Clinical and etiological characteristics of severe hemorrhagic fever caused by coinfection of hantaan orthohantavirus and severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS) usually have different infection routes, and coinfection is relatively rare. This study examines the clinical and etiological characteristics of coinfection by these two pathogens to provide important references for clinical diagnosis and treatment. Blood samples from 22 clinically diagnosed patients with HFRS were collected for molecular detection of HFRS and common tick and mouse borne diseases. Inoculate the blood of six severe and critically patients into cells to isolate and proliferate potential viruses, and retest the cell culture to determine the pathogen. In addition, complete data were collected from these 22 HFRS and concurrent SFTS patients, and white blood cells (WBCs), platelet (PLT), blood urea nitrogen (BUN), creatinine (Cr) and other data were compared and analyzed. A total of 31 febrile patients, including 22 HFRS patients and 9 SFTS patients, were collected from September 2021 to October 2022. Among these HFRS patients, 11 were severe or critical. Severe and critical HFRS patients were characterized by rodent exposure history, pharyngeal and conjunctival hyperemia, abnormal WBC and PLT counts, and elevated BUN and Cr values. Virus isolation and molecular detection on blood samples from 6 patients showed that three of the six severe patients were positive for hantaan virus (HTNV), and two of the three HTNV positives were also positive for SFTS bunyavirus (SFTSV). The two coinfected patients exhibited different clinical and laboratory characteristics compared to those infected by either virus alone. Coinfection of HTNV and SFTSV leads to severe and complex hemorrhagic fever. Laboratory characteristics, such as the indicators of WBC, PLT, BUN, and Cr, may differ between HFRS and SFTS. These findings have implications and provide references for the diagnosis and treatment of coinfected cases.

Brain plasticity following lumbar disc herniation treatment with spinal manipulation therapy based on resting-state functional magnetic resonance imaging.

As a prevalent spine disorder, Lumbar disc herniation (LDH) has been affecting more than 2 % of the worldwide population and is characterised by uncertain causes and recurring episodes. Studying the brain activity of patients could potentially provide insights into its pathogenesis and significantly enhance therapy. Therefore, we here examined brain function in patients under Spinal Manipulative Therapy (SMT). By analysing regional homogeneity (ReHo) at different frequency bands, we identified the discrepancies in brain activity between LDH patients and healthy people, highlighting the frequency dependence of spontaneous low-frequency oscillations among patients with LDH. Choosing seeds based on the peak ReHo differences helped to elucidate the functional connectivity alterations in the brain regions of LDH. Overall, this study showed that SMT significantly reduced pain, improved dysfunction, and partially rectified aberrant local consistency and functional connection in patients with LDH, not only offering insights into the pathophysiology of LDH from a neurological standpoint, but also providing inspiration for the development of new therapies based on neurobiology.

Enamine Acylation Enabled Desymmetrization of Malonic Esters.

Asymmetric enamine alkylation represents a powerful tool for stereoselective C-C bond formation; in contrast, the development of enantioselective enamine acylation remains elusive. Here, we report that a chiral phosphoric acid can render an in-situ-formed enamine to undergo a stereoselective intramolecular α-carbon acylation, providing an alternative approach for the synthesis of useful pyrrolinones and indolinones bearing tetrasubstituted stereocenters. Utilizing an effective integration of the desymmetrization strategy and bifunctional organocatalysis, the first example of enantioselective enamine acylation is achieved by employing readily available aminomalonic esters and cyclic ketones. Instead of reactive and moisture-sensitive acyl chlorides, common esters with low electrophilicity were successfully used as efficient acylating reagents via hydrogen bonding interactions. The utility is demonstrated in the concise and enantioselective synthesis of (+)-LipidGreen I and II. Experimental studies and DFT calculations establish the reaction pathway and the origin of stereocontrol.

Effect of moxibustion on ATP-sensitive potassium channel (KATP) of bladder in detrusor overactivity rats. / 隔姜隔盐灸"神阙"å¯¹é€¼å°¿è‚Œè¿‡åº¦æ´»åŠ¨å¤§é¼ è†€èƒ±ATP敏感性钾离子通道的影响.

