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Background and aims: The increasing incidence of cardiovascular diseases has created an urgent need for safe and effective anti-thrombotic agents. Leech, as a traditional Chinese medicine, has the effect of promoting blood circulation and removing blood stasis, but its real material basis and mechanism of action for the treatment of diseases such as blood stasis and thrombosis have not been reported.Methods: In this study, Whitmania Pigra Whitman (WPW), Hirudo nipponica Whitman (HNW) and Whitmania acranutata Whitman (WAW) were hydrolyzed by biomimetic enzymatic hydrolysis to obtain the active peptides of WPW (APP), the active peptides of HNW (APH) and the active peptides of WAW (APA), respectively. Then their structures were characterized by sykam amino acid analyzer, fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectrometer and LC-MS. Next, the anti-thrombotic activities of APP, APH and APA were determined by carrageenan-induced tail vein thrombosis model in mice, and the anti-thrombotic mechanisms of high-dose APP group (HAPP), high-dose APH group (HAPH) and high-dose APA group (HAPA) were explored based on UHPLC-Q-Exactive Orbitrap mass spectrometry.Results: The results showed that the amino acid composition of APP, APH and APA was consistent, and the proportion of each amino acid was few different. The results of FT-IR and CD showed that there were no significant differences in the proportion of secondary structures (such as β-sheet and random coil) and infrared absorption peaks between APP, APH and APA. Mass spectrometry data showed that there were 43 common peptides in APP, APH and APA, indicating that the three have common material basis. APP, APH and APA could significantly inhibit platelet aggregation, reduce black-tail length, whole blood viscosity (WBV), plasma viscosity (PV), and Fibrinogen (FIB), and prolong coagulation time, including activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT). In addition, 24 metabolites were identified as potential biomarkers associated with thrombosis development. Among these, 19, 23, and 20 metabolites were significantly normalized after administration of HAPP, HAPH, and HAPA in the mice, respectively. Furthermore, the intervention mechanism of HAPP, HAPH and HAPA on tail vein thrombosis mainly involved in linoleic acid metabolism, primary bile acid biosynthesis and ether lipid metabolism.Conclusion: Our findings suggest that APP, APH and APA can exert their anti-blood stasis and anti-thrombotic activities by interfering with disordered metabolic pathways in vivo, and there is no significant difference in their efficacies.

Casing connection is a common connection method in oil and gas reservoir production, and the tripping of casing will seriously hinder the production process. To study the casing tripping process and the minimum tensile load required for casing tripping under different loosening buckle states, three kinds of casing tripping tensile tests were carried out. The thread morphology of the casing head and casing coupling was analyzed by local cutting at the end of the experiment, and the thread failure area was analyzed by scanning electron microscope, and then other loosening states were studied and analyzed using numerical simulation. The research results show that as the number of loosening buckles increases, the minimum tensile load required for the casing head and casing coupling to trip decreases. The observation of the thread shape shows that the thread part of the casing head was seriously damaged. Scanning electron microscopy results show that the fracture mode at the thread of the casing head is ductile fracture. Numerical simulation results show that the maximum stress area during the tripping process is at the contact position between the thread heads. Based on the experimental and numerical simulation results, the relationship between the number of casing loosening and the minimum tensile load required for casing tripping is obtained. The research results can be used as the experimental and theoretical basis for the investigation of casing tripping accidents and can also provide experimental reference for the design of the next-generation of casing.

IntroductionThe deep-sea environment is always characterized by high hydrostatic pressure, fluctuating temperatures, heavy metals, darkness, and others. The Vesicomyidae inhabit cold seep zones, hydrothermal vents, and other chemically reduced environments.MethodsTo enhance the understanding of the adaptation mechanisms of clams in extreme environments, a comprehensive proteomic study was conducted on the cold seep clam Archivesica marissinica and shallow water clam Ruditapes philippinarum.ResultsA total of 4,557 proteins were identified from the comparative groups. The Gene Ontology results indicated that the differentially expressed proteins (DEP) for the comparative group Rpgill vs. Amgill were enriched in the nitrogen compound metabolic process, and others. The comparative analysis for Amfoot vs. Amgill and Ammantle vs. Amgill revealed significant enrichment of the differential proteins that were involved in metal ion transport, divalent inorganic cation transport, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the comparative group Rpgill vs. Amgill was significantly enriched in the regulation of actin cytoskeleton, lysosome, and others. The proteins that exhibited differential expression in the cold seep clam’ different tissues were also enriched in important pathways, such as lysosome, fatty acid degradation, nitrogen metabolism.DiscussionThe further analysis identified crucial response proteins involved in various biological pathways. For example, the pattern recognition receptors, such as galectin and peptidoglycan recognition protein, participated in recognition of symbiotic microorganisms. The lysosome pathway members, such as cathepsin and saposins, were engaged in the degradation process of symbiont proteins during symbiont digestion. Profilin and gelsolin from actin cytoskeleton pathway might be pressure-related proteins. Furthermore, carbonic anhydrases from nitrogen metabolism KEGG pathway provide inorganic carbon for symbiotic bacteria. Additionally, Mn superoxide dismutase plays a role in the scavenging of superoxide anion radicals and antioxidant activity. Then, arginine kinases facilitate the low temperature adaptation of deep-sea shellfish with its cold adaptation characters. These findings offer novel perspectives on the proteins that are implicated in A. marisica’s response to cold seep environments, thereby contributing to the understanding of deep-sea biological adaptation and the preservation of deep-sea ecosystems.

Eupolyphaga sinensis Walker (ESW) is a traditional Chinese medicine formulation used to treat hyperlipidemia. However, the hypolipidemic effect of the active peptides from E. sinensis Walker (APE) is incompletely understood. We studied the hypolipidemic effect of APE and explored the impact of APE on the gut microbiota (GM) in rats suffering from hyperlipidemia. APE was prepared by enzymatic digestion, and its structure was characterized using various methods. The anti-hyperlipidemic activity of APE was assessed using a high-fat diet (HFD)-induced model in zebrafish and rats. In rats, HFD administration caused abnormalities of lipid metabolism and disturbances of the GM and amino acid (AA) profile in plasma. The abundance of bacteria of the phyla Firmicutes and Bacteroides was increased significantly (p

Abstract Solar‐driven photodegradation for water treatment faces challenges such as low energy conversion rates, high maintenance costs, and over‐sensitivity to the environment. In this study, we develop reusable concave microlens arrays (MLAs) for more efficient solar photodegradation by optimizing light distribution. Concave MLAs with the base radius of ∼5 μm are fabricated by imprinting convex MLAs to polydimethylsiloxane elastomers. Concave MLAs possess a non‐contact reactor configuration, preventing MLAs from detaching or being contaminated. By precisely controlling the solvent exchange, concave MLAs are fabricated with well‐defined curvature and adjustable volume on femtoliter scale. The focusing effects of MLAs are examined, and good agreement is presented between experiments and simulations. The photodegradation efficiency of organic pollutants in water is significantly enhanced by 5.1‐fold, attributed to higher intensity at focal points of concave MLAs. Furthermore, enhanced photodegradation by concave MLAs is demonstrated under low light irradiation, applicable to real river water and highly turbid water.

