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Abstract Diabetes mellitus (DM) is a chronic metabolic disease that is highly susceptible to kidney injury. Di’ao XinXueKang capsules (DXXK) is a novel Chinese herbal medicine that has been used in clinical trials for the therapy of DM and kidney disease, but the underlying pharmacological mechanism remains unclear. This study aims to integrate network pharmacology, molecular docking and in vivo experiments to explore the potential mechanisms of DXXK in the treatment of diabetic kidney injury. The chemical constituents of DXXK were extracted from the ETCM and Batman-TCM databases, and then evaluated for their pharmacological activity via the Swiss ADME platform. Multiple disease databases were searched and integrated for DM-related targets. Overlapping targets were then collected to construct a protein–protein interaction (PPI) network. KEGG and GO enrichment analyses were performed based on the Metascape database, and molecular docking was performed using AutoDock Vina software. The main components in DXXK were analyzed by HPLC. The results of network pharmacology and molecular docking were validated in an animal model of DM induced by the combination of a high-fat diet (HFD) and streptozotocin (STZ). We screened and obtained 7 ingredients and identified dioscin, protodioscin, and pseudoprotodioscin as the major components of DXXK by HPLC. A total of 2,216 DM-related pathogenic genes were obtained from DrugBank, GeneCards, OMIM, and DisGeNET databases. KEGG and GO enrichment analyses indicated that the TGF-beta signaling pathway is a critical pathway associated with DM therapy. Molecular docking revealed that the ingredients in DXXK bind to the pivotal targets TGFβ1, Smad2, and Smad3. In diabetic mice, we found that DXXK alleviated diabetic symptoms, lowered blood glucose, improved insulin tolerance, and modulated lipid metabolism. Furthermore, DXXK attenuated renal lesions and fibrosis by downregulating TGFβ1, Smad2, and Smad3. Collectively, our results suggest that DXXK has the potential to regulate glucolipid metabolism in DM, and it may serve as a viable therapeutic option for renoprotection by inhibiting of the TGF-β1/Smad2/3 pathway.

BackgroundSarcopenia and rotator cuff tears are common among elderly patients. However, the role of sarcopenia in the management of rotator cuff tears has been often overlooked. This study aimed to elucidate the effects of sarcopenia-related traits on rotator cuff tears.MethodsTwo-sample Mendelian randomization (MR) analyses based on genome-wide association study data were used to evaluate the causal relationships among appendicular lean mass (ALM), usual walking pace, low hand grip strength, and rotator cuff tears. Multivariate Mendelian randomization (MVMR) analyses were used to evaluate the direct effects of each muscle trait on the causal relationship.ResultsUnivariate MR analysis showed that ALM and usual walking pace were causally related to rotator cuff tears (odds ratio (OR) = 0.895; 95% confidence interval (CI), 0.758-0.966, P

IntroductionThere is a close and complex interaction between the elements in the aboveground-underground ecosystem during the growth and development of plants. Specifically, when the aboveground part of plants is infected by pathogens, it induces the plant rhizosphere to synthesize specific root exudates. Consequently, a group of beneficial rhizosphere soil bacteria is recruited to help plants resist diseases. However, the changes in the rhizosphere soil bacterial community of plants under infection by oomycete pathogens remain unknown.MethodsThree experimental treatments were set up in this experiment: soils inoculated with P. nicotianae, no-inoculation with P. nicotianae, and a control. The control treatment was composed of soils without transplanted tobacco plants, with the pathogen inoculated twice at an interval of eight days to ensure a successful P. nicotianae infection. P. nicotianae inoculation treatments were designed using the hyphal block inoculation method. In the non-inoculation treatment, tobacco plants were grown normally without pathogen inoculation. The tobacco plants were grown in a greenhouse.ResultsThis study demonstrates that tobacco plants recruit microorganisms at the rhizosphere level as a defense mechanism against disease after infection by the oomycete pathogen Phytophthora nicotianae. Specific rhizosphere soil bacteria were screened in vitro to promote tobacco growth in a biofilm-forming manner, which induced the systemic resistance of the plants to P. nicotianae. The recruitment of rhizosphere soil bacteria to the inter-root zone of tobacco plants after infection by P. nicotianae can help subsequently cultivated tobacco plants in the same soil resist pathogen infestation.DiscussionIn conclusion, the present study confirms that infestation caused by oomycete pathogens alters the composition of the plant rhizosphere soil bacterial community and recruits a specific group of beneficial microorganisms that induce disease resistance and promote plant growth, thereby maximizing the protection of progeny grown in the same soil against the disease.

BackgroundRecent studies have yielded conflicting results regarding the relationship between smoking history and the effectiveness of immune checkpoint inhibitors (ICIs) for advanced lung cancer. While some studies have suggested that smoking may enhance the response to immunotherapy in patients with lung cancer, other findings indicate the contrary. Therefore, we conducted a systematic review and meta-analysis to thoroughly examine this association.MethodsWe searched the PubMed, Embase, and Scopus databases for clinical trials comparing immunotherapy with conventional chemotherapy as the primary treatment for advanced lung cancer. A random effects model was used to synthesize hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also conducted predefined subgroup analyses to investigate the efficacy disparities between never-smokers and smokers who were administered immunotherapy alone or in combination with chemotherapy, as well as the differences between former and current smokers under similar treatment modalities.ResultsOur analysis included data from 17 Phase III clinical trials involving 10,283 patients. The findings indicate that immunotherapy benefits both smokers and never-smokers with lung cancer or non-small cell lung cancer, yielding pooled HRs for OS of 0.74 (95% CI: 0.59–0.92) and 0.73 (95% CI: 0.67–0.80), respectively. A significant interaction effect was not observed (HR: 0.98, 95% CI: 0.77–1.24, pinteraction = 0.14), and the tumor type, immunotherapy combination, and type of immunotherapy did not differ among the groups in the subgroup analyses. Similarly, both former and current smokers experienced a significant survival benefit from immunotherapy, with pooled HRs for OS of 0.79 (95% CI: 0.68–0.91) and 0.71 (95% CI: 0.59–0.87), respectively. However, a significant interaction effect was also not observed (HR: 0.91, 95% CI: 0.74–1.11, pinteraction = 0.14).ConclusionOur findings suggest that smoking status does not affect the effectiveness of immunotherapy for lung cancer treatment. However, additional high-quality clinical trials are needed to confirm this conclusion.Systematic review registrationhttps://inplasy.com/register/, identifier INPLASY2023110058.

Background: The detailed clinical phenotype of patients carrying the α-galactosidase gene (GLA) c.548 G > A/p.Gly183Asp (p.G183D) variant in Fabry disease (FD) has not been thoroughly documented in the existing literature. Methods: This paper offers a meticulous overview of the clinical phenotype and relevant auxiliary examination results of nine confirmed FD patients with the p.G183D gene variant from two families. Pedigree analysis was conducted on two male patients with the gene variant, followed by biochemical and genetic screening of all high-risk relatives. Subsequently, evaluation of multiple organ systems and comprehensive instrument assessment were performed on heterozygotes of the p.G183D gene variant. Results: The study revealed that all patients exhibited varying degrees of cardiac involvement, with two demonstrating left ventricular wall thickness exceeding 15 mm on echocardiography, and the remaining six exceeding 11 mm. Impaired renal function was evident in all six patients with available blood test data, two of whom underwent kidney transplantation. Eight cases reported neuropathic pain, and five experienced varying degrees of stroke or transient ischemic attack (TIA). Conclusion: This study indicates that the GLA p.G183D gene variant can induce premature organ damage, particularly affecting the heart, kidneys, and nervous system.

