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Abstract The new power system puts forward higher requirements for the functionality, real-time performance and reliability of relay protection equipment. Therefore, this paper designs a monitoring platform for the operation of relay protection equipment at distribution network side under the background of new power system. The platform obtains the running state of relay protection equipment by establishing simulation models of different types of relay protection equipment on the distribution network side. The fault time, fault type and current action of relay protection equipment at distribution network side are analyzed to realize the monitoring of operation state. At the same time, the visual representation method of monitoring data based on three-dimensional parallel scattergram and human-computer interaction is adopted for human-computer interaction, and the electromechanical protection device is controlled to realize current quick-break protection and overcurrent protection. The experimental results show that the platform can effectively monitor the operation of relay protection equipment on the distribution network side in real time and accurately judge the action of the equipment, and the application effect is good.

Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.

Abstract Introduction Acute myocardial infarction (AMI) is a serious, deadly disease with a high incidence. However, it remains unclear how necroptosis affects the pathophysiology of AMI. Using bioinformatic analyses, this study investigated necroptosis in AMI. Methods We obtained the GSE66360 dataset related to AMI by the GEO database. Venn diagrams were used to identify necroptosis-related differential genes (NRDEGs). The genes with differential expression in AMI were analyzed using gene set enrichment analysis, and a PPI network was established. A transcription factor prediction and enrichment analysis were conducted for the NRDEGs, and the relationships between AMI, NRDEGs, and immune cells were determined. Finally, in the additional dataset, NRDEG expression levels, immune infiltration, and ROC curve analysis were confirmed, and gene expression levels were further verified experimentally. Results GSEA revealed that necroptosis pathways were significantly enriched in AMI. We identified 10 NRDEGs, including TNF, TLR4, FTH1 and so on. Enrichment analysis indicated that the NOD-like receptor and NF-kappa B signaling pathways were significantly enriched. Four NRDEGs, FTH1, IFNGR1, STAT3, and TLR4, were identified; however, additional datasets and further experimental validation are required to confirm their roles. In addition, we determined that a high abundance of macrophages and neutrophils prompted AMI development. Conclusions In this study, four potential genes that affect the development of AMI through necroptosis (FTH1, IFNGR1, STAT3, and TLR4) were identified. In addition, we found that a high abundance of macrophages and neutrophils affected AMI. This helps determine the pathological mechanism of necroptosis and immune cells that influence AMI and provides a novel strategy for targeted therapy.

Background Apolipoprotein C3 (apo C3) is primarily secreted by the liver and is involved in promoting sterile inflammation and organ damage under pathological conditions. Previous studies have shown that apo C3 is abundant in the plasma exosomes of patients with aortic dissection (AD), but its specific role in AD remains unclear. Methods and Results In vivo, adeno‐associated virus was used to knock down hepatic apo C3 expression in an AD mouse model to assess the impact of liver‐derived apo C3 on the development of AD. In vitro, recombinant apo C3 protein was added to the culture medium of J774A.1 macrophages to evaluate its effect on macrophage polarization and to identify the underlying mechanisms. Additionally, the effect of apo C3 on the function of aortic endothelial and smooth muscle cells was explored. Apo C3 in the aortas of AD mice was found to originate from abnormal hepatic secretion, which enters the bloodstream and subsequently deposits in the aorta. Adeno‐associated virus–mediated hepatic apo C3 knockdown significantly reduced AD incidence (P=0.0036), macrophage infiltration (P=0.0004), and collagen deposition in the aorta (P=0.0016). Similarly, inhibiting the apo C3 receptor Toll‐like receptor 2 significantly lowered AD incidence (P=0.0352). In vitro, recombinant apo C3 protein promoted M1 polarization and matrix metalloproteinase secretion in macrophages by activating the Toll‐like receptor 2/NLR family pyrin domain containing 3 pathway. Additionally, apo C3 increased adhesion molecule expression in endothelial cells and induced inflammation, chemotaxis, and apoptosis in vascular smooth muscle cells. Conclusions Our findings highlight the role of abnormally secreted hepatic apo C3 in promoting aortic inflammation.

Previously, animal breeding prioritized enhancing key economic traits to improve production efficiency, leading to a gradual difference in meat quality. However, the genetic factors influencing meat quality remain unclear. To identify key genetic pathways contributing to meat quality, native Chinese yellow-feathered chicken (Qingyuan Partridge Chicken, QPC; female, n=10), and commercial chicken broiler (Cobb broiler, CB; female, n=10) were used for meat quality assessment through metabolomics, proteomics, and phosphoproteomics sequencing. The results show that QPC had lower pH (93.12%), shear force (81.46%), cooking loss (69.29%), moisture content (93.24%) and muscle fiber area (46.04%), but higher meat color values (a*(163.65%) and b*(250.27%)), drip loss (146.32%), and intramuscular fat content (382.01%) than CB (p < 0.05). Metabolomic, proteomic, and phosphoproteomic analyses were jointly conducted, revealing significant differences in energy metabolism strategies. Higher glycolytic enzyme activity was observed in QPC (ENO1, GAPDH, GPI, PFKM, PKM, and TPI1, p < 0.05), while more energetic phosphate compounds were stored in CB. CB had higher Na+/K+ Pump protein abundance (SCN4A, LOC107051305, ATP1B4, ATP12A, ATP1A1, and ATP1A2, p < 0.05) and phosphorylation (ATP1A2-Ser662, p < 0.05) and Ca2+ channel protein abundance (ATP2B4, SRL, CACNB1, CACNA1S, CACNA2D1, CAMK2G, LOC107050717 and TNNC2, p < 0.05) than QPC. In QPC, CAMKII autophosphorylation activated downstream protein and increased Ca2+. These results suggest CB is more contractile than QPC, contributing to meat quality between CB and QPC.