OBJECTIVES: To observe the effect of ginger-salt-partitioned moxibustion on ATP-sensitive potassium (KATP) channel of bladder in detrusor overactivity (DO) rats. METHODS: Female SD rats were randomly divided into sham operation, model, moxibustion and antagonist groups (n=9 in each group). Thorax (T) 10 spinal cord transection was performed by surgery. Ginger-salt partitioned moxibustion was applied to "Shenque" (CV8) for 3 cones, once daily for 14 consecutive days. Rats of the antagonist group were intraperitoneally injected with KATP channel specific antagonist glibenclamide (10 µg·kg-1·d-1) once daily for 14 consecutive days. Urodynamic tests were performed after treatment. The distribution and expression of KATP channel tetrameric subunit (SUR2B) in the bladder of rats was observed by immunofluorescence. The protein and mRNA expression levels of SUR2B in bladder tissue were detected by Western blot and qPCR respectively. RESULTS: Compared with the sham operation group, rats of the model group showed intensive and large phasic contractions of the detrusor during bladder filling, the frequency and amplitude of phasic contractions of the detrusor 5 min before leakage were significantly increased (P<0.001)；the voiding threshold pressure was significantly decreased (P<0.001)；the bladder perfusion volume was increased (P<0.001)；the SUR2B protein and mRNA expression in bladder tissue were significantly reduced (P<0.001). Compared with the model group and the antagonist group, the above-mentioned indicators in the moxibustion group were all reversed (P<0.01, P<0.001, P<0.05). CONCLUSIONS: Ginger-salt partitioned moxibustion can reduce the frequency and amplitude of detrusor phase contraction during bladder filling and prolong the time of first phase contraction in DO rats, which may be associated with up-regulating the expression level of KATP channel protein and mRNA, promoting the outflow of potassium ions, and inhibiting the inflow of calcium ions, thus improve the stability of detrusor during storage.

Relationship Between Growth Mindset and Self-Control Amongst Chinese Primary School Students: A Longitudinal Study.

Purpose: Growth mindset and self-control, both recognized as pivotal qualities with significant impacts on personal success, possess respective robust predictive power for academic achievement and broader life outcomes. However, the bidirectional relationship between them remains largely unexplored. This study aims to investigate whether growth mindset, conceptualized as the belief that abilities can be developed through effort and support, prospectively predicts the development of self-control over time. Additionally, it endeavors to explore whether self-control, a crucial positive psychological trait, exerts an influence on the fostering of growth mindset. In summary, our research focuses on elucidating the bidirectional relationship between growth mindset and self-control among Chinese primary school students. Participants and Methods: The current research recruited a sample of 428 primary school students, aged 9-12, from China (214 females, mean age = 9.64 ± 1.21) to participate in a longitudinal study. Participants underwent two follow-up assessments of growth mindset and self-control over a six-month period. Results: The correlation analysis revealed significant associations between growth mindset at T1 and self-control at T2, as well as between self-control at T1 and growth mindset at T2(r = 0.23 to 0.25, ps < 0.01). Cross-lagged analysis found that growth mindset at T1 positively predicted self-control at T2 (ß = 0.11, p = 0.04), while self-control at T1 did not significantly predict growth mindset at T2. Conclusion: The results suggest that growth mindset exerts a direct impact on self-control among primary school students. This finding extends the scope of research concerning growth mindset and provides important theoretical inspiration and practical guidance for educators, parents and counselling professionals in assisting students to enhance self-control.

Mining expressed sequence tag (EST) microsatellite markers to assess the genetic differentiation of five Hynobius species endemic to Taiwan.

Taiwan harbors five endemic species of salamanders (Hynobius spp.) that inhabit distinct alpine regions, contributing to population fragmentation across isolated "sky islands". With an evolutionary history spanning multiple glacial-interglacial cycles, these species represent an exceptional paradigm for exploring biogeography and speciation. However, a lack of suitable genetic markers applicable across species has limited research efforts. Thus, developing cross-amplifying markers is imperative. Expressed sequence-tag simple-sequence repeats (EST-SSRs) that amplify across divergent lineages are ideal for species identification in instances where phenotypic differentiation is challenging. Here, we report a suite of cross-amplifying EST-SSRs from the transcriptomes of the five Hynobius species that exhibit an interspecies transferability rate of 67.67%. To identify individual markers exhibiting cross-species polymorphism and to assess interspecies genetic diversity, we assayed 140 individuals from the five species across 84 sampling sites. A set of EST-SSRs with a high interspecies polymorphic information content (PIC = 0.63) effectively classified these individuals into five distinct clusters, as supported by discriminant analysis of principal components (DAPC), STRUCTURE assignment tests, and Neighbor-joining trees. Moreover, pair-wise FST values > 0.15 indicate notable between-cluster genetic divergence. Our set of 20 polymorphic EST-SSRs is suitable for assessing population structure within and among Hynobius species, as well as for long-term monitoring of their genetic composition.