Previous research indicates that post-fault grid-forming (GFM) converters only work in current limiting control (CLC) mode. However, converters integrating the current saturation algorithm (CSA) can operate in both constant voltage control (CVC) and CLC modes. This paper firstly derives the angle-switched model of the grid-connected system governed by CSA and virtual synchronous generator (VSG). Then, combining the fault and three types of post-fault trajectories, critical clearing angle is analytically formulated through the Segmental Equal Area Criterion (SEAC). Finally, a range of values for the saturated current angle is proposed to ensure that the system is stabilized in CVC mode. Notably, the optimal saturated current angle, which is the minimum value within the range, provides the maximum critical clearing angle.

Abstract Aims Recurrent heart failure hospitalization (HFH) is an important feature of the progression of heart failure (HF). In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, we analysed risk factors for recurrent HFH events in HF patients with preserved ejection fraction (HFpEF) and developed a risk prediction model for recurrent HFH. Methods and results This analysis focused on the subset of TOPCAT participants enrolled in the Americas (n = 1767). Recurrent HFH was defined as two or more hospitalizations for HF during the follow‐up period. Lasso regression and multivariate logistic regression were used to screen the risk factors, and the risk prediction model of recurrent HFH was established. During a median follow‐up period of 3.4 (95% confidence interval: 3.3–3.6) years, 72.2% (542 of 751 total hospitalizations) of HFH events occurred in 9.4% (n = 163) of patients with recurrent HFHs. Patients in the recurrent HFH group had higher cardiovascular mortality rate [6.2 per 100 patient‐years (PY) vs. 3.8 per 100 PY, P = 0.016] and all‐cause mortality rate (10.0 per 100 PY vs. 6.8 per 100 PY, P = 0.015) than those in the non‐recurrent HFH group. The model consisting of nine predictors has moderate predictive power for recurrent HFH events in patients with HFpEF (AUC = 0.75, Brier score = 0.08). Decision curve analysis showed a net clinical benefit from the application of the prediction model. Conclusions In patients with HFpEF, the majority of HFHs occur in a small proportion of patients with repeated hospitalizations, who typically have more comorbidities and are at higher risk of death. The predictive model developed in this study helps to identify patients at high risk of recurrent HFH.

The current global climate is complex with an increasing frequency of extreme weather events. The randomness, variability, and intermittency of new energy sources pose significant challenges for the balance between power generation and consumption in electricity grids. This challenge is particularly pronounced during extreme weather events such as cold waves, which aggravate the challenges of power supply stability. Accurate prediction of the wind power output can reduce the need for system backup capacity, ensuring the stable operation and reliability of the power system. However, current prediction models do not effectively consider the impact of extreme weather, leading to low prediction accuracy and large deviations. Additionally, the mechanisms by which extreme weather affects wind power differ from those under normal weather conditions. Extreme weather events such as cold waves are rare, and sample data are scarce, making it difficult to establish precise prediction models. To address these issues, this study proposes a wind power output prediction correction method based on time-series generative adversarial networks. First, a time-series generative adversarial network algorithm was used to generate samples from meteorological and power data, constructing an extreme weather meteorological and power database to effectively address the issue of sample scarcity. Second, the improved particle swarm algorithm (IPSO) and Bayesian optimization (BO) algorithm were used to optimize the parameters of single-prediction algorithms such as eXtreme gradient boosting (XGBoost) and least absolute shrinkage and selection operator (LASSO). Subsequently, by combining the algorithm performance and principle of maximum diversity, the optimal algorithm combination was determined using the evaluation indicators of the prediction error and Pearson correlation coefficients to construct an extreme weather power prediction model under the stacking ensemble learning framework, overcoming the limitations of single algorithms and effectively improving the prediction accuracy. Finally, Support Vector Regression (SVR) was used to construct a power prediction correction model for similar days, correcting the predictions. Through verification using an actual cold wave case study, the proposed method demonstrated significantly improved prediction accuracy and performance compared to single algorithms and conventional prediction models.

BackgroundDiabetes that only appears or is diagnosed during pregnancy is referred to as gestational diabetes mellitus (GDM). The maternal physiological immune profile is essential for a positive pregnancy outcome. However, the causal relationship between GDM and immunophenotypes is not fully defined.MethodsBased on the high-density genetic variation data at the genome-wide level, we evaluated the logical associations between 731 specific immune mediators and GDM using bidirectional Mendelian randomization (MR). The inverse variance weighted (IVW) was the main method employed for MR analysis. We performed multiple methods to verify the robustness and dependability of the MR results, and sensitivity measures were applied to rule out potential heterogeneity and horizontal pleiotropy.ResultsA substantial causal association between several immune mediators and GDM was detected. After FDR testing, HLA DR++ monocyte %leukocyte and HLA DR on plasmacytoid DC were shown to increase the risk of GDM; in contrast, CD127 on CD28+ CD45RA+ CD8br and CD19 on PB/PC were shown to attenuate the effect of GDM. Moreover, the progression of GDM has been shown to decrease the maternal levels of CD39+ activated Treg AC, CD39+ activated Treg %CD4 Treg, CD39+ resting Treg AC, CD39+ resting Treg %CD4 Treg, and CD39+ CD8BR %T cell.ConclusionsOur findings support a possible causal association between GDM and various immunophenotypes, thus facilitating the provision of multiple options for preventive recognition as well as for the diagnostic and therapeutic management of GDM in clinical practice.

Fe-based MIL-101(Fe) MOFshavea high potential to capture CO2 due to their high porosity, porous structure,and significant interaction with CO2, but the photogenerated electron and hole recombination phenomenon is relatively obvious. Copper tetracarboxyphenyl porphyrin (Cu-TCPP) was incorporated into MIL-101(Fe) as a photosensitive material to forma heterostructure. This enhanced the light absorption capability and the photogenerated electron-hole pairs separation in the composite catalyst. Based on the above factors, the current study reported the synthesis of MIL-101(Fe) by hydrothermal method, and a new composite photocatalyst Cu-TCPP@MIL-101(Fe) was prepared by using Cu-TCPP as a copper source with different mass ratios. Themorphologicaland structural characterizationof the composite catalyst was carried out by XRD, SEM, TEM, BET, and FT-IR, and the CO2 reduction performance of the composite catalyst Cu-TCPP@MIL-101(Fe) was determined by a vacuum CO2 reduction system under simulated sunlight irradiation. The results revealed that MIL-101(Fe) was loaded with Cu-TCPP with the formation of type II heterojunctions that are capable of inhibitingthe electron-hole recombination with improved light absorption capacity, and accelerated reduction rate of CO2. The reduction rateof CO2 into CO was found to be 29 μmol·g−1·h−1.

Abstract Background Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM. Methods GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels. Results GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-β and IL-10, preventing inflammation and preserving mouse pregnancy. Conclusion Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health.

Casparian strip membrane domain proteins (CASPs), regulating the formation of Casparian strips in plants, serve crucial functions in facilitating plant growth, development, and resilience to abiotic stress. However, little research has focused on the characteristics and functions of AhCASPs in cultivated peanuts. In this study, the genome-wide identification and expression analysis of the AhCASPs gene family was performed using bioinformatics and transcriptome data. Results showed that a total of 80 AhCASPs members on 20 chromosomes were identified and divided into three subclusters, which mainly localized to the cell membrane. Ka/Ks analysis revealed that most of the genes underwent purifying selection. Analysis of cis elements suggested the possible involvement of AhCASPs in hormonal and stress responses, including GA, MeJA, IAA, ABA, drought, and low temperature. Moreover, 20 different miRNAs for 37 different AhCASPs genes were identified by the psRNATarget service. Likewise, transcriptional analysis revealed key AhCASPs responding to various stresses, hormonal processing, and tissue types, including 33 genes in low temperature and drought stress and 41 genes in tissue-specific expression. These results provide an important theoretical basis for the functions of AhCASPs in growth, development, and multiple stress resistance in cultivated peanuts.

