TU-net), was developed for the prediction of four glioma molecular expressions simultaneously. To evaluate the model performance, the accuracy rate, recall, precision, F1-score, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: The proposed ViT model achieved high accuracy in predicting IDH, MGMT, Ki67 and P53 expression in gliomas. Among the three networks using the ViT model, TU-net achieved the best results with the highest values of accuracy (range, 0.937-0.969), precision (range, 0.949-0.972), recall (range, 0.873-0.991), F1-score (range, 0.910-0.981) and AUC (range, 0.976-0.984). Comparisons were also made between our ViT model and convolutional neural network (CNN)-based models, and the proposed ViT model outperformed the existing CNN-based models. CONCLUSION: Vision Transformer is a reliable approach for the prediction of glioma molecular biomarkers and can be a viable alternative to CNNs.

Fe-doping induced surface Fe2+/Fe3+ cycle and activated redox-inert TiO2 for enhanced Hg(II) electrochemical sensing: An efficient strategy to strengthen the redox activity.

Recently, Fe-based metal oxide with a variable-valence ability (i.e., the Fe2+/Fe3+ cycle) can participate in the redox of target heavy metal ions (HMIs) and enhance the electrochemical signal, which have attracted significant attention. However, it has not yet been proved whether iron-based metal oxides with variable-valence ability can activate the variable valence behavior of inert metal oxides (i.e., TiO2) and enable them to participate in the redox of target HMIs. Herein, we develop an efficient Fe-doped strategy to activate TiO2 nanoparticles for the electrochemical detection of Hg(II). TiO2 nanoparticles with the 5% Fe-doped content (FT5) possess the best detection sensitivity of 400.63 µA µM-1 cm-2 for Hg(II), which is dramatically higher than that of pure TiO2. The synergistic effects of enhanced adsorption by OVs and promoted redox activity by surface Fe2+/Fe3+ and Ti3+/Ti4+ cycle help FT5 to obtain an excellent electrochemical detection performance of Hg(II). In detail, Fe doping tune the concentration of oxygen vacancies (OVs) in TiO2 nanoparticles, which contributes to improving the adsorption ability of Hg(II). The exposed OVs on the surface of Fe-doped TiO2 nanoparticles form numerous hydroxyl groups (-OH) in water, and the hydroxyl groups can bond with Hg(II), tremendously accelerating the capture of Hg(II). Upon successfully obtaining OVs, the Ti3+ species are created in TiO2, achieving the activation of TiO2. Moreover, it is found that large amount surface Fe2+/Fe3+ and Ti3+/Ti4+ cycle on FT5 can accelerated the redox of Hg(II) and then favor to electrochemical detection performance. This study emphasizes that doping transition metal elements with variable valence states can control OVs concentration and successfully activate inert metal oxides.

High Levels of Heat Shock Protein 47 in the Aqueous Humor of Patients with Acute Primary Angle Closure.

INTRODUCTION: Acute primary angle closure (APAC) is often characterized by acute elevation of intraocular pressure (IOP) accompanied by severe ocular and systemic symptoms. Excessive collagen accumulation, which can be caused by upregulated heat shock protein 47 (HSP47) expression, can produce scarring in rat conjunctival blebs. Meanwhile, the presence of HSP47 in human aqueous humor and its levels are yet to be determined. METHODS: We examined 32 consecutive patients with APAC and 16 age-matched participants without APAC scheduled for cataract surgery who were enrolled as a control group. Aqueous humor samples were collected from all subjects at the time of surgery and compared between the subjects with and without APAC. RESULTS: The levels of HSP47 in the aqueous humor of patients with APAC (1,210.4 ± 450.2 pg/mL) were found to be significantly increased (P = 0.001) compared with those in the control group (863.4 ± 240.0 pg/mL). Notably, the levels of HSP47 negatively correlated with the age of patients with APAC (P = 0.023). CONCLUSION: HSP47 was upregulated in the aqueous humor of patients with APAC and may play a role in scarring after trabeculectomy for APAC.

Ultra-sensitive electroanalysis of toxic 2,4-DNT on o-CoxFe1-xSe2 solid solution: Fe-doping-induced c-CoSe2 phase transition to form electron-rich active sites.

