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We confirm the previously revised stereochemistry of spiroviolene by X-ray crystallographically characterizing a hydrazone derivative of 9-oxospiroviolane, which is synthesized by hydroboration/oxidation of spiroviolene followed by oxidation of the resultant hydroxy group. An unexpected thermal boron migration occurred during the hydroboration process of spiroviolene that resulted in the production of a mixture of 1α-hydroxyspiroviolane, 9α- and 9β-hydroxyspiroviolane after oxidation. The assertion of the cis-orientation of the 19- and 20-methyl groups provided further support for the revised cyclization mechanism of spiroviolene.

Scientific and accurate prediction of the consumption of equipment maintenance spare parts is crucial to improve the efficiency of equipment failure disposal and enhance the competitiveness of enterprises. However, the consumption of some maintenance spare parts is usually affected by a variety of factors, with strong randomness and uncertainty, and it is difficult to accurately predict them. In this paper, a multi-level migration learning CNN-ISE-Attention-BiLSTM prediction model for maintenance spare parts is designed through the study of neural networks, time series and attention mechanisms. Through several sets of experiments, it is proved that the model can better solve the problems of insufficient mining of key information due to insufficient data samples of maintenance spare parts consumption and insufficient mining of spare parts consumption law by ordinary neural networks, and better achieve the prediction of non-stationary maintenance spare parts, which is of great significance for the implementation of the scientific management of maintenance spare parts in enterprises.

Pimaranes are diterpenoid natural products with poorly characterised biosynthetic pathways. Here pimaranetype diterpenoid synthases are functionally and structurally characterised and shown to exploit distinct modes of intermediate stabilisation.

In contrast to the conventional forced wave generator which consists of cam and flexible bearing in harmonic drive, the novel forced wave generator retains cam but cancels flexible bearing. In this article, the lubrication characteristics of the novel forced wave generator in harmonic drive is studied. First, an elliptical sliding bearing (ESB) model of simplified structure between the novel forced wave generator and the flex spline is established. Further, the computational fluid dynamics (CFD) method is employed to study the effect of some factors on the lubrication characteristics of the ESB model including elliptical gap ratio, width, and rotational speed. According to the analysis, the elliptical gap ratio has a great impact and its optimal value is 3, which is used in the design of the novel forced wave generator. Last, the practical design of the novel forced wave generator in harmonic drive is given, which can provide a basis for design and optimization of a forced wave generator without flexible bearing of the harmonic drive.

Abstract Recently, the organic functionalization of polyoxometalates (POMs) has drawn increasing interest, and an easy and effective route to achieve organic derivatives is of great importance. Herein, the first reported synthesis of a tosyl ester derivative of the polyoxometalate (Bu4N)2[V6O13{(OCH2)3CCH2SO3C7H4}2]·2.5CH3CN (compound 1) was performed by using DMAP as an activating reagent and triethylamine as an HCl scavenger. The tosyl ester was transformed into an azide or halide group by using sodium azide or sodium bromide, respectively, as the nucleophilic agent. Two derivatives of POMs, (Bu4N)2[V6O13{(OCH2)3CCH2N3}2]·4CH3CN (compound 2) and (Bu4N)2[V6O13{(OCH2)3CCH2Br}2] (compound 3), were easily obtained. All the compounds were structurally and compositionally characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy, NMR spectroscopy, ESI-MS, UV-Vis spectroscopy and TGA. This work provides a new route for the functional group transformation of organic derivatives of polyoxometalates.

Abstract The Mu Us Sandy Land is a region characterized by wind-blown sand and soil erosion in northern China. To enhance the soil quality of this area, various organic materials were incorporated into the mixed soil at a volume ratio of 1:2 for feldspathic sandstone to sand. Culture was conducted in the field and under constant temperature conditions in laboratory culture chambers. Four treatments were established in the experiment, each calculated based on weight ratio and controlled (with no organic material added, CK); single application of straw (5% straw, P1); single application of biochar (5% biochar, P2); combined application of biochar and straw (5% biochar + 5% straw, P3). After 90 days of culture, soil samples were collected for analysis of various indicators such as soil aggregate particle size distribution, water stability of soil aggregates, mean weight diameter, mean geometric diameter, and fractal dimension using dry sieving and wet sieving methods. The objective is to establish a scientific basis and provide technical support for addressing the challenges associated with compound soil and implementing rational fertilization measures. The research results indicate that: (1) The quantity of aggregates > 0.25 mm under different treatments follows the order CK 0.25 (x) of compound soil, with a correlation coefficient of up to 0.9851. In conclusion, the incorporation of organic materials can effectively enhance the proportion of macroaggregates in compound soil consisting of Feldspathic sandstone and sand, thereby improving soil stability and erosion resistance. The optimal outcome is achieved through the combined application of biochar and straw. Indoor culture proves to be more effective than field culture, while wet sieving accurately reflects the structural characteristics of compound soil under both dry and wet sieving treatments.