With the increasing popularity of wireless networks and the development of smart cities, the Mobile Crowdsourcing System (MCS) has emerged as a framework for automatically assigning spatiotemporal tasks to workers. The study of mobile crowdsourcing makes a valuable research contribution to community service and urban route planning. However, previous algorithms have faced challenges in effectively addressing task allocation issues with massive spatial data. In this paper, we propose a novel solution to the spatiotemporal task allocation problem using a knowledge graph. Firstly, we construct a robust spatiotemporal knowledge graph (STKG) and employ a knowledge graph embedding algorithm to learn the representations of nodes and edges. Next, we utilize these representations to build a task transition graph, which is a weighted and learning-based graph that highlights important neighbors for each task. We then apply a simplified Graph Convolutional Network (GCN) and an RNN-based model to enhance task representations and capture sequential transition patterns on the task transition graph. Furthermore, we design a similarity function to facilitate personalized task allocation. Through experimental results, we demonstrate that our solution achieves higher accuracy compared to existing approaches when tested on three real datasets. These research findings are significant as they contribute to an 18.01% improvement in spatiotemporal task allocation accuracy.

Aiming at the problem that although the existing redactable blockchain schemes that support trapdoor revocation could revoke the redaction permissions of trapdoor holders, but they were unable to limit the number of redactions using trapdoors, indicating an issue where the management of editing permissions was not adequately refined, a revocable chameleon hash with limited number of redactions was proposed, based on which a new redactable blockchain scheme was proposed.Specifically, the proposed scheme included a master trapdoor, a subordinate trapdoor, and the generated witness.The subordinate trapdoor was deployed for data modification, while the master trapdoor was employed to revoke the subordinate trapdoor, thus accomplishing the objective of revoking editing permissions.Meanwhile, the witness was developed to strictly limit the number of edits via the subordinate trapdoor to one time.The proposed scheme is proved to be secure under the standard complexity assumptions.Theoretical analysis and simulation experiments indicate that the proposed scheme has advantages in terms of security guarantee, when compared with the existing schemes supporting trapdoor revocation.At the same time it introduces little additional computation overhead, and thus has certain practicality.

Abstract Background Myopia and obesity in children and adolescents have become serious public health problems that endanger public health, especially in China. Unhealthy lifestyle behaviors are environmental drivers of both myopia and obesity. This protocol describes a study to evaluate the effectiveness of “22510SS”, that is 2 h of daytime outdoor activities (‘2’); Limit screen time to no more than 2 h per day (‘2’); Consume at least 5 servings of fruits and vegetables daily (‘5’); Attain 1 h of physical activity daily (‘1’); Consume 0 sugar-sweetened beverages (‘0’); Reasonable sleep duration (‘S’); Regular supervision (‘S’). A school-based, multifaceted intervention strategy for myopia and obesity prevention, and to assess and explore the implementation of “22510SS” with regards to acceptability, feasibility, adoption, usage and maintenance. Methods and analysis This study aims to develop a comprehensive intervention strategy "22510SS" based on the socio-ecological model, and A two-arm cluster randomized trial with a parallel-group of a 1:1 allocation ratio in 36 primary and secondary schools to test its evidence-based intervention programs on the effects and implementation of myopia and obesity epidemics in children and adolescents in grades 4 and 7. The primary outcomes will include differences in visual acuity, body mass index, outdoor activity indicators, screen time, fruit and vegetable intake, high-quality protein intake, sugar-sweetened beverage intake, sleep duration, and level of monitoring among children and adolescents. Secondary outcomes will assess the acceptability, feasibility, uptake, use, and maintenance of the intervention. Effects on the primary and secondary outcomes will be analyzed using linear and logistic regression analyses, as well as difference-in-difference analysis, taking into account cluster effects and possible confounding factors. Process assessments will also be conducted through quantitative and qualitative analyses, including acceptability, feasibility, gender, adoption, implementation, and sustainability. Discussion This study will evaluate the effectiveness of “22510SS” and examine its implementation in the school-based network nesting family and clinic. Following this intervention study, the integrated intervention program focused on myopia and obesity among children and adolescents have great potential to be implemented in China to promote and support healthy lifestyle behavior change and reduce the risk of myopia and obesity in children and adolescents. Trial registration NCT05275959. Registered 23 Mach 2022.

Purpose: To investigate 7-year changes in corneal densitometry (CD) and its influencing factors following small incision lenticule extraction (SMILE) for moderate to high myopia. Methods: A total of 32 patients (52 eyes) with a mean spherical equivalent (SE) refraction of -6.30 ± 1.30 D who underwent SMILE were recruited for this prospective study. Pre- and postoperative CD and corneal aberrations were measured by an oculus Pentacam system, and patients were followed up to 7 years. The CD evolution over time and its influencing factors were explored. Results: No complications were observed after SMILE. There was a significant time effect on postoperative CD (P < 0.05). The CD values at the 0-to-2 and 2-to-6 mm of the anterior layer increased at the first day (P < 0.05) and declined to baselines at 1 year postoperatively; after that, CD values at any zone and any corneal layer presented a decreasing trend over time (all P < 0.05). Multivariate analysis showed that postoperative CD was positively correlated with age and optical zone (OZ), whereas negatively correlated with SE, corrected distance visual acuity (CDVA), and corneal aberrations (higher-order aberrations, Coma0 and Coma90) (all P < 0.05). Generalized estimating equation revealed that age, SE, CDVA, OZ, and Coma0 were the main factors influencing postoperative CD values (all P < 0.05). Conclusion: CD manifested a long-term decreasing trend in moderate to high myopia treated with SMILE. Its main influencing factors are age, SE, CDVA, OZ, and Coma0.

Based on the survey data of 1707 high-quality farmers in Guangdong and Jiangxi provinces in China, this article uses the DEA-tobit model and propensity score matching method to explore the impact of water-saving technology adoption on agricultural production efficiency from a micro perspective. The research results show that the adoption of water-saving technology by high-quality farmers can significantly improve agricultural production efficiency. By comparing the results with the baseline regression using propensity score matching method, the study findings are found to be robust. The mechanism and results of the study indicate that agricultural subsidy policies play a regulatory role between water-saving technology adoption and the agricultural production efficiency of high-quality farmers. Further analysis reveals that the impact of water-saving technology on the production efficiency of different types of high-quality farmers varies. Specifically, water-saving technology has a greater impact on the production efficiency of farmer cooperatives and agricultural enterprises compared to large-scale farming households and family farms. Therefore, policy recommendations are proposed to improve the water-saving agricultural technology system, among other aspects.

Digital technology is shaping our traditional agriculture in unprecedented ways. As a new engine to empower farmers and promote common prosperity in rural areas, the development of the digital economy can help revitalize rural industries, providing strong support for increasing industrial value-added income and farmers' income levels. Based on 676 pooled cross-section data of high-quality farmers in China Guangdong Province from 2020-2021, the article empirically examines the impact of digital technology adoption on the production and business income of high-quality farmers and explores its mechanism of action, based on theoretical analysis and using the ERM model. It is found that the use of digital technology helps to increase the income of high quality farmers in production and business, but effects vary for different income levels and different types of high quality farmers. In addition, tests of the mechanism of action suggest that the introduction of digital technologies can mitigate the negative impact of market distance on the income of high quality farmers in production and business. After applying variable substitution, model replacement, and propensity score matching (PSM) for robustness checks, the research findings still hold true. Therefore, efforts should be made to speed up the upgrading of rural digital technology and other infrastructure, increase training for high quality farmers to improve their digital literacy through multiple channels, for the better marketing of agricultural products.

