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Background Traumatic brain injury (TBI) can cause damage to the blood-brain barrier, resulting in neuroinflammatory reactions and brain edema that seriously affect the recovery of neurological function. We hypothesize that an enriched environment (EE) regulates the TLR2/NF-κB signaling pathway and thereby modulates the integrity of the blood-brain barrier to achieve neuroprotective effects. Objective This study evaluated the expression of toll-like receptor (TLR)-2 after TBI in a rat model, with the aim of determining whether TLR2/NF-κB improves secondary brain injury by inhibiting the release of inflammatory factors and reducing brain edema. Methods We established a TBI model using Sprague-Dawley rats and implemented EE intervention or TLR2 siRNA to reduce TLR2. Western-blot analysis, real-time PCR, immunofluorescence staining, ELISA, TUNEL and FJC staining, wet–dry methods, rotarod testing, and neurological scoring were then applied for analysis. Results Our results revealed that TLR2 was activated after TBI in rats and that EE or silencing of TLR2 with TLR2 siRNA reduced the level of inflammation, significantly alleviating brain edema, neuronal apoptosis, and degeneration. TBI exacerbated brain edema and nerve damage caused by TLR2/NF-κB signaling, and EE appeared to regulate neuroinflammation and brain edema by reducing TLR2. Conclusions Inhibition of TLR2 with EE might constitute a successful approach in the management of TBI.

BackgroundThe status of sentinel lymph nodes is crucial for prognosis and treatment decisions in breast cancer patients. This study aimed to evaluate the predictive value of combined methylene blue and indocyanine green for sentinel lymph node metastasis in breast cancer.MethodsThis prospective cohort study enrolled 90 clinically node-negative breast cancer patients. Methylene blue and indocyanine green were injected locally before surgery. Sentinel lymph nodes were grouped based on fluorescence intensity and methylene blue staining. A binary logistic regression model was established using 285 lymph node groups to predict metastatic risk.ResultsA total of 475 lymph nodes were identified, with 33 being metastatic. The metastatic risk reached 70% for partially blue-stained and weakly fluorescent lymph nodes between 1-2 cm. The model revealed associations between lymph node size, dye staining patterns, and metastatic risks (P

Sensory signals from the body’s visceral organs (e.g. the heart) can robustly influence the perception of exteroceptive sensations. This interoceptive–exteroceptive interaction has been argued to underlie self-awareness by situating one’s perceptual awareness of exteroceptive stimuli in the context of one’s internal state, but studies probing cardiac influences on visual awareness have yielded conflicting findings. In this study, we presented separate grating stimuli to each of subjects’ eyes as in a classic binocular rivalry paradigm – measuring the duration for which each stimulus dominates in perception. However, we caused the gratings to ‘pulse’ at specific times relative to subjects’ real-time electrocardiogram, manipulating whether pulses occurred during cardiac systole, when baroreceptors signal to the brain that the heart has contracted, or in diastole when baroreceptors are silent. The influential ‘Baroreceptor Hypothesis’ predicts the effect of baroreceptive input on visual perception should be uniformly suppressive. In contrast, we observed that dominance durations increased for systole-entrained stimuli, inconsistent with the Baroreceptor Hypothesis. Furthermore, we show that this cardiac-dependent rivalry effect is preserved in subjects who are at-chance discriminating between systole-entrained and diastole-presented stimuli in a separate interoceptive awareness task, suggesting that our results are not dependent on conscious access to heartbeat sensations.

Brain Muscle ARNT-Like Protein 1 (BMAL1) suppresses oxidative stress in brain injury during surgery. Epigallocatechin-3-gallate (EGCG), a monomer in green tea, has been identified as an antioxidant and a potential agonist for BMAL1. In this work, the mechanism by which BMAL1 is regulated was investigated, as well as the therapeutic effect of EGCG on surgically injured rats. The pathological environment after brain injury during surgery was simulated by excising the right frontal lobe of rats. Rats received an intraperitoneal injection of EGCG immediately after surgery. Neurological scores and cerebral edema were recorded after surgery. Fluoro-Jade C staining, TUNEL staining, western blot, and lipid peroxidation analyses were conducted 3 days later. Here we show that the endogenous BMAL1 level decreased after brain injury. Postoperative administration of EGCG up-regulated the content of BMAL1 around the cerebral cortex, reduced the oxidative stress level, reduced neuronal apoptosis and the number of degenerated neurons, alleviated cerebral edema, and improved neurological scores in rats. This suggests that BMAL1 is an effective target for treating surgical brain injury, as well as that EGCG may be a promising agent for alleviating postoperative brain injury.

