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This paper systematically studies the changes in the microstructure and magnetic properties of CoFeSiBNb series metallic fibers before and after AC annealing. The influence of current intensity on the magneto-impedance (MI) effect of the fibers is analyzed and the mechanism of current annealing to improve the MI characteristics is further revealed. The results show that the surface of the CoFeSiBNb metallic fibers before and after AC annealing is smooth and continuous, the tensile strength of CoFeSiBNb3 fiber is 5.15 GPa and it is the most stable and fracture-reliable. After AC annealing, metallic fibers' general magnetic properties and MI ratio increase at first with current intensity and then decrease at higher intensities. Specifically, the 140 mA AC annealed metallic fiber shows excellent magnetic properties with Ms, μm, Hc, and Mr values reaching 94.38 emu/g, 0.4326, 34.36 Oe, and 13.94 emu/g, respectively. With an excitation frequency of f = 1 MHz, the fiber's [ΔZ/Zmax]max, ξmax, Hk, and Hp reached 216.81%, 31.04 %/Oe, 1 Oe, and 2 Oe, respectively. During the current annealing process, Joule heat eliminates residual stresses in the fibers while forming atomically ordered micro-domains, which improves the degree of its organizational order. Meanwhile, a stable toroidal magnetic field is generated, which promotes the distribution of the magnetic domain structure of the fibers, thereby improving the MI effect.

Abstract Introduction This study aimed to establish an animal model of open abdomen (OA) through temporary abdominal closure via different techniques. Methods Adult male Sprague–Dawley rats were randomly divided into three groups: group A (OA with polypropylene mesh alone); group B (OA with polypropylene mesh combined with a patch); and group C (OA with polypropylene mesh and a sutured patch). Vital signs, pathophysiological changes, and survival rates were closely monitored in the rats for 7 days after surgery. Abdominal X‐rays and histopathological examinations were performed to assess abdominal organ changes and wound healing. Results The results showed no significant difference in mortality rates among the three groups (p > 0.05). However, rats in group B exhibited superior overall condition, cleaner wounds, and a higher rate of wound healing compared to the other groups (p

Abstract Special-cause burn injuries are usually more severe and difficult to manage, and often contribute to a high mortality in severely injured patients. The aim of this study was to present the epidemiological characteristics of special-cause burn in a major regional burn center in China between 2004 and 2021 and determine the risk factors associated with the mortality of burn patients. A total of 33,619 burn patients were included the study, among which 4,452 (13.2%) were special-cause burn patients. Compared to the thermal burn group, the special-cause burn patients were usually male, elder, married and III-IV degree of burn with onset of upper extremity in summer and autumn. Moreover, a greater proportion of patients in the special-cause burn group underwent surgical treatment and amputation and had a higher median hospital stay and treatment costs. During the multivariate logistic regression, older age, male, unmarried, winter, III-IV degree of burn, ≥ 3 burn sites, and larger total body surface area (TBSA) of burn were significantly associated with higher burn mortality (all P 0.05). These results suggested that special cause-burn patients suffer more severe injuries, resulting in longer hospital stays and higher health care expenditures, but it did not significantly increase the mortality risk. Therefore, burn clinicians should not only have the responsibility to cure burns, but also need to know and popularize burn epidemiological characteristic and precaution.

The age of artificial intelligence emphasises the possibility of justification and the dialectical aspects of legal reasoning. The need for validity in legal reasoning mainly stems from the existence of exceptions to rules and conflicts between rules. Formal logic may well account for exceptions to rules and thus characterise cancellable reasoning. The presented article focuses on legal issues related to Artificial Intelligence (AI) that are being discussed in the scientific community because of their importance for understanding the mechanisms of law realisation. Some of the most pressing issues in the application of artificial intelligence include: transparency of algorithms, cybersecurity vulnerabilities, unfairness, bias and discrimination, lack of adversariality, legal personality issues, intellectual property issues, adverse effects on employees, privacy and data protection issues, liability for damages and lack of liability. Recognising the importance of artificial intelligence in the field of law, and acknowledging that the field requires constant reassessment and flexibility, this article develops a discussion that is important given the seriousness of the impact of artificial intelligence technologies on legal actors. on legal issues related to Artificial Intelligence (AI) that are being discussed in the scientific community because of their importance for understanding the mechanisms of law realisation. Some of the most pressing issues in the application of artificial intelligence include: transparency of algorithms, cybersecurity vulnerabilities, unfairness, bias and discrimination, lack of adversariality, legal personality issues, intellectual property issues, adverse effects on employees, privacy and data protection issues, liability for damages and lack of liability. Recognising the importance of artificial intelligence in the field of law, and acknowledging that the field requires constant reassessment and flexibility, this article develops a discussion that is important given the seriousness of the impact of artificial intelligence technologies on legal actors.

Background:Polygonum multiflorum shows dual hepatoprotective and hepatotoxic effects. The bioactive components responsible for these effects are unknown. This study investigates whether cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (cis-TSG), a stilbene glycoside, has hepatoprotective and/or hepatotoxic effects in a liver injury model.Methods: C57BL/6J mice were administered α-naphthylisothiocyanate (ANIT) to induce cholestasis, followed by treatment with cis-TSG. Hepatoprotective and hepatotoxic effects were assessed using serum biomarkers, liver histology, and metabolomic and lipidomic profiling. Transcriptomic analysis were conducted to explore gene expression changes associated with lipid and bile acid metabolism, inflammation, and oxidative stress.Results and Discussion: ANIT administration caused significant liver injury, evident from elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and dysregulated lipid metabolism. cis-TSG treatment markedly reduced ALT and AST levels, normalized lipid profiles, and ameliorated liver damage, as seen histologically. Metabolomic and lipidomic analyses revealed that cis-TSG influenced key pathways, notably glycerophospholipid metabolism, sphingolipid metabolism, and bile acid biosynthesis. The treatment with cis-TSG increased monounsaturated and polyunsaturated fatty acids (MUFAs and PUFAs), enhancing peroxisome proliferator-activated receptor alpha (PPARα) activity. Transcriptomic data confirmed these findings, showing the downregulation of genes linked to lipid metabolism, inflammation, and oxidative stress in the cis-TSG-treated group. The findings suggest that cis-TSG has a hepatoprotective effect through modulation of lipid metabolism and PPARα activation.