Abstract IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, resulting in end‐stage renal disease and increased mortality rates. Prognostic biomarkers reflecting molecular mechanisms for effective IgAN management are urgently needed. Analysis of kidney single‐cell transcriptomic sequencing data demonstrated that IgAN expressed high‐expression levels of inflammatory cytokines TNFSF10, TNFSF12, CCL2, CXCL1, and CXCL12 than healthy controls (HCs). We also measured the urine proteins in 120 IgAN (57 stable and 63 progressive) and 32 HCs using the proximity extension assay (PEA), and the multivariable and least absolute shrinkage and selection operator (LASSO) logistic regression analysis both revealed that CXCL12, MCP1 were the prognostic significant variables to predict IgAN progression severity. These two proteins exhibited negative correlation with the estimated glomerular filtration rate (eGFR) and patients with higher expression levels of these two proteins had a higher probability to have poorer renal outcome. We further developed a risk index model utilizing CXCL12, MCP1, and baseline clinical indicators, which achieved an impressive area under the curve (AUC) of 0.896 for prediction of IgAN progression severity. Our study highlights the significance of the inflammatory protein biomarkers for noninvasive prediction of IgAN severity and progression, offering valuable insights for clinical management.

Abstract Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. Recent clinical trials of the nerve growth factor (NGF) inhibitors in OA patients have suggested adverse effects of NGF inhibition on joint structure. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNFα to attenuate NF-κB activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression in mice. NGFR deficiency hyper-activates NF-κB in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-κB activation. Together, this study suggests a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.

Objectives Geriatric Nutritional Risk Index (GNRI) is a new and simple index recently introduced to assess nutritional status, and its predictive value for clinical outcomes has been demonstrated in patients with chronic kidney disease. However, the association between the GNRI and prognosis has not been evaluated so far in patients with acute kidney injury (AKI), especially in those receiving continuous renal replacement therapy (CRRT).Methods A total of 1096 patients with severe AKI initiating CRRT were identified for inclusion in this retrospective observational study. Patients were divided into three groups according to GNRI tertiles, with tertile 1 as the reference. The outcomes of interest were the 28- and 90-days of all-cause mortality. The associations between GNRI and clinical outcomes were estimated using multivariate Cox proportional hazards model analysis.Results The overall mortality rates at 28- and 90-days were 61.6% (675/1096) and 71.5% (784/1096), respectively. After adjusting for multiple confounding factors, GNRI was identified as an independent prognostic factor for 28-days all-cause mortality (HR, 0.582; 95% CI, 0.467–0.727; p

Abstract Background The relationship between the gut mycobiome and end-stage renal disease (ESRD) remains largely unexplored. Methods In this study, we compared the gut fungal populations of 223 ESRD patients and 69 healthy controls (HCs) based on shotgun metagenomic sequencing data, and analyzed their associations with host serum and fecal metabolites. Results Our findings revealed that ESRD patients had a higher diversity in the gut mycobiome compared to HCs. Dysbiosis of the gut mycobiome in ESRD patients was characterized by a decrease of Saccharomyces cerevisiae and an increase in various opportunistic pathogens, such as Aspergillus fumigatus, Cladophialophora immunda, Exophiala spinifera, Hortaea werneckii, Trichophyton rubrum, and others. Through multi-omics analysis, we observed a substantial contribution of the gut mycobiome to host serum and fecal metabolomes. The opportunistic pathogens enriched in ESRD patients were frequently and positively correlated with the levels of creatinine, homocysteine, and phenylacetylglycine in the serum. The populations of Saccharomyces, including the HC-enriched Saccharomyces cerevisiae, were frequently and negatively correlated with the levels of various toxic metabolites in the feces. Conclusions Our results provided a comprehensive understanding of the associations between the gut mycobiome and the development of ESRD, which had important implications for guiding future therapeutic studies in this field.

Enlarging the M-Nx active-site density is an effective route to enhance the ORR performance of M-N-C catalysts. In this work, a single-atom catalyst Cu–N@Cu–N–C with enlarged Cu–N4 active site density was prepared by the second doping and pyrolysis (SDP) of Cu–N–C derived from Cu-doped zeolite imidazole frameworks. The half-wave potentials of Cu–N@Cu–N–C were measured as 0.85 V in alkaline electrolyte and 0.75 V in acidic media, which was 50 mV and 60 mV higher than that of Cu–N–C, respectively. N2 adsorption–desorption isotherm curves and corresponding pore distribution analysis were used to verify the successful filling of additional Cu and N in micropores of Cu–N–C after SDP. The obvious increase in Cu contents for Cu–N@Cu–N–C (1.92 wt%) compared with Cu–N–C (0.88 wt%) tested by ICP demonstrated the successful doping of Cu into Cu–N–C. XAFS analysis confirmed the presence of Cu–N4 single-atom active centers in Cu–N@Cu–N–C. The N 1 s high-resolution XPS results proved a great increase in Cu–N4 contents from 13.15% for Cu–N–C to 18.36% for Cu–N@Cu–N–C. The enhanced ORR performance of Cu–N@Cu–N–C was attributed to the enlargement of Cu–N4 active site density, providing an effective route for the preparation of efficient and low-cost ORR catalysts.