Abstract A century ago, the Warburg effect was first proposed, revealing that cancer cells predominantly rely on glycolysis during the process of tumorigenesis, even in the presence of abundant oxygen, shifting the main pathway of energy metabolism from the tricarboxylic acid cycle to aerobic glycolysis. Recent studies have unveiled the dynamic transfer of mitochondria within the tumor microenvironment, not only between tumor cells but also between tumor cells and stromal cells, immune cells, and others. In this review, we explore the pathways and mechanisms of mitochondrial transfer within the tumor microenvironment, as well as how these transfer activities promote tumor aggressiveness, chemotherapy resistance, and immune evasion. Further, we discuss the research progress and potential clinical significance targeting these phenomena. We also highlight the therapeutic potential of targeting intercellular mitochondrial transfer as a future anti-cancer strategy and enhancing cell-mediated immunotherapy. Graphical Abstract Mitochondrial Transfer in the Tumor Microenvironment. This review elaborates in detail on the molecular mechanisms and pathophysiological significance behind the mitochondrial transfer occurring between tumor cells and their microenvironment. This biological phenomenon of mitochondrial transfer is prevalent in a variety of cancers, including both solid tumors and hematologic malignancies, with a high incidence in acute myeloid leukemia (AML), breast cancer, and gliomas. The review also discusses therapeutic approaches targeting mitochondrial transfer, with a special focus on its application in immunotherapy, particularly in CAR-T cell therapy, where it has begun to show unique advantages

The aim of study was to analyze the differences in nutritional elements and flavor substances between the Dali Yangpao and purple walnut kernels, two kinds of walnut kernels were used as raw materials, the content of amino acids, fatty acids, essential nutrients and mineral elements were determined separately, and the volatile components between the two walnut kernels were detected by gas chromatography mass spectrometry (GC-MS). The results showed that compared to those of the Yangpao walnut kernels, the purple walnut kernels had a higher content of total amino acid, essential amino acid, and umami amino acid (P

The development of a high-performance ferroelectric piezo-photocatalyst is an efficient strategy for advancing sustainability within the environmental and energy sectors. Yet, a major challenge lies in the creation of a strong polarized electric field that can effectively hinder charge recombination, both within the bulk and on the surface of catalysts. Herein, we synthesize a series of Nb-doped Bi4Ti3O12 nanosheets via a facile one-pot hydrothermal method to achieve synergistically enhanced piezo-photocatalytic performance in CO2 reduction and pollutant degradation. The optimized doped Bi4Ti3O12 demonstrates remarkable efficiency in the conversion of CO2 into CO, with a high production rate of 72.7 μmol∙g−1∙h−1 without using co-catalysts or any sacrificial agent, surpassing the performance of unmodified Bi4Ti3O12 by up to 4.69 folds. Additionally, our catalyst demonstrates ultra-fast piezo-photocatalytic degradation of organic pollutant Rhodamine B (RhB) at low concentrations and exceptional piezo-photocatalytic activity at high concentrations, outperforming most previously reported state-of-the-art catalysts. The systematic corroboration of catalyst characterization and experimental analysis reveals that the synergistic effect arises from the amplified macroscopic polarization induced by lattice distortion caused by the larger Nb ions, thereby improving piezo-photocatalytic efficiency. This research thus offers valuable insights into the direct design and fabrication of versatile catalytic systems, with applications spanning CO2 valorization and beyond.