BackgroundActivated neutrophils release depolymerized chromatin and protein particles into the extracellular space, forming reticular Neutrophil Extracellular Traps (NETs). This process is accompanied by programmed inflammatory cell death of neutrophils, known as NETosis. Previous reports have demonstrated that NETosis plays a significant role in immune resistance and microenvironmental regulation in cancer. This study sought to characterize the function and molecular mechanism of NETosis-correlated long non-coding RNAs (NCLs) in the prognostic treatment of liver hepatocellular carcinoma (LIHC).MethodsWe obtained the transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and evaluated the expression of NCLs in LIHC. A prognostic signature of NCLs was constructed using Cox and Last Absolute Shrinkage and Selection Operator (Lasso) regression, while the accuracy of model was validated by the ROC curves and nomogram, etc. In addition, we analyzed the associations between NCLs and oncogenic mutation, immune infiltration and evasion. Finally, LIHC patients were classified into four subgroups based on consensus cluster analysis, and drug sensitivity was predicted.ResultsAfter screening, we established a risk model combining 5 hub-NCLs and demonstrated its reliability. Independence checks suggest that the model may serve as an independent predictor of LIHC prognosis. Enrichment analysis revealed a concentration of immune-related pathways in the high-risk group. Immune infiltration indicates that immunotherapy could be more effective in the low-risk group. Upon consistent cluster analysis, cluster subgroup 4 presented a better prognosis. Sensitivity tests showed the distinctions in therapeutic effectiveness among various drugs in different subgroups.ConclusionOverall, we have developed a prognostic signature that can discriminate different LIHC subgroups through the 5 selected NCLs, with the objective of providing LIHC patients a more precise, personalized treatment regimen.

IntroductionTobacco root-knot nematode (RKN) is a highly destructive soil-borne disease worldwide. However, there is a lack of research on the relationship between RKN and tobacco root microbial community composition under large-scale geographical conditions in China.MethodsIn this study, we collected 65 samples from 28 main tobacco-growing areas across 10 provinces in China and conducted 16S rDNA sequencing to investigate the dynamic microbial changes in tobacco soil infected by RKN compared to healthy tobacco soil. Based on the analysis of rhizosphere soil bacterial communities, changes after RKN infection, and soil environmental factors.ResultsWe found the 28 tobacco-growing areas could be divided into two distinct groups with different microbial compositions and varying responses to RKN infection. In group1 of the provinces of Anhui, Henan, Shanxi, and Heilongjiang, Vicinamibacteria dominated the bacterial community, while Acidobacteriae was present in low abundance. In contrast, group2 of the other six provinces (Yunnan, Guizhou, Chongqing, Guangxi, Hubei, and Shandong) exhibited an opposite pattern. After infected by RKN, the genera Chitinophaga increased significant in group 1, while the genera Rhodococcus in group 2 exhibited a substantial increase. Alpha-diversity analysis revealed that RKN-infected tobacco exhibited a richer and more diverse rhizosphere soil bacterial community compared to healthy tobacco in most growing areas. A total of 12 kinds of soil environmental factors were measured in healthy and RKN-infected tobacco soil, and based on the co-occurrence and correlation analysis between environmental factors and microbial species, the pH level, calcium (Ca), magnesium (Mg), phosphorus (P), iron (Fe), and sodium (Na) were identified as key environmental factors influencing the population composition of rhizosphere microorganisms during RKN infection. We observed that RKN infection further increased the pH in weakly alkaline group 1 soil, while weakly acidic group 2 soil experienced a further decrease in pH. Furthermore, we identified three genera as potential biocontrol or plant growth-promoting bacteria for tobacco.DiscussionThese findings provide valuable reference data for managing RKN disease in different tobacco-growing areas and contribute to the exploration of new and effective biological control methods.

Abstract Background Pelvic parameters have been taken into consideration for the evaluation of the outcomes of bracing in AIS. To discuss the stress required to correct the pelvic deformity related to Lenke5 adolescent idiopathic scoliosis (AIS) by finite element analysis, and provide a reference for the shaping of the pelvic region of the brace. Methods An three-dimensional (3D) corrective force on the pelvic area was defined. Computed tomography images were used to reconstruct a 3D model of Lenke5 AIS. Computer-aided engineering software Abaqus was used to implement finite element analysis. By adjusting the magnitude and position of corrective forces, coronal pelvic coronal plane rotation (PCPR) and Cobb angle (CA) of lumbar curve in the coronal plane, horizontal pelvic axial plane rotation, and apical vertebra rotation (AVR) were minimized to achieve the best effect on the spine and pelvic deformity correction. The proposed corrective conditions were divided into three groups: (1) forces applied on X-axis; (2) forces applied both in the X- and Y-axis; and (3) forces applied along the X-, Y-, and Z-axis at the same time. Results In three groups, CA correction reduced by 31.5%, 42.5%, and 59.8%, and the PCPR changed to 12°, 13°, and 1° from 6.5°, respectively. The best groups of correction forces should simultaneously locate on the sagittal, transverse, and coronal planes of the pelvis. Conclusions For Lenke5 AIS, 3D correction forces can sufficiently reduce scoliosis and pelvic asymmetrical state. Force applied along the Z-axis is vital to correct the pelvic coronal pelvic tilt associated with Lenke5 AIS.

Obesity is a multifactorial chronic metabolic disease with multiple complications. Crataegus pinnatifida (CP) and Wolfiporia extensa (WE) are traditional functional foods with improving metabolic health properties. This study demonstrated the effect of CP and WE combination on ameliorating obesity induced by a high-fat diet (HFD). Moreover, the CP-WE food pair ameliorated HFD-induced metabolic disorders, including glucose intolerance, insulin resistance, hyperlipidemia, and hepatic steatosis. 16S rRNA gene amplicon sequencing and analysis revealed that CP combined with WE reshaped the composition of gut microbiota in HFD-fed mice. Furthermore, correlation analysis revealed a substantial association between the obesity-related parameters and the shifts in predominant bacterial genera influenced by the food pair intervention. In conclusion, this study demonstrated that the CP-WE food pair ameliorated HFD-induced obesity and reshaped gut microbiota composition, providing a promising approach to combat obesity through specific food combinations.

The main production area of Camellia vietnamensis (C. vietnamensis) is in the low mountain and hilly areas of southern China. The low survival rate of seedlings caused by drought is one of the main obstacles restricting the development of the C. vietnamensis industry. An exploration of the key adaptation mechanism of C. vietnamensis to drought stress is important in order to improve its drought resistance. We conducted a study on the morphological, physiological, biochemical, and drought resistance-related genes of five C. vietnamensis cultivars grown in Hainan province under varying degrees of drought stress. The results indicate that drought stress can lead to a decrease in the relative water content and photosynthetic capacity of C. vietnamensis leaves. Compared with the control, the drought damage index, malondialdehyde, relative electrical conductivity, soluble protein, soluble sugar and proline contents of the five C. vietnamensis cultivars increased with drought-stress duration and degree. With increasing drought-stress intensity, the activity of antioxidant enzymes and the content of related metabolites (total polyphenols, total flavonoids, tea saponins) gradually increased, and the expression levels of phenylpropanoid pathway-related genes (Cv4CL1, CvCAD1, CvCAD2, CvPOX1, CvPOX2, CvPOX3) were upregulated. Based on the results of the drought tolerance coefficients, principal component analysis, and hierarchical cluster analysis, we classified five C. vietnamensis cultivars into drought-tolerant cultivars (‘Haida 1’); moderately drought-tolerant cultivars (‘Haida 4’ and ‘Wanhai 4’); and drought-sensitive cultivars (‘Wanhai 3’ and ‘Wanhai 1’). The results of this study provide a theoretical basis for the promotion and cultivation of C. vietnamensis and the selection of drought-resistant cultivars.

To further reveal the molecular mechanisms underlying the formation of continuous cropping disorders in patchouli, this study analyzed the function of calcium dependent protein kinase (CDPK) genes at the molecular level in patchouli continuous cropping disorders. The findings unveiled the presence of 45 PcCDPK genes within the complete patchouli genome dataset. These genes exhibited a range of molecular weights from 50.78 to 78.96 kDa and aliphatic index values spanning from 74.42 to 88.49, and are shown to be hydrophilic proteins. The evolution of 45 PcCDPK members was divided into 4 subfamilies, with a total of 65 pairs of collinear genes. Each PcCDPK contains a STKc-CAMK domain and four EF-hand structures exhibiting a certain degree of conservatism during evolution. Transcriptome data further supported the significance of PcCDPK25 and PcCDPK38 genes, showing substantial upregulation, which was corroborated by qRT-PCR results. The 1629 bp and 1716 bp CDS sequences were obtained by cloning the PcCDPK25 and PcCDPK38 genes, respectively, and subcellular localization showed that both proteins were localized on the plasma membrane. This comprehensive study provides molecular-level confirmation of the pivotal roles played by CDPK genes in the emergence of continuous cropping challenges in patchouli plants, establishing a crucial foundation for a deeper comprehension of the molecular mechanisms underpinning these obstacles.