Identifying priority conservation areas (PCAs) on the basis of ecosystem services (ESs) trade-offs is a crucial step in achieving optimal ecosystem management in the BTH, noting the complex spatio-temporal and scaling effects inherent in these ecosystems. A cross-scale quantification of spatial and temporal changes in ecosystem services and their correlations was conducted in the BTH. Furthermore, the Ordered Weighting Algorithm (OWA) was introduced to simulate a variety of scenarios in order to determine the PCAs and to explore the drivers of ES in the PCAs. The results indicated that Food supply (FS), Water yield (WY), and Soil retention (SR) in the BTH increased by 16.4 × 104t/hm2, 81.81 mm, and 37081.29 t/hm2, respectively. In contrast, Carbon storage (CS) and Habit quality (HQ) exhibited a decrease of 0.01 t/hm2 and 0.03. Spatially, the high-value areas of ESs at the county scale exhibited greater clustering. At the county scale, there were two trade-offs and eight synergies in 2000, and four trade-offs and six synergies by 2020. In contrast, at the raster scale, there were two trade-offs and eight synergies from 2000 to 2020. The mechanisms of change were similar and exhibited spatial heterogeneity. Scenario 6 represents the optimal priority conservation area, exhibiting the most balanced conservation efficiency of each ecosystem service. This scenario enables the simultaneous conservation of multiple ESs. The natural factors within the PCAs exert a stronger influence on ESs than socio-economic factors. The inclusion of interacting factor effects will enhance the explanatory power of the drivers. The findings of this study can serve as a theoretical foundation for cross-scale ecosystem service management decisions.

Refractory high-entropy alloys (RHEAs) have a great potential in high-temperature electronics, extensive aerospace and biomedical applications due to their unique strength and ductility. Herein, the effects of alloying elements on the mechanical and electronic properties of NbTaTiZrX (X = V, Mo, Hf, W and Re) RHEAs are investigated by using the density functional theory (DFT) in combination with the special quasi-random structure (SQS) and virtual crystal approximation (VCA) methods. The calculated results show that alloying of Mo, W and Re with high elastic modulus can enhance the strength and the hardness of RHEAs. Among them, NbTaTiZrRe RHEA with the best strengthening effect has a yield strength of exceeds 2 GPa, which is notably higher than other considered high-entropy alloys. For alloying of V and Hf, the ductility of RHEAs is improved, and among which, NbTaTiZrHf RHEA has a relatively best ductility. Compared with other NbTaTiZrX RHEAs, spiral dislocations in NbTaTiZrHf RHEA are more prone to nucleate, and which confirms its excellent ductility. Moreover, the reduction of pseudo energy gaps and the formation of Hf–Hf strong metallic bonds further confirm its metallic ductility from the electronic density of states and charge density. The theoretical predictions in this study are congruent with the existing experimental data, and have certain theoretical guidance relevance for enhancing the mechanical characteristics of NbTaTiZrX (X = V, Mo, Hf, W and Re) RHEAs.

Abstract Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1β (IL-1β), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.

Abstract The 5′-end capping of nascent pre-mRNA represents the initial step in RNA processing, with evidence demonstrating that guanosine addition and 2′-O-ribose methylation occur in tandem with early steps of transcription by RNA polymerase II, especially at the pausing stage. Here, we determine the cryo-EM structures of the paused elongation complex in complex with RNGTT, as well as the paused elongation complex in complex with RNGTT and CMTR1. Our findings show the simultaneous presence of RNGTT and the NELF complex bound to RNA polymerase II. The NELF complex exhibits two conformations, one of which shows a notable rearrangement of NELF-A/D compared to that of the paused elongation complex. Moreover, CMTR1 aligns adjacent to RNGTT on the RNA polymerase II stalk. Our structures indicate that RNGTT and CMTR1 directly bind the paused elongation complex, illuminating the mechanism by which 5’-end capping of pre-mRNA during transcriptional pausing.

In this paper, the microstructure and mechanical properties of CoCrFeNiMox (x = 0, 0.1, 0.3, 0.5, 0.7, and 1.0) high-entropy alloys (HEAs) prepared with high-vacuum arc melting method were studied in detail. After Mo-doping, the strengthening mechanism of HEAs mainly included the component segregation strengthening and the second phase strengthening. Cr and Mo elements were enriched at the grain boundary of HEAs, which leaded to the formation of σ phase and strengthens the alloys. The microhardness and strength increased with Mo contents, while the elongation decreased gradually. Among which, the higher microhardness, yield strength, and ultimate tensile strength of CoCrFeNiMo0.3 alloy reach 205.96 HV, 292.22 MPa, and 593.25 MPa, respectively, in compared with other alloys. More importantly, the percentage elongation of which remains 37.36%, and the microhardness distribution was uniform with an average value of 7.4 GPa and an elastic modulus of 263.6 GPa. The research findings presented in this paper could serve as a valuable theoretical basis and practical foundations for the strengthening efforts of face centered cubic (FCC) HEAs.

Abstract Objective Increasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH). Methods A total of 383 patients (aged 24–76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (

Abstract Background Understanding the molecular mechanisms of Alzheimer’s disease (AD) has important clinical implications for guiding therapy. Impaired amyloid beta (Aβ) clearance is critical in the pathogenesis of sporadic AD, and blood monocytes play an important role in Aβ clearance in the periphery. However, the mechanism underlying the defective phagocytosis of Aβ by monocytes in AD remains unclear. Methods Initially, we collected whole blood samples from sporadic AD patients and isolated the monocytes for RNA sequencing analysis. By establishing APP/PS1 transgenic model mice with monocyte-specific cystatin F overexpression, we assessed the influence of monocyte-derived cystatin F on AD development. We further used a nondenaturing gel to identify the structure of the secreted cystatin F in plasma. Flow cytometry, enzyme-linked immunosorbent assays and laser scanning confocal microscopy were used to analyse the internalization of Aβ by monocytes. Pull down assays, bimolecular fluorescence complementation assays and total internal reflection fluorescence microscopy were used to determine the interactions and potential interactional amino acids between the cystatin F protein and Aβ. Finally, the cystatin F protein was purified and injected via the tail vein into 5XFAD mice to assess AD pathology. Results Our results demonstrated that the expression of the cystatin F protein was specifically increased in the monocytes of AD patients. Monocyte-derived cystatin F increased Aβ deposition and exacerbated cognitive deficits in APP/PS1 mice. Furthermore, secreted cystatin F in the plasma of AD patients has a dimeric structure that is closely related to clinical signs of AD. Moreover, we noted that the cystatin F dimer blocks the phagocytosis of Aβ by monocytes. Mechanistically, the cystatin F dimer physically interacts with Aβ to inhibit its recognition and internalization by monocytes through certain amino acid interactions between the cystatin F dimer and Aβ. We found that high levels of the cystatin F dimer protein in blood contributed to amyloid pathology and cognitive deficits as a risk factor in 5XFAD mice. Conclusions Our findings highlight that the cystatin F dimer plays a crucial role in regulating Aβ metabolism via its peripheral clearance pathway, providing us with a potential biomarker for diagnosis and potential target for therapeutic intervention.