Abstract To enhance the drilling efficiency and extend the service life of PDC (Polycrystalline Diamond Composite) bits in shale formations, this study delves into the rock-breaking mechanisms of special-shaped cutters through a comprehensive experimental approach. This involves optimizing the cutter designs, conducting laboratory experiment and field testing. Among the various cutter geometries considered, concave, axe, planar, and triangular cutters are chosen as the focal points for unit rock-breaking experiments. These tests aim to assess their cutting loads and cutting specific energy to gain a deeper understanding of their performance characteristics. Based on experimental, the debris characteristics are analyzed. Based on the understanding of the shale-breaking characteristics of special-shaped cutters, field testing is performed using a novel PDC bit with a special-shaped cutter. Compared with planar cutters, the concave cutter and the triangular cutter generate lower cutting loads and cutting specific energy. Under identical conditions, the average cutting force and cutting specific energy of concave cutter at different cutting depths are reduced by 16.1% and 19.6% Specifically, the concave cutter generates the largest debris when operated under similar conditions, which is beneficial for increasing rock-breaking efficiency. Laboratory experiment indicate that compared to conventional drill bits, the novel drill bit experiences an increase in torque of approximately 9.8% with increasing WOB (weight on bit). Under high WOB, the ROP (rate of penetration) increases by about 75.4%, while the mechanical specific energy decreases by nearly 40%. Additionally, the novel bit vibration characteristics remain superior to conventional drill bits. Field testing shows that the average ROP of the novel bit and total footage drilled increase by up to 13.3% and 27.2%, respectively, in comparison with those for the conventional bit. The research results are helpful to speed up the efficiency of shale gas drilling.

IntroductionCapping actin protein, gelsolin-like (CAPG) is a potential therapeutic target in various cancers. However, the potential immunotherapeutic effects and prognostic value of CAPG in uterine corpus endometrial carcinoma (UCEC) remain unclear.MethodsThe characterization, methylation effects, prognostic value, targeted miRNAs of CAPG, and the correlation of CAPG with immune cell infiltration and ferroptosis in UCEC were investigated using multiple public databases and online tools. Furtherly, we explored the potential physiological function of CAPG using EdU and Transwell migration assays, identified the cell localization and expression of CAPG and GPX4 by immunofluorescence, and detected the intracellular Fe2+ levels using a FerroOrange fluorescent probe in Ishikawa cells. Additionally, the OncoPredict package was used to analyze the potential chemotherapeutic drugs for UCEC.ResultsCAPG showed generally high expression in tumor group. The overall survival rate of the high-risk group was significantly lower than that of the low-risk group. Enrichment analysis indicated that CAPG is involved in immune-related pathways and is closely associated with the tumor microenvironment. CAPG expression levels were affected by abnormal DNA methylation and/or targeted miRNAs, infiltration levels and marker genes of various immune cells, thereby impacting immune response, ferroptosis, and patient prognosis. Ferroptosis analysis indicated that ALOX5 and VLDLR were the top CAPG-related ferroptosis markers; glutathione metabolism levels in tumor group were generally high, and decitabine was a ferroptosis inducer. CAPG-siRNA suppressed the cell proliferation and invasion, and markedly elevated the expression levels of immune-related genes IL8, TNF, TLR4 and the intracellular Fe2+ levels. CAPG co-located with GPX4 in nucleus and co-regulated ferroptosis and metabolism in Ishikawa cells. Moreover, four chemotherapy drugs showed better sensitivity to UCEC patients in the low-risk cohort.ConclusionsCAPG may serve as a potential biomarker of UCEC owing to its role in modulating the immune response and ferroptosis, providing novel perspectives for combined immunotherapy of UCEC.

Abstract A‐type granite is a favorable rock for the study of crustal evolution, crust‐mantle interaction and metallogenesis. However, the origin of A‐type granite remains controversial. In this study, we report high‐precision Ca isotopic compositions of a co‐genetic suite of A‐type granites from the Lower Yangtze River Belt (LYRB) in eastern China. Our results show that the δ44/40Ca of the A‐type granites ranges from 0.55 ± 0.11‰ to 1.44 ± 0.06‰, and is negatively correlated with CaO, Sr and Ba contents and Eu/Eu*, indicating that the Ca isotope fractionation of A‐type granites is dominated by plagioclase and potassium feldspar. There is kinetic fractionation of Ca isotopes during A‐type granite magma evolution. Sample BSL‐7, the least evolved sample, revealed that it had a low δ44/40Ca of 0.59‰, which is significantly lower than that of the upper continental crust (δ44/40Ca = 0.71–0.72‰) and the bulk silicate earth (δ44/40Ca = 0.94‰). The low δ44/40Ca can be best explained by partial melting of the enriched mantle metasomatized by subduction material. Combined with the geodynamic background of the LYRB, we propose that the formation of A‐type granites in the LYRB originates from partial melting of the enriched mantle, triggered by early Cretaceous ridge subduction of the Pacific and Izanagi plates.