Abstract Objective To study the biomechanical characteristics of various tissue structures of different sizes of 3D printed Cage in lumbar interbody fusion. Methods A finite element model of normal spine was reconstructed and verified. Pedicle screws and Cage of different sizes were implanted in the L4/5 segment to simulate lumbar interbody fusion. The range of motion of the fixed and cephalic adjacent segment, the stress of the screw-rod system, the stress at the interface between cage and L5 endplate, and intervertebral disc pressure of the adjacent segment were calculated and analyzed. Results The range of motion and intervertebral disc pressure of the adjacent segment of each postoperative model were larger than those of the intact model, but there was not much difference between them. The stress of cage-endplate interface was also larger than that of the intact model. However, the difference is that the stress of the endplate and the screw-rod system has a tendency to decrease with the increase of the axial area of cage. Conclusions Cage with larger axial area in lumbar interbody fusion can reduce the stress of internal fixation system and endplate, but will not increase the range of motion and intervertebral disc pressure of adjacent segment. It has a certain effect in preventing the cage subsidence, internal fixation system failure and screw rod fracture.

Abstract Background At present, research on spinal shortening is mainly focused on the safe distance of spinal shortening and the mechanism of spinal cord injury, but there is no research on the biomechanical characteristics of different shortening distances. The purpose of this study was to study the biomechanical characteristics of spine and internal fixation instruments at different shortening distances by the finite element (FE) method. Methods An FE model of lumbar L1-S was established and referred to the previous in vitro experiments to verify the rationality of the model by verifying the Intradiscal pressure (IDP) and the range of motion (ROM) of the motion segment. Five element models of spinal shortening were designed under the safe distance of spinal shortening, and the entire L3 vertebra and both the upper and lower intervertebral discs were resected. Model A was not shortened, while models B-E were shortened by 10%, 20%, 30% and 50% of the vertebral body, respectively. Constraining the ROM of the sacrum in all directions, a 7.5 N ·m moment and 280 N follower load were applied on the L1 vertebra to simulate the motion of the lumbar vertebrae in three planes. The ROM of the operated segments, the Von Mises stress (VMS) of the screw-rod system, the VMS of the upper endplate at the interface between the titanium cage and the L4 vertebral body, and the ROM and the IDP of the adjacent segment (L5/S) were recorded and analysed. Results All surgical models showed good stability at the operated segments (L1-5), with the greatest constraint in posterior extension (99.3-99.7%), followed by left-right bending (97.9-98.7%), and the least constraint in left-right rotation (84.9-86.3%) compared with the intact model. The VMS of the screw-rod system and the ROM and IDP of the distal adjacent segments of models A-E showed an increasing trend, in which the VMS of the screw-rod system of model E was the highest under flexion (172.5 MPa). The VMS of the endplate at the interface between the cage and L4 upper endplate of models A-E decreased gradually, and these trend were the most obvious in flexion, which were 3.03, 2.95, 2.83, 2.78, and 2.61 times that of the intact model, respectively. Conclusion When performing total vertebrae resection and correcting the spinal deformity, if the corrected spine has met our needs, the distance of spinal shortening should be minimized to prevent spinal cord injury, fracture of internal fixations and adjacent segment disease (ASD).

Abstract Background Advancements in medicine and the popularity of lumbar fusion surgery have made lumbar adjacent segment disease (ASDz) increasingly common, but there is no mature plan for guiding its surgical treatment. Therefore, in this study, four different finite element (FE) ASDz models were designed and their biomechanical characteristics were analysed to provide a theoretical basis for clinical workers to choose the most appropriate revision scheme for ASDz. Methods According to whether internal fixation was retained, different FE models were created to simulate ASDz revision surgery, and flexion, extension, axial rotation and lateral bending were simulated by loading. The biomechanical characteristics of the adjacent segments of the intervertebral disc and the internal fixation system and the range of motion (ROM) of the lumbar vertebrae were analysed. Results The difference in the ROM of the fixed segment between FE models that did or did not retain the original internal fixation was less than 0.1°, and the difference was not significant. However, the stress of the screw–rod system when the original internal fixation was retained and prolonged fixation was performed with dual-trajectory screws was less than that when the original internal fixation was removed and prolonged fixation was performed with a long bar. Especially in axial rotation, the difference between models A and B is the largest, and the difference in peak stress reached 30 MPa. However, for the ASDz revision surgery segment, the endplate stress between the two models was the lowest, and the intradiscal pressure (IDP) of the adjacent segment was not significantly different between different models. Conclusion Although ASDz revision surgery by retaining the original internal fixation and prolonging fixation with dual-trajectory screws led to an increase in stress in the fusion segment endplate, it provides stability similar to ASDz revision surgery by removing the original internal fixation and prolonging fixation with a long bar and does not lead to a significant change in the IDP of the adjacent segment while avoiding a greater risk of rod fracture.

BackgroundThe aim of this study was to investigate the diagnostic accuracy of KRAS mutation detection using plasma sample of patients with non-small cell lung cancer (NSCLC).MethodsDatabases of Pubmed, Embase, Cochrane Library, and Web of Science were searched for studies detecting KRAS mutation in paired tissue and plasma samples of patients with NSCLC. Data were extracted from each eligible study and analyzed using MetaDiSc and STATA.ResultsAfter database searching and screening of the studies with pre-defined criteria, 43 eligible studies were identified and relevant data were extracted. After pooling the accuracy data from 3341 patients, the pooled sensitivity, specificity and diagnostic odds ratio were 71%, 94%, and 59.28, respectively. Area under curve of summary receiver operating characteristic curve was 0.8883. Subgroup analysis revealed that next-generation sequencing outperformed PCR-based techniques in detecting KRAS mutation using plasma sample of patients with NSCLC, with sensitivity, specificity, and diagnostic odds ratio of 73%, 94%, and 82.60, respectively.ConclusionCompared to paired tumor tissue sample, plasma sample showed overall good performance in detecting KRAS mutation in patients with NSCLC, which could serve as good surrogate when tissue samples are not available.

Pogostemon cablin is a well-known protected species widely used in medicine and spices, however the underlying molecular mechanisms and metabolite dynamics of P. cablin flower development remain unclear due to the difficulty in achieving flowering in this species. A comparison of the transcriptome and widely targeted metabolome during P. cablin flower development was first performed in this study. Results showed that a total of 13,469 differentially expressed unigenes (DEGs) and 371 differentially accumulated metabolites (DAMs) were identified. Transcriptomic analysis revealed that the DEGs were associated with starch and sucrose metabolism, terpenoid biosynthesis and phenylpropanoid biosynthesis. Among these DEGs, 75 MIKC-MADS unigenes were associated with the development of floral organs. Gibberellins (GAs), auxin, and aging signaling might form a cross-regulatory network to regulate flower development in P. cablin. According to the metabolic profile, the predominant DAMs were amino acids, flavonoids, terpenes, phenols, and their derivatives. The accumulation patterns of these predominant DAMs were closely associated with the flower developmental stage. The integration analysis of DEGs and DAMs indicated that phenylpropanoids, flavonoids, and amino acids might be accumulated due to the activation of starch and sucrose metabolism. Our results provide some important insights for elucidating the reproductive process, floral organ, and color formation of P. cablin flowers at the molecular level. These results will improve our understanding of the molecular and genetic mechanisms involved in the floral development of P. cablin.