In today's modern world, marketing is a fruitful source to grow a business by reaching a larger audience. This paper considers a popular social media source called LinkedIn.com as a way of marketing or reaching a larger audience. We consider a regression approach to explore the statistically significant role of the LinkedIn medium as a tool for reaching a larger audience. In addition to statistically exploring the role of the LinkedIn medium in the financial sector, we also introduce a new Weibull-based probability distribution, namely, the exponential TX inverse Weibull (for short'ETXI-Weibull') distribution. The ETXI-Weibull distribution is specially designed for analyzing LinkedIn marketing data. The beauty of the ETXI-Weibull distribution is that it satisfies the heavy-tailed characteristics, which are explored visually and mathematically. For the ETXI-Weibull distribution, the estimators are derived whose performances are evaluated visually and numerically through a simulation study. The ETXI-Weibull distribution is applied practically by considering the LinkedIn marketing data set as an example. Using certain established statistical tests, we observe that the ETXI-Weibull distribution provides an optimal fit to the LinkedIn marketing data set. Furthermore, a bivariate extension of the exponential TX inverse Weibull model is also introduced. Finally, the bivariate extension of the exponential TX inverse Weibull model is illustrated by modeling the LinkedIn marketing and sales data.

In this paper, a fixed-time consensus control algorithm is proposed for non-triangular structure stochastic nonlinear multi-agent systems (SNMASs) with input saturation via the command-filtered backstepping design method. Fuzzy logic systems are employed to identify the nonlinear dynamics of each agent. By introducing the fixed-time command filter and constructing the fractional power error compensation mechanism, the "complexity explosion" problem is effectively avoided, and the influence of filtered errors is eliminated in a fixed time. Based on the fixed-time stability theory, it strictly proves that all signals in the closed-loop system are fixed-time bounded in probability, and the consensus error converges to a sufficiently small neighborhood of the origin in probability within a fixed time. Finally, a comparison simulation example verifies the effectiveness and superiority of the proposed fixed-time consensus control strategy.

Abstract Accurately predicting population mortality rates is crucial for effective retirement insurance and economic policy formulation. Recent advancements in deep learning time series forecasting (DLTSF) have led to improved mortality rate predictions compared to traditional models like Lee-Carter (LC). This study focuses on mortality rate prediction in large clusters across Europe. By utilizing PCA dimensionality reduction and statistical clustering techniques, we integrate age features from high-dimensional mortality data of multiple countries, analyzing their similarities and differences. To capture the heterogeneous characteristics, an adaptive adjustment matrix is generated, incorporating sequential variation and spatial geographical information. Additionally, a combination of graph neural networks and a transformer network with an adaptive adjustment matrix is employed to capture the spatiotemporal features between different clusters. Extensive numerical experiments using data from the Human Mortality Database validate the superiority of the proposed GT-A model over traditional LC models and other classic neural networks in terms of prediction accuracy. Consequently, the GT-A model serves as a powerful forecasting tool for global population studies and the international life insurance field.

Abstract Pseudomonas aeruginosa, a common nosocomial pathogen, relies on siderophores to acquire iron, crucial for its survival in various environments and during host infections. However, understanding the molecular mechanisms of siderophore regulation remains incomplete. In this study, we found that the BfmRS two-component system, previously associated with biofilm formation and quorum sensing, is essential for siderophore regulation under high osmolality stress. Activated BfmR directly bound to the promoter regions of pvd, fpv, and femARI gene clusters, thereby activating their transcription and promoting siderophore production. Subsequent proteomic and phenotypic analyses confirmed that deletion of BfmRS reduces siderophore-related proteins and impairs bacterial survival in iron-deficient conditions. Furthermore, phylogenetic analysis demonstrated the high conservation of the BfmRS system across Pseudomonas species, functional evidences also indicated that BfmR homologues from Pseudomonas putida KT2440 and Pseudomonas sp. MRSN12121 could bind to the promoter regions of key siderophore genes and osmolality-mediated increases in siderophore production were observed. This work illuminates a novel signaling pathway for siderophore regulation and enhances our understanding of siderophore-mediated bacterial interactions and community establishment.

Abstract The long-term erosion of rock by solution can induce a series of karst problems. Therefore, this study focused on limestone and conducted dynamic dissolution experiments under deionized water and CO2 solution conditions to study the deterioration mechanism of limestone under nonequilibrium conditions. The results showed that the degree of degradation of the mechanical properties of the samples in a CO2 solution was obviously greater. In a deionized water environment, the degradation of the mechanical properties of the sample is mainly controlled by the physical softening action of the solution. In the CO2 solution environment, the degradation process can be divided into two stages. In the early stage of the experiment (10 days to 20 days), the degradation of mechanical properties of the sample is also controlled by the physical softening action of the solution. With increasing soaking time, the main rock-forming minerals of limestone gradually react with the CO2 solution, the degradation of the sample is controlled mainly by the chemical corrosion of the CO2 solution, and its degradation rate is much greater than that of physical softening. The results can be used as a reference for assessing the long-term stability of underground engineering in limestone karst development areas.

The incompletely eliminated Treponema pallidum (T. pallidum) during primary syphilis chancre infection can result in the progression of secondary, tertiary, or latent syphilis in individuals, suggesting that T. pallidum has successfully evaded the immune response and spread to distant sites. The mechanism underlying the dissemination of T. pallidum is unclear. Here, a syphilitic rabbit model dorsal-injected with recombinant Tp0136 protein or Tp0136 antibody subcutaneously was used to demonstrate the role of Tp0136 protein in promoting the dissemination of T. pallidum to the testis and angiogenesis in vivo; vascular endothelial cell line HMEC-1 was employed to display that Tp0136 protein enhances the angiogenesis. Furthermore, the three-dimensional microfluidic angiogenesis system showed that the angiogenesis would heighten vascular permeability. Then transcriptome sequencing analysis, in conjunction with cell-level validation, elucidated the critical role of the PI3K-AKT signaling pathway in the promotion of angiogenesis by Tp0136 protein, resulting in heightened permeability. These findings elucidate the strategy employed by T. pallidum in evading immune clearance.

ABSTRACTThe evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum’s mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the “pseudo-expression” of MHC class I on the surface of T. pallidum (hereafter referred to a “pseudo-expression” of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

BackgroundThe escalating global burden of diabetes and its associated cognitive impairment underscores the urgency for effective interventions. Bergenin shows promise in regulating glucose metabolism, mitigating inflammation, and improving cognitive function. Zebrafish models offer a unique platform for assessing drug efficacy and exploring pharmacological mechanisms, complemented by subsequent investigations in cell and rat models.MethodsThe experimental subjects included zebrafish larvae (CZ98:Tg (mpeg1:EGFP)ihb20Tg/+), adult zebrafish (immersed in 2% glucose), BV2 cell line (50 mM glucose + 10 μm Aβ1-42), and a streptozotocin (STZ) bilateral intracerebroventricular injection rat model. Bergenin’s effects on the toxicity, behavior, and cognitive function of zebrafish larvae and adults were evaluated. The Morris water maze assessed cognitive function in rats. Neuronal histopathological changes were evaluated using HE and Nissl staining. qPCR and Western blot detected the expression of glycolysis enzymes, inflammatory factors, and Bergenin’s regulation of PPAR/NF-κB pathway in these three models.Results1) In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased ins expression and increased expression of irs1, irs2a, and irs2b, suggesting a reduction in insulin resistance. It also altered the expression of pparg and rela. 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1β, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus.ConclusionBergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.