Most of the previous SOC equalization methods for microgrid energy storage target DC microgrids and use centralized control structures, while in recent years many researchers have begun to focus on a decentralized, communication-based implementation of distributed control structures. In this paper, based on the existing research, we use the multi-agent system (MAS) structure and dynamic consistency algorithm (DCA) to realize the estimation of the SOC mean value of microgrid energy storage obtained by each agent in the system. For the problems of the iterative convergence that exists in the distributed control, such as being too slow, too frequent communication, stability, etc., we optimally select the parameters of the consistency iterative summation to improve convergence. In addition, we use the event-driven method to further reduce the unnecessary communication frequency. Finally, a numerical simulation model of the AC microgrid is established by Matlab to verify the effectiveness of the method, which reduces the communication volume by about 50% while maintaining the effect of the control strategy.

Introduction: Currently, revealing how to prevent and control hyperuricemia has become an essential public health issue. Sulforaphane has a wide range of applications in the management of hyperuricemia. Objective: The study objective was to verify the uric acid-lowering effects and the regulation of the gut-kidney axis mediated by sulforaphane and identify host-microbial co-metabolites in hyperuricemia. Methods: A hyperuricemia model was established by administering feedstuffs with 4% potassium oxonate and 20% yeast. Forty male Sprague–Dawley rats were randomly divided into the normal control, hyperuricemia, allopurinol, and sulforaphane groups. Animals were treated by oral gavage for six consecutive weeks, and then phenotypic parameters, metabolomic profiling, and metagenomic sequencing were performed. Results: Sulforaphane could lower uric acid by decreasing urate synthesis and increasing renal urate excretion in hyperuricemic rats (P＜0.05). We identified succinic acid and oxoglutaric acid as critical host-gut microbiome co-metabolites. Moreover, sulforaphane improved the diversity of microbial ecosystems and functions, as well as metabolic control of the kidney. Notably, sulforaphane exerted its renoprotective effect through epigenetic modification of Nrf2 and interaction between gut microbiota and epigenetic modification in hyperuricemic rats. Conclusion: We revealed that sulforaphane could ameliorate the progression of hyperuricemia by reprogramming the gut microbiome and metabolome. Our findings may provide a good means for efficiently preventing and treating hyperuricemia.

Context Acute promyelocytic leukaemia (APL) is a malignant hematological tumour characterized by the presence of promyelocytic leukaemia–retinoic acid receptor A (PML-RARA) fusion protein. Cinobufagin (CBG) is one of the main effective components of toad venom with antitumor properties. However, only a few reports regarding the CBG treatment of APL are available.Objective We explored the effect and mechanism of action of CBG on NB4 and NB4-R1 cells.Materials and methods We evaluated the viability of NB4 and NB4-R1 cells treated with 0, 20, 40, and 60 nM CBG for 12, 24, and 48 h. After treatment with CBG for 24 h, Bcl-2 associated X (Bax), B-cell lymphoma 2 (Bcl-2), β-catenin, cyclin D1, and c-myc expression was detected using western blotting and real-time polymerase chain reaction. Caspase-3 and PML-RARA expression levels were detected using western blotting.Results CBG inhibited the viability of NB4 and NB4-R1 cells. The IC50 values of NB4 and NB4-R1 cells treated with CBG for 24 h were 45.2 nM and 37.9 nM, respectively. CBG induced NB4 and NB4-R1 cell apoptosis and PML-RARA degradation in a caspase-dependent manner and inhibited the β-catenin signalling pathway.Discussion and conclusion CBG induced NB4 and NB4-R1 cell apoptosis and PML-RARA degradation in a caspase-dependent manner by inhibiting the β-catenin signalling pathway. This study proposes a novel treatment strategy for patients with APL, particularly those with ATRA-resistant APL.

In this study, we investigated the association between altered methylation in the maternal placenta and hyperglycaemia and explored the epigenetic mechanisms underlying gestational diabetes mellitus (GDM). Reduced representation bisulphite sequencing (RRBS) and RNA sequencing (RNA-seq) were performed on placental tissues obtained from women with GDM and healthy controls. Further, pyrosequencing, correlation analyses, and linear regression analyses were performed to valuate relationships between aberrantly methylated-differentially expressed genes and clinical parameters. The EMBOSS and JASPAR databases were used for a computational analysis of CpG islands and transcription factor-binding sites in the TRIM67 promoter region. A CpG island with a length of 264 bp in the placental TRIM67 promoter region in the GDM group exhibited significant hypermethylation at four CpG sites. The hypermethylation of the TRIM67 promoter region in the maternal placenta showed a significant, positive correlation with the 1 h and 2 h oral glucose tolerance test (OGTT) values and a negative correlation with lipoprotein(a). Placental DNA methylation levels in the TRIM67 promoter region were markedly elevated in GDM and were associated with blood glucose and lipid levels during healthy pregnancy.