The spatial variability of river hydrochemistry in coal-grain composite areas is influenced by natural processes and human activities. However, there is little information thus far on the hydrochemical characteristics of river water and the spatial variability in coal–grain composite areas under the influence of multiple superimposed effects. In this study, river water samples (n = 31) were collected in a coal-grain composite area in the northern plain of Anhui Province (China). The main hydrochemical ions and stable isotopes (δ2H-H2O, δ18O-H2O, δ34S-SO42- and δ18O-SO42-) were then investigated. The objective was to analyze the spatial characteristics and controlling indicators of the main hydrochemical ions via multivariate statistical and isotope analysis methods. The values of δ34S-SO42- and δ18O-SO42- in river water ranged from 7.5 ‰ to 17.5 ‰ and from 4.4 ‰ to 10.7 ‰, respectively. According to the clustering analysis method, the river water samples were divided into two groups. Bayesian mixed model analysis indicated that the sources of SO42- in river water mainly included soil sulfate and mine drainage, with contribution proportions of 74.0 ± 3.1 % and 18.4 ± 4.1 % in River Group I, respectively, and 77.2 ± 3.0 % and 11.1 ± 5.1 % in River Group II, respectively. These results suggested that the controlling indicators of the spatial distribution characteristics of river hydrochemistry were natural processes (water–rock interactions) and human activities (coal mining, manure release and sewage discharge). The results could provide valuable information for regional water resource management, development, and similar coal–grain composite areas elsewhere.

Abstract Purpose The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) and identify clinical risk factors associated with WMH. Experimental design This multiple‐center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non‐small cell lung cancer (NSCLC) who received or did not receive EGFR‐TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2‐year follow‐up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. Results Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR‐TKI and 92 (32%) patients with NSCLC without EGFR‐TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR‐TKI treatment was independently associated with the WMH progression (EGFR‐TKI: aRR 2.72, 95% confidence interval [CI] 1.46–5.06, p = .002). Interleukin (IL)‐2, IL‐4, and IL‐10 were associated with increased WMH in the adjusted model (IL‐2: aRR 1.55 [95% CI 1.06–2.25], p = .023; IL‐4: aRR 1.66 [95% CI 1.13–2.43], p = .010; IL‐10: aRR 1.48 [95% CI 1.06–2.06], p = .020). Conclusion Patients with NSCLC who received EGFR‐TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL‐2, IL‐4, and IL‐10 may be used as potential biomarkers to monitor the risk of increased WMH burden

BackgroundPrior epidemiological studies have established a correlation between inflammatory cytokines and inflammatory bowel disease (IBD). However, the nature of this relationship remains uncertain. Mendelian randomization (MR) study has the advantages of avoiding confounding and reverse causality compared with traditional observational research.ObjectiveWe aimed to evaluate whether genetically determined circulating levels of cytokines are associated with the risk of IBD by using the MR approach.Materials and methodsWe selected genetic variants associated with circulating levels of 28 cytokines at the genome-wide significance level from a genome-wide association study (GWAS) including 8,293 individuals. Summary-level data for IBD (including Crohn’s disease and ulcerative colitis) were obtained from the International Inflammatory Bowel Disease Genetics Consortium and UK Biobank. We performed the primary analysis using the inverse-variance weighted method, as well as sensitivity analyses to test the stability of our results. We subsequently replicated the results of IBD in the UK Biobank dataset. A reverse MR analysis was also conducted to evaluate the possibility of reverse causation.ResultsGenetically predicted elevated levels of interleukin-17 (IL-17) and monokine induced by interferon-gamma (MIG) were associated with an increased risk of IBD[odds ratio (OR): 1.52, 95% confidence interval (CI):1.10-2.08, P =0.010 for IL-17 and OR: 1.58, 95% CI: 1.24-2.00, P = 1.60×10-4 for MIG]. Moreover, we observed suggestive associations between β-NGF and MIP-1β with the risk of Crohn’s disease (OR: 0.71, 95% CI: 0.52-0.98, P = 0.039) and ulcerative colitis (OR: 1.08, 95% CI: 1.01-1.15, P= 0.019). In the reverse MR study, there was no evidence of causal effects of IBD and these cytokines.ConclusionOur study suggests the potential causal associations of IL-17 and MIG with IBD. Further studies are needed to determine whether IL-17 and MIG or their downstream effectors could be useful in the management of IBD.

Calcium-dependent protein kinases (CDPKs) are an important class of calcium-sensitive response proteins that play an important regulatory role in response to abiotic stresses. To date, little is known about the CDPK genes in white clover. White clover is a high-quality forage grass with high protein content, but it is susceptible to cold stress. Therefore, we performed a genome-wide analysis of the CDPK gene family in white clover and identified 50 members of the CDPK genes. Phylogenetic analysis using CDPKs from the model plant Arabidopsis divided the TrCDPK genes into four groups based on their sequence similarities. Motif analysis showed that TrCDPKs within the same group had similar motif compositions. Gene duplication analysis revealed the evolution and expansion of TrCDPK genes in white clover. Meanwhile, a genetic regulatory network (GRN) containing TrCDPK genes was reconstructed, and gene ontology (GO) annotation analysis of these functional genes showed that they contribute to signal transduction, cellular response to stimuli, and biological regulation, all of which are important processes in response to abiotic stresses. To determine the function of TrCDPK genes, we analyzed the RNA-seq dataset and found that most TrCDPK genes were highly up-regulated under cold stress, particularly in the early stages of cold stress. These results were validated by qRT-PCR experiments, implying that TrCDPK genes are involved in various gene regulatory pathways in response to cold stress. Our study may help to further investigate the function of TrCDPK genes and their role in response to cold stress, which is important for understanding the molecular mechanisms of cold tolerance in white clover and improving its cold tolerance.

Deep eutectic solvents (DES) doping is an important method to realize the preparation and modification of PEDOT:PSS films in aqueous solution, but there is no systematic research focusing on its action mechanism in polymerization process. A series of in-situ characterizations were conducted to investigate the effect of DES doping on properties and structure. The UV–Vis spectra indicated the DES doping can strengthen the π−π* stacking interaction and conjugation stabilization of PEDOT:PSS, and then lead to stronger photovoltaic conversion ability. The in situ FTIR spectra revealed the hydrogen bonds were incorporated into the polymer chain during polymerization process. The CV and SEM analysis results suggested that DES doping delayed passivation nucleation stage of PEDOT:PSS film in the thickness direction and remained a stable polymerization rate. The XPS spectra of S 2p proved DES doping decrease the interaction between PEDOT and PSS. Comprehensive experiments demonstrate that the structure-induced effects of DES can trigger structural reorganization in line conformation of PEDOT:PSS/DESs. It is structure-induced effects of DES that delays passivation nucleation stage in polymerization and improves the optical absorption contrast, maximum current density and some other properties efficently.