Background: Transanal total mesorectal excision has emerged as a potential solution to certain limitations associated with laparoscopic total mesorectal excision in rectal cancer patients. Differences in surgical approaches have raised questions regarding their impact on the risk of postoperative urinary retention, with limited data available from large scale randomized clinical study. Objective: To report incidence of postoperative urinary retention and evaluate the associated risk factors for transanal total mesorectal excision. Design: In this randomized controlled trial (ClinicalTrials. gov NCT06147492), we retrieved 524 patients who received total mesorectal excision (TME) for stage I–III rectal cancer between June 2019 and April 2022, and the patients were randomly assigned in a 1:1 ratio to undergo either taTME or laTME. Patients: We enrolled 524 patients who underwent total mesorectal excision for stage I–III rectal cancer between June 2019 and April 2022. Main outcome measures: The incidence of postoperative urinary retention. Results: Among the 524 enrolled patients, 261 were randomized to the laTME group, while 263 were were randomized the taTME group. The median age was 58 years, and 340 participants (64.8 %) were male. Notably, 37 individuals (7.0 %) experienced postoperative urinary retention during the follow-up period, with no significant disparity was observed between the taTME and laTME groups (6.8 % and 7.2 %, respectively, P = 0.98). Risk factors associated with PUR in patients following taTME encompassed early removal of the urinary catheter (P = 0.006), net infusion rate >4.09 ml kg−1.h−1 (P = 0.006), and an age surpassing 65 years (P = 0.0321). Limitations: The generalizability of the findings outside specialist rectal cancer centers may be limited. Conclusions: Transanal total mesorectal excision was not found to heighten the risk of postoperative urinary retention. Nonetheless, it is advisable removing postoperative catheter beyond the initial day and exercising caution in the administration of intravenous fluids in clinical practice for taTME procedures.

BackgroundSchisanlactone E, also known as XueTongSu (XTS), is an active compound extracted from the traditional Tujia medicine Kadsura heteroclita (“XueTong”). Recent studies highlight its anti-inflammatory and antioxidant properties, yet the mechanisms of XTS’s therapeutic effects on Alzheimer’s disease (AD) are unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of XTS in AD.MethodsTen C57BL/6 mice were assigned to the control group (NC), and twenty APP/PS1 transgenic mice were randomly divided into the model group (M) (10 mice) and the XTS treatment group (Tre) (10 mice). After an acclimatization period of 7 days, intraperitoneal injections were administered over a 60-day treatment period. The NC and M groups received saline, while the Tre group received XTS at 2 mg/kg. Learning and memory abilities were assessed using the Morris Water Maze (MWM) test. Histopathological changes were evaluated using hematoxylin and eosin (HE) and Nissl staining, and immunofluorescence was used to assess pathological products and glial cell activation. Cytokine levels (IL-1β, IL-6, TNF-α) in the hippocampus were quantified by qPCR. 16S rDNA sequencing analyzed gut microbiota metabolic alterations, and metabolomic analysis was performed on cortical samples. The KEGG database was used to analyze the regulatory mechanisms of XTS in AD treatment.ResultsXTS significantly improved learning and spatial memory in APP/PS1 mice and ameliorated histopathological changes, reducing Aβ plaque aggregation and glial cell activation. XTS decreased the expression of inflammatory cytokines IL-1β, IL-6, and TNF-α. It also enhanced gut microbiota diversity, notably increasing Akkermansia species, and modulated levels of metabolites such as isosakuranetin, 5-KETE, 4-methylcatechol, and sphinganine. Pathway analysis indicated that XTS regulated carbohydrate metabolism, neuroactive ligand-receptor interactions, and alanine, aspartate, and glutamate metabolism, mitigating gut microbiota dysbiosis and metabolic disturbances.ConclusionXTS ameliorates cognitive deficits, pathological changes, and inflammatory responses in APP/PS1 mice. It significantly modulates the gut microbiota, particularly increasing Akkermansia abundance, and influences levels of key metabolites in both the gut and brain. These findings suggest that XTS exerts anti-AD effects through the microbial-gut-brain axis (MGBA).

As network infrastructures continue to grow and traffic encryption technologies evolve at a rapid pace, the task of classifying encrypted traffic has become significantly more intricate. These emerging encryption methods render conventional approaches ineffectual in discerning traffic types, consequently posing novel challenges to network security and administration. Evidently, conventional traffic classification techniques are inadequate when it comes to encrypted traffic. Consequently, researchers have turned to machine learning and deep learning models to address this challenge, achieving remarkable results in this domain. Nonetheless, contemporary deep learning models exhibit a propensity to overly depend on self-attention mechanisms while processing 2D feature maps. This mechanism typically focuses only on individual query-key pairs, neglecting the rich contextual information among adjacent keys, thereby limiting their performance in encrypted traffic classification. To address this limitation, our study examines an innovative approach called CoTNet. The CoT module is integrated into the ResNet model to more comprehensively exploit the contextual associations among input keys. This innovation engenders a sturdier and more potent classification model, adept at comprehensively capturing the inherent patterns and correlated information within input features. The suggested method enhances the ResNet model by substituting the conventional 3x3 convolution operations with CoT modules, thereby more effectively harnessing the contextual associations among input keys. In particular, we integrate self-attention mechanisms at various model levels to more thoroughly capture the inherent patterns and correlated information within input features. Experimental results on two real-world datasets show that CoTNet outperforms multiple state-of-the-art methods in the encrypted traffic classification task.

Abstract Purpose This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus. Methods Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C0/Dose). Results The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C0/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43). Conclusions CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.

Abstract Bi‐mode Insulated Gate Transistor (BIGT), owing to its notable attributes in power density and compact dimensions, holds promising applications in the realm of high power converters. However, its characteristic of the voltage drop in diode mode controlled by gate‐emitter voltage poses significant challenges for low‐loss operation. This paper investigates the relationship between BIGT's on‐state voltage drop in diode mode and its gate‐emitter voltage in detail. By combining simulation and experimental analysis, recommended the gate‐emitter voltage values are provided. Furthermore, a novel driver optimization scheme is proposed to automatically lower the gate voltage during reverse conduction, which can effectively reduce the reverse on‐state losses of the BIGT. Experimental validation demonstrates a 10.6% reduction in reverse on‐state voltage drop, showcasing the efficacy of the proposed driver optimization scheme.