Abstract Background Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited. Methods Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins. Results After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR. Conclusions RES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.

Abstract Background Diabetic kidney disease (DKD) is a major complication of diabetes and the leading cause of end-stage renal disease worldwide. Renal inflammation and infiltration of immune cells contribute to the development and progression of DKD. Thus, the aim of the present study was to identify and validate immune-related biomarkers and analyze potential regulators including transcription factors (TFs), microRNAs (miRNAs), and drugs for DKD. Methods Immune-related genes from the ImmPort database and glomeruli samples from GSE1009 and GSE30528 were used to identify differentially expressed immune-related genes (DEIRGs) of DKD. The expression level and clinical correlation analyses of DEIRGs were verified in the Nephroseq database. Murine podocytes were cultured to construct the high glucose-induced podocyte injury model. The reliability of the bioinformatics analysis was experimentally validated by RT-qPCR in podocytes. Networks among DEIRGs, regulators, and drugs were constructed to predict potential regulatory mechanisms for DKD. Results DKD-associated DEIRGs were identified. CCL19 and IL7R were significantly upregulated in the DKD group and negatively correlated with glomerular filtration rate (GFR). GHR, FGF1, FYN, VEGFA, F2R, TGFBR3, PTGDS, FGF9, and SEMA5A were significantly decreased in the DKD group and positively correlated with GFR. RT-qPCR showed that the relative mRNA expression levels of GHR, FGF1, FYN, TGFBR3, PTGDS, FGF9, and SEMA5A were significantly down-regulated in the high glucose-induced podocyte injury group. The enriched regulators for DEIRGs included 110 miRNAs and 8 TFs. The abnormal expression of DEIRGs could be regulated by 16 established drugs. Conclusions This study identified immune-related biomarkers, regulators, and drugs of DKD. The findings of the present study provide novel insights into immune-related diagnosis and treatment of DKD.

With the rapid development of wind energy, the subsynchronous oscillations (SSO) involved with wind conversion systems, has been the focus of academic concern. To analyse the subsynchronous control interaction (SSCI) issue of multi-converters (wind-power converter and widespread SVGs), the state matrix of a typical PMSGs-based offshore wind farm system including SVGs is constructed . It is proposed that SVGs in wind farm may cause SSCI issue by their uncoordinated control targets. Under certain conditions, the SSCI between SVGs forms the dominant oscillation mode, delivered with variation of the SSO frequency. By calculating the influence factors along with different converters, it can be concluded that unreasonable parameter configuration of converters and variations of operating conditions affect the SSCI characteristics. At last, time domain simulation is used to verify the SSCI mechanism and characteristics of the PMSG-based offshore wind farm and SVGs.

IntroductionObservational studies have reported the association between gut microbiota and the risk of lower respiratory tract infections (LRTIs). However, whether the association reflects a causal relationship remains obscure.MethodsA bidirectional twosample Mendelian randomization (MR) analysis was conducted by assessing genome-wide association study (GWAS) summary statistics for gut microbiota taxa and five common LRTIs. MR methods including inverse-variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode were used to analyze the causality. Gene pleiotropy was tested using MR-Egger regression and MR-PRESSO methods. Cochran’s Q test was used to check for heterogeneity. Leave-one-out analysis was used to assess the stability of effect sizes. Detected significant associations were validated by using an independent LRTI GWAS summary statistics dataset. An optional MR method of causal analysis using summary effect estimates (CAUSE) was further performed as a validation to avoid potential false-positive results.ResultsAccording to the MR-Egger estimates in forward MR analysis, a causal effect of gut Blautia on increased odds of bronchiectasis and pneumonia was suggested. MR-Egger regression pleiotropy intercept methods detected no significant horizontal pleiotropy between the instrumental variables of these associations. MR-PRESSO global test examined no potential horizontal pleiotropy. Cochran’s Q test showed that no heterogeneity biased the results. The leave-one-out sensitivity analyses suggested robust causality results. These associations with consistent effect direction were successfully replicated in IVW analysis by using the validation GWAS dataset. However, these evidence of causality did not survive after applying strict Bonferroni correction or CAUSE analysis. The reverse MR analysis failed to achieve consistent results in the effect of LRTIs on gut microbiota through comprehensive discovery and validation processes.DiscussionThis study established no strong causality between genetically predicted gut microbiome and the risk of lower respiratory tract infections. However, specific subtypes of microbial genera, such as Blautia, were identified as potential influencers and require further investigation, particularly at the species or strain levels.