Objectives Hypertension is a chronic disease with multiple causative factors that involve metabolic disturbances and can cause various complications. However, the metabolic characteristics of hypertension at different stages are still unclear. This study aimed to explore the metabolic changes induced by hypertension at different ages. Methods Spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were divided into four groups according to age: 5-week-old SHR (n = 6), 5-week-old WKY rats (n = 6), 32-week-old SHR (n = 6), and 32-week-old WKY rats (n = 6). Metabolites were analyzed in primary tissues (serum, heart, lung, kidney, brain, and brown adipose) using a non-targeted metabolomics approach. Results Thirty-five metabolites and nine related metabolic pathways were identified in 5-week-old SHR, mainly related to the metabolism of amino acids. Fifty-one metabolites and seven related metabolic pathways were identified in the 32-week-old SHR, involving glycolysis, lipid, and amino acid metabolisms. Conclusion This experiment elucidates the metabolic profile of SHR at different ages and provides a basis for predicting and diagnosing hypertension. It also provides a reference for the pathogenesis of hypertension.

ABSTRACTThe adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Abstract Objectives Patients with vascular anomalies (VAs) who receive oral sirolimus may be at high risk of infectious complications. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) has been advocated. However, there have been few evidence-based analyses on this topic. This study assessed the effect of prophylactic TMP-SMZ on the incidence of infections in VA patients receiving sirolimus monotherapy. Methods A retrospective, multicenter chart review was performed on all VA patients receiving sirolimus treatment from August, 2013 to January, 2021. Results Before January 2017, 112 patients were treated with sirolimus without antibiotic prophylaxis. In the subsequent period, 195 patients were treated with TMP-SMZ for at least 12 months during sirolimus therapy. The percentage of patients with at least one serious infection during the initial 12 months of sirolimus treatment did not differ between the groups (difference, 1.1%; 95% CI − 7.0–8.0%). We observed no difference in the incidence of individual infection or total adverse events between the groups. The rate of sirolimus discontinuation due to adverse events did not differ significantly between groups. Conclusions We demonstrated that prophylactic TMP-SMZ does not decrease the incidence of infection or improve tolerance in VA patients receiving sirolimus monotherapy.

Abstract Background As the rate of multiple pregnancies increases, delayed interval delivery (DID) is increasingly being implemented to improve perinatal outcomes. But there are no international guidelines for DID in multiple pregnancies. We report a case of DID in a quadruplet pregnancy and review the relevant literature to summarize the management of DID in multiple pregnancies. Case presentation A 22-year-old woman, 22 2/7 weeks' gestation, with quadruplets, was admitted to the hospital for a first cervical cerclage due to cervical dilation. Twenty-five days later, it was found that the cervix was dilated again, so after removing the cervical cerclage, the first quadruplet was delivered vaginally (25 6/7 weeks), and a second cervical cerclage was performed. Four days later, due to re-dilation of the cervix, after removal of the cervical cerclage, the second quadruplet was delivered vaginally (26 3/7 weeks), followed by a third cervical cerclage. Six days later, the pregnancy was terminated by cesarean section due to fetal distress, and the third and fourth quadruplets were delivered (27 2/7 weeks). The patient had no postoperative complications, and all four infants were treated in the neonatal intensive care unit and discharged successfully. Conclusion This case emphasizes that comprehensive management of delayed interval delivery can improve perinatal outcomes in multiple pregnancies, including anti-infection, tocolytic therapy, practice to promote fetal lung, and cervical cerclage.

Abstract Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.

Abstract Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infants, with distinct disease stages and durations. Despite the fact that the majority of IHs can regress spontaneously, a small percentage can cause disfigurement or even be fatal. The mechanisms underlying the development of IH have not been fully elucidated. Establishing stable and reliable IH models provides a standardized experimental platform for elucidating its pathogenesis, thereby facilitating the development of new drugs and the identification of effective treatments. Common IH models include the cell suspension implantation model, the viral gene transfer model, the tissue block transplantation model, and the most recent three-dimensional (3D) microtumor model. This article summarizes the research progress and clinical utility of various IH models, as well as the benefits and drawbacks of each. Researchers should select distinct IH models based on their individual research objectives to achieve their anticipated experimental objectives, thereby increasing the clinical relevance of their findings.

Abstract Prostate cancer (PCa) is the second most prevalent malignancy in males across the world. A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa. Herein, we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients, including gene mutations, mRNA/protein/surface protein distributions, and pharmaceutical responses. The multi-omics analyses identify Anterior Gradient 2 (AGR2) as a pre-operative prognostic biomarker in PCa. Through the drug library screening, we describe crizotinib as a selective compound for malignant PCa primary cells. We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations. Surprisingly, the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model. Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses, allowing for more precise diagnosis and therapies.

Abstract Background Non-involuting congenital hemangiomas (NICHs) are fully formed vascular tumors at birth with distinctive clinical, radiologic, and histopathological profiles. In the literature, there is no effective therapy strategy for patients with NICH except surgery. Currently, no cell line or animal model exists for studying the mechanism of NICH and drug validation. We plan to construct a new strategy by constructing NICH organoids for further study. Result Here, we report a novel NICH organoid system construction and optimization process. Both HE and immunohistological staining exactly matched NICH tissue. We further performed transcriptome analysis to elucidate the characteristics of NICH organoids. Both NICH tissue and NICH organoids manifested similar trends in download sites. NICH organoids display novel features to new cells derived from organoids and show spectacular multiplication capacity. In the preliminary verification, we found that cells splitting from NICH organoids were human endothelial cells. Drug validation demonstrated that trametinib, sirolimus, and propranolol showed no inhibitory effects on NICH organoids. Conclusion Our data show that this new NICH-derived organoid faithfully captured the features of this rare vascular tumor. Our study will boost further research on the mechanism of NICH and drug filtering in the future.