In the event of a major power outage in the power systems, there is an urgent need to investigate entire-process coordinated restoration strategies for the transmission systems (TSs) and distribution systems (DSs), aiming to accelerate the restoration speed of generating units, network reconfiguration, and load restoration. Furthermore, it is imperative to address the multiple uncertainties that arise during the restoration process to mitigate potential security risks associated with the restoration. Hence, an adaptive ADMM-based entire-process distributed restoration method of TSs and DSs considering CVaR is proposed in this paper. Firstly, an entire-process distributed restoration model of TSs and DSs considering CVaR is proposed to maximize the total restoration benefits of TSs and DSs. Then, an adaptive ADMM-based distributed solving algorithm for the coordinated restoration model of the TSs and DSs is introduced, which incorporates adaptive penalty parameter adjustments, leading to faster convergence compared to the standard ADMM. Finally, case studies on an improved 179-bus transmission system are employed to verify that the proposed restoration method can achieve higher restoration benefits and faster convergence speed compared to existing restoration models.

BackgroundThe aim of this study was to identify the predictive factors for adverse clinical events after surgery in patients with acute type A aortic dissection (AAAD), and to explore the predictive value of preoperative prognostic nutritional index (PNI) combined with D-dimer for these events.MethodsThis study was a retrospective analysis of clinical data of 153 patients with AAAD who underwent emergency surgery at our center from January 2019 to January 2022. Patients were divided into adverse event group and non-adverse event group based on whether they experienced adverse clinical events after surgery. Univariate and multivariable logistic regression analyses were performed to identify the risk factors for adverse events, and the predictive efficacy was evaluated by the area under the receiver operating characteristic curve (ROC-AUC).ResultsA total of 153 AAAD patients were included in the study, and were divided into the adverse event group (n = 46) and the non-adverse events group (n = 107) based on whether or not they experienced clinical adverse events after surgery. The optimal cutoff value was determined using ROC curves, and multivariate logistic regression analysis was performed. Ultimately, it was found that preoperative PNI 15.05 were independent predictors of postoperative clinical adverse events in AAAD patients. The odd ratios (OR) value for preoperative PNI 15.05 is 7.572 [95% CI: 3.094–20.220, p 15.05 are independent predictive factors for postoperative adverse events during hospitalization in patients with AAAD. The combination of these two indicators can improve the predictive accuracy, which is superior to using either variable alone.

The rapid development of wind power has imposed many challenges on the operation of the power system. Energy storage system has broad application prospects in promoting wind power to the grid. However, the high price of the energy storage restricts the development of the combined wind energy-storage system. In order to deal with the power fluctuation of the large-scale wind power grid connection, we propose an allocation strategy of energy storage capacity for combined wind-storage system considering the wind power output volatility and battery storage system’s own operational constraints. The model aims to maximize the annual avenue of the cogeneration system, which allows for the investment fee, operation and maintenance fee and penalty cost of the combined system. The calculation results validate the effectiveness of the optimal allocation strategy.

BackgroundChronic inflammation plays a crucial role in tissue injury, osteoporosis, and fracture. The dietary inflammatory index (DII) is a tool for assessing the potential for inflammation in the diet. However, the association between the DII and fractures remains controversial from previous studies. ObjectiveWe aimed to explore the correlation between the DII and fracture risk in Chinese adults. MethodsWe included 11,999 adults (5519 men and 6480 women) who were a part of the China Health and Nutrition Survey (1997-2015) prospective cohort. A 3-day, 24-hour meal review method was used to calculate the DII score. The fractures were identified using a questionnaire. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for fractures. Subgroup, sensitivity, and restricted cubic spline analyses were performed. ResultsDuring the 18 years of follow-up (median follow-up 9.0 years), 463 men and 439 women developed fractures. The median DII score was 0.64 (IQR −1.74 to 1.46) for the total sample, 0.75 (IQR −1.68 to 1.50) for men, and 0.53 (IQR −1.79 to 1.42) for women. The DII score had a positive correlation with the risk of fracture among women but not among men. For men, after adjusting for covariates, the HRs for quintiles of DII were 1, 0.96 (95% CI 0.66-1.41), 1.05 (95% CI 0.74-1.49), 0.89 (95% CI 0.62-1.26), and 0.94 (95% CI 0.67-1.34; trend: P=.62). The HRs for women were 1, 1.13 (95% CI 0.72-1.79), 1.24 (95% CI 0.83-1.86), 1.51 (95% CI 1.02-2.22), and 1.62 (95% CI 1.10-2.39; trend: P=.004). The restricted cubic spline analysis showed a significant association between fracture risk and DII score in women (overall association: P=.01); as the DII scores were >0.53, HRs showed a significant upward trend. Women aged

By analyzing traditional distributed energy resource (DER) modeling methods, this paper proposes a feasible method of DER modeling based on static generator in the simulation software — DIgSILENT. Behavioral model is proposed in this paper to simplify the DER model, in which simple electronic circuits or mathematical functions are used to reflect the physical characteristics of a certain model. With the application of the modeling method, the battery energy storage system (BESS) are implemented in DIgSILENT simulation environment. In each simulation case, the behavioral model as well as the control strategy is illustrated and the simulation result is analyzed in the end.