NLRP1 inhibits lung adenocarcinoma growth through mediating mitochondrial dysregulation in an inflammasome-independent manner.

NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NLRP1 in LUAD. Decreased NLRP1 expression was identified in LUAD, which was associated with a poor prognosis. Overexpression of NLRP1 inhibited tumor growth in vitro and in vivo. Mechanically, this effect was observed regardless of inflammasome activation. Further studies revealed that overexpression of NLRP1 downregulated the phosphorylation of DRP1 and promoted mitochondrial fusion, which was mediated by inhibition of NF-κB activity. NF-κB agonist could neutralize the effect of NLRP1 on mitochondrial dynamics. In addition, LUAD sensitivity to cisplatin was enhanced by decreased mitochondrial fission resulting from up-regulated NLRP1. In conclusion, our findings demonstrated an unexpected role of NLRP1 in LUAD by modulating mitochondrial activities, which provides strong evidence for its potential in LUAD treatment.

Chemically programmed metabolism drives a superior cell fitness for cartilage regeneration.

The rapid advancement of cell therapies underscores the importance of understanding fundamental cellular attributes. Among these, cell fitness-how transplanted cells adapt to new microenvironments and maintain functional stability in vivo-is crucial. This study identifies a chemical compound, FPH2, that enhances the fitness of human chondrocytes and the repair of articular cartilage, which is typically nonregenerative. Through drug screening, FPH2 was shown to broadly improve cell performance, especially in maintaining chondrocyte phenotype and enhancing migration. Single-cell transcriptomics indicated that FPH2 induced a super-fit cell state. The mechanism primarily involves the inhibition of carnitine palmitoyl transferase I and the optimization of metabolic homeostasis. In animal models, FPH2-treated human chondrocytes substantially improved cartilage regeneration, demonstrating well-integrated tissue interfaces in rats. In addition, an acellular FPH2-loaded hydrogel proved effective in preventing the onset of osteoarthritis. This research provides a viable and safe method to enhance chondrocyte fitness, offering insights into the self-regulatory mechanisms of cell fitness.

Amugulang virus, a novel hantavirus harboured by small rodents in Hulunbuir, China.

The Hulunbuir region, known for its diverse terrain and rich wildlife, is a hotspot for various natural epidemic diseases. Between 2021 and 2023, we collected 885 wild rodent samples from this area, representing three families, seven genera, and eleven species. Metagenomic analysis identified three complete nucleic acid sequences from the S, M, and L segments of the Hantaviridae family, which were closely related to the Khabarovsk virus. The nucleotide coding sequences for S, M, and L (1392 nt, 3465 nt, and 6491 nt, respectively) exhibited similarities of 82.34%, 81.68%, and 81.94% to known sequences, respectively, while protein-level analysis indicated higher similarities of 94.92%, 94.41%, and 95.87%, respectively. Phylogenetic analysis placed these sequences within the same clade as the Khabarovsk, Puumala, Muju, Hokkaido, Topografov, and Tatenalense viruses, all of which are known to cause febrile diseases in humans. Immunofluorescence detection of nucleic acid-positive rodent kidney samples using sera from patients with hemorrhagic fever and renal syndrome confirmed the presence of viral particles. Based on these findings, we propose that this virus represents a new member of the Hantaviridae family, tentatively named the Amugulang virus, after its primary distribution area.

Analysis of variation of serum CEA, SCC, CYFRA21-1 in patients with lung cancer and their diagnostic value with EBUS-TBNA.

Background: To explore the variation of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and squamous cell carcinoma (SCC) antigen in patients with lung cancer (LC) and their diagnostic value with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Methods: This study examined the diagnostic value of serum tumor marker testing and EBUS-TBNA joint detection for LC in 150 patients with suspected LC. Results: Compared to benign patients, the serum levels of CYFRA21-1, SCC, and CEA in LC were higher (P<0.05). In patients with squamous cell carcinoma (LSCC), small cell lung cancer (SCLC), and lung adenocarcinoma, lung adenocarcinoma had higher serum CEA levels (P<0.05). In comparison, LSCC patients had higher serum SCC and CYFRA21-1 levels (P<0.05). As compared to each index detected alone, the AUC of combined detection of each index to diagnose LC and identify pathological types of LC was elevated. Conclusions: The clinical significance of serum CYFRA21-1, SCC, and CEA conjugated with EBUS-TBNA is demonstrated for diagnostic purposes and identification of LC pathological types.