Abstract Background The triglyceride-glucose (TyG) index, a simple measure of insulin resistance, is associated with intracranial atherosclerosis (ICAS) and stroke. In hypertensive populations, this association may be pronounced. The aim was to investigate the relationship between TyG and symptomatic intracranial atherosclerosis (sICAS) and recurrence risk in ischemic stroke patients with hypertension. Methods This prospective, multicenter cohort study included patients with acute minor ischemic stroke with a preadmission diagnosis of hypertension from September 2019 to November 2021 with a 3-month follow-up. The presence of sICAS was determined by a combination of clinical manifestations, the location of the infarction, and the corresponding artery with moderate-to-severe stenosis. ICAS burden was determined by the degree and number of ICAS occurrences. Fasting blood glucose (FBG) and triglyceride (TG) were measured to calculate TyG. The main outcome was ischemic stroke recurrence during the 90-day follow-up. Multivariate regression models were used to explore the association of TyG, sICAS, and ICAS burden with stroke recurrence. Results There were 1281 patients with a mean age of 61.6 ± 11.6 years; 70.1% were male, and 26.4% were diagnosed with sICAS. There were 117 patients who experienced stroke recurrence during follow-up. Patients were categorized according to quartiles of TyG. After adjusting for confounders, the risk of sICAS was greater (OR 1.59, 95% CI 1.04–2.43, p = 0.033) and the risk of stroke recurrence was significantly higher (HR 2.02, 95% CI 1.07–3.84, p = 0.025) in the fourth TyG quartile than in the first quartile. The restricted cubic spline (RCS) plot revealed a linear relationship between TyG and sICAS, and the threshold value for TyG was 8.4. Patients were then dichotomized into low and high TyG groups by the threshold. Patients with high TyG combined with sICAS had a higher risk of recurrence (HR 2.54, 95% CI 1.39–4.65) than patients with low TyG without sICAS. An interaction effect on stroke recurrence between TyG and sICAS was found (p = 0.043). Conclusion TyG is a significant risk factor for sICAS in hypertensive patients, and there is a synergistic effect of sICAS and higher TyG on ischemic stroke recurrence. Trial registration number: The study was registered on 16 August 2019 at https://www.chictr.org.cn/showprojen.aspx?proj=41160 (No. ChiCTR1900025214).

Abstract Hypertension is a global public health issue and the leading cause of premature death in humans. Despite more than a century of research, hypertension remains difficult to cure due to its complex mechanisms involving multiple interactive factors and our limited understanding of it. Hypertension is a condition that is named after its clinical features. Vascular function is a factor that affects blood pressure directly, and it is a main strategy for clinically controlling BP to regulate constriction/relaxation function of blood vessels. Vascular elasticity, caliber, and reactivity are all characteristic indicators reflecting vascular function. Blood vessels are composed of three distinct layers, out of which the endothelial cells in intima and the smooth muscle cells in media are the main performers of vascular function. The alterations in signaling pathways in these cells are the key molecular mechanisms underlying vascular dysfunction and hypertension development. In this manuscript, we will comprehensively review the signaling pathways involved in vascular function regulation and hypertension progression, including calcium pathway, NO-NOsGC-cGMP pathway, various vascular remodeling pathways and some important upstream pathways such as renin-angiotensin-aldosterone system, oxidative stress-related signaling pathway, immunity/inflammation pathway, etc. Meanwhile, we will also summarize the treatment methods of hypertension that targets vascular function regulation and discuss the possibility of these signaling pathways being applied to clinical work.

Abstract As the particularly popular green energy, geothermal resources are gradually favored by countries around the world, and the development model centered on geothermal dew point cannot meet the increasing geothermal demand. In this paper, a GIS model combining PCA and AHP is proposed, aiming to select the advantages of geothermal resources at the regional scale and analyze the main influencing indicators. Through the combination of the two methods, both data and empirical can be considered, then the geothermal advantage distribution on the area can be displayed through GIS software images. A multi-index evaluation system is established to qualitatively and quantitatively evaluate the mid-high temperature geothermal resources in Jiangxi Province, and carry out the evaluation of the dominant target areas and the analysis of geothermal impact indicators. The results show that it is divided into 7 geothermal resource potential areas and 38 geothermal advantage targets, and the determination of deep fault is the most critical index of geothermal distribution. This method is suitable for large-scale geothermal research, multi-index and multi-data model analysis and precise positioning of high-quality geothermal resource targets, which can meet the needs of geothermal research at the regional scale.

Path planning for an unmanned vehicle in an off-road uncertain environment is important for navigation safety and efficiency. Regarding this, a global improved A* algorithm is presented. Firstly, based on remote sensing images, the artificial potential field method is used to describe the distribution of risk in the uncertain environment, and all types of ground conditions are converted into travel time costs. Additionally, the improvements of the A* algorithm include a multi-directional node search algorithm, and a new line-of-sight algorithm is designed which can search sub-nodes more accurately, while the risk factor and the passing-time cost factor are added to the cost function. Finally, three kinds of paths can be calculated, including the shortest path, the path of less risk, and the path of less time-cost. The results of the simulation show that the improved A* algorithm is suitable for the path planning of unmanned vehicles in a complex and uncertain environment. The effectiveness of the algorithm is verified by the comparison between the simulation and the actual condition verification.

Acinetobacter baumannii has developed multiple drug resistances, posing a significant threat to antibiotic efficacy. LysECD7, an endolysin derived from phages, could be a promising therapeutic agent against multi-drug resistance A. baumannii. In this study, in order to further enhance the antibacterial efficiency of the engineered LysECD7, a few lipopolysaccharide-interacting peptides (Li5, MSI594 and Li5-MSI) were genetically fused with LysECD7. Based on in vitro antibacterial activity, the fusion protein Lys-Li5-MSI was selected for further modifications aimed at extending its half-life. A cysteine residue was introduced into Lys-Li5-MSI through mutation (Lys-Li5-MSIV12C), followed by conjugation with a C16 fatty acid chain via a protonation substitution reaction(V12C-C16). The pharmacokinetic profile of V12C-C16 exhibited a more favorable characteristic in comparison to Lys-Li5-MSI, thereby resulting in enhanced therapeutic efficacy against lethal A. baumannii infection in mice. The study provides valuable insights for the development of novel endolysin therapeutics and proposes an alternative therapeutic strategy for combating A. baumannii infections.

In this work, the evolution of mechanical properties of binary Al–Li alloys with four approximately equal gradient Li contents (0.91–3.98 wt.%) under aging conditions is thoroughly investigated. The alloys undergo aging treatments at 175 °C for x hours (x = 0–120 h), and the peak-aged times of the four alloys are 6 h, 12 h, 48 h and 48 h, respectively, as the Li concentration increases. Both in the solution-treated and peak-aged states, the elastic modulus of binary Al–Li alloys exhibits an approximately linear increase with increasing Li content, consistent with trends predicted by density functional theory (DFT) calculations. Due to the presence of Al3Li precipitates, the modulus of higher-Li-concentration alloys in the peak-aged state increases by approximately 1.4–2.5% compared with that of alloys in the solution-treated state. Additionally, the study finds that increasing Li content significantly enhances the tensile strength and yield strength of the alloy but decreases its ductility, leading to a transition in fracture mode from ductile to brittle, as evidenced by a microscopic analysis of fracture surfaces. Under peak-aged (175 °C/48 h), the alloy with the highest Li content exhibits the maximum tensile strength of 341 MPa and a yield strength of 296 MPa, while its elongation is the lowest at 2.1%. These findings contribute to a deeper understanding of the effects of aging precipitates on the mechanical properties of Al–Li alloys, providing fundamental guidance for the design of future generations of Al–Li alloys.