Modular multilevel converters have found a large number of applications in high-voltage and high-power DC transmission due to their modularity, scalability, multi-equality and other advantages. The two typical topologies in MMC systems are half-bridge sub-module structure and full-bridge sub-module structure. Half-bridge sub-module is widely used in MMC systems by virtue of its simple control structure, high conversion efficiency and low cost. Insulated gate bipolar transistor (IGBT) failures, especially open-circuit failures, are a major factor in the reliable operation of MMC systems. Fast and accurate positioning of the open circuit fault location and removal of the fault submodule is of great significance for handling MMC system faults. Aiming at the current situation of the fault location of the MMC system, this paper compares the error of the predicted median capacitance voltage with the actual value , and proposes an accurate diagnosis method for MMC lower IGBT tube open circuit faults. This method is suitable for one or more IGBT lower tube open-circuit fault conditions, and can quickly locate the faulty submodule within 5ms. Finally, an MMC simulation system with 8 sub-modules is built based on MATLAB/Simulink, which effectively verifies the accuracy of the proposed method.

Abstract Background Sarcopenia was thought to be associated with adverse outcomes and will cause lots of health expenditure. But the relationship between sarcopenia and catastrophic health expenditure (CHE) had been little explored. Here, we examined the distribution of sarcopenia in relation to medical and payment burdens. Methods We used data from three waves of China Health and Retirement Longitudinal Study including 14 130 participants from 9077 households aged over 50 years old. Sarcopenia was operationalized according to the Asian Working Group for Sarcopenia 2019. Medical expenditure was obtained by self‐reported data, and CHE was identified by WHO definitions. We used the negative binomial regression model and logistic mixed‐effects models to examine the associations between sarcopenia and medical and CHE. Results A total of 14 130 participants [52.2% female, aged 60.8 (SD 9.3)] from 9077 households were included in this study. The prevalence of sarcopenia was 19.8%, 11.9% for moderate sarcopenia, and 7.9% for severe sarcopenia, respectively. We identified 1416 household CHE events in all three waves. Severe sarcopenia was associated with an increase in the number of inpatient visits [incidence rate ratio 1.31, 95% confidence interval (CI): 1.03–1.66, P = 0.03] and the risk of CHE (odds ratio: 1.04, 95% CI: 1.01–1.07, P

An exploratory study was undertaken to examine the prevalence of infants’ feeding patterns in Beijing, China, as well as the factors linked to infants’ self-feeding proportion during the introduction of complementary foods, and the impact of professional feeding guidance on this proportion. A total of 122 families with infants aged 6–11 months from Beijing were included in the study. A descriptive analysis was employed to assess the prevalence of infants’ feeding patterns, while generalized linear model analysis was utilized to investigate the factors associated with these patterns. All families were provided with comprehensive and personalized professional guidance regarding the introduction of complementary foods for infants. However, 64 families were lost to follow-up, leaving 58 families who were re-evaluated and queried after one month. To exclude the influence of infants aging, both the 64 families prior to receiving feeding guidance, and the 58 families after receiving feeding guidance, were included in the analysis. The families with infants aged 6–8 months and 9–11 months were compared separately based on the presence or absence of feeding guidance. Statistical tests, including the Wilcoxon rank-sum test and χ2 test, were conducted to assess any significant differences. The study revealed that the proportion of infants engaging in self-feeding was found to be remarkably low (10% [0%, 40%]). Furthermore, a significant positive association was observed between the proportion of infants engaging in self-feeding and their age (p < 0.001). Notably, after receiving professional feeding guidance, the proportion of infants engaging in self-feeding significantly increased (from 1% [0%, 20%] to 30% [10%, 50%], p < 0.001 for infants aged 6–8 months; from 20% [10%, 50%] to 40% [30%, 50%], p < 0.001 for infants aged 9–11 months). These findings contribute valuable insights for improving postnatal care practices during the introduction of complementary foods for infants.

Abstract Background Evidence on the association between exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) and blood glucose concentrations in pregnant women is inconsistent. This study aimed to examine the association between PFAS exposure and the concentrations of fasting plasma glucose (FPG) and one-hour plasma glucose (1 h-PG) after a 50-g oral glucose tolerance test in pregnant women. Methods The study was based on the Shanghai-Minhang Birth Cohort, in which 1292 pregnant women were recruited. Among them, 981 women provided blood samples (at 12–16 gestational weeks) for PFAS measurement. FPG data collected from 856 women at 12–20 GW and 1 h-PG data collected from 705 women at 20–28 GW were obtained through medical records from the routine prenatal care system. High FPG or 1 h-PG was defined as ≥90th percentile of FPG or 1 h-PG. The analysis of eight PFASs was conducted in this study: perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), and perfluorotridecanoic acid (PFTrDA). The odds ratios (ORs) and associated 95% confidence intervals (CIs) were estimated to determine the associations of each PFAS compound with high FPG and 1 h-PG from a logistic regression model. Results After adjustment for potential confounders, most PFASs were positively associated with high 1 h-PG concentrations. The OR for high 1 h-PG concentrations was 1.87 (95% CI: 1.15–3.05) with a one log unit increase of PFOS; similar associations were observed for PFNA (OR: 2.15, 95% CI: 1.24–3.74), PFDA (OR: 1.61, 95% CI: 1.10–2.44), PFUdA (OR: 1.71, 95% CI: 1.12–2.62), and PFDoA (OR: 1.34, 95% CI: 1.00–1.81). When the PFAS concentrations were categorized into three groups by tertiles, the highest tertiles of PFOS, PFOA, PFNA, PFDA, PFDoA, and PFTrDA had a statistically significant increase in the risk of high 1 h-PG concentrations compared with the lowest tertiles. No statistically significant association was observed between PFAS exposure and high FPG. Conclusion PFAS exposure was associated with an increased risk of high 1 h-PG among pregnant women, but no such association was observed for FPG.