Abstract Histone lysine crotonylation (Kcr), as a posttranslational modification, is widespread as acetylation (Kac); however, its roles are largely unknown in kidney fibrosis. In this study, we report that histone Kcr of tubular epithelial cells is abnormally elevated in fibrotic kidneys. By screening these crotonylated/acetylated factors, a crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) is found to remarkably increase histone 3 lysine 9 crotonylation (H3K9cr) level without influencing H3K9ac in kidneys and tubular epithelial cells. The integrated analysis of ChIP-seq and RNA-seq of fibrotic kidneys reveal that the hub proinflammatory cytokine IL-1β, which is regulated by H3K9cr, play crucial roles in fibrogenesis. Furthermore, genetic and pharmacologic inhibition of ACSS2 both suppress H3K9cr-mediated IL-1β expression, which thereby alleviate IL-1β-dependent macrophage activation and tubular cell senescence to delay renal fibrosis. Collectively, our findings uncover that H3K9cr exerts a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive drug target to slow fibrotic kidney disease progression.

This paper investigates the tightening and anti-loosening performance of phosphated spring washers (i.e., PSW) and galvanized spring washers (i.e., GSW), considering three torques and comparing them with galvanized flat washers (i.e., GFW). Subsequently, a finite element model of the spring washer connecting bolt was established and validated, further investigating the force performance of the spring washer and the stress distribution in the thread area. Finally, a quantitative evaluation method for the anti-loosening performance of spring washers was proposed. The results show that the preload of GSW is maximum after the nut is tightened, and the loss of preload can be supplied by the flattened spring washer. At the same time, the inner ring of the spring washer is sticking, while the outer ring is sliding. Similarly, the contact pressure of the washer decreases radially. During the lateral vibration process, the decrease curve of preload consists of three stages: initial stage, stable stage, and loosening rotation stage. Specifically, GSW has the best anti-loosening performance, because the wear of the zinc layer increases friction. More importantly, the spring washer compensates for the gap between the nut contact surface during transverse vibration, ensuring uniform force distribution in the threaded area and effectively improving the anti-loosening performance.

This study aimed to provide evidence for co-administration of the COVID-19 and EV71 vaccines in children aged 3 to 5 years. We conducted a phase 4, open-label, randomized, and controlled study. A total of 520 children were randomly allocated to two groups: Group C received the COVID-19 and EV71 vaccines simultaneously, while Group N received the two vaccines separately. The primary immunogenicity endpoints were the seroconversion rates of anti-SARS-CoV-2 and anti-EV71 antibodies 28 days after the second dose of each respective vaccine. Before vaccination, none of the participants was seropositive for anti-SARS-CoV-2 antibodies, and the baseline seropositivity for anti-EV71 antibodies was low (Group C: 14.86%; Group N: 17.83%). After completing full vaccination, the seroconversion rate of anti-SARS-CoV-2 antibodies reached 100% in both groups, while for anti-EV71 antibodies, the seroconversion rates were 97.99% in Group C and 98.70% in Group N. The lower limit of the 95% confidence interval for the difference in seroconversion rates between the two groups for both COVID-19 and EV71 vaccines met the predefined non-inferiority criteria. Six months post-vaccination, the antibody levels remained high for both vaccines, with the seropositive rates of anti-SARS-CoV-2 antibodies at 91.21% in Group C and 92.77% in Group N, and the seropositive rates of anti-EV71 antibodies at 99.16% in Group C and 99.15% in Group N. Safety analysis revealed a lower incidence of adverse reactions in Group C compared to Group N (28.85% vs 45.56%), primarily solicited. Co-administration of the COVID-19 and EV71 vaccines demonstrated a positive safety profile and non-inferior immune responses.Trial registration Number NCT04993365 (ClinicalTrials.gov).

Predicting computational intensity (CI) is essential for domain decomposition and load balance in parallel geoprocessing. However, traditional CI prediction is limited in capturing the heterogeneity of spatial domain, leading to poor accuracy and load imbalance. Leveraging recent advancements in deep learning from Artificial Intelligence (AI), this paper proposes a deep learning-based approach for predicting CI and enhancing domain decomposition, which reduces the dependency on expert knowledge through automatic feature learning. In the approach, Convolutional Neural Networks are employed to capture the heterogeneity of spatial domain, encompassing structural, distribution, and topological characteristics. A fully connected layer is then utilized for CI prediction and optimized domain decomposition. Comparative experiments were implemented between the proposed approach and three traditional methods, using two cases: spatial intersection on vector data and peak perilousness assessment. The results demonstrate that the proposed approach achieves a speedup ratio of 19.8 and a parallel efficiency of 0.82. The findings highlight the advantages of the proposed approach in terms of parallel performance and usability. This study serves as a valuable reference for illustrating how deep learning can enhance parallel geoprocessing, providing a roadmap for applying deep learning techniques to geocomputations and fostering further advancements of AI GIS.