How to achieve the sensitive electroanalysis of organics pollution in water environment is vital significance, but it is limited by their redox inert and the ambiguous detection mechanism. Herein, Fe-doping-induced structural phase transition engineering is designed to make the cubic (c-) CoSe2 to orthorhombic (o-) CoSe2, accompanying with the formation of o-CoxFe1-xSe2 solid solution. By controlling the Fe doping amount, the fully orthogonalized C1F1 (the mole ratio of Co/Fe is 1:1) electrode acquires a high sensitivity of 0.293 µA µM-1 toward 2,4-Dinitrotoluene (2,4-DNT) detection. Besides, C1F1 exhibits excellent stability, reproducibility and practicality for 2,4-DNT detection. Combined with experimental studies and theoretical calculations, it is shown that during the phase transition, electrons are transferred from Co to Fe, forming electron-rich Fe active sites. The Fe sites can match well with free 2,4-DNT molecules and then accelerate the reduction process of 2,4-DNT. A series of experiments including DFT and electrochemistry demonstrate that the doping-induced structural phase transition strategy can improve the adsorption performance of the material and also enhance the catalytic ability, thereby enhancing the electrochemical sensitivity. The co-engineering of morphology and phase transition of metal selenides by doping will provide inspiration for the design of sensitive sensing interfaces for organic pollutants.

Kinsenoside alleviates inflammation and fibrosis in experimental NASH mice by suppressing the NF-κB/NLRP3 signaling pathway.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) has replaced viral hepatitis as the main driver of the rising morbidity and mortality associated with cirrhosis and liver cancer worldwide, while no FDA-approved therapies are currently known. Kinsenoside (KD), naturally isolated from Anoectochilus roxburghii, possesses multiple biological activities, including lipolysis, anti-inflammation, and hepatoprotection. However, the effects of KD on NASH remain unclear. PURPOSE: This study aimed to explore the roles of KD in NASH and its engaged mechanisms. METHODS: Two typical animal models of NASH, mice fed a methionine-choline-deficient (MCD) diet (representing non-obese NASH) and mice fed a high-fat and -fructose diet (HFFD) (representing obese NASH), were used to investigate the effect of KD on NASH in vivo. Transcriptome sequencing was performed to elucidate the underlying mechanisms of KD. Lipopolysaccharide (LPS)-stimulated THP-1 cells and transforming growth factor ß1 (TGF-ß1)-activated LX-2 cells were applied to further explore the effects and mechanisms of KD in vitro. RESULTS: The intragastric administration of KD remarkably alleviated MCD/HFFD-induced murine NASH almost in a dose-dependent manner. Specifically, KD reduced lipid accumulation, inflammation, and fibrosis in the liver of NASH mice. KD ameliorated alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), and malondialdehyde (MDA) abnormalities. In addition, it decreased the level of serum proinflammatory factors (IL-12p70, IL-6, TNF-α, MCP-1, IFN-γ) and the hepatic expression of typical fibrosis-related molecules (α-SMA, Col-I, TIMP-1). Mechanically, KD attenuated the MCD/HFFD-induced NASH through the inhibition of the NF-κB/NLRP3 signaling pathway. Consistently, KD reduced inflammation stimulated by LPS in THP-1 cells via suppressing the NF-κB/NLRP3 pathway. Furthermore, it prevented the activation of LX-2 cells directly, by inhibiting the proliferation stimulated by TGF-ß1, and indirectly, by inactivating the NLRP3 inflammasome in macrophages. CONCLUSION: For the first time, the practical improvement of NASH by KD was revealed. Our study found that KD exerted its alleviative effects on NASH through the inhibition of the NF-κB/NLRP3 signaling pathway. Given its hepatoprotective and nontoxic properties, KD has the potential to be a novel and effective drug to treat NASH.

Correlation analysis of adverse outcomes for the selective reduction of twin pregnancies.