Abstract Artificial peroxisomes (APEXs) or peroxisome mimics have caught a lot of attention in nanomedicine and biomaterial science in the last decade, which have great potential in clinically diagnosing and treating diseases. APEXs are typically constructed from a semipermeable membrane that encloses natural enzymes or enzyme‐mimetic catalysts to perform peroxisome‐/enzyme‐mimetic activities. The recent rapid progress regarding their biocatalytic stability, adjustable activity, and surface functionality has significantly promoted APEXs systems in real‐life applications. In addition, developing a facile and versatile system that can simulate multiple biocatalytic tasks is advantageous. Here, the recent advances in engineering cell membrane‐cloaked catalysts as multifaceted APEXs for diverse biomedical applications are highlighted and commented. First, various catalysts with single or multiple enzyme activities have been introduced as cores of APEXs. Subsequently, the extraction and function of cell membranes that are used as the shell are summarized. After that, the applications of these APEXs are discussed in detail, such as cancer therapy, antioxidant, anti‐inflammation, and neuron protection. Finally, the future perspectives and challenges of APEXs are proposed and outlined. This progress review is anticipated to provide new and unique insights into cell membrane‐cloaked catalysts and to offer significant new inspiration for designing future artificial organelles.

Microbial communities are an important component of mangrove ecosystems. In order to reveal the diversity of endophytic fungi in the mangrove ferns Acrostichum speciosum and A. aureum in China, the internal transcribed spacer (ITS) regions of endophytic fungi in four plant tissues (leaves, petioles, roots, and rhizomes) from three locations (Zhanjiang, Haikou, and Wenchang) were sequenced. The richness, species composition, and community similarity were analyzed. The main results are as follows: the dominant fungi in A. speciosum and A. aureum belonged to the phyla Ascomycota and Basidiomycota, accounting for more than 75% of the total identified fungi; in terms of species composition at the operational taxonomic unit (OTU) level, the endophytic fungi in A. aureum were more diverse than those in A. speciosum, and the endophytic fungi in rhizomes were more diverse than in other tissues. In Zhanjiang, both A. speciosum and A. aureum showed the richest diversity of endophytic fungi, both at the OTU classification level and in terms of species composition. Conversely, the richness of endophytic fungi in the samples of A. speciosum from Wenchang and Haikou is extremely low. The regional differences in dominant fungi increase with the degrading of taxonomic levels, and there were also significant differences in the number of unique fungi among different origins, with Zhanjiang samples having a larger number of unique fungi than the other locations. There were significant differences in the dominant fungi among different tissues, with Xylariales being the dominant fungi in rhizomes of A. speciosum and Hypocreales being the dominant fungi in the petioles, roots, and rhizomes of A. aureum. Overall, the community similarity of endophytic fungi among locations is moderately dissimilar (26–50%), while the similarity between tissues is moderately similar (51–75%). The low diversity of endophytic fungi could be one of the main reasons for the endangerment of A. speciosum. The protection of the diversity of endophytic fungi in the underground parts of A. speciosum is essential for the conservation of this critically endangered mangrove fern.

Metabolic syndromes (MetS) and related cardiovascular diseases (CVDs) pose a serious threat to human health. MetS are metabolic disorders characterized by obesity, dyslipidemia, and hypertension, which increase the risk of CVDs’ initiation and development. Although there are many availabile drugs for treating MetS and related CVDs, some side effects also occur. Considering the low-level side effects, many natural products have been tried to treat MetS and CVDs. A five-cyclic triterpenoid natural product, oleanolic acid (OA), has been reported to have many pharmacologic actions such as anti-hypertension, anti-hyperlipidemia, and liver protection. OA has specific advantages in the treatment of MetS and CVDs. OA achieves therapeutic effects through a variety of pathways, attracting great interest and playing a vital role in the treatment of MetS and CVDs. Consequently, in this article, we aim to review the pharmacological actions and potential mechanisms of OA in treating MetS and related CVDs.

Abstract Background Spontaneous abortions (SA) is amongst the most common complications associated with pregnancy in humans, and the underlying causes cannot be identified in roughly half of SA cases. We found miR-135a-5p to be significantly upregulated in SA-associated villus tissues, yet the function it plays in this context has yet to be clarified. This study explored the function of miR-135a-5p and its potential as a biomarker for unexplained SA. Method RT-qPCR was employed for appraising miR-135a-5p expression within villus tissues with its clinical diagnostic values being assessed using ROC curves. The effects of miR-135a-5p in HTR-8/SVneo cells were analyzed via wound healing, Transwell, flow cytometry, EdU, CCK-8, and tube formation assays. Moreover, protein expression was examined via Western blotting, and interactions between miR-135a-5p and PTPN1 were explored through RIP-PCR, bioinformatics analyses and luciferase reporter assays. Results Relative to normal pregnancy (NP), villus tissue samples from pregnancies that ended in unexplained sporadic miscarriage (USM) or unexplained recurrent SA (URSA) exhibited miR-135a-5p upregulation. When this miRNA was overexpressed in HTR-8/SVneo cells, their migration, proliferation, and cell cycle progression were suppressed, as were their tube forming and invasive activities. miR-135a-5p over-expression also downregulated the protein level of cyclins, PTPN1, MMP2 and MMP9. In RIP-PCR assays, the Ago2 protein exhibited significant miR-135a-5p and PTPN1 mRNA enrichment, and dual-luciferase reporter assays indicated PTPN1 to be a bona fide miR-135a-5p target gene within HTR-8/SVneo cells. Conclusion miR-135a-5p may suppress trophoblast migratory, invasive, proliferative, and angiogenic activity via targeting PTPN1, and it may thus offer value as a biomarker for unexplained SA.

Casparian strip membrane domain protein-like (CASPL) genes are key genes for the formation and regulation of the Casparian strip and play an important role in plant abiotic stress. However, little research has focused on the members, characteristics, and biological functions of the patchouli PatCASPL gene family. In this study, 156 PatCASPL genes were identified at the whole-genome level. Subcellular localization predicted that 75.6% of PatCASPL proteins reside on the cell membrane. A phylogenetic analysis categorized PatCASPL genes into five subclusters alongside Arabidopsis CASPL genes. In a cis-acting element analysis, a total of 16 different cis-elements were identified, among which the photo-responsive element was the most common in the CASPL gene family. A transcriptome analysis showed that p-hydroxybenzoic acid, an allelopathic autotoxic substance, affected the expression pattern of PatCASPLs, including a total of 27 upregulated genes and 30 down-regulated genes, suggesting that these PatCASPLs may play an important role in the regulation of patchouli continuous cropping obstacles by affecting the formation and integrity of Casparian strip bands. These results provided a theoretical basis for exploring and verifying the function of the patchouli PatCASPL gene family and its role in continuous cropping obstacles.

The role that underwater image translation plays assists in generating rare images for marine applications. However, such translation tasks are still challenging due to data lacking, insufficient feature extraction ability, and the loss of content details. To address these issues, we propose a novel multi-scale image translation model based on style-independent discriminators and attention modules (SID-AM-MSITM), which learns the mapping relationship between two unpaired images for translation. We introduce Convolution Block Attention Modules (CBAM) to the generators and discriminators of SID-AM-MSITM to improve its feature extraction ability. Moreover, we construct style-independent discriminators that enable the discriminant results of SID-AM-MSITM to be not affected by the style of images and retain content details. Through ablation experiments and comparative experiments, we demonstrate that attention modules and style-independent discriminators are introduced reasonably and SID-AM-MSITM performs better than multiple baseline methods.

To overcome the shortcomings of available forward-secure identity-based signature （IBS） scheme in terms of actual practicability and secret key update efficiency， the notion of identity-based puncturable signature （IBPS） scheme was proposed based on the idea of puncturable public-key encryption scheme.Specifically， the syntax and security notion of IBPS were given， and then a concrete IBPS scheme was constructed based on Bloom filter.Under the computational Diffie-Hellman assumption， the proposed scheme achieved the existential unforgeability in the random oracle model.The performance analysis and implementation results demonstrate that， compared with traditional forward-secure IBS schemes， the proposed scheme provides more practical fine-grained forward secrecy， and has higher efficiency of secret key update.