Equivalent circuit parameters of an induction motor are highly susceptible to various undesired factors. These phenomena primarily include effects of higher order time and space harmonics, temperature, magnetic saturation, and skin-effect. Traditional approaches model these equivalent circuit parameters via temperature, iron saturation, and slotting effects. However, the impacts of harmonic fields generated by the spatial magnetomotive force components as well as that of skin effect in motor inductances are not considered. The proposed work therefore presents an improved inductance estimation considering the impact of total harmonic distortion in the magnetomotive force with a power function-based formulation. Since the induction motor performance is sensitive to its rotor circuit parameters, another realistic variation taken up in this work includes the impact of iron saturation, and skin effect altogether on rotor leakage inductance and rotor bar resistance. Additionally, the effects of non-linearity, such as temperature variations, are incorporated into the magnetizing inductance, while the permeance of rotor tooth-bridge segments is considered in the rotor leakage inductance and bar resistance. The effectiveness of the proposed model is demonstrated with simulation and experimental results of a 13 kW three-phase induction motor prototype for a wide range of operations. This method significantly improves the modelling of inductances, enhancing the accuracy of the electromagnetic torque predictions over a wide range of operating speeds. Achieving net-zero carbon emissions is crucial for transportation electrification, which necessitates the use of high-speed traction motors in electric vehicles that require a reliable design. Therefore, an improved method is proposed that effectively captures the non-linear effects in predicting the parameters and performance including the output torque of the machine.

Regarding the terminal localization in distributed MIMO networks, an indoor terminal localization system using a single access point (AP) based on distributed MIMO networks was proposed.Firstly, the AP’s antennas were arranged at different locations in the room, and the compressed sensing algorithm was used to estimate the angle of departure (AoD) and time of flight (ToF) of the receiving path on each antenna of the terminal device.Secondly, AoDs and ToFs of multiple paths were combined to establish a nonlinear localization model, and an improved Levenberg-Marquardt algorithm was used to solve the problem.Then, theoretical analysis has been examined for the factors that influence the localization error, and the criteria for the antenna layout was provided.Finally, electromagnetic simulation software was used to build simulation environment and conducted the simulation for system verification.Moreover, software-defined radio platforms were used to conduct practical tests.Both simulation and experimental results indicate that the performance of the proposed localization system is superior to existing single-AP localization systems based on natural multipath.

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns. It takes ∼24 h for tri-gas incubator to achieve steady cell hypoxia, which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion (IR) injury. Inspired from the structure of native intestinal villi, we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on co-axial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold. The chip was featured on: (i) eight times the oxygen exchange efficiency compared with the conventional device, tri-gas incubator, (ii) implantation of intestinal organoid reproducing all types of intestinal epithelial cells, and (iii) bio-responsiveness to hypoxia and reoxygenation (HR) by presenting metabolism disorder, inflammatory reaction, and cell apoptosis. Strikingly, it was found for the first time that Olfactomedin 4 (Olfm4) was the most significantly down-regulated gene under a rapid HR condition by sequencing the RNA from the organoids. Mechanistically, OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation, thus it could be used as a therapeutic target. Altogether, this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo, and sets an example of next-generation multisystem-interactive organoid chip for finding precise therapeutic targets of IR injury.

BackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China.MethodsA multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as “confirmed,” “probable,” or “possible” TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome—assessed using the modified Barthel disability index—were recorded and compared.FindingsA total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 “not TBM.” Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298–11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372–10.761), age > 60 years (OR = 3.566; 95%CI: 1.022–12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027–5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score 60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

Background: The significance of Kirsten rat sarcoma viral oncogene (KRAS) mutation in colorectal cancer (CRC) is well established; yet, its association with KRAS expression and prognosis warrants further investigation. While high KRAS expression is commonly linked with poorer prognosis in other cancers, its role in CRC remains relatively understudied. Objective: To explore the correlation between KRAS expression, KRAS status, prognosis, and tumor-infiltrating T lymphocyte density in CRC. Design: Single-center retrospective study. Methods: Conducted between 2010 and 2020, this study utilized tumor samples to assess KRAS expression and quantify CD3+/CD8+ T lymphocytes. The Cox proportional hazards model and linear regression analysis were employed to examine the relationship between KRAS expression, prognosis, and tumor-infiltrating T lymphocytes. Results: This study included 265 CRC patients who underwent radical surgery. No significant association was observed between KRAS expression and KRAS status ( p > 0.05). High KRAS expression was associated with poorer overall survival and disease-free survival ( p 0.05). Notably, KRAS expression showed a negative correlation with the density of CD8+ T lymphocytes in tumor tissue ( p

Background Stroke is a disease with high morbidity, disability, and mortality. Immune factors play a crucial role in the occurrence of ischemic stroke (IS), but their exact mechanism is not clear. This study aims to identify possible immunological mechanisms by recognizing immune-related biomarkers and evaluating the infiltration pattern of immune cells. Methods We downloaded datasets of IS patients from GEO, applied R language to discover differentially expressed genes, and elucidated their biological functions using GO, KEGG analysis, and GSEA analysis. The hub genes were then obtained using two machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)) and the immune cell infiltration pattern was revealed by CIBERSORT. Gene-drug target networks and mRNA-miRNA-lncRNA regulatory networks were constructed using Cytoscape. Finally, we used RT-qPCR to validate the hub genes and applied logistic regression methods to build diagnostic models validated with ROC curves. Results We screened 188 differentially expressed genes whose functional analysis was enriched to multiple immune-related pathways. Six hub genes (ANTXR2, BAZ2B, C5AR1, PDK4, PPIH, and STK3) were identified using LASSO and SVM-RFE. ANTXR2, BAZ2B, C5AR1, PDK4, and STK3 were positively correlated with neutrophils and gamma delta T cells, and negatively correlated with T follicular helper cells and CD8, while PPIH showed the exact opposite trend. Immune infiltration indicated increased activity of monocytes, macrophages M0, neutrophils, and mast cells, and decreased infiltration of T follicular helper cells and CD8 in the IS group. The ceRNA network consisted of 306 miRNA-mRNA interacting pairs and 285 miRNA-lncRNA interacting pairs. RT-qPCR results indicated that the expression levels of BAZ2B, C5AR1, PDK4, and STK3 were significantly increased in patients with IS. Finally, we developed a diagnostic model based on these four genes. The AUC value of the model was verified to be 0.999 in the training set and 0.940 in the validation set. Conclusion Our research explored the immune-related gene expression modules and provided a specific basis for further study of immunomodulatory therapy of IS.