Diabetic nephropathy is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Therefore, we must find effective prevention and treatment approaches to the problem. Oat has a long history of use for its nutritional and medicinal properties, such as maintaining physiological blood glucose levels. Oat β glucan is one of the major bioactive substances produced by oat. However, the protective effects of oat β glucan on diabetic nephropathy are still unclear. This study generated a rat model of diabetic nephropathy to explore the potent therapeutic ability and mechanism of oat β glucan in renal function by 16S rRNA genes sequencing. Diabetic nephropathy model was established in forty rats by left nephrectomy and single intraperitoneal injection of streptozotocin. These rats were randomly divided into the model group and three oat β glucan intervention groups. Twenty rats underwent sham operation and were randomly divided into normal control group and oat β glucan control group. Animals were treated by oral gavage for 8 consecutive weeks. The results showed that oat β glucan reduced blood glucose level and improved renal function (P < 0.05). Oat β glucan significantly improved serum inflammatory levels (P < 0.05). The diversity of intestinal microflora in diabetic nephropathy rats decreased with time prolongation, while oat β-glucan reversed the result. Compared with the model group at week 8, the abundances of Eubacterium, Butyricicoccus, and Ruminococcus were elevated significantly after oat β glucan intervention (P < 0.05). Correlation analysis indicated that abundances of Eubacterium, Butyricicoccus, and Ruminococcus were significantly negatively correlated with the levels of renal impairment markers. In summary, the findings of this study showed that oat β glucan can increase the diversity of intestinal flora, regulate the composition of intestinal flora, modulate intestinal flora metabolism, alleviate the inflammatory response, and further delay the development of diabetic nephropathy. Therefore, oat β glucan has the potential to be developed into the novel and safe drug for diabetic nephropathy.

Previous studies have shown that BmSPI39, a serine protease inhibitor of silkworm, can inhibit virulence-related proteases and the conidial germination of insect pathogenic fungi, thereby enhancing the antifungal capacity of Bombyx mori. The recombinant BmSPI39 expressed in Escherichia coli has poor structural homogeneity and is prone to spontaneous multimerization, which greatly limits its development and application. To date, the effect of multimerization on the inhibitory activity and antifungal ability of BmSPI39 remains unknown. It is urgent to explore whether a BmSPI39 tandem multimer with better structural homogeneity, higher activity and a stronger antifungal ability can be obtained by protein engineering. In this study, the expression vectors of BmSPI39 homotype tandem multimers were constructed using the isocaudomer method, and the recombinant proteins of tandem multimers were obtained by prokaryotic expression. The effects of BmSPI39 multimerization on its inhibitory activity and antifungal ability were investigated by protease inhibition and fungal growth inhibition experiments. In-gel activity staining and protease inhibition assays showed that tandem multimerization could not only greatly improve the structural homogeneity of the BmSPI39 protein, but also significantly increase its inhibitory activity against subtilisin and proteinase K. The results of conidial germination assays showed that tandem multimerization could effectively enhance the inhibitory ability of BmSPI39 on the conidial germination of Beauveria bassiana. A fungal growth inhibition assay showed that BmSPI39 tandem multimers had certain inhibitory effects on both Saccharomyces cerevisiae and Candida albicans. The inhibitory ability of BmSPI39 against these the above two fungi could be enhanced by tandem multimerization. In conclusion, this study successfully achieved the soluble expression of tandem multimers of the silkworm protease inhibitor BmSPI39 in E. coli and confirmed that tandem multimerization can improve the structural homogeneity and antifungal ability of BmSPI39. This study will not only help to deepen our understanding of the action mechanism of BmSPI39, but also provide an important theoretical basis and new strategy for cultivating antifungal transgenic silkworms. It will also promote its exogenous production and development and application in the medical field.