All-silicon terahertz absorbers have attracted considerable interest. We present a design and numerical study of an all-silicon polarization-insensitive terahertz metamaterial absorber. The meta-atoms of the metamaterial absorber are square silicon rings which can be viewed as gratings. By properly optimizing the structure of the meta-atom, we achieve a broadband absorptivity that is above 90% ranging from 0.77 THz to 2.53 THz, with a relative bandwidth of 106.7%. Impedance matching reduces the reflection of the terahertz waves and the (0, ±1)-order diffraction induce the strong absorption. The absorption of this absorber is insensitive to the polarization of the terahertz wave and has a large incident angle tolerance of up to 60 degrees. The all-silicon metamaterial absorber proposed here provides an effective way to obtain broadband absorption in the terahertz regime. Metamaterial absorbers have outstanding applications in terahertz communication and imaging.

In this paper, we construct an academic literature knowledge graph based on the relationship between documents to facilitate the storage and research of academic literature data. Keywords are an important type of node in the knowledge graph. To solve the problem that there are no keywords in some documents for several reasons in the process of knowledge graph construction, an improved keyword extraction algorithm called TP-CoGlo-TextRank is proposed by using word frequency, position, word co-occurrence frequency, and a word embedding model. By combining the word frequency and position in the document, the importance of words is distinguished. By introducing the GloVe word-embedding model, which brings the external knowledge of documents into the TextRank algorithm, and combining the internal word co-occurrence frequency in the documents, the word-adjacency relationship is transferred non-uniformly. Finally, the words with the highest scores are combined into phrases if they are adjacent in the original text. The validity of the TP-CoGlo-TextRank algorithm is verified by experiments. On this basis, the Neo4j graph database is used to store and display the academic literature knowledge graph, to provide data support for research tasks such as text clustering, automatic summarization, and question-answering systems.

Trueperella pyogenes can cause various infections in the organs and tissues of different livestock (including pigs, cows, goats, and sheep), including mastitis, endometritis, pneumonia, or abscesses. Moreover, diseases induced by T. pyogenes cause significant economic losses in animal husbandry. In recent large-scale investigations, T. pyogenes has been identified as one of the main pathogens causing endometritis in lactating cows. However, the main treatment for the above-mentioned diseases is still currently antibiotic therapy. Understanding the impact of endometritis associated with T. pyogenes on the fertility of cows can help optimize antibiotic treatment for uterine diseases, thereby strategically concentrating the use of antimicrobials on the most severe cases. Therefore, it is particularly important to continuously monitor the prevalence of T. pyogenes and test its drug resistance. This study compared the uterine microbiota of healthy cows and endometritis cows in different cattle farms, investigated the prevalence of T. pyogenes, evaluated the genetic characteristics and population structure of isolated strains, and determined the virulence genes and drug resistance characteristics of T. pyogenes. An amount of 186 dairy cows were involved in this study and 23 T. pyogenes strains were isolated and identified from the uterine lavage fluid of dairy cows with or without endometritis.

With the development of society, there is an increasingly urgent demand for light-weight, high-strength, and high-temperature-resistant structural materials. High-entropy alloys (HEAs) owe much of their unusual properties to the selection among three phases: solid solution (SS), intermetallic compound (IM), and mixed SS and IM (SS and IM). Therefore, accurate phase prediction is crucial for guiding the selection of element combinations to form HEAs with desired properties. Light high-entropy alloys (LHEAs), as a significant branch of HEAs, exhibit excellent performance in terms of specific strength. In this study, we employ a machine learning (ML) method to realize the design of light-weight high-entropy alloys based on solid solutions. We determined the Gradient Boosting Classifier model as the best machine learning model through a two-step feature and model selection, in which its accuracy and F1_Score achieve 0.9166 and 0.8923. According to the predicted results, we obtained Al28Li35Mg15Zn10Cu12 LHEAs, which are mainly composed of 90% solid solution. This alloy accords with the prediction results of machine learning. But it is made up of a two-phase solid solution. In order to obtain a light-weight high-entropy alloy dominated by a single solid solution, we designed Al24Li15Mg26Zn9Cu26 LHEAs on the basis of machine learning prediction results accompanied by expert experience. Its main structure includes a single-phase solid solution. Our work provides an alternative approach to the computational design of HEAs and provides a direction for future exploration of light-weight high-entropy alloys.

To address the issues of signal waveform distortion and inter-symbol interference, both of which lead to performance degradation in airborne laser communication due to multipath transmission in airborne air-to-air channels, theoretical analysis and Monte Carlo ray tracing (MCRT) simulation methods were employed. Based on airborne application conditions, this research conducted numerical simulations of the Gaussian beam multipath transmission in an air-to-air channel, with a focus on analyzing the impact of meteorological conditions, communication distance, transmitter power, and initial pulse width on the pulse time spreading characteristics of received optical signals. In addition, an analysis of these parameters’ impact on the inter-symbol interference (ISI) and bit error rate (BER) was conducted. The research findings can serve as a reference for the design of anti-interference techniques in airborne laser communication links.

Defined benefit (DB) pension plans are a primary type of pension schemes with the sponsor assuming most of the risks. Longevity-indexed bonds have been used to hedge or transfer risks in pension plans. Our objective is to study an aggregated DB pension plan’s optimal risk management problem focusing on minimizing the solvency risk over a finite time horizon and to investigate the investment strategies in a market, comprising a longevity-indexed bond and a risk-free asset, under stochastic nominal interest rates. Using the dynamic programming technique in the stochastic control problem, we obtain the closed-form optimal investment strategy by solving the corresponding Hamilton–Jacobi–Bellman (HJB) equation. In addition, a comparative analysis implicates that longevity-indexed bonds significantly reduce solvency risk compared to zero-coupon bonds, offering a strategic advantage in pension fund management. Besides the closed-form solution and the comparative study, another novelty of this study is the extension of actuarial liability (AL) and normal cost (NC) definitions, and we introduce the risk neutral valuation of liabilities in DB pension scheme with the consideration of mortality rate.

Alcohol-associated liver disease (ALD) is a condition that develops due to prolonged and excessive alcohol consumption. It encompasses various stages of liver damage, including fatty liver, alcoholic hepatitis, and cirrhosis. Immune cells, particularly macrophages, of various types play a significant role in the onset and progression of the disease. Macrophages observed in the liver exhibit diverse differentiation forms, and perform a range of functions. Beyond M1 and M2 macrophages, human macrophages can polarize into distinct phenotypes in response to various stimuli. Recent advancements have improved our understanding of macrophage diversity and their role in the progression of ALD. This mini-review provides a concise overview of the latest findings on the role and differentiation of macrophages in ALD. Additionally, it discusses potential therapeutic targets associated with macrophages and explores potential therapeutic strategies.