ABSTRACTNeurensin-2 (NRSN2) performs a pro-carcinogenic function in multiple cancers. However, the function of NRSN2 in HPV-infected laryngeal carcinoma (LC) remains unclear. HPV transfection was performed in LC cells. The mRNA and protein levels were monitored using RT-qPCR, immunoblotting, and IF. Cell viability and proliferation were found using the CCK-8 assay and Edu staining. Cell invasion, migration, and apoptosis were probed using the Transwell, wound healing, and flow cytometry, respectively. The autophagosome was observed using TEM. NRSN2 was overexpressed in HPV-transfected LC cells. Inhibition of NRSN2 restrained the autophagy and malignant behavior of HPV-transfected LC cells. Meanwhile, the inhibition of AMPK/ULK1 pathway limited the increased autophagy of HPV-transfected LC cells caused by NRSN2 overexpression. Furthermore, NRSN2 knockdown inhibits autophagy by suppressing AMPK/ULK1 pathway, thereby restraining the malignant behavior of HPV-transfected LC cells. Our research confirmed that HPV transfection increased the autophagy and malignant behavior of LC cells by regulating the NRSN2-mediated activation of the AMPK/ULK1 pathway, offering a new target for cure of LC.

ABSTRACTThe increasing incidence of diseases caused by Coxsackievirus A6 (CV-A6) and the presence of various mutants in the population present significant public health challenges. Given the concurrent development of multiple vaccines in China, it is challenging to objectively and accurately evaluate the level of neutralizing antibody response to different vaccines. The choice of the detection strain is a crucial factor that influences the detection of neutralizing antibodies. In this study, the National Institutes for Food and Drug Control collected a prototype strain (Gdula), one subgenotype D1, as well as 13 CV-A6 candidate vaccine strains and candidate detection strains (subgenotype D3) from various institutions and manufacturers involved in research and development. We evaluated cross-neutralization activity using plasma from naturally infected adults (n = 30) and serum from rats immunized with the aforementioned CV-A6 strains. Although there were differences between the geometric mean titer (GMT) ranges of human plasma and murine sera, the overall trends were similar. A significant effect of each strain on the neutralizing antibody test (MAX/MIN 48.0 ∼16410.3) was observed. Among all strains, neutralization of the S112 strain by 15 different sera resulted in higher neutralizing antibody titers (GMTS112 = 132.0) and more consistent responses across different genotypic immune sera (MAX/MIN = 48.0). Therefore, S112 may serve as a detection strain for NtAb testing in various vaccines, minimizing bias and making it suitable for evaluating the immunogenicity of the CV-A6 vaccine.

Individuals with neuromuscular pathologies are often prescribed an ankle-foot orthosis (AFO) to improve their gait mechanics by decreasing pathological movements of the ankle and lower limb. AFOs can resist or assist excessive or absent muscular forces that lead to tripping, instability, and slow inefficient gait. However, selecting the appropriate AFO with mechanical characteristics, which limit pathological ankle motion in certain phases of the gait cycle while facilitating effective ankle movement during other phases, requires careful clinical decision-making. The aim of this study is to propose an explicit methodology for the adjustment of multi-function articulated AFOs in clinical settings. A secondary aim is to outline the evidence supporting this methodology and to identify gaps in the literature as potential areas for future research. An emerging class of AFO, the multi-function articulated AFO, offers features that permit more comprehensive, iterative, and reversible adjustments of AFO ankle alignment and resistance to ankle motion. However, no standard method exists for the application and optimization of these therapeutic devices in the clinical setting. Here we propose an evidence-guided methodology applicable to the adjustment of multi-function articulated AFOs in the clinical setting. Characteristic load–deflection curves are given to illustrate the idealized yet complex resistance-angle behavior of multi-function articulated AFOs. Research is cited to demonstrate how these mechanical characteristics can help mitigate specific pathologic ankle and knee kinematics and kinetics. Evidence is presented to support the effects of systematic adjustment of high resistance, alignable, articulated AFOs to address many typical pathomechanical patterns observed in individuals with neuromuscular disorders. The published evidence supporting most decision points of the algorithm is presented with identified gaps in the evidence. In addition, two hypothetical case examples are given to illustrate the application of the method in optimizing multi-function articulated AFOs for treating specific gait pathomechanics. This method is proposed as an evidence-guided systematic approach for the adjustment of multi-function articulated AFOs. It utilizes observed gait deviations mapped to specific changes in AFO alignment and resistance settings as a clinical tool in orthotic treatment for individuals with complex neuromuscular gait disorders.