Summary: Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies. Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18–70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ −1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691. Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and −0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11–0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported. Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients. Funding: The study was supported by Hansoh Medical Development Group.

Background: Binafuxi granules are a traditional Uighur medicine (TUM) for treating the common cold with fever. However, high-quality clinical studies supporting its efficacy and safety are lacking. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial, patients with common cold and fever were randomly assigned to a high-dose group, low-dose group, and placebo group in a 1:1:1 ratio. Outcomes were time to fever relief, time to fever clearance, proportion of afebrile patients, time to symptom disappearance, rate of symptom disappearance, effective rate, emergency drug usage and safety assessment. Results: A total of 235 patients were recruited. Of these, 234 were included in the full analysis set (FAS), and 217 were included in the per-protocol set (PPS). In the FAS analysis, the median time to fever relief was 6.00 h, 5.54 h and 10.65 h (P = 0.31) in the high-dose group, low-dose group and placebo group, respectively. The median time to fever clearance was 18.29 h, 20.08 h and 25.00 h (P = 0.0018), respectively, and the proportion of afebrile patients was 92.4%, 89.7% and 71.4% (P = 0.0002), respectively. There was a significant difference in the disappearance time and disappearance rate of all symptoms and of individual symptoms. No serious adverse events were found. Conclusions: Binafuxi granules can dose-dependently shorten the fever course and improve clinical symptoms in patients suffering from the common cold with fever. Trial Registration: This trial was registered at Chinese Clinical Trial Registry (ChiCTR-IIR-17013379).

Diabetic kidney disease (DKD) is emerging rapidly as the leading cause of chronic kidney disease (CKD) worldwide. In this 3-year prospective, multicenter cohort study, a total of 1138 pre-dialysis CKD patients were recruited. Patients were categorized into two groups according to the etiologies of DKD and non-diabetic kidney disease (NDKD). Propensity score matching was performed to adjust for confounding factors, resulting in 197 patients being assigned to DKD and NDKD groups, respectively. The primary endpoints were 50% estimated glomerular filtration rate (eGFR) decline and initiation of kidney replacement therapy (KRT). The secondary endpoints were all-cause death and the development of cardiovascular disease (CVD) events. We found that DKD patients have a higher risk to develop 50% eGFR decline endpoint (HR:2.30, 95%CI [1.48–3.58], p

Background: Prenatal stress (PS) can induce depression in offspring, but the underlying mechanisms are still unknown. Objective: The aim of this work was to investigate the mechanism that underlies PS-induced depressive-like behavior in offspring. Methods: A prenatal restraint stress procedure was developed in which pregnant rats at GD14 to GD20 were placed head-first into a well-ventilated bottle three times each day and for 45 min each time. Depressive-like behavior in the male offspring was examined using the sucrose preference test (SPT) and the forced swim test (FST). The level of glutamate and the expression levels of GluN2A, p-CaMKII and myelin basic protein (MBP) in the hippocampus of PS-susceptible (PS-S) offspring were also evaluated. To clarify the mechanism by which PS leads to depression in offspring, the effects of excessive corticosterone were also investigated using an in vitro “injured neuronal” model. Results: The glutamate level in the hippocampus of PS-S male offspring was significantly elevated compared to controls. The expression levels of GluN2A and p-CaMKII were also altered. In addition, the optical density of MBP staining and the expression levels of MBP mRNA and MBP protein were decreased, demonstrating impaired myelinization in the hippocampus. Treatment of PS-S offspring with the GluN2A receptor antagonist NVP-AAM077 resulted in antidepressant-like effects in the FST, as well as rescue of the MBP and p-CaMKII abnormalities. Conclusions: These findings indicate that GluN2A is a promising target in the development of pharmacotherapies for PS-induced depression.

Introduction: High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease, whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN. Methods: A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus and kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline or kidney failure, was evaluated using Cox models. Results: Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238–5.400, p = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783–0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756–0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95% CI, 1.791–14.944; p = 0.002). Conclusion: Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression.