BACKGROUND: Due to the extensive development of assisted reproductive technology, the number of twin pregnancies has increased significantly over recent decades. Twin pregnancy is the most representative type of multiple pregnancies and is associated with high infant morbidity and mortality. Perinatal complications of twin pregnancy are also markedly increased compared with those of single pregnancy. Transabdominal selective reduction (SR) is a remedial intervention. This study aimed to research the adverse outcomes of transabdominal selective reduction of twin pregnancy and the correlation between the reduction week and pregnancy outcomes. OBJECTIVE: The purpose of this study was to examine the adverse outcomes of the transabdominal selective reduction of twin pregnancy and the correlation between the reduction week and pregnancy outcomes. METHODS: A retrospective cohort study of the transabdominal reduction of twin pregnancy was conducted in a single prenatal diagnosis medical centre from September 2012 to October 2020. According to chorionicity, women with twin pregnancies were divided into 2 groups: dichorionic (DC) twin pregnancies and monochorionic (MC) twin pregnancies. Women with DC twin pregnancies underwent potassium chloride reduction, and those with MC twin pregnancies underwent radiofrequency ablation (RFA). The reduction indications included pregnancy complications, foetal abnormalities, and maternal factors. The perinatal outcomes of different chorionic twins after reduction were analysed. Each foetus with an adverse outcome was included. The relative relationship between the reduction weeks and delivery weeks of twins was examined by correlation analysis. RESULTS: A total of 161 women were included in this study. A total of 112 women had DC twin pregnancies, and 49 women had MC twin pregnancies. Preterm delivery rates were significantly higher in the MC twin reduction group than in the DC twin reduction group prior to 37 weeks (53.1% vs. 29.5%, P = 0.004). The mean gestational age at delivery of the foetuses in the DC twin group that underwent SR was significantly older than that of those in the MC twin group that underwent SR (36.9 ± 4.0 vs. 33.5 ± 6.6 weeks, P = 0.001). The number of DC twins that underwent SR and were delivered after 37 weeks was obviously greater than that of the MC twins that underwent SR (70.5% vs. 46.9%, P = 0.004). The foetal survival rate was 95.5% in the DC twin reduction group and 77.6% in the MC twin reduction group. If the indication of TTTS was not included, there was no significant difference in the foetal survival rate of the DC and MC twin reduction groups (95.5% vs. 86.2%, P = 0.160). Cotwin death 1 week after reduction was greater in the MC group (6.1% vs. 0%, P = 0.027). Compared to other indications, this finding indicated that a significantly lower proportion of women remained undelivered after selective reduction with the indication of TTTS. There was a significant negative correlation between the reduction weeks and delivery weeks of the two groups (P < 0.01), and the best opportunity for reduction was before 22 weeks of gestation. CONCLUSION: These findings highlighted an obviously negative correlation between the reduction week and delivery week. The transabdominal selective reduction of twin pregnancy should be considered for a lower rate of miscarriage or premature delivery if the reduction week takes place earlier in pregnancy. The rate of preterm delivery was the lowest when transabdominal selective reduction was completed before 22 weeks of gestation. Compared with other RFA indications, a higher rate of premature delivery was shown for MC twins with a reduction indication of TTTS. TTTS with sIUGR might be one of the reasons for the adverse outcomes of reduction for MC twin pregnancy.

Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway.

OBJECTIVE: Moxibustion, a common therapy in traditional Chinese medicine, has potential benefits for treating decreased ovarian reserve (DOR). The present study investigates the protective effect of moxibustion in a rat model of DOR and explores the possible mechanisms. METHODS: Sixty-four female Sprague-Dawley rats were randomly divided into four groups: control, DOR, moxibustion (MOX), and hormone replacement therapy (HRT). The DOR rat model was established by intragastric administration of 50 mg/kg Tripterygium glycoside suspension (TGS), once daily for 14 days. MOX and HRT treatments were given from the day TGS administration was initiated. The ovarian reserve function was evaluated by monitoring the estrus cycle, morphological changes in ovaries, levels of serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), pregnancy rate and embryo numbers. Terminal-deoxynucleotidyl transferase-mediated nick-end-labeling staining was used to identify ovarian granulosa cell apoptosis, while the protein and mRNA expressions of Bax, B-cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in ovarian tissues were examined by immunohistochemistry, Western blot and quantitative reverse transcription-polymerase chain reaction. RESULTS: Compared with the DOR group, MOX improved the disordered estrous cycle, promoted follicular growth, reduced the number of atresia follicles, increased the concentrations of serum E2 and AMH, and decreased serum FSH and LH concentrations. More importantly, the pregnancy rate and embryo numbers in DOR rats were both upregulated in the MOX treatment group, compared to the untreated DOR model. Further, we found that the MOX group had reduced apoptosis of ovarian granulosa cells, increased Bcl-2 expression and reduced expression of Bax. Furthermore, the PI3K/AKT signaling pathway was triggered by the moxibustion treatment. CONCLUSION: Moxibustion improved ovarian function and suppressed apoptosis of ovarian granulosa cells in a rat model of DOR induced by TGS, and the mechanism may involve the PI3K/AKT signaling pathway.

Quercetin inhibits invasion and angiogenesis of esophageal cancer cells.