It was found that silkworm serine protease inhibitors BmSPI38 and BmSPI39 were very different from typical TIL-type protease inhibitors in sequence, structure, and activity. BmSPI38 and BmSPI39 with unique structure and activity may be good models for studying the relationship between the structure and function of small-molecule TIL-type protease inhibitors. In this study, site-directed saturation mutagenesis at the P1 position was conducted to investigate the effect of P1 sites on the inhibitory activity and specificity of BmSPI38 and BmSPI39. In-gel activity staining and protease inhibition experiments confirmed that BmSPI38 and BmSPI39 could strongly inhibit elastase activity. Almost all mutant proteins of BmSPI38 and BmSPI39 retained the inhibitory activities against subtilisin and elastase, but the replacement of P1 residues greatly affected their intrinsic inhibitory activities. Overall, the substitution of Gly54 in BmSPI38 and Ala56 in BmSPI39 with Gln, Ser, or Thr was able to significantly enhance their inhibitory activities against subtilisin and elastase. However, replacing P1 residues in BmSPI38 and BmSPI39 with Ile, Trp, Pro, or Val could seriously weaken their inhibitory activity against subtilisin and elastase. The replacement of P1 residues with Arg or Lys not only reduced the intrinsic activities of BmSPI38 and BmSPI39, but also resulted in the acquisition of stronger trypsin inhibitory activities and weaker chymotrypsin inhibitory activities. The activity staining results showed that BmSPI38(G54K), BmSPI39(A56R), and BmSPI39(A56K) had extremely high acid–base and thermal stability. In conclusion, this study not only confirmed that BmSPI38 and BmSPI39 had strong elastase inhibitory activity, but also confirmed that P1 residue replacement could change their activity and inhibitory specificity. This not only provides a new perspective and idea for the exploitation and utilization of BmSPI38 and BmSPI39 in biomedicine and pest control, but also provides a basis or reference for the activity and specificity modification of TIL-type protease inhibitors.

Abstract Background Hericium erinaceus, also known as lion’s mane mushroom, is a widely distributed edible and medicinal fungus in Asian countries. H. erinaceus harbors diverse bioactive metabolites with anticancer, immunomodulating, anti-inflammatory, antimicrobial, antihypertensive, antidiabetic and neuroprotective properties. Although the chemical synthesis processes of these bioactive metabolites are known, the biosynthetic processes remain unknown. Results In this study, we obtained the transcriptomes of six H. erinaceus strains using next-generation RNA sequencing and investigated the characteristics of the transcriptomes and biosynthesis of bioactive compounds, especially polysaccharides. The transcriptomes ranged in size from 46.58 to 58.14 Mb, with the number of unigenes ranging from 20,902 to 37,259 across the six H. erinaceus strains. Approximately 60% of the unigenes were successfully annotated by comparing sequences against different databases, including the nonredundant (NR), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), clusters of orthologous groups for eukaryotic complete genomes (KOG) and Swiss-Prot databases. Most of the transcripts were putatively involved in signal transduction, carbohydrate metabolism, translation, transport and catabolism, and amino acid metabolism. Genes involved in polysaccharide biosynthesis were identified, and these genes encoded phosphoglucomutase (PGM), glucose phosphate isomerase (PGI), UDP-glucose pyrophosphorylase (UGP), glycoside hydrolase family proteins, glycosyltransferase family proteins and other proteins. Moreover, the putative pathway for the intracellular polysaccharide biosynthesis of H. erinaceus was analyzed. Additionally, the open reading frames (ORFs) and simple sequence repeats (SSRs) were predicted from the transcriptome data of the six strains. Conclusions Overall, the present study may facilitate the discovery of polysaccharide biosynthesis processes in H. erinaceus and provide useful information for exploring the secondary metabolites in other members of the Basidiomycetes genus.

Sarcopenia a recognised geriatric syndrome. This study aims to evaluate the prevalence of possible sarcopenia, sarcopenia and severe sarcopenia among older Chinese adults and to identify any associated factors for possible sarcopenia according to the updated diagnostic criteria of the Asian Working Group for Sarcopenia 2019 (AWGS 2019). We used data from the China Health and Retirement Longitudinal Study (CHARLS). The main outcome of this study was possible sarcopenia. Handgrip strength was measured via a dynamometer. The muscle mass was estimated by anthropometric measures. Physical performance was measured by 5-time chair stand test and gait speed test. A multivariate logistic regression model with stepwise method was employed to identify factors associated with possible sarcopenia. A total of 6172 participants aged 60-94 years were included. The prevalence of possible sarcopenia, sarcopenia and severe sarcopenia was 38.5%, 18.6%, and 8.0%, respectively. Age, rural area, falls, higher C-reactive protein (CRP), and chronic diseases (including hypertension, chronic lung diseases, heart disease, psychiatric disease and arthritis) were associated with a higher risk of possible sarcopenia. Conversely, alcohol consumption, higher gait speed and high levels of hemoglobin were associated with decreased risk of possible sarcopenia. However, the associations between possible sarcopenia with alcohol consumption, heart disease, psychiatric disease and hemoglobin were not significant after Bonferroni correction. Our study reported a relatively high prevalence of sarcopenia among older Chinese population, and identified a range of factors associated with sarcopenia. We also found rural elders are more vulnerable to sarcopenia than urban elders. Additionally, we discovered systemic inflammation might be one of the contributing factors between sarcopenia and related comorbidities. We believe the findings of this study would help to identify individuals at high risk of sarcopenia early and therefore implement the prevention and treatment strategies to reduce the disease burden in China.