Adult (3 month) mice with cardiac-specific overexpression of adenylyl cyclase (AC) type VIII (TGAC8) adapt to an increased cAMP-induced cardiac workload (~30% increases in heart rate, ejection fraction and cardiac output) for up to a year without signs of heart failure or excessive mortality. Here, we show classical cardiac hypertrophy markers were absent in TGAC8, and that total left ventricular (LV) mass was not increased: a reduced LV cavity volume in TGAC8 was encased by thicker LV walls harboring an increased number of small cardiac myocytes, and a network of small interstitial proliferative non-cardiac myocytes compared to wild type (WT) littermates; Protein synthesis, proteosome activity, and autophagy were enhanced in TGAC8 vs WT, and Nrf-2, Hsp90α, and ACC2 protein levels were increased. Despite increased energy demands in vivo LV ATP and phosphocreatine levels in TGAC8 did not differ from WT. Unbiased omics analyses identified more than 2,000 transcripts and proteins, comprising a broad array of biological processes across multiple cellular compartments, which differed by genotype; compared to WT, in TGAC8 there was a shift from fatty acid oxidation to aerobic glycolysis in the context of increased utilization of the pentose phosphate shunt and nucleotide synthesis. Thus, marked overexpression of AC8 engages complex, coordinate adaptation "circuity" that has evolved in mammalian cells to defend against stress that threatens health or life (elements of which have already been shown to be central to cardiac ischemic pre-conditioning and exercise endurance cardiac conditioning) that may be of biological significance to allow for proper healing in disease states such as infarction or failure of the heart.

Abstract This letter studies the secrecy performance for a two‐way integrated satellite terrestrial relay networks. Particularly, multiple legitimate users along with maximal user scheduling scheme are applied in the considered networks. In addition, the closed‐form expression for the secrecy outage probability of the considered two‐way networks is obtained. Moreover, to investigate the impacts of the system parameters on the secrecy performance in high signal‐to‐noise ratio regime, the asymptotic analysis for the secrecy outage probability is further derived. Finally, Monte Carlo simulation results are provided to prove the theoretical results.

Based on electrical power systems, leveraging renewable energy generation technology, and information technology, the energy internet fuses power grids, gas networks, heat/cold supply networks, electric transportation networks, etc. into an interconnected energy sharing network. The energy internet is an important technology for promoting renewable energy integration and improving energy efficiency. However, due to the complexity of multiple energy networks and the significant differences between them, the planning, operation, and control of energy internet presents several technical difficulties. Mainstream research only divides the complex system of energy internet into three systems: energy grid system, value creation system, and information support system. Under each system, how the State Grid Corporation of China develops related technologies has not been detailed, and the technical system framework composed of internal logical connection of each technical point is not yet mature. Based on general system structure theory, the technical system framework for the provincial power grid corporations to construct regional energy internet is constructed, and it proposes a technical route for the development of provincial energy internet based on local conditions in this paper. It can guide different affiliated companies in the field of energy internet technology that should be focused on research, and support the development of related technologies.

Abstract The thalassemia of Hemoglobin H-Constant Spring disease (HbH-CS) is the most common type of Thalassemia in non-transfusion thalassemia. Interestingly, the clinical manifestations of the same genotype of thalassemia can be vastly different, likely due to epigenetic regulation. Here, we used microarray technology to reveal the epigenetic regulation of m6A in modifiable diseases and demonstrated a role of BCL2A1 in disease regulation. In this study, we revealed that methylating enzyme writers including METTL16, WTAP, CBLL1, RBM15B, and ZC3H13 displayed low expression and the demethylating enzyme ALKBH5, along with reader proteins including IGF2BP2 and YTHDF3 exhibited high expression. In addition, BCL2A1 was hypo-methylated and showed low expression. We also revealed that the BCL2A1 methylation level and IGF2BP2 expression were negatively correlated. Additionally, the mRNAs expression between ALKBH5 and IGF2BP2 were positively correlated. In HbH-CS, most genes were hypo-methylated. This included BCL2A1, which may play an important role in the process of red blood cell differentiation and development of HbH-CS. Moreover, the mRNA-M6A methylation status may be regulated by the demethylating enzyme ALKBH5 via IGF2BP2.

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. MicroRNAs (miRNAs) are known to be important regulators of GC. This study aims to investigate the role of miRNA (miR)-497 in GC. We demonstrated that the expression of miR-497 was downregulated in human GC tissues. After N-methyl-N-nitrosourea treatment, the incidence of GC in miR-497 knockout mice was significantly higher than that in wild-type mice. miR-497 overexpression suppressed GC cell proliferation, cell-cycle progression, colony formation, anti-apoptosis ability, and cell migration and invasion capacity. Additionally, miR-497 overexpression decreased the expression levels of cell division cycle 42 (CDC42) and integrin β1 (ITGB1) and inhibited the phosphorylation of focal adhesion kinase (FAK), paxillin (PXN), and serine-threonine protein kinase (AKT). Furthermore, overexpression of miR-497 inhibited the metastasis of GC cells in vivo, which could be counteracted by CDC42 restoration. Furthermore, the focal adhesion of GC cells was found to be regulated by miR-497/CDC42 axis via ITGB1/FAK/PXN/AKT signaling. Collectively, it is concluded that miR-497 plays an important role in the repression of GC tumorigenesis and progression, partly via the CDC42/ITGB1/FAK/PXN/AKT pathway.

Burns can impair the barrier function of the skin, and small burns can also cause high mortality. The WHO has described that over 180,000 people die of burns worldwide each year. Thus, the treatment of burn wounds is a major clinical challenge. Chitooligosaccharides (COS) are alkaline amino oligosaccharides with small molecular weights obtained by enzyme or chemical degradation of chitosan. With the characteristics of biocompatibility, water solubility and degradability, it has attracted increasing attention in the fields of biomedicine. In the present study, we used COS to treat deep second-degree burn wounds of rat skin and found that COS was able to promote wound healing. We also revealed that COS could promote fibroblast proliferation. Transcriptome sequencing analysis was performed on COS-treated fibroblasts to identify the underlying mechanisms. The results showed that COS was able to promote wound healing through regulation of the mitogen-activated protein kinase (MAPK) pathway and growth factor Hepatocyte Growth Factor (HGF). Our results provide a potential drug for burn wound therapy and the related molecular mechanism.

PurposeTo investigate long-term trends in corneal densitometry and associated influencing factors following small incision lenticule extraction (SMILE).MethodsA comparative study was performed among 72 eyes of 38 patients undergoing SMILE. Eyes were divided into moderate myopia [mean spherical equivalent (SE),−4.22 ± 0.68D] and high myopia (mean SE,−7.63 ± 1.09 D) groups. Visual acuity, manifest refraction, corneal topography and corneal densitometry (CD) were evaluated preoperatively and 3 years postoperatively.ResultsThe efficacy indices at last postoperative follow-up (42.47 ± 0.51 months) were 0.92 ± 0.21 and 0.97 ± 0.22, the safety indices were 1.12 ± 0.17 and 1.14 ± 0.21 for high and moderate myopia, respectively (all P > 0.05). CD values in the 0–6 mm zone of the posterior corneal layer was statistically significantly lower than the preoperative values in both groups. Postoperative CD values (0–2 mm zone) in the posterior layer of the high myopia group were statistically significantly lower than in the moderate myopia group (P = 0.025); CD values (2–6 mm zone) in the anterior layer were higher in the high myopia group (P = 0.026). Correlation analyses showed that CD values in the 0–2 mm middle layer were negatively correlated with lenticule thickness in high myopia (r = −0.411, P = 0.016); there was a negative correlation between the CD values (0–6 mm) and corneal oblique trefoil in this group (P < 0.05).ConclusionCorneal transparency in the 0–6 mm zone of the posterior cornea increased following SMILE in moderate and high myopia. Long-term CD values in high myopia may be correlated with oblique trefoil and lenticule thickness.