Abstract Miniature pigs are an ideal animal model for translational research to evaluate stem cell therapies and regenerative applications. While the derivation of induced pluripotent stem cells (iPSCs) from miniature pigs has been demonstrated, there is still a lack of a reliable method to generate and maintain miniature pig iPSCs. In this study, we derived iPSCs from fibroblasts of Wisconsin miniature swine (WMS), Yucatan miniature swine (YMS), and Göttingen minipigs (GM) using our culture medium. By comparing cells of the different pig breeds, we found that YMS fibroblasts were more efficiently reprogrammed into iPSCs, forming colonies with well-defined borders, than WMS and GM fibroblasts. We also demonstrated that YMS iPSC lines with a normal pig karyotype gave rise to cells of the three germ layers in vitro and in vivo. Mesenchymal stromal cells expressing phenotypic characteristics were derived from established iPSC lines as an example of potential applications. In addition, we found that the expression level of the switch/sucrose nonfermentable component BAF60A regulated by STAT3 signaling determined the efficiency of pig iPSC generation. The findings of this study provide insight into the underlying mechanism controlling the reprogramming efficiency of miniature pig cells to develop a viable strategy to enhance the generation of iPSCs for biomedical research.

Abstract Background Approximately 5% of adults have an episode of acute bronchitis each year, accounting for more than 10 million medical visits yearly. The primary goal of treatment is reduction of symptoms. Currently, available medications are questionable in effectiveness and safety and are not recommended for routine use in clinical practice. Although Chinese herbal medicine has been widely used in the management of acute bronchitis in China, evidence-based data is lacking. This trial aims to evaluate the efficacy and safety of Tanreqing oral liquid in the treatment of acute bronchitis with phlegm-heat obstructing lungs syndrome. Methods/design This study is a prospective, multi-center, randomized, double-blinded, parallel-group, placebo-controlled trial. A total of 270 acute bronchitis adult patients with phlegm-heat obstructing lungs syndrome will be enrolled from outpatients and emergency departments at nine study centers across China. All included patients will be randomly allocated to receive Tanreqing oral liquid or placebo oral liquid, 20 mL three times daily for seven consecutive days. The primary outcome will be cough resolution rate. Secondary outcomes will include change of bronchitis symptoms scores from baseline to post-treatment, cough relief rate, time to cough resolution, time to cough relief, resolution rate of a single symptom, combination medicine use, change of traditional Chinese medicine syndrome score from baseline to post-treatment, and adverse events. Discussion This trial may provide an alternative treatment option for acute bronchitis patients, especially those in outpatients and emergency departments. It may also add evidence to Chinese herbal medicine for treating acute bronchitis. Trial registration Chinese Clinical Trial Registry ChiCTR2000040264 . Registered on 26 November 2020

Abstract Background To investigate the prevalence of vascular calcification based on the ankle‐brachial index (ABI) value and analyse the risk factors for vascular calcification in the general population. Methods A cross-sectional study was conducted to collect clinical, laboratory, and lifestyle data in individuals aged 30–70 recruited from the physical examination centre. The automatic arteriosclerosis detector was used to measure the ABI. Difference tests, correlation analyses, and multivariate logistic regression analyses were performed to identify risk factors for vascular calcification. Results The overall prevalence of vascular calcification was 24.39% in 1033 subjects. The prevalence of vascular calcification in males was much higher than that in females (27.80% vs. 17.49%, P

Abstract Background Long noncoding RNAs (lncRNAs) are involved in physiological and pathological processes. However, no studies have been conducted on the relationship between lncRNAs and renal aging. Results First, we evaluated the histopathology of young (3-month-old) and old (24-month-old) C57BL/6J mouse kidneys. Masson trichrome staining and PAS staining showed interstitial collagen deposition and fibrosis, mesangial matrix expansion, a thicker basement membrane and renal interstitial fibrosis in old mouse kidneys. Senescence-associated β-galactosidase (SA-β-gal)-positive areas in the kidneys of old mice were significantly elevated compared to those of young mice. Then, we analyzed the differential expression of lncRNAs and mRNAs in the kidneys of young and old mouse kidneys by RNA-seq analysis. 42 known and 179 novel differentially expressed lncRNAs and 702 differential mRNAs were detected in the mouse kidney. Next, we focused on the differentially expressed mRNAs and lncRNAs by RNA-seq. GO and KEGG analyses were performed based on differentially expressed mRNAs between young and old mouse kidneys. Transregulation based on RIsearch and the correlation coefficient of mRNA-lncRNA were also calculated. The mRNA-lncRNA network was constructed by choosing a Spearman correlation coefficient > 0.9 or