Since it may be employed to guide the production of high-quality plant protein as a partial substitute for animal protein using sono-physico-chemical effects, it is important to investigate the mixing of animal and plant protein in ultrasound (UID)-assisted processing systems. A study group of sono-physico-chemical processing with five distinct soy protein isolate (SPI)/ sarcoplasmic protein (SPN) ratios was developed in this work. The results showed that adding additional SPN to the mixed protein can increase its sono-physico-chemical impact, and this effect is greatest when the ratio of SPI to SPN is 1:3. The high SPN group's grafting rate rose from 39.13% to 55.26% in comparison to the high SPI content group. Quercetin (Que) may more readily modify SPN than SPI in the “dual protein” system used in this work, highlighting the critical function of plant protein in controlling the effects of UID-assisted processing in the “dual protein” system. Changes in apparent viscosity and microstructure are the primary parameters that affect the severity of sono-physico-chemical effects in SPI/SPN mixed protein systems, in addition to structural variables.

IntroductionThe intestinal microbiota participates in host physiology and pathology through metabolites, in which short-chain fatty acids (SCFAs) are considered principal products and have extensive influence on intestine homeostasis. It has been reported that skin ulceration syndrome (SUS), the disease of Apostichopus japonicus caused by Vibrio splendidus, is associated with the alteration of the intestinal microbiota composition.MethodTo investigate whether the intestinal microbiota affects A. japonicus health via SCFAs, in this study, we focus on the SCFA profiling and intestinal barrier function in A. japonicus treated with V. splendidus.Results and discussionWe found that V. splendidus could destroy the mid-intestine integrity and downregulate the expression of tight junction proteins ZO-1 and occludin in A. japonicus, which further dramatically decreased microorganism abundance and altered SCFAs contents. Specifically, acetic acid is associated with the largest number of microorganisms and has a significant correlation with occludin and ZO-1 among the seven SCFAs. Furthermore, our findings showed that acetic acid could maintain the intestinal barrier function by increasing the expression of tight junction proteins and rearranging the tight junction structure by regulating F-actin in mid-intestine epithelial cells. Thus, our results provide insights into the effects of the gut microbiome and SCFAs on intestine barrier homeostasis and provide essential knowledge for intervening in SUS by targeting metabolites or the gut microbiota.

Abstract The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS‐CoV‐2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID‐19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S‐82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10‐3), were closely associated with the presence of SARS‐CoV‐2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID‐19 cases in 2020, S82‐IgG titers were higher in NAbs‐positive samples (p = 0.002) than in NAbs‐negative samples using enzyme‐linked immunosorbent assay. We further collected 66 plasma samples from another cohort infected by Omicron BA.1 virus in 2022. Compared with the samples with lower S82‐IgG titers, NAb titers were significantly higher in the samples with higher S82‐IgG titers (p = 0.04). Our findings provide insights into the understanding of the decay‐associated signatures of SARS‐CoV‐2 NAbs.

It is critical to increase the cooling channel's thermal-hydraulic performance for the sake of hot component safety and lowering power consumption during fluid transport. In this work, a hybrid V-shaped and spherical dimple structure is designed and numerically analysed to evaluate the heat transfer and fluid flow features in the rectangular cooling channel when the Reynolds number is 8500-50,000. The thermal-hydraulic performances of the cooling channel are compared with the spherical dimple only, the V-shaped dimple only, and the hybrid V-shaped and spherical dimple structure, and the effect of the spacing between the V-shaped dimple and spherical dimple in the hybrid V-shaped and spherical dimple structure on the fluid flow and heat transfer is also investigated. The findings show that the presence of longitudinal vortexes originating from the V-shaped dimple effectively eliminates the recirculation zone in the spherical dimple of the hybrid V-shaped and spherical dimple structure. Consequently, this leads to an improvement in heat transfer within the channel featuring the hybrid V-shaped and spherical dimple structure. Compared with spherical dimple only and V-shaped dimple only, the performance evaluation index of the hybrid V-shaped and spherical dimple structure under equal pumping power increases by up to 11.9% and 13.3%, respectively.

The taxonomic composition and abundance of phytoplankton have a direct impact on marine ecosystem dynamics and global environment change. Phytoplankton classification is crucial for phytoplankton analysis, but it is challenging due to their large quantity and small size. Machine learning is the primary method for automatically performing phytoplankton image classification. As large-scale research on marine phytoplankton generates overwhelming amounts of data, more powerful computational resources are required for the success of machine learning methods. Recently, quantum machine learning has emerged as a potential solution for large-scale data processing by harnessing the exponentially computational power of quantum computers. Here, for the first time, we demonstrate the feasibility of using quantum deep neural networks for phytoplankton classification. Hybrid quantum-classical convolutional and residual neural networks are developed based on the classical architectures. These models strike a balance between the limited function of current quantum devices and the large size of phytoplankton images, making it possible to perform phytoplankton classification on near-term quantum computers. Our quantum models demonstrate superior performance compared to their classical counterparts, exhibiting faster convergence, higher classification accuracy and lower accuracy fluctuation. The present quantum models are versatile and can be applied to various tasks of image classification in the field of marine science.

Background The growth of urbanization in the 20th and 21st centuries has resulted in unprecedented ecological security issues. The imbalance between urban development and internal ecological security is a growing concern. Methods Based on the urban development process and the characteristics of ecosystem resilience, the corresponding urbanization evaluation system (“scale-structure-benefit”) and ecosystem resilience assessment model (“resistance-adaptability-restoring”) were constructed to explore the changes in each dimension as well as to analyze the spatial and temporal changes and driving effects of the coupled coordination level of urbanization and ecological resilience using the coupled coordination degree (CCD) model and geographically and temporally weighted regression (GTWR). Results (1) From 2005 to 2020, urbanization levels increased (from 0.204 to 0.264, respectively), whereas the level of ecological resilience gradually decreased (from 0.435 to 0.421, respectively). The spatial distribution of urbanization is rather steady, with a “high-northeast low-southwest” pattern of regional distribution; however, the spatial distribution pattern of ecological resilience is essentially the reverse. (2) During the study period, there was an improvement in the level of coordination between urbanization and ecological resilience, with an increase from 0.524 to 0.540. However, the main coordination type remained the same, with over 46% being at the basic coordination stage. The relative development type was dominated by the lagging urbanization stage, with the lagging ecological resilience and synchronous development stages accounting for a smaller proportion, and the space was distributed in a block-like cluster. (3) The running results of the GTWR show that the core dimensions of the whole region are scale, benefit, and structure, and the impact of each dimension shows obvious spatial heterogeneity. Cities with different levels of relative development also have different central dimensions. This research will provide support for the coordination of urban development in areas where economic construction and ecological resilience are not coordinated, and will contribute to the sustainable development of urban areas.