[Spatiotemporal Distributions and Variations in Summertime Ozone Photochemical Production Regimes over Shanxi].

Satellite-based formaldehyde（HCHO）columns and tropospheric nitrogen dioxide columns were observed using the Ozone Monitoring Instrument（OMI），and groundbased observations of ozone（O3）for May-August from 2013 to 2022 were connected to calculate the threshold values of the HCHO to NO2 ratio（FNR）in Shanxi Province. Then，the spatiotemporal distributions and variations in summertime ozone photochemical production regimes were analyzed. The results showed that：① The volatile organic compound（VOC） -sensitive regime area（FNR < 2.3）was obviously reduced，while the VOCs-NOx transitional regime（FNR between 2.3-4.1）area increased in the early years and then decreased， and NO x -sensitive regime area expanded significantly in summer from 2013 to 2022 over Shanxi Province. ② The increased summertime FNR during 2013 to 2019 was associated with the co-effect of increased HCHO columns and decreased tropospheric NO2 columns. The Shanxi Province was generally under an NOx regime since 2016，which reflected the remarkable effect of NO x emission reductions；however，there was a shift from a VOC-sensitive regime to a VOCs-NOx transitional regime，in which O3 pollution aggravation was widespread under the background of decreased NOx emissions. The decrease in O3 concentration during 2020 to 2022 followed the synergistical declines in HCHO columns and tropospheric NO2 columns. ③ The O3 weekend effects were reversed in Linfen and Yuncheng but were persistent in the other nine cities. Satellite-based weekend HCHO and NO2 levels were higher than those on weekdays in some cities of Shanxi Province，indicating that the O3 weekend effect was not only dependent on the changes of precursors emissions but was also closely related to O3 photochemical production sensitivity. The results indicated the necessity of simultaneous controls in NOx emissions and VOCs emissions for ozone abatement plans over Shanxi Province. In addition，Taiyuan，Yangquan，Yuncheng，and Jincheng should continue to promote reduction in NOx emissions.

The anti-COVID-19 drug nirmatrelvir crosses the blood‒brain barrier and exhibits herb-drug pharmacokinetic interactions with Scutellaria baicalensis formulations.

Aim of the study: Our hypothesis is that nirmatrelvir can penetrate the blood‒brain barrier and reach effective concentrations in the brain. Furthermore, herbal formulations can help maintain nirmatrelvir levels in the body, suggesting potential interactions between these medications. Materials and methods: To investigate this hypothesis, an animal model combining multisite microdialysis, ultrahigh-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) methods was developed to monitor nirmatrelvir levels in the blood and brain of rats. Results: The pharmacokinetic results showed that the area under the curve (AUC) of nirmatrelvir in the blood and brain was 798.3 ± 58.56 and 187.2 ± 23.46 min µg/mL, respectively, after the administration of nirmatrelvir alone (15 mg/kg, iv). When the Scutellaria baicalensis formulations were administered for five consecutive days prior to drug administration, the AUC of nirmatrelvir in the blood increased. Conclusions: These results provide constructive preclinical information that the concentrations of nirmatrelvir in the blood and brain were greater than the effective concentration (EC90) for more than 6 h, and the Scutellaria baicalensis formulations had synergistic pharmacokinetic effects by increasing the concentration of nirmatrelvir in the blood.

Identification of copper death-associated molecular clusters and immunological profiles for lumbar disc herniation based on the machine learning.

Lumbar disc herniation (LDH) is a common clinical spinal disorder, yet its etiology remains unclear. We aimed to explore the role of cuproptosis-related genes (CRGs) and identify potential diagnostic biomarkers. Our analysis involved interrogating the GSE124272 and GSE150408 datasets for differential gene expression profiles associated with CRGs and immune characteristics. Molecular clustering was performed on LDH samples, followed by expression and immune infiltration analyses. Using the WGCNA algorithm, specific genes within CRG clusters were identified. After selecting the most predictive genes from the optimal model, four machine learning models were constructed and validated. This study identified nine CRGs associated with copper-regulated cell death. Two copper-containing molecular clusters linked to death were detected in LDH samples. Elevated expression and immune infiltration levels were found in LDH patients, particularly in CRG cluster C2. Utilizing XGB, five genes were identified for constructing a diagnostic model, achieving an area under the curve values of 0.715. In conclusion, this research provides valuable insights into the association between LDH and copper-regulated cell death, alongside proposing a promising predictive model.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

Low concentrations of tetrabromobisphenol A promote the biofilm formation of methicillin-resistant Staphylococcus aureus.