Abstract High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Abstract Due to the rapid development of today's industry, it not only greatly accelerates the consumption of energy, but also causes serious pollution to the environment. Therefore, reducing energy waste and recovering energy has become an important research direction today. This paper introduces the future development trend of renewable energy, discusses the progress of recovery of nonpolluting energy such as marine, bioenergy and thermal energy, and analyzes the efficiency and social benefits of various types of energy recovery. Energy recovery methods for natural gas pipelines are briefly analyzed, and current research advances in energy pressure recovery devices are provided, leading to a summary of methods to improve the efficiency of fluid energy recovery. Finally, it is concluded that although the current energy sources are diversified, the most valued energy sources at present and in the future should be solar energy and ocean, which are infinitely recyclable. This paper will benefit researchers to further understand and study the various aspects of energy recovery.

In this paper, vacuum annealing has been adopted to introduce atomic cluster micro-regions inside Gd-based metallic microfibers to further explore the effect of the structural changes on the magnetocaloric properties and the mechanism which is systematically expressed. The experimental results indicate that the as-prepared Gd-based metallic microfibers have favorable amorphous formation ability and thermal stability. After annealing @ 380 °C, the maximum magnetic entropy change −ΔSmmax, refrigerating capacity (RC), and relative cooling power (RCP) values of the Gd-based metallic microfibers are 7.20 J/kg·K, 459.4 J/kg, and 588.7 J/kg, respectively. Combined with the transmission electron microscopy analysis results, the internal organizational order of the annealed microfibers is significantly altered, and the atomic clusters formed in localized regions, which reduce the magnetocrystalline anisotropy of the microfibers. While under the uni-action of an external magnetic field, the magnetic moment rotation state and magnetic domain structure distribution of the micro-region atoms will be changed obviously, thereby changing the general magnetic properties and magnetocaloric properties of the metallic microfibers. The above research results can promote the engineering application of Gd-based metallic microfibers in the field of magnetic refrigeration.

An automatic composition system that includes music generation and music assessment is designed in this paper. In terms of music generation, we modify the Transformer-XL model for generating music. The Mask mechanism based on Transformer-XL is improved to make the attention of model tend to pay on the bidirectional information, so that the generated popular piano music forms a coherent whole. In terms of music assessment, we combine objective and subjective assessment to judge the generated music in a comprehensive way. Meanwhile, we put forward a new objective assessment method, namely the piano roll classification scoring network. It converts music into pictures and uses classification models in the CV, enabling the network itself to classify and score the generated music. The assessment results from subjective and objective experiments show that by improving the Mask mechanism of Transformer-XL, the model is trained to be better and the generated music could achieve the effect of imitating the real music.

Introduction: Patients undergoing maintenance hemodialysis are vulnerable to coronavirus disease 2019 (COVID-19), exhibiting a high risk of hospitalization and mortality. Thus, early identification and intervention are important to prevent disease progression in these patients. Methods: This was a two-center retrospective observational study of patients on hemodialysis diagnosed with COVID-19 at the Lingang and Xuhui campuses of Shanghai Sixth People’s Hospital. Patients were randomized into the training (130) and validation cohorts (54), while 59 additional patients served as an independent external validation cohort. Artificial intelligence-based parameters of chest computed tomography (CT) were quantified, and a nomogram for patient outcomes at 14 and 28 days was created by screening quantitative CT measures, clinical data, and laboratory examination items, using univariate and multivariate Cox regression models. Results: The median dialysis duration was 48 (interquartile range, 24–96) months. Age, diabetes mellitus, serum phosphorus level, lymphocyte count, and chest CT score were identified as independent prognostic indicators and included in the nomogram. The concordance index values were 0.865, 0.914, and 0.885 in the training, internal validation, and external validation cohorts, respectively. Calibration plots showed good agreement between the expected and actual outcomes. Conclusion: This is the first study in which a reliable nomogram was developed to predict short-term outcomes and survival probabilities in patients with COVID-19 on hemodialysis. This model may be helpful to clinicians in treating COVID-19, managing serum phosphorus, and adjusting the dialysis strategies for these vulnerable patients to prevent disease progression in the context of COVID-19 and continuous emergence of novel viruses.

Hypertension induces cardiac fibrotic remodelling characterised by the phenotypic switching of cardiac fibroblasts (CFs) and collagen deposition. We tested the hypothesis that Wnt1-inducible signalling pathway protein-1 (WISP-1) promotes CFs’ phenotypic switch, type I collagen synthesis, and in vivo fibrotic remodelling. The treatment of human CFs (HCFs, n = 16) with WISP-1 (500 ng/mL) induced a phenotypic switch (α-smooth muscle actin-positive) and type I procollagen cleavage to an intermediate form of collagen (pC-collagen) in conditioned media after 24h, facilitating collagen maturation. WISP-1-induced collagen processing was mediated by Akt phosphorylation via integrin β1, and disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS-2). WISP-1 wild-type (WISP-1+/+) mice and WISP-1 knockout (WISP-1−/−) mice (n = 5–7) were subcutaneously infused with angiotensin II (AngII, 1000 ng/kg/min) for 28 days. Immunohistochemistry revealed the deletion of WISP-1 attenuated type I collagen deposition in the coronary artery perivascular area compared to WISP-1+/+ mice after a 28-day AngII infusion, and therefore, the deletion of WISP-1 attenuated AngII-induced cardiac fibrosis in vivo. Collectively, our findings demonstrated WISP-1 is a critical mediator in cardiac fibrotic remodelling, by promoting CFs’ activation via the integrin β1-Akt signalling pathway, and induced collagen processing and maturation via ADAMTS-2. Thereby, the modulation of WISP-1 levels could provide potential therapeutic targets in clinical treatment.

Abstract Oxidative stress plays a crucial role in the pathogenesis of hepatic encephalopathy (HE), but the mechanism remains unclear. GABAergic neurons in substantia nigra pars reticulata (SNr) contribute to the motor deficit of HE. The present study aims to investigate the effects of oxidative stress on HE in male mice. The results validate the existence of oxidative stress in both liver and SNr across two murine models of HE induced by thioacetamide (TAA) and bile duct ligation (BDL). Systemic mitochondria-targeted antioxidative drug mitoquinone (Mito-Q) rescues mitochondrial dysfunction and oxidative injury in SNr, so as to restore the locomotor impairment in TAA and BDL mice. Furthermore, the GAD2-expressing SNr population (SNrGAD2) is activated by HE. Both overexpression of mitochondrial uncoupling protein 2 (UCP2) targeted to SNrGAD2 and SNrGAD2-targeted chemogenetic inhibition targeted to SNrGAD2 rescue mitochondrial dysfunction in TAA-induced HE. These results define the key role of oxidative stress in the pathogenesis of HE.