China initiated its healthcare reform in 2009 to provide accessible and affordable healthcare to all. We summarised China’s drug reforms between 2009 and 2020 using the WHO framework. China has initiated comprehensive drug policies to address different issues, including: (1) issuing or amending major regulations with changes in institutional settings; (2) implementing the marketing authorisation holder system and bioequivalence assessment to improve the quality of drugs; (3) leveraging accelerated market approval and insurance listing to encourage needs-driven innovation and improve the access to new drugs; (4) introducing compulsory licensing to address major public health threats when needed; (5) scaling up the National Essential Medicine Policy and introducing pharmacoeconomic evaluation in National Reimbursable Drug List to promote rational use of medicine and evidence-based selection; (6) applying differentiated pricing strategies and scaling up zero mark-up policies to form a new financing mechanism; (7) adapting bulk procurement and placing strict regulations on the supply chain management to ensure supply and reduce the cost; (8) empowering pharmacists to improve the rational use of medicine; and (9) using procurement and supply chain digital platforms to inform decision and improve efficiency. China’s drug reform has adopted a phased and systemic approach that mobilises multiple policy levers including governance, regulation and financing. Despite the progress, emerging challenges in implementation, coordination and capacity need to be addressed. Cross-cutting lessons from China’s drug reforms include aligning the drug reform with the overall health reforms, adapting a systemic approach that mobilised policy levers and stakeholders and informing policy decision by conducting pilot studies.

BackgroundSince 2011, through the Community-Based Colorectal Cancer Screening Program in Shanghai, China (SHcsp), residents aged >50 years were offered initial colorectal cancer screening using the fecal immunochemical test (FIT) and risk assessment questionnaire (RAQ) for free. Colonoscopy was then recommended for positive results.ObjectiveTo evaluate the cost-effectiveness of the Community-Based Colorectal Cancer Screening Program in Shanghai, China from the payer perspective.MethodsThis analysis estimated the long-term cost and effectiveness of the 2014–2016 SHcsp based on real-world follow-up data from the SHcsp database, Shanghai Cancer Registry System, vital statistics from Shanghai Municipal Center for Disease Control and Prevention and inpatient CRC expense data from hospitals. A decision-tree model and Markov model were constructed to simulate the 25-year health outcomes. The screening branch was the cohort with a definite diagnosis of adenoma, advanced adenoma, and CRC. The other branch was residents who were neither screened nor treated until CRC symptoms appeared. A payer prospective was adopted to measure direct costs and effectiveness by life years (LYs) and quality-adjusted life years (QALYs) gained, and were discounted by 3%. Stimulation robustness was tested by one-way sensitivity analysis.ResultsOf 1,097,656 residents, 13,250 were diagnosed with adenoma, advanced adenoma, or CRC. Assuming those had not been found through screening, SHcsp resulted in 1,570.1 LYs and 13,984.3 QALYs gained at an extra cost of USD9.96 million. The incremental cost-effectiveness ratio (ICER) was USD6,342.02 per LY and USD712.08 per QALY obtained, far below the threshold of USD59,598 of three-time GDP per capita in Shanghai.ConclusionThe SHcsp was cost-effective than no screening strategy. The results were generalisable to the Chinese population for mass CRC screening.

Background: Physical inactivity is highly prevalent in patients with hemodialysis, and a large body of evidence reported the positive effect of different exercise modalities on their health outcomes. However, the effective dosage of exercise for hemodialysis patients still requires verification.Objective: We aimed to determine the most effective exercise intensity and modality for improvements in physical function, blood pressure control, dialysis adequacy, and health-related quality of life for hemodialysis patients.Design: Systematic review with network meta-analysis of randomized trials.Data sources: Five electronic databases (PubMed, EMBASE, Web of Science, Cochrane CENTRAL, and Scopus) were searched for randomized controlled trials. Data extraction and quality appraisal were conducted by two authors independently. Data were analyzed by the R (version.3.6.2) and the Stata (version.15.0).Result: We included 1893 patients involving four exercise modalities and six exercise intensities. Combined training (aerobic exercise plus resistance exercise) has been the top-ranking exercise modality for improving the 6-min walk test (6MWT) (surface under the cumulative ranking curve analysis (SUCRA) score, 90.63), systolic blood pressure control (SUCRA score, 77.35), and diastolic pressure control (SUCRA score, 90.56). Moreover, the top-ranking exercise intensity was moderate–vigorous for 6MWT (SUCRA score, 82.36), systolic blood pressure (SUCRA score, 77.43), and diastolic blood pressure (SUCRA score, 83.75). Regarding dialysis adequacy and health-related quality of life, we found no exercise modality or intensity superior to the placebo.Conclusion: This network meta-analysis indicated that combined training and moderate–vigorous intensity might be the most effective interventions to improve 6MWT and blood pressure control. This finding helps further guide clinical exercise prescriptions for hemodialysis patients.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021268535].