Abstract Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate‐lowering therapy to prevent or delay CKD is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney diseases. Here, we aim to investigate whether and how macrophage integrin αM (ITGAM) contributes to hyperuricemia‐related CKD. In vivo, we explored dynamic characteristics of renal tissue in hyperuricemia‐related CKD mice. By incorporating transcriptomics and phosphoproteomics data, we analyzed gene expression profile, hub genes and potential pathways. In vitro, we validated bioinformatic findings under different conditions with interventions corresponding to core nodes. We found that hyperuricemia‐related CKD was characterized by elevated serum uric acid levels, impaired renal function, activation of macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed Itgam as the potential core gene, which was associated with focal adhesion signaling. Notably, we confirmed the upregulated expression of macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys. In vitro, through silencing Itgam, inhibiting p‐FAK or p‐AKT1 phosphorylation, and concurrent inhibiting of p‐FAK while activating p‐AKT1 all contributed to the modulation of macrophage M2 polarization. Our results indicated targeting macrophage ITGAM might be a promising therapeutic approach for preventing CKD.

Abstract Developing high‐efficiency and stable bifunctional electrocatalysts for water splitting remains a great challenge. Herein, NiMoO4 nanowires as sacrificial templates to synthesize Mo‐doped NiFe Prussian blue analogs are employed, which can be easily phosphorized to Mo‐doped Fe2xNi2(1‐x)P nanotubes (Mo‐FeNiP NTs). This synthesis method enables the controlled etching of NiMoO4 nanowires that results in a unique hollow nanotube architecture. As a bifunctional catalyst, the Mo‐FeNiP NTs present lower overpotential and Tafel slope of 151.3 (232.6) mV at 100 mA cm−2 and 76.2 (64.7) mV dec−1 for HER (OER), respectively. Additionally, it only requires an ultralow cell voltage of 1.47 V to achieve 10 mA cm−2 for overall water splitting and can steadily operate for 200 h at 100 mA cm−2. First‐principles calculations demonstrate that Mo doping can effectively adjust the electron redistribution of the Ni hollow sites to optimize the hydrogen adsorption‐free energy for HER. Besides, in situ Raman characterization reveals the dissolving of doped Mo can promote a rapid surface reconstruction on Mo‐FeNiP NTs to dynamically stable (Fe)Ni‐oxyhydroxide layers, serving as the actual active species for OER. The work proposes a rational approach addressed by electron manipulation and surface reconstruction of bimetallic phosphides to regulate both the HER and OER activity.