The effect and underlying mechanism of tetrabromobisphenol A (TBBPA), a plastic additive, on biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA USA300) remain unknown. This study first investigated the impact of different concentrations of TBBPA on the growth and biofilm formation of USA300. The results indicated that a low concentration (0.5 mg/L) of TBBPA promoted the growth and biofilm formation of USA300, whereas high concentrations (5 mg/L and 10 mg/L) of TBBPA had inhibitory effects. Further exploration revealed that the low concentration of TBBPA enhance biofilm formation by promoting the synthesis of extracellular proteins, release of extracellular DNA (eDNA), and production of staphyloxanthin. RTqPCR analysis demonstrated that the low concentration of TBBPA upregulated genes associated with extracellular protein synthesis (sarA, fnbA, fnbB, aur) and eDNA formation (atlA) and increased the expression of genes involved in staphyloxanthin biosynthesis (crtM), suggesting a potential mechanism for enhanced resistance of USA300 to adverse conditions. These findings shed light on how low concentrations of TBBPA facilitate biofilm formation in USA300 and highlight the indirect impact of plastic additives on pathogenic bacteria in terms of human health. In the future, in-depth studies about effects of plastic additives on pathogenicity of pathogenic bacteria should be conducted. CAPSULE: The protein and eDNA contents in biofilms of methicillin-resistant Staphylococcus aureus are increased by low concentrations of TBBPA.

Establishment and characterization of a rat model of scalp-cranial composite defect for multilayered tissue engineering.

Composite cranial defects have individual functional and aesthetic ramifications, as well as societal burden, while posing significant challenges for reconstructive surgeons. Single-stage composite reconstruction of these deformities entail complex surgeries that bear many short- and long-term risks and complications. Current research on composite scalp-cranial defects is sparse and one-dimensional, often focusing solely on bone or skin. Thus, there is an unmet need for a simple, clinically relevant composite defect model in rodents, where there is a challenge in averting healing of the skin component via secondary intention. By utilizing a customizable (3D-printed) wound obturator, the scalp wound can be rendered non-healing for a long period (more than 6 weeks), with the cranial defect patent. The wound obturator shows minimal biotoxicity and will not cause severe endocranium-granulation adhesion. This composite defect model effectively slowed the scalp healing process and preserved the cranial defect, embodying the characteristics of a "chronic composite defect". In parallel, an autologous reconstruction model was established as the positive control. This positive control exhibited reproducible healing of the skin within 3 weeks with variable degrees of osseointegration, consistent with clinical practice. Both models provide a stable platform for subsequent research not only for composite tissue engineering and scaffold design but also for mechanistic studies of composite tissue healing.

Biportal Endoscopic Spinal Cord Stimulation Paddle Lead Implantation: Technical Note and Preliminary Clinical Results.

OBJECTIVE: This study aims to elucidate a novel, minimally invasive surgical technique using a biportal endoscope for the implantation of spinal cord stimulation (SCS) paddle leads and to report the preliminary results of its clinical application. MATERIALS AND METHODS: The perioperative data of patients who underwent the biportal endoscopic SCS paddle lead implantation in our department were collected; the surgical procedure was delineated, and the clinical outcomes were assessed. RESULTS: From February 2022 to December 2023, six patients underwent biportal endoscopic SCS paddle lead implantation. The median follow-up time was nine months (range one to three months). The median intraoperative blood loss was 30 mL (range 25-50 mL), and the median operative time was 87.5 minutes (range 75-110 minutes). One patient experienced severe neck pain during the operation, whereas the other five patients experienced no surgical complications. One patient was found to have a slight lead migration three months after surgery, which did not affect the therapeutic effect. The median visual analogue scale (VAS) of the surgical area was 0.5 (range 0-2), 2.5 (range 1-4), and 0.5 (range 0-1) during the operation and one day and one week after the operation, respectively. The median VAS of the six patients' primary disease was 8 (range 7-9) before surgery and 2.5 (range 1-4) at the last postoperative follow-up (pain reduction ≥50%). CONCLUSION: Paddle lead systems for SCS can be implanted successfully using a biportal endoscopic technique.

Cerebroprotein hydrolysate-I ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via the p53/SAT1/ALOX15 signalling pathway.