The present study aimed to evaluate the effects of lutein on blue LED light-induced retinal injury. Animals were randomly assigned to six groups. Distilled water (normal control and water-light group), corn oil (solvent-light group), or 25, 50, or 100 mg/kg lutein in corn oil (three lutein treatment groups) were administered intragastrically for 30 days. The experimental rats (all groups other than the normal control group) were exposed to 1500 lx for 1.5 h after pretreatment. Lutein pretreatment significantly attenuated the decrease in the electroretinogram (ERG) a-wave and b-wave amplitudes and the thinning of the photoreceptor cell layer caused by apoptosis; inhibited light-induced oxidative stress in the retinal tissues; and suppressed the increase in inflammatory cytokine levels. Moreover, the expression of BCO2 was significantly upregulated with lutein supplementation in retinas exposed to light. Our results suggested that lutein protected the retina for light induced retinal damage by inhibiting oxidative stress and inflammation.

Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RM-related biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1,799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM–receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

In this study, we examined whether smoking and drinking affect sperm quality and the DNA methylation of the repetitive element LINE-1, MEST, P16, H19, and GNAS in sperm. Semen samples were obtained from 143 male residents in a minority-inhabited district of Guizhou province in southwest China. Quantitative DNA methylation analysis of the samples was performed using MassARRAY EpiTYPER assays. Sperm motility was significantly lower in both the nicotine-exposed (P = 0.0064) and the nicotine- and alcohol-exposed (P = 0.0008) groups. Follicle-stimulating hormone (FSH) levels were higher in the nicotine-exposed group (P = 0.0026). The repetitive element LINE-1 was hypermethylated in the three exposed groups, while P16 was hypomethylated in the alcohol and both the alcohol and nicotine exposure groups. Our results also show that alcohol and nicotine exposure altered sperm cell quality, which may be related to the methylation levels of MEST and GNAS. In addition, MEST, GNAS, and the repetitive element LINE1 methylation was significantly associated with the concentration of sperm as well as FSH and luteinizing hormone levels.

Background: The goal of the present study was to investigate the wound-healing potential of marine collagen peptides (MCPs) from chum salmon skin administered to rats following cesarean section (CS). Methods: Ninety-six pregnant Sprague-Dawley rats were randomly divided into four groups: a vehicle group and three MCP groups. After CS, rats were intragastrically given MCPs at doses of 0, 0.13, 0.38, 1.15 g/kg*bw, respectively. On postoperative days 7, 14, and 21, the uterine bursting pressure, skin tensile strength, hydroxyproline (Hyp) concentrations, and histological and immunohistochemical characteristics of the scar tissue were examined. Results: In the MCP groups, the skin tensile strength, uterine bursting pressure, and Hyp were significantly higher than those in the vehicle group at all three time points (p

Care for diabetic wounds remains a significant clinical problem. The present study was aimed at investigating the effect of skin gelatin from Chum Salmon on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 48 rats, of which 32 were diabetes. The diabetic rats were orally treated daily for 14 days with skin gelatin from Chum Salmon (2 g/kg) or its vehicle. Sixteen non-diabetic control rats received the same amount of water as vehicle-treated non-diabetic rats. Rats were killed to assess the rate of wound closure, microvessel density (MVD), vascular endothelial growth factor (VEGF), hydroxyproline (HP) contents in wound tissues and nitrate in plasma and wound tissue at 7 and 14 days after wounding. Skin gelatin-treated diabetic rats showed a better wound closure, increased MVD, VEGF, hyproxyproline and NO contents and a reduced extent of inflammatory response. All parameters were significant (P < 0.05) in comparison to vehicle-treated diabetic group. In light of our finding that skin gelatin of Chum Salmon promotes skin wound repair in diabetic rats, we propose that oral administration of Chum Salmon skin gelatin might be a beneficial method for treating wound disorders associated with diabetes.

Previous studies have suggested that fat mass-and obesity-associated (FTO) gene is associated with body mass index (BMI) and the risk of obesity. This study aims to assess the association of five FTO polymorphisms (rs9939609, rs8050136, rs1558902, rs3751812 and rs6499640) with obesity and relative parameters in Han Chinese adolescents.We examined a total of 401 adolescents, 223 normal weights (58.7% boys, 41.3% girls), 178 overweight (60.1% boys, 39.9% girls), aging from 14 to 18-years-old, recruited randomly from public schools in the central region of Wuxi, a southern city of China. DNA samples were genotyped for the five polymorphisms by Sequenom Plex MassARRAY. Association of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin (FIns), triglyceride (TG) and cholesterol (TC) were investigated.1) Serum FPG, FIns, TG and TC were statistically significant higher than that in normal control group. 2) We found that BMI was higher in the rs9939609 TA+AA, rs8050136 AC+AA, rs1558902 TA+AA and rs3751812 GT+TT genotypes than in wild TT genotypes (rs9939609: P = 0.038; rs1558902: P = 0.038;), CC genotypes(rs8050136: P = 0.024) and GG genotypes (rs3751812: P = 0.024), which were not significant on adjusting for multiple testing. 3) In case-control studies, five polymorphisms were not significantly associated with overweight (p>0.05), haplotype analyses showed non-haplotype is significantly associated with a higher risk of being overweight (p>0.05). 4) There existed no significant statistical difference about FPG, FIns, TG and TC in genotype model for any SNP.Our study has conducted a genetic association study of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin (FIns), triglyceride (TG) and cholesterol (TC). Our study found BMI of subjects with A allele of FTO rs9939609 is higher than that with T allele. Further studies on other polymorphisms from FTO and increasing the sample size are needed.