BACKGROUND: Esophageal carcinoma has poor prognosis and novel therapies for esophageal carcinoma are urgently needed. Quercetin is a natural flavonoid compound that can be found in many foods. In this study, we investigated the effects of quercetin on invasion and angiogenesis of esophageal cancer cells. METHODS: Human esophageal cancer cell line Eca109 was treated with 5 µg/mL or 10 µg/mL of quercetin. Colony formation assay was performed. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. Human umbilical vein/vascular endothelium cells (CLR-1730) were treated with Eca109 conditioned medium, and the effects of quercetin on CLR-1730 were evaluated by wound healing and tube formation assays. Protein levels of VEGF-A, MMP9, and MMP2 were determined by Western blotting. RESULTS: The ability of colony forming in Eca109 was reduced with the administration of 10 µg/mL quercetin, but there was no difference between the 5 µg/mL quercetin group and control. The migration distance and the number of invasive cells were significantly reduced in the 10 µg/mL quercetin group. At the lower level of quercetin at 5 µg/mL, only the invasion of cells was significantly inhibited. In endothelial cells treated with Eca109 conditioned medium, cell migration and tube forming ability were suppressed. The decreased protein levels of VEGF-A, MMP9, and MMP2 were observed at the 10 µg/mL quercetin group. CONCLUSION: Quercetin suppressed the invasion and angiogenesis of esophageal cancer cells, and the effects were associated with the decreased expression of VEGF-A, MMP2, and MMP9.

Cobalt encapsulated in bamboo-like N-doped carbon nanotubes for highly sensitive electroanalysis of Pb(II): enhancement based on adsorption and catalysis.

Carbon nanotubes (CNTs) are recognized as desirable candidates to fabricate electrochemical sensing interfaces owing to their high surface area and excellent electron conductivity. However, the poor catalytic properties of CNTs significantly hinder their further application in electrochemical detection. Herein, for the first time we combined defective CNTs with catalytically active cobalt nanoparticles (Co NPs) to give cobalt encapsulated in a bamboo-like N-doped carbon nanotube nanocomposite (Co/N-CNTs). The novel constructed Co/N-CNTs are used as a modifier on a bare glass carbon electrode for the electrochemical detection of Pb(ii). As a result, the positive effect of adsorption and catalysis on Co/N-CNT shows a significant improvement in the electroanalytical performance towards Pb(ii) with a sensitivity of 69.74 µA µM-1 and a limit of detection of 0.039 µM. Moreover, the stability and practical applications of Co/N-CNTs towards Pb(ii) in real water samples obtained from a mining subsidence area were also considered. This method shows great promise, achieving an outstanding electroanalysis efficiency with noble-metal-free nanocomposite sensors based on the combination of carbon and transition metals.

Ultrastructural study of closed macular hole- preliminary application of a novel high magnification module combining with OCT.

BACKGROUND: As a novel high magnification module (HMM) combining with OCT (OCT-HMM) is able to detect the microstructure of retina, we apply it to explore the ultrastructure of the macula after closure of the idiopathic macular hole (IMH) by surgery. METHODS: This is an observational case series study in which patients with full-thickness IMHs who had undergone successful macular closure by vitrectomy and internal limiting membrane peeling and healthy subjects were recruited. After comprehensive ophthalmic examinations, the images of macular area were obtained and collected by professional operators using OCT-HMM. Then images were independently analyzed by 4 masked vitreoretinal specialists. RESULTS: A total of 24 IMH eyes and 42 healthy eyes were examined. HMM images were obtained in 10 IMH eyes. Among them, 4 eyes whose macula closed completely with recovery of photoreceptor layer presented a dark arc nasal to the fovea, oriented to the optic, and the notch of arc faced temporally. Six eyes in which the macula closed incompletely with photoreceptor cells loss revealed a dark ring with uneven bright spots inside. The other 14 eyes failed to obtain clear images by OCT-HMM. The contra lateral eyes of the patients and the healthy subjects' eyes succeeded to obtain the HMM images which displayed evenly grey background thickly covered with tiny bright dots that was in similar size and evenly and widely distributed and there no dark arc or ring. OCT B-scan and IR images could be acquired in all of the IMH and healthy eyes. CONCLUSION: The preliminary application of HMM has supplied us a brand-new insight into the microstructure of closed IMH. A dark arc sign could be detected with OCT-HMM in the macula which was functionally closed after surgery that was probably the healing mark on a microstructure photoreceptors level. Its existence and shape indicated that the functional closure followed by a retinal displacement mainly horizontally from temporal side to nasal side but not symmetric centripetally.