This study provides a viable path to save energy by means of e-commerce development. Taking the national e-commerce demonstration cities (NEDC) pilots policy implemented in China as a quasi-natural experiment, based on the city panel data from 2006 to 2019, this study applies the multi-period difference-in-difference (DID) method to evaluate the effect of NEDC on energy saving in pilot cities. The empirical results suggest that the NEDC policy obviously contributes to energy conservation. The treated cities reduced energy consumption by 14.2% as a result of the implementation of NEDC, relative to the untreated cities. The conclusions remain valid after conducting robustness tests such as placebo test, instrumental variables regression, propensity score matching-difference-in-difference (PSM-DID), and synthetic difference-in-difference (SDID). The NEDC achieves energy-saving effects through technological innovation, industrial restructuring, and economic agglomeration. Furthermore, the heterogeneity analysis indicates that, in cities with high levels of human capital, well-developed information infrastructure, non-resource-based cities, and favorable business environments, the impact of NEDC on energy saving is more significant. Analysis of spatial effects shows that the implementation of NEDC has negative externalities, increasing energy consumption in the surrounding area. In the context of the digital economy, this paper presents new insights on the relationship between e-commerce and energy consumption and provides policy direction for countries looking for energy-saving solutions.

BackgroundChina is facing the challenge of rising prevalence and ballooning burden of chronic non-communicable diseases (NCDs); however, the Chinese middle- and older-aged population considerably lack preventive behaviors. Health shocks (HS), widely defined as sudden health deterioration brought on by diseases or accidents, bring a “teachable moment” to motivate changes in preventive behaviors.ObjectiveThis study aims to examine the effect of HS on changes in preventive behaviors, including personal health practices and preventive care utilization.MethodsHS was defined as any five chronic disease diagnoses (cancer, heart disease, stroke, diabetes, and hypertension). The impacts of HS on smoking, drinking, and exercise, physical examination were estimated. The panel data of 13,705 respondents were obtained from the latest two waves of the China Health and Retirement Longitudinal Study (CHARLS) in 2015 and 2018. A multilevel propensity score match difference-in-difference (multilevel PSM-DID) model was constructed.ResultsHS significantly decreased smoking (OR = 0.59, p < 0.05) and drinking (OR = 0.62, p < 0.01) and increased the utilization of auxiliary inspection in physical examination (OR = 1.19, p < 0.1). Major HS had significantly considerable and specific effects on reducing smoking and drinking (OR = 0.37 and 0.56, p < 0.01), while minor HS had relatively small effects on reducing smoking (OR = 0.74, p < 0.05) and drinking (OR = 0.69, p < 0.01), but extensive effects on initiating exercise (OR = 1.32, p < 0.05), physical examination (OR = 1.18, p < 0.1), and auxiliary inspection (OR = 1.30, p < 0.05).ConclusionAfter HS, there is a teachable moment to promote positive changes in preventive behaviors. Guided by the 5A's brief intervention model (Ask, Advise, Assess, Assist, Arrange), tailored interventions should be targeted at these populations to reduce the risk of the progression and complications of existing diseases, prevent the related comorbidity, and prolong the expected life-span.

Abstract Aims/Introduction Type 2 diabetes mellitus has been a leading cause of chronic kidney disease (CKD), with a heterogeneous distribution worldwide. Optimal healthcare planning requires an understanding of how the burden of CKD as a result of type 2 diabetes mellitus has changed over time and geographic location, as well as the potential roles of sociodemographic, clinical and behavioral factors in these changes. Materials and Methods We used the Global Burden of Disease data from 1990 to 2017 at the global, regional and national levels to investigate changes in the incidence, death and disability‐adjusted life years of CKD as a result of type 2 diabetes mellitus, incorporating both epidemiological research and risk factor monitoring. Results The incident cases of CKD as a result of type 2 diabetes mellitus worldwide in 2017 had increased by 74% compared with 1990; total disability‐adjusted life years had increased by 113%, mainly attributable to population expansion and demographic transition. The Sociodemographic Index was significantly and negatively correlated with overall CKD as a result of type 2 diabetes mellitus burden. However, in 82 countries and territories, the burden was not alleviated in parallel with socioeconomic development. Conclusions CKD as a result of type 2 diabetes mellitus has been the main contributor to the increasing burden of CKD over the past several decades. We suggest a more pragmatic approach focusing on early diagnosis, primary care and adequate follow up to reduce mortality and the long‐term burden in low‐to‐middle Sociodemographic Index regions. Interventions should address high systolic blood pressure, as well as overweight and obesity problems, especially in high‐income regions.

Abstract Nano‐MgO was successfully fabricated by a facile, inexpensive, and environment‐friendly synthetic method using filter paper as a bio‐template. The influence of the concentration of raw material Mg(CH3COO)2·4H2O on the textural properties of nano‐MgO was investigated, and the as‐prepared nano‐MgO was characterized by X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive X‐ray analysis, thermo gravimetric analysis, Fourier transform infrared spectroscopy. The results of the experiment show the synthetic MgO fibres are composed of 20 nm tiny particles with a surface area of 68.28 m2/g and a pore width of 13 nm. When the concentration of Mg(CH3COO)2·4H2O solution was 0.03 mol/L, the product MgO copied the micro‐morphology of the filter paper. In addition, the photocatalytic activity of the prepared sample was investigated, and the results showed that the nano‐MgO prepared by this method has a higher catalytic activity than that prepared without a template.