ImportanceEarly neurological deterioration (END) is a critical complication in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT), with a need for reliable prediction tools to guide clinical interventions.ObjectiveThis study aimed to develop and validate a rating scale, utilizing clinical variables and multisystem laboratory evaluation, to predict END after IVT.Design, setting, and participantsThe Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke (TRAIS) cohort enrolled consecutive AIS patients from 14 stroke centers in China (Jan 2018 to Jun 2022).OutcomesEND defined as NIHSS score increase >4 points or death within 24 h of stroke onset.Results1,213 patients (751 in the derivation cohort, 462 in the validation cohort) were included. The CNS-LAND score, a 9-point scale comprising seven variables (CK-MB, NIHSS score, systolic blood pressure, LDH, ALT, neutrophil, and D-dimer), demonstrated excellent differentiation of END (derivation cohort C statistic: 0.862; 95% CI: 0.796–0.928) and successful external validation (validation cohort C statistic: 0.851; 95% CI: 0.814–0.882). Risk stratification showed END risks of 2.1% vs. 29.5% (derivation cohort) and 2.6% vs. 31.2% (validation cohort) for scores 0–3 and 4–9, respectively.ConclusionCNS-LAND score is a reliable predictor of END risk in AIS patients receiving IVT.

Among various sunscreen materials, zinc oxide and titanium dioxide are excellent physical sunscreen components; however, these two materials tend to aggregate and form micrometer-sized particles that may impact their performance. This study utilizes fine grinding techniques to break up the aggregated oxide particles into small nanoparticles with a narrow size distribution averaging around 200 nm in diameter. The ground zinc oxide and titanium dioxide particles exhibit enhanced ability in absorbing and scattering ultraviolet radiation compared to their original state before grinding. Consequently, this research offers innovative concepts as well as approaches towards developing highly efficient yet low-toxic physical sunscreen components while significantly contributing to the preparation process optimization for mixed material performance.

Difenoconazole (DFZ) is a classical triazole fungicide that causes immunosuppression in non-target organisms. Ferulic acid (FA) is a polyphenolic molecule found in nature that has antioxidant and anti-inflammatory activities. The purpose of this investigation was to see if FA could prevent DFZ-induced immunosuppression and to identify the potential mechanisms. Carp were exposed to 1/10 LC50 of DFZ as well as fed normal feed or feed containing dietary additive FA for 30 d. It was found that DFZ-induced immunosuppression could be improved by FA, as evidenced by upregulation of Hb, C3 and IgM and downregulation of LDH. It was then investigated that FA could ameliorate DFZ-induced splenic injury through p53-mediated apoptosis. At the same time, enhancing the levels of CAT, GSH and T-AOC in spleen and transcription levels Nrf2 signaling pathway related genes indicated that FA reduced oxidative damage caused by DFZ by blocking the Nrf2 signaling pathway. In addition, FA inhibited the inflammatory response triggered by TRAF/TAK1/NF-κB signaling pathway, downregulated the transcript levels of pro-inflammatory factors (il-1β, tnf-α, il-6) and the level of NLRP3 inflammasome (NRLP3, ASC, Caspase 1), and upregulated the transcript levels of anti-inflammatory factors (tgf-β1, il-10). In conclusion, the above results suggested that FA mediated TRAF/TAK1/NF-κB, Nrf2, and p53 pathways to attenuate DFZ-induced inflammation, oxidative stress, and apoptosis thereby enhancing the immune capacity of carp.

Abstract Background The peaberry bean in Arabica coffee has exceptional quality compared to the regular coffee bean. Understanding the molecular mechanism of bean quality is imperative to introduce superior coffee quality traits. Despite high economic importance, the regulatory aspects of bean quality are yet largely unknown in peaberry. A transcriptome analysis was performed by using peaberry and regular coffee beans in this study. Results The result of phenotypic analysis stated a difference in the physical attributes of both coffee beans. In addition, transcriptome analysis revealed low genetic differences. Only 139 differentially expressed genes were detected in which 54 genes exhibited up-regulation and 85 showed down-regulations in peaberry beans compared to regular beans. The majority of differentially expressed genes had functional annotation with cell wall modification, lipid binding, protein binding, oxidoreductase activity, and transmembrane transportation. Many fold lower expression of Ca25840-PMEs1, Ca30827-PMEs2, Ca30828-PMEs3, Ca25839-PMEs4, Ca36469-PGs. and Ca03656-Csl genes annotated with cell wall modification might play a critical role to develop different bean shape patterns in Arabica. The ERECTA family genes Ca15802-ERL1, Ca99619-ERL2, Ca07439-ERL3, Ca97226-ERL4, Ca89747-ERL5, Ca07056-ERL6, Ca01141-ERL7, and Ca32419-ERL8 along lipid metabolic pathway genes Ca06708-ACOX1, Ca29177-ACOX2, Ca01563-ACOX3, Ca34321-CPFA1, and Ca36201-CPFA2 are predicted to regulate different shaped bean development. In addition, flavonoid biosynthesis correlated genes Ca03809-F3H, Ca95013-CYP75A1, and Ca42029-CYP75A2 probably help to generate rarely formed peaberry beans. Conclusion Our results provide molecular insights into the formation of peaberry. The data resources will be important to identify candidate genes correlated with the different bean shape patterns in Arabica.

With the construction of the modern power system, power load forecasting is significant to keep the electric Internet of Things in operation. However, it usually needs to collect massive power load data on the server and may face the problem of privacy leakage of raw data. Federated learning can enhance the privacy of the raw power load data of clients by frequently transmitting model updates. Concerning the increasing communication burden of resource-heterogeneous clients resulting from frequent communication with the server, a communication-efficient federated learning algorithm based on Compressed Model Updates and Lazy uploAd (CMULA-FL) was proposed to reduce the communication cost. CMULA-FL also integrates the error compensation strategy to improve the model utility. First, the compression operator is used to compress the transmitted model updates, of which large norms are uploaded to reduce the communication cost of each epoch and transmission frequency. Second, by measuring the error of compression and lazy upload, the error is accumulated to the next epoch to improve the model utility. Finally, based on simulation experiments on the benchmark power load data, the results show that the communication cost decreases at least 60% with controlled loss of model prediction compared with baseline.

Abstract Background Sodium formononetin-3ʹ-sulphonate (Sul-F) may alleviate I/R injury in vivo with uncertain mechanism. Endoplasmic reticulum (ER) stress-mediated apoptosis participates in the process of cerebral ischemia‐reperfusion (I/R) injury. Our aim is to figure out the effect of Sul-F on cerebral I/R injury and to verify whether it works through suppressing ER stress-mediated apoptosis. Results The cerebral lesions of middle cerebral artery occlusion (MCAO) model in SD rats were aggravated after 24 h of reperfusion, including impaired neurological function, increased infarct volume, intensified inflammatory response and poor cell morphology. After intervention, the edaravone (EDA, 3 mg/kg) group and Sul-F high-dose (Sul-F-H, 80 mg/kg) group significantly alleviated I/R injury via decreasing neurological score, infarct volume and the serum levels of inflammatory factors (TNF-α, IL-1β and IL-6), as well as alleviating pathological injury. Furthermore, the ER stress level and apoptosis rate were elevated in the ischemic penumbra of MCAO group, and were significantly blocked by EDA and Sul-F-H. In addition, EDA and Sul-F-H significantly down-regulated the ER stress related PERK/eIF2α/ATF4 and IRE1 signal pathways, which led to reduced cell apoptosis rate compared with the MCAO group. Furthermore, there was no difference between the EDA and Sul-F-H group in terms of therapeutic effect on cerebral I/R injury, indicating a therapeutic potential of Sul-F for ischemic stroke. Conclusions Sul-F-H can significantly protects against cerebral I/R injury through inhibiting ER stress-mediated apoptosis in the ischemic penumbra, which might be a novel therapeutic target for ischemic stroke.