GMI characteristics of Co-based metallic microfibers under different stresses are tested by stress torsional magneto-impedance comprehensive platform. The internal stress distribution of microfibers is simulated with ANSYS finite element software and the fracture mechanism is analyzed based on fracture morphology. The experimental results indicate that tensile stress can enhance the GMI effect of metallic microfibers, and the significant [ΔZ/Zmax]max of 293.63% at a frequency of 3 MHz is obtained under the tensile stress of 482 MPa. The simulation results demonstrate that the internal stress concentration occurs at clamping end under tensile stress, and which accumulating on the surface of microfibers after applying torsional strain, thus weakening GMI effect. The fracture morphology will change with external stress, some vein-shaped patterns and molten drops can be seen in the cross-section under tensile stress, and the helical vein-shaped patterns appear with the application of torsional strain. In addition, the circular domain wall energy will be increased due to magnetoelastic anisotropy has been affected by tensile stress, which promotes an increment of circular magnetic permeability, thus improving the GMI effect of microfibers. However, the appearance of helical anisotropy after torsional strain is added will weaken the circular domain wall energy.

The Righi–Leduc heat flux generated by the self-generated magnetic field in the ablative Rayleigh–Taylor instability driven by a laser irradiating thin targets is studied through two-dimensional extended-magnetohydrodynamic simulations. The perturbation structure gets into a low magnetization state though the peak strength of the self-generated magnetic field could reach hundreds of teslas. The Righi–Leduc effect plays an essential impact both in the linear and nonlinear stages, and it deflects the total heat flux towards the spike base. Compared to the case without the self-generated magnetic field included, less heat flux is concentrated at the spike tip, finally mitigating the ablative stabilization and leading to an increase in the velocity of the spike tip. It is shown that the linear growth rate is increased by about 10% and the amplitude during the nonlinear stage is increased by even more than 10% due to the feedback of the magnetic field, respectively. Our results reveal the importance of Righi–Leduc heat flux to the growth of the instability and promote deep understanding of the instability evolution together with the self-generated magnetic field, especially during the acceleration stage in inertial confinement fusion.

Background: Alzheimer’s disease (AD), an age-associated neurodegenerative disorder, currently lacks effective clinical therapeutics. Traditional Chinese Medicine (TCM) holds promising potential in AD treatment, exemplified by Danggui Shaoyao San (DSS), a TCM formulation. The precise therapeutic mechanisms of DSS in AD remain to be fully elucidated. This study aims to uncover the therapeutic efficacy and underlying mechanisms of DSS in AD, employing an integrative approach encompassing gut microbiota and metabolomic analyses.Methods: Thirty Sprague-Dawley (SD) rats were allocated into three groups: Blank Control (Con), AD Model (M), and Danggui Shaoyao San (DSS). AD models were established via bilateral intracerebroventricular injections of streptozotocin (STZ). DSS was orally administered at 24 g·kg−1·d−1 (weight of raw herbal materials) for 14 days. Cognitive functions were evaluated using the Morris Water Maze (MWM) test. Pathological alterations were assessed through hematoxylin and eosin (HE) staining. Bloodstream metabolites were characterized, gut microbiota profiled through 16S rDNA sequencing, and cortical metabolomics analyzed. Hippocampal proinflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using RT-qPCR, and oxidative stress markers (SOD, CAT, GSH-PX, MDA) in brain tissues were measured with biochemical assays.Results: DSS identified a total of 1,625 bloodstream metabolites, predominantly Benzene derivatives, Carboxylic acids, and Fatty Acyls. DSS significantly improved learning and spatial memory in AD rats and ameliorated cerebral tissue pathology. The formulation enriched the probiotic Ligilactobacillus, modulating metabolites like Ophthalmic acid (OA), Phosphocreatine (PCr), Azacridone A, Inosine, and NAD. DSS regulated Purine and Nicotinate-nicotinamide metabolism, restoring balance in the Candidatus Saccharibacteria-OA interplay and stabilizing gut microbiota-metabolite homeostasis. Additionally, DSS reduced hippocampal IL-1β, IL-6, TNF-α expression, attenuating the inflammatory state. It elevated antioxidative enzymes (SOD, CAT, GSH-PX) while reducing MDA levels, indicating diminished oxidative stress in AD rat brains.Conclusion: DSS addresses AD pathology through multifaceted mechanisms, encompassing gut microbiome regulation, specific metabolite modulation, and the mitigation of inflammation and oxidative stress within the brain. This holistic intervention through the Microbial-Gut-Brain Axis (MGBA) underscores DSS’s potential as an integrative therapeutic agent in combatting AD.

Bisphenol S (BPS) is a raw material that is used extensively in various manufacturing processes but possesses a high detection rate in human red blood cells (RBCs). Accordingly, BPS is a potential toxicant in disturbing the function of RBCs and causing RBC-related diseases. To date, the effects and mechanisms of BPS-induced RBC-related diseases have not been elucidated. Here, using different models, including rats, zebrafish embryos and RBCs, the underlying mechanism of RBC-related diseases induced by BPS was explored. The accumulation of BPS in tissue was colon > kidney > liver > plasma > testicle > heart > brain in SD rats orally administered BPS (10 and 50 mg/kg bw/day) for 32 days, which was similar in both 10 mg/kg bw/day and 50 mg/kg bw/day group. Rats given BPS orally developed hyperlipidemia and increased RBC membrane cholesterol, as well as changes in RBC morphology and function. Moreover, BPS at the concentrations measured in rats plasma caused oxidative stress and phosphatidylserine exposure in vitro RBCs. These combined factors led to RBC aggregation in blood and an increasing in the number of RBCs in the blood vessels of the liver in rats. The dynamic visual observation of RBCs in vein vessels of zebrafish embryos exposed to BPS at 0, 1, 10 and 100 μg/L further found that the flow of RBCs in the tail vein is slow or even immobile, posing the risk of venous thrombosis. The present study provides new insight into the links between environmental pollutants and venous thrombosis.

Objective To systematically evaluate the incidence of adverse transfusion reactions in Chinese children, so as to provide scientific basis for prevention and early intervention. Methods Literature databases such as PubMed, EMbase, The Cochrane Library, CNKI, Wanfang and VIP were searched in terms of the incidence of adverse transfusion reactions in Chinese children from January 2000 to December 2022. Two researchers extracted literature data independently according to the inclusion and exclusion criteria and conducted quality evaluation of included studies according to AHRQ quality evaluation scale. Statistical analysis was performed using Stata 14.0 software. Results A total of 870 literatures were retrieved, and 13 were included in the study, with a total of 181 274 cases with blood transfusion. Meta-analysis showed that the overall incidence of adverse transfusion reactions in Chinese children was 0.79%[95%CI (0.54%, 1.04%)]. The incidence of adverse reactions of red blood cells, platelets and plasma were 0.34%[95%CI (0.15%, 0.54%)], 2.94%[95%CI (1.60%, 4.28%)] and 0.31%[95%CI (0.19%, 0.43%)], respectively. The incidence of fever reaction and anaphylaxis reaction were 0.22%[95%CI (0.13%, 0.31%)] and 0.46%[95%CI (0.30%, 0.61%)] respectively. Conclusion The overall incidence of adverse transfusion reactions in Chinese children is low, but the incidence of adverse reactions of platelet transfusion is high, which needs further prevention and control.