Abstract Background Despite close link exists between cough severity and quality of life (QoL), whether gender difference is implied in the effect of cough on QoL has not been studied yet. This study primarily aims to investigate whether the association between cough severity and QoL is modified by gender in patients with postinfectious cough. Methods Secondary analyses were performed in 180 participants with postinfectious cough in a multisite randomized controlled trial. Baseline demographics, clinical characteristics and score of cough specific quality of life questionnaire (CQLQ) were collected. Linear regression analyses were conducted to examine gender difference in CQLQ score and the association between cough severity and CQLQ score. Results Difference between women and men was not significant in CQLQ total score in the unadjusted analysis (P = 0.077). Women had a 2.20-point higher CQLQ total score than men (95% confidence interval (CI) 0.11–4.30; P = 0.039), after adjusting for age, cough duration, cough severity, and clinical center. Gender significantly modified the association between cough severity and CQLQ total score (coefficient 1.80, 95% CI 0.29–3.30; P = 0.020), after adjusting for age, cough duration, and study center. An increase of 1-point in cough severity was associated with a 2.55-point (95% CI 1.16–3.95) increase in CQLQ total score in women versus a 1.26-point (95% CI 0.20–2.31) increase in men (P = 0.020). Conclusions Female sex may be associated with worse QoL than men, and women’s QoL may be more significantly impaired as cough symptom deteriorates. Gender difference should be taken into account in the clinical settings and research of cough and cough related QoL. Trial registration: Chinese Clinical Trial Registry, ChiCTRTRC12002297. Registered 19 June 2012, http://www.chictr.org.cn/abouten.aspx .

As the offshore wind installations are moving further from shore, the transmission distance also increases. Synthesize the cost of construction and maintenance, as well as the technical maturity, grid-connection via AC network will still be a preferred power delivery method for offshore wind power projects in the near future. However, according to the “8•9” blackout in the UK, there is sub-synchronous oscillation (SSO) risk in the AC network connected offshore wind projects, which was attributed to the mismatch between the power electronic source and the power grid. In this article, both eigenvalue analysis and time-domain simulation method are used to evaluate the operating SSO stability of grid integration of large scale offshore wind power. It suggests that transmission system via long distance cables naturally forms a weak AC network, and the SSO characteristics of AC grid connected offshore wind farm is closely related to the wind turbine parameters, offshore distance and the active power output level. At last, the principle of parameter configuration in offshore wind turbines is proposed based on different offshore distances.

IntroductionIncreasing evidence supports the idea that the disruption of epithelial tight junction proteins (TJPs) caused by accumulation of uremia toxins, such as homocysteine (Hcy), is one of the most important mechanisms underlying the damage of intestinal barrier function (IBF) in chronic kidney disease (CKD). Since the decrease of hypoxia inducible factor-1α (HIF-1α) is reported to be involved in Hcy-induced cell injury, and the upregulation of microRNA-223 (miR-223) plays a vital protective role in the impairment of IBF in the experimental colitis, we investigated the effect of HIF-1α stabilizer roxadustat on the disruption of TJPs induced by Hcy and CKD and the underlying mechanism.MethodsChronic kidney disease was induced in rats via 5/6 nephrectomy. In a series of experiments, the rats were treated orally with roxadustat of different doses. The expression of tight junction proteins, HIF-1α, and miR-223 was analyzed in different groups by western blotting analysis, RT-qPCR techniques and immunofluorescence. A series of experiments with cultured Caco2 cells was performed.ResultsThe results showed that the expression of TJPs (occludin, claudin-1, and ZO-1) decreased significantly, accompanied by the reduction of HIF-1α and miR-223 in Hcy-treated Caco2 cells and colonic mucosa of uremic rats. The reduction of HIF-1α and miR-223 was reversed by roxadustat and the decrease of TJPs expression was attenuated in both Caco2 cells induced by Hcy and colon tissue of CKD rats. Furthermore, transfection with miR-223 mimics increased the expression of TJPs, while transfection with miR-223 inhibitor decreased their expression in Caco2 cells. MiR-223 inhibitor applied before roxadustat treatment partly diminished the effect of roxadustat on TJPs expression in Caco2 cells.ConclusionThese results indicated that roxadustat attenuated the disruption of epithelial TJPs induced by Hcy in Caco2 cells and the damage of colonic epithelium in CKD rats through the upregulation of miR-223 induced by HIF-1α. A novel insight into the IBF dysfunction in CKD was provided, and it suggests a potential therapeutic use of roxadustat for the IBF dysfunction besides anemia in CKD.