Ferroptosis, an iron-dependent lipid peroxidation-driven cell death pathway, has been linked to the development of Alzheimer's disease (AD). However, the role of ferroptosis in the pathogenesis of AD remains unclear. Cerebroprotein hydrolysate-I (CH-I) is a mixture of peptides with neurotrophic effects that improves cognitive deficits and reduces amyloid burden. The present study investigated the ferroptosis-induced signalling pathways and the neuroprotective effects of CH-I in the brains of AD transgenic mice. Seven-month-old male APPswe/PS1dE9 (APP/PS1) transgenic mice were treated with intraperitoneal injections of CH-I and saline for 28 days. The Morris water maze test was used to assess cognitive function. CH-I significantly improved cognitive deficits and attenuated beta-amyloid (Aß) aggregation and tau phosphorylation in the hippocampus of APP/PS1 mice. RNA sequencing revealed that multiple genes and pathways, including ferroptosis-related pathways, were involved in the neuroprotective effects of CH-I. The increased levels of lipid peroxidation, ferrous ions, reactive oxygen species (ROS), and altered expression of ferroptosis-related genes (recombinant solute carrier family 7, member 11 (SLC7A11), spermidine/spermine N1-acetyltransferase 1 (SAT1) and glutathione peroxidase 4 (GPX4)) were significantly alleviated after CH-I treatment. Quantitative real-time PCR and western blotting were performed to investigate the expression of key ferroptosis-related genes and the p53/SAT1/arachidonic acid 15-lipoxygenase (ALOX15) signalling pathway. The p53/SAT1/ALOX15 signalling pathway was found to be involved in mediating ferroptosis, and the activation of this pathway was significantly suppressed in AD by CH-I. CH-I demonstrated neuroprotective effects against AD by attenuating ferroptosis and the p53/SAT1/ALOX15 signalling pathway, thus providing new targets for AD treatment.

Rationally Improved Surface Charge Density of Triboelectric Nanogenerator with TiO2-MXene/Polystyrene Nanofiber Charge Trapping Layer for Biomechanical Sensing and Wound Healing Application.

Triboelectric nanogenerators (TENGs) have become reliable green energy harvesters by converting biomechanical motions into electricity. However, the inevitable charge leakage and poor electric field (EF) of conventional TENG result in inferior tribo-charge density on the active layer. In this paper, TiO2-MXene incorporated polystyrene (PS) nanofiber membrane (PTMx NFM) charge trapping interlayer is introduced into single electrode mode TENG (S-TENG) to prevent electron loss at the electrode interface. Surprisingly, this charge-trapping mechanism augments the surface charge density and electric output performance of TENGs. Polyvinylidene difluoride (PVDF) mixed polyurethane (PU) NFM is used as tribo-active layer, which improves the crystallinity and mechanical property of PVDF to prevent delamination during long cycle tests. Herein, the effect of this double-layer capacitive model is explained experimentally and theoretically. With optimization of the PTMx interlayer thickness, S-TENG exhibits a maximum open-circuit voltage of (280 V), short-circuit current of (20 µA) transfer charge of (120 nC), and power density of (25.2 µW cm-2). Then, this energy is utilized to charge electrical appliances. In addition, the influence of AC/DC EF simulation in wound healing management (vitro L929 cell migration, vivo tissue regeneration) is also investigated by changing the polarity of trans-epithelial potential (TEP) distribution in the wounded area.

The role of the AMPK/ERK1/2 signaling pathway in neuronal oxidative stress damage following cerebral ischemia-reperfusion.

Cerebral ischemia-reperfusion injury involves a series of pathophysiological processes that occur when blood supply is restored after cerebral vascular obstruction, leading to neuronal damage. The AMPK/ERK1/2 signaling pathway has been identified as crucial in this process, although the exact mechanisms underlying the induction of ischemia-reperfusion injury remain unclear. In this study, we investigated the involvement of the AMPK/ERK1/2 signaling pathway in neuronal oxidative stress damage following cerebral ischemia-reperfusion by establishing animal and cell models. Our experimental results demonstrated that cerebral ischemia-reperfusion leads to oxidative stress damage, including cell apoptosis and mitochondrial dysfunction. Moreover, further experiments showed that inhibition of AMPK and ERK1/2 activity, using U0126 and Compound C respectively, could alleviate oxidative stress-induced cellular injury, improve mitochondrial morphology and function, reduce reactive oxygen species levels, increase superoxide dismutase levels, and suppress apoptosis. These findings clearly indicate the critical role of the AMPK/ERK1/2 signaling pathway in regulating oxidative stress damage and cerebral ischemia-reperfusion injury. The discoveries in this study provide a theoretical basis for further research and development of neuroprotective therapeutic strategies targeting the AMPK/ERK1/2 signaling pathway.