Abstract Tacrolimus (Tac) is a common immunosuppressant that used in organ transplantation. However, its therapeutic index is narrow, and it is prone to adverse side effects, along with an increased risk of toxicity, namely, cardio-, nephro-, hepato-, and neurotoxicity. Prior metabolomic investigations involving Tac-driven toxicity primarily focused on changes in individual organs. However, extensive research on multiple matrices is uncommon. Hence, in this research, the authors systemically evaluated Tac-mediated toxicity in major organs, namely, serum, brain, heart, liver, lung, kidney, and intestines, using gas chromatography−mass spectrometry (GC-MS). The authors also employed multivariate analyses, including orthogonal projections to the latent structure (OPLS) and t-test, to screen 8 serum metabolites, namely, D-proline, glycerol, D-fructose, D-glucitol, sulfurous acid, 1-monopalmitin (MG (16:0/0:0/0:0)), glycerol monostearate (MG (0:0/18:0/0:0)), and cholesterol. Metabolic changes within the brain involved alterations in the levels of butanamide, tartronic acid, aminomalonic acid, scyllo-inositol, dihydromorphine, myo-inositol, and 11-octadecenoic acid. Within the heart, the acetone and D-fructose metabolites were altered. In the liver, D-glucitol, L-sorbose, palmitic acid, myo-inositol, and uridine were altered. In the lung, L-lactic acid, L-5-oxoproline, L-threonine, phosphoric acid, phosphorylethanolamine, D-allose, and cholesterol were altered. Lastly, in the kidney, L-valine and D-glucose were altered. Our findings will provide a systematic evaluation of the metabolic alterations in target organs within a Tac-driven toxicity mouse model.

Abstract Psoriasis is currently an incurable skin disorder mainly driven by a chronic inflammatory response. We found that subcutaneous application of umbilical cord- derived mesenchymal stem/stromal cells (MSCs) primed by IFN-γ and TNF-α, referred to as MSCs-IT, exhibited remarkable therapeutic efficacy on imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Neutrophil infiltration, a hallmark of psoriasis, was significantly reduced after treatment with MSCs-IT. We further demonstrated that the effects of MSCs-IT were mediated by tumor necrosis factor (TNF) stimulating gene-6 (TSG-6), which was greatly upregulated in MSCs upon IFN-γ and TNF-α stimulation. MSCs transduced with TSG-6 siRNA lost their therapeutic efficacy while recombinant TSG-6 applied alone could also reduce neutrophil infiltration and alleviate the psoriatic lesions. Furthermore, we demonstrated that TSG-6 could inhibit neutrophil recruitment by decreasing the expression of CXCL1, which may be related to the reduced level of STAT1 phosphorylation in the keratinocytes. Thus, blocking neutrophil recruitment by MSCs-IT or TSG-6 has potential for therapeutic application in human psoriasis.

Abstract Protein neddylation is catalyzed by a neddylation activating enzyme (NAE, E1), an E2 conjugating enzyme, and an E3 ligase. In various types of human cancers, the neddylation pathway is abnormally activated. Our previous study validated that the neddylation E2 UBE2F is a promising therapeutic target in lung cancer. Although the NAE inhibitor MLN4924/pevonedistat is currently under clinical investigation as an anti-cancer agent, there are no small molecules available that selectively target UBE2F. Here, we report, for the first time, the discovery, via structure-based virtual screen and chemical optimization, of such a small molecule, designated as HA-9104. HA-9104 binds to UBE2F, reduces its protein levels, and consequently inhibits cullin-5 neddylation. Blockage of cullin-5 neddylation inactivates cullin-RING ligase-5 (CRL5) activity, leading to accumulation of the CRL5 substrate, NOXA, to induce apoptosis. Moreover, HA-9104 appears to form the DNA adduct via its 7-azaindole group to induce DNA damage and G2/M arrest. Biologically, HA-9104 effectively suppresses the growth and survival of lung cancer cells and confers radiosensitization in both in vitro cell culture and in vivo xenograft tumor models. In summary, we discovered a small molecule, designated HA-9104, that targets the UBE2F-CRL5 axis with anti-cancer activity alone or in combination with radiation.

A new power system with new energy as the main body will be built. Wind power generation will become an important part of the new power system. Compared with onshore wind power, offshore wind power has become a research hotspot with the advantages of abundant wind resources, high utilization rate, close distance from power load, easy power transmission and consumption. However, with the large-scale offshore wind turbine capacity and the improvement of the proportion of wind power, its disadvantages of weak impact load resistance, weak grid friendliness, large volume and high cost are becoming increasingly prominent. In view of the above problems, this paper carries out the research on the design and modeling of double rotor double machine wind turbine generation system. The research contents include the designing the structure, analyzing the working principle, establishing the math model and proposing the control strategy. The system designed in this paper has the characteristics of strong impact load resistance, good power quality, high power grid stability and reliability, small volume, light weight and low cost.

Background: Cold exposure (CE) can effectively modulate adipose tissue metabolism and improve metabolic health. Although previous metabolomics studies have primarily focused on analyzing one or two samples from serum, brown adipose tissue (BAT), white adipose tissue (WAT), and liver samples, there is a significant lack of simultaneous analysis of multiple tissues regarding the metabolic changes induced by CE in mice. Therefore, our study aims to investigate the metabolic profiles of the major tissues involved.Methods: A total of 14 male C57BL/6J mice were randomly assigned to two groups: the control group (n = 7) and the CE group (n = 7). Metabolite determination was carried out using gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to identify metabolites exhibiting differential expression between the two groups.Results: In our study, we identified 32 discriminant metabolites in BAT, 17 in WAT, 21 in serum, 7 in the liver, 16 in the spleen, and 26 in the kidney, respectively. Among these metabolites, amino acids, fatty acids, and nucleotides emerged as the most significantly altered compounds. These metabolites were found to be associated with 12 differential metabolic pathways closely related to amino acids, fatty acids, and energy metabolism.Conclusion: Our study may provide valuable insights into the metabolic effects induced by CE, and they have the potential to inspire novel approaches for treating metabolic diseases.