Abstract In order to study the pseudo entropy of timelike subregions holographically, the previous smooth space-like extremal surface was recently generalized to mix space-like and time-like segments and the area becomes complex value. This paper finds that, if one tries to use such kind of piecewise smooth extremal surfaces to compute timelike entanglement entropy holographically, the complex area is not unique in general. We then generalize the original holographic proposal of spacelike entanglement entropy to pick up a unique area from all allowed “space-like+time-like” piecewise smooth extremal surfaces for a timelike subregion. We give some concrete examples to show the correctness of our proposal.

In the field of remote sensing image captioning (RSIC), mainstream methods typically adopt an encoder–decoder framework. Methods based on this framework often use only simple feature fusion strategies, failing to fully mine the fine-grained features of the remote sensing image. Moreover, the lack of context information introduction in the decoder results in less accurate generated sentences. To address these problems, we propose a two-stage feature enhancement model (TSFE) for remote sensing image captioning. In the first stage, we adopt an adaptive feature fusion strategy to acquire multi-scale features. In the second stage, we further mine fine-grained features based on multi-scale features by establishing associations between different regions of the image. In addition, we introduce global features with scene information in the decoder to help generate descriptions. Experimental results on the RSICD, UCM-Captions, and Sydney-Captions datasets demonstrate that the proposed method outperforms existing state-of-the-art approaches.

Composite foundations have been widely used and promoted in practical engineering applications. However, research on the joint-bearing mechanism of piles and soil within composite foundations is still not comprehensive enough. This paper proposes a method for calculating the additional internal forces of piles and soil within composite foundations. Based on a three-dimensional finite element analysis, this study investigates the variation patterns of the stress, displacement, and additional internal forces of piles and soil in the depth direction under the action of upper loads when using friction piles and end-bearing piles. This research aims to reveal the bearing performance of piles and soil. The results showed that, under the same conditions and due to the presence of end-bearing effects, the internal forces experienced by the entire pile body of the end-bearing piles were more uniform, exhibiting significant advantages in resisting deformation and being able to withstand larger loads. Additionally, the diffusion mechanism of the vertical forces, stresses, and displacements of piles and soil is discussed. Due to the negative frictional resistance of soil and the influence of pile end-bearing effects, the distribution of internal forces and the displacements of piles and soil exhibited different characteristics. This study provides a scientific reference for the theoretical analysis and design of composite foundations.

The purple-leaf phenotype in pak choi is due to the accumulation of anthocyanin. The main regulated genes are unclear. The gene controlling the purple-leaf phenotype was mapped on A03 using BSA-seq, but the candidate interval was not further narrowed with InDel markers. Based on our previous study, we hypothesized that the candidate gene that regulates purple leaves in pak choi may also be the Dark_Pur gene from B. juncea. Using the Dark_Pur-1 marker to identify P1, P2, F1, and F2, it was confirmed that the purple trait in purple-leaf pak choi was controlled by the Dark_Pur gene from B. juncea through distant hybridization. A DNA segment of approximately 514 Kb containing the Dark_Pur gene was reintroduced into pak choi from B. juncea. Meanwhile, a new purple pak choi germplasm line was created with green pak choi × purple B. juncea via distant hybridization, which proved that distant hybridization is an effective method for creating new germplasms. Furthermore, the purple-leaf phenotypes of 20 pak choi varieties were identified, and the purple-leaf traits of all lines were derived from B. juncea via distant hybridization. At present, few studies have focused on the background of the purple trait in pak choi; however, in this study, our results suggest that there is a high probability that the purple trait in pak choi may be completely derived from purple B. juncea via distant hybridization. This study also lays a good foundation for research on the creation of new germplasms through distant hybridization among the Brassica species.

Gastric ulcers significantly impact the quality of life of patients, the pathogenesis of which is closely associated with Helicobacter pylori (HP) infection. Oxidative stress is involved in the pathological mechanism of gastric ulcers. Recently, adenosine A2B Receptor (A2BR) was reported to activate the p38MAPK pathway. However, the role of A2BR in gastric ulcers remains unknown. In the present study, the biological function of A2BR in HP-induced gastric ulcers was investigated to explore novel targets for gastric ulcers. GES-1 cells were infected with HP, followed by incubation with 10 μM BAY60-6583 (A2BR agonist) and 25 nM PSB1115 (A2BR antagonist). In HP-infected GES-1 cells, an increased apoptotic rate, enhanced migration ability, excessive release of reactive oxygen species (ROS), increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity were observed, accompanied by the activation of p38MAPK signaling, which were dramatically aggravated by BAY60-6583 and alleviated by PSB1115. In animal experiments, rats were treated with 2 mg/kg BAY60-6583 and 10 mg/kg PSB1115, followed by gastric ulcer modeling 30 min later. In HP-infected rats, increased ulcer area, elevated pepsin activity, increased hematoxylin and eosin (HE) pathological scores, increased MDA levels, and decreased SOD activity were observed, which were further aggravated by BAY60-6583 and ameliorated by PSB1115. Finally, the effects of A2BR activation on apoptosis, migration, oxidative stress, and p38MAPK signaling in HP-infected GES-1 cells were reversed by an inhibitor of the p38MAPK pathway. Collectively, A2BR facilitated the pathogenesis of HP-induced gastric ulcers by inducing oxidative stress through p38MAPK activation.

The energy usage of parallel chillers systems accounts for 25–40 % of the total energy cost of a building. In light of global warming concerns and the need for energy conservation, it is essential to distribute the load of the parallel chillers systems effectively to achieve energy savings in buildings. Accordingly, this study presents a multi-strategy improved sparrow search algorithm (MSSA) to address optimization of the optimal chillers loading (OCL) problem. The proposed algorithm augments the basic sparrow search algorithm (SSA) by introducing the Sine chaotic map, Levy flight method, and Cauchy variation to enhance diversity, avoid local optima, and increase global and local search capacities. We use 9 benchmark functions to check the performance of the proposed MSSA algorithm, and the results are better than the selected algorithms such as particle swarm algorithm (PSO), harris hawks optimization (HHO), artificial rabbit optimization (ARO) and sparrow search algorithm (SSA). In addition, MSSA is applied to two typical cases to demonstrate its performance to optimal chillers loading and the results indicate that the MSSA outperforms similar algorithms. This study validates that MSSA can provide a promising solution to resolve the OCL problem.