Ferroptosis is closely associated with the pathophysiology of myocardial ischemia. Hydroxysafflor yellow A (HSYA), the main active ingredient in the Chinese herbal medicine safflower, exerts significant protective effects against myocardial ischemia/reperfusion injury (MI/RI). The aim of this study was to investigate the protective effects of HSYA against MI/RI and identify the putative underlying mechanisms. An in vivo model of acute MI/RI was established in C57 mice. Subsequently, the effects of HSYA on myocardial tissue injury were evaluated by histology. Lipid peroxidation and myocardial injury marker contents in myocardial tissue and serum and iron contents in myocardial tissue were determined using biochemical assays. Mitochondrial damage was assessed using transmission electron microscopy. H9C2 cardiomyocytes were induced in vitro by oxygen–glucose deprivation/reoxygenation, and ferroptosis inducer erastin was administered to detect ferroptosis-related indicators, oxidative-stress-related indicators, and expressions of ferroptosis-related proteins and HIF-1α. In MI/RI model mice, HSYA reduced myocardial histopathological damage, ameliorated mitochondrial damage in myocardial cells, and decreased total cellular iron and ferrous ion contents in myocardial tissue. HSYA increased the protein levels of SLC7A11, HIF-1α, and GPX4 and mitigated erastin- or HIF-1α siRNA-induced damage in H9C2 cells. In summary, HSYA alleviated MI/RI by activating the HIF-1α/SLC7A11/GPX4 signaling pathway, thereby inhibiting ferroptosis.

In this article, we studied the robust security transmission design for multi-user peer-to-peer relay networks, where all users demand secure communication and the eavesdropper is passive. Although the previous researches have designed the physical-layer security schemes under perfect channel state information, this study focuses on investigating the robust transmission design in the presence of a passive eavesdropper. Our goal is to maximize the artificial noise power to confuse the passive eavesdropper and subject to the worst-case signal-to-interference-noise-ratio constraints for all users under a bounded spherical region for the norm of the channel state information error vector from the relays to the destinations and the individual power constraints of all relay nodes. Mathematically, the original robust problem is difficult to solve due to its non-linearity and non-convexity. We propose to adopt S-Procedure and rank relaxation techniques to convert it to a semidefinite programming convex problem. The numerical results show the advantage of the proposed robust method.

Amino acid metabolism could exert regulatory effects on Monascus pigments (MPs) biosynthesis. In this work, MPs biosynthesis regulated by methionine and S-adenosylmethionine (SAM) was investigated in Monascus purpureus RP2. The results indicated that the addition of methionine in fermentation significantly reduced MPs production by 60–70%, and it induced a higher expression of SAM synthetase Mon2A2272 and consequently led to SAM accumulation. However, the addition of SAM in fermentation promoted MPs production by a maximum of 35%, while over-expression of the gene Mon2A2272 led to a decrease in MPs yield, suggesting that SAM synthetase and SAM were likely to play different regulatory roles in MPs biosynthesis. Furthermore, the gene transcription profile indicated that SAM synthetase expression led to a higher expression of the transcriptional regulatory protein of the MPs biosynthesis gene cluster, while the addition of SAM gave rise to a higher expression of MPs biosynthesis activator and the global regulator LaeA, which probably accounted for changes in MPs production and the mycelium colony morphology of M. purpureus RP2 triggered by methionine and SAM. This work proposed a possible regulation mechanism of MPs biosynthesis by SAM metabolism from methionine. The findings provided a new perspective for a deep understanding of MPs biosynthesis regulation in M. purpureus.

When a ship sailing on the sea encounters flooding events, quickly predicting the flooding time of the compartments in the damaged area is beneficial to making evacuation decisions and reducing losses. At present, decision-makers obtain flooding data through various sensors arranged on board to predict the time of compartment flooding. These data help with the calculation of the flooding time in emergency situations. This paper proposes a new approach to obtaining the compartment flooding time. Specifically in damage scenarios, based on Convolutional Neural Network and Recurrent Neural Network (CNN-RNN), using a composite neural network framework estimates the time when the compartment’s flooding water reaches the target height. The input of the neural network is the flooding images of the damaged compartment. Transfer learning is utilized in the paper. The ResNet18 model in Pytorch is used to extract the spatial information from the flooding images. The Long Short-Term Memory (LSTM) model is then applied to predict when the compartment flooding water reaches the target height. Experimental results show that, for the damaged compartment, the flooding time predicted by the neural network is 85% accurate while the others’ accuracy is more than 91%. Intuitively, when it comes to the actual flooding event, the composite neural network’s average prediction error for compartment flooding time is approximately 1 min. To summarize, these results suggest that the composite neural network proposed above can provide flooding information to assist decision-makers in emergency situations.

Semiconductor photocatalysis is an effective strategy for solving the problems of increasing energy demand and environmental pollution. ZnIn2S4-based semiconductor photocatalyst materials have attracted much attention in the field of photocatalysis due to their suitable energy band structure, stable chemical properties, and good visible light responsiveness. In this study, ZnIn2S4 catalysts were modified by metal ion doping, the construction of heterojunctions, and co-catalyst loading to successfully prepare composite photocatalysts. The Co-ZnIn2S4 catalyst synthesized by Co doping and ultrasonic exfoliation exhibited a broader absorption band edge. Next, an a-TiO2/Co-ZnIn2S4 composite photocatalyst was successfully prepared by coating partly amorphous TiO2 on the surface of Co-ZnIn2S4, and the effect of varying the TiO2 loading time on photocatalytic performance was investigated. Finally, MoP was loaded as a co-catalyst to increase the hydrogen production efficiency and reaction activity of the catalyst. The absorption edge of MoP/a-TiO2/Co-ZnIn2S4 was widened from 480 nm to about 518 nm, and the specific surface area increased from 41.29 m2/g to 53.25 m2/g. The hydrogen production performance of this composite catalyst was investigated using a simulated light photocatalytic hydrogen production test system, and the rate of hydrogen production by MoP/a-TiO2/Co-ZnIn2S4 was found to be 2.96 mmol·h−1·g−1, which was three times that of the pure ZnIn2S4 (0.98 mmol·h−1·g−1). After use in three cycles, the hydrogen production only decreased by 5%, indicating that it has good cycle stability.

The integrated energy system (IES) is an important energy supply method for mitigating the energy crisis. A station-and-network–coordinated planning method for the IES, which considers the integrated demand responses (IDRs) of flexible loads, electric vehicles, and energy storage is proposed in this work. First, based on load substitution at the user side, an energy-station model considering the IDR is established. Then, based on the characteristics of the energy network, a collaborative planning model is established for the energy station and energy network of the IES, considering the comprehensive system investment, operation and maintenance, and clean energy shortage penalty costs, to minimize the total cost. This can help optimize the locations of the power lines and natural gas pipelines and the capacities of the equipment in an energy station. Finally, simulations are performed to demonstrate that the proposed planning method can help delay or reduce the construction of new lines and energy-station equipment, thereby reducing the investment required and improving the planning economics of the IES.

This paper analyzes the network architecture of the Iridium system, Orbcomm system, Narrow Band-Internet of Things (NB-IoT) and Long Range Radio (Lo Ra) in the satellite 5G mobile communication system. A new Dynamic Routing based on Multi-factor Forwarding (MF-DR) protocol is proposed. This paper simulates the ladder-type data fusion algorithm in terms of energy consumption in the Wireless Sensor Network (WSN), the number of surviving nodes in the WSN, the communication traffic in the WSN, and the applicability of the ladder-type fusion algorithm. This verifies the superiority of the improved data fusion algorithm.