The prevention of chronic wound formation has already been a primary subject in wound management, particularly for deep wounds. The electrospun nanofiber membranes hold tremendous potential in the prevention of chronic wounds due to their micro/nano pore structures. Currently, many natural and synthetic materials have been utilized in the fabrication of nanofiber membranes. However, striking a balance between the structural stability and the biocompatibility remains challenging. It is necessary not only to ensure the long-term durability of nanofiber membranes but also to enhance their biocompatibility for alleviating patients' suffering. In this study, we reported a nanofiber membrane dressing with excellent biocompatibility and mechanical properties, which is potential for the treatment of deep wounds. The basal material chosen for the preparation of the nanofiber membrane was a co-polyester (NI-LPGD5) synthesized by non-isocyanate polyurethane (NIPU) and polyglycolic acid with a dihydroxy structure (LPGD—synthesized from glycolic acid and neopentyl glycol). Moreover, curcumin was also added as a bioactive substance to enhance the pro-healing effect of dressings. The physicochemical properties of the prepared nanofiber membranes were characterized through various physicochemical tools. Our results demonstrated that the NI-LPGD5 co-polymer can be electrospun into smooth fibers. Meanwhile, curcumin-loaded nanofiber membranes (Cur/NI-LPGD5) also exhibited a favorable microscopic morphology. The fabricated membranes exhibited suitable mechanical properties, outstanding hygroscopic-swelling rate and water vapor transmittance. Besides, in vitro cell culturing, the cells on the NI-LPGD5 membrane maintained their maximum viability. The potential of in vivo wound healing was further demonstrated through animal experiments. The experimental results showed that the nanofiber membranes effectively prevented chronic wounds from forming and promoted granulation tissue growth without replacing the dressing throughout the healing process. We also found that these nanofiber membranes could effectively promote the expression of related biomarkers to accelerate wound healing, particularly the Cur/NI-LPGD5 membrane. In conclusion, the fabricated membranes possess suitable physicochemical properties and promising bioactivity. As a result, it effectively prevented the formation of chronic wounds and demonstrated significant potential in reducing the frequency of dressing changes.

Chlorophyll (Chl)-mediated oxygenic photosynthesis supports life on earth. From a view of evolution, ‘survival of the fittest’ facilitates oxygenic photosynthetic organisms evolved from cyanobacteria to higher plants by ever more sophisticated photosystems including antennae, Chls, and carotenoids. Increasing advances highlight (1) the H subunit of magnesium chelatase (CHLH)-mediated Chl biosynthesis at the branch point that also channels to heme biosynthesis by the common tetrapyrrole pathway, associated to various GUN (genomes uncoupled) anterograde signals; (2) the multiple functions of carotenoids generated by mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways, also linked to several hormonal and anterograde signals; (3) the size and composition of the modularly-assembled pigment-protein supercomplexes vary with green lineages adaptive to growth niches at genetic and structural levels, showing more Chls with more growth and fitness. Under favorable environments, the photosynthetic electron transfer chain (PETC) is responsible for sugar biosynthesis, fundamental to plant growth by auxin and cytokinin. While under stressful environments, the impeded PETC triggers ROS, consequently triggering both phytohormone signaling (ABA, SA, JA, and Eth) and retrograde signaling (PAP, MEcPP, and GUNs). These regulators weave a crosstalk network between nucleus-to-plastid anterograde signaling and plastid-to-nucleus retrograde signaling, finally fine-tuning plant development and adaptation. In this review, we outline photosystematic evolution and chloroplast-derived signals, paving the way to understanding plant survival and fitness by optimizing sugar biosynthesis and utilization.

Objective: Circular RNAs (circRNAs) significantly influence the invasion, metastasis, gene expression, proliferation, and apoptosis of tumor cells. However, the roles of circRNAs in laryngeal squamous cell carcinoma (LSCC) remain largely unexplored. This study aims to examine circRNA expression patterns in LSCC and adjacent non-tumorous tissues, with the goal of uncovering potential biomarkers for LSCC. Methods: Tissue samples were collected from both the tumor and adjacent normal tissues of ten patients who had undergone surgical resection. The profiling of circRNAs was conducted through transcriptomic sequencing and analytical bioinformatics approaches. A ternary regulatory network based on the competitive endogenous RNA (ceRNA) hypothesis was established, linking target circRNAs to clinical immunohistochemical parameters for comparison. Verification of target circRNAs in LSCC tissues was performed using quantitative real-time PCR (RT-qPCR), whereas target mRNAs were analyzed through immunohistochemistry. Results: A total of 126 significantly different circRNAs were identified, including 40 up-regulated genes and 86 down-regulated genes. Furthermore, 92 circRNA-miRNA-mRNA regulatory relationship axes related to clinical immunohistochemical indicators were found based on 5 candidate circRNAs. Interestingly, all axes related to the target genes MKI67 and TP53 were found to compete with the same circRNA: hsa_circ_0069,399. Further verification confirmed that the hsa_circ_0069,399 expression was overtly upregulated in tumor tissues from LSCC patients, which was consistent with the sequencing results. Conclusion: hsa_circ_0069,399 could be a potential prognostic marker for LSCC.