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Abstract Breast cancer (BC) stands as a predominant global malignancy, significantly contributing to female mortality. Recently uncovered, histone lysine lactylation (kla) has assumed a crucial role in cancer progression. However, the correlation with lncRNAs remains ambiguous. Scrutinizing lncRNAs associated with Kla not only improves clinical breast cancer management but also establishes a groundwork for antitumor drug development. We procured breast tissue samples, encompassing both normal and cancerous specimens, from The Cancer Genome Atlas (TCGA) database. Utilizing Cox regression and XGBoost methods, we developed a prognostic model using identified kla-related lncRNAs. The model's predictive efficacy underwent validation across training, testing, and the overall cohort. Functional analysis concerning kla-related lncRNAs ensued. We identified and screened 8 kla-related lncRNAs to formulate the risk model. Pathway analysis disclosed the connection between immune-related pathways and the risk model of kla-related lncRNAs. Significantly, the risk scores exhibited a correlation with both immune cell infiltration and immune function, indicating a clear association. Noteworthy is the observation that patients with elevated risk scores demonstrated an increased tumor mutation burden (TMB) and decreased tumor immune dysfunction and exclusion (TIDE) scores, suggesting heightened responses to immune checkpoint blockade. Our study uncovers a potential link between Kla-related lncRNAs and BC, providing innovative therapeutic guidelines for BC management.

Abstract Background There are few studies on death education models for nursing students in China. It is of great significance to construct a model of nursing students’ death education combined with clinical practice. This study aims to evaluate the effect of death education on nursing students based on the Peace of Mind Tea House. Methods The randomized controlled trial commenced from February 7 to March 18, 2021,featuring a two-month intercession at a hospital situated in Xiamen, China. The research subjects were chosen using a convenient sampling approach with nursing students from the hospital's internship program. Ninety-two participants were enrolled, with 46 in each group. Thirteen participants were lost to follow-up, corresponding to 14% of the total study population. The samples were then allocated randomly into either the intervention group or the control group. In addition to their hospital internship, the intervention group participated in six death education courses that focused on cognitive, emotional, and motor skills as well as the “Peace of Mind Tea House” program. Control participants will undergo regular internships. Before and two weeks after the course, both groups were evaluated for death anxiety, attitude towards death, and the meaning of life to assess the intervention's effectiveness. Results In the fear of death item of the Death Attitude Scale and the meaning of life section, the post-test score minus the pre-test score of the intervention group were 2.50 ± 3.90 (p = 0.011), and 8.90 ± 11.07 (p = 0.035), respectively. During the communication and sharing session of the reassurance card activity, 41 participants (95.3%) found the activity meaningful. Conclusion Our data analysis demonstrates that nursing students have accepted and acknowledged the Peace of Mind Tea House-based education on death, which positively impacted their attitudes towards deathand the meaning of life. The content of death education should be integrated with traditional culture, and a new model of death education should be constructed with the Heart to Heart cards as its core. This research presents proof of the efficacy of implementing appropriate death education for nursing students, and provides a successful intervention plan to alleviate their future death anxiety and develop a positive outlook on death. Trial registration This study was approved by the Ethical Committee of Xiamen University School of Medicine (No. XDYX202304K21)(Date:18/01/2021). Written consent to participate was obtained from all the students.

Abstract Background This study aimed to investigate the potential variance in the prevalence of early‐onset scoliosis among children aged 4–7 years and analyze the influencing factors. The goal was to establish a crucial reference point for monitoring and evaluating spinal curvature development in preschoolers, ultimately to reduce the occurrence of adverse health outcomes. Methods Children aged 4–7 years within the main urban area of Nanjing were selected using a stratified random sampling method. A team of four senior therapists conducted screenings for spinal curvature among children using visual inspection, the Adams forward bending test, and an electronic scoliometer to measure the angle of trunk rotation (ATR) and identify children displaying signs of scoliosis. Children with suspected scoliosis in the initial screening underwent X‐ray Cobb angle assessment for confirmation. The prevalence of early‐onset scoliosis was then determined from the screening results. R version 4.2.0 software was used to analyze the factors associated with scoliosis among children using partial least squares structural equation modeling. Results A total of 2281 children were included in this study, consisting of 1211 boys and 1070 girls, with a mean age of 5.44 ± 0.81 years (ranging from 4 to 7 years). Among them, 7.58% exhibited positive signs of scoliosis, 5.87% had early‐onset scoliosis, and the positive predictive value was 77.5%. Significant differences in ATR were observed among children in different age groups (Kruskal–Wallis = 15, p = 0.0104) and by sex (t = 3.17, p = 0.00153). Significant variations in ATR were noted in children with scoliosis (t = −22.7, p

Abstract Background The binary diagnosis of Metabolic Syndrome(MetS) fails to accurately evaluate its severity, and the association between MetS severity and frailty progression remains inadequately elucidated. This study aims to clarify the relationship between the severity of MetS and the progression of frailty among the middle-aged and elderly population in China. Method Participants from the 2011–2018 China Health and Retirement Longitudinal Study(CHARLS) were included for a longitudinal analysis. The study employs a frailty index(FI) based on 32 health deficits to diagnose frailty and to assess FI trajectories. An age-sex-ethnicity-specific MetS scoring model (MetS score) was used to assess metabolic syndrome severity in Chinese adults. The Cumulative MetS score from 2012 to 2015 was calculated using the formula: (MetS score in wave 1 + MetS score in wave 3) / 2 × time(2015 - 2012). The association between MetS score, Cumulative MetS score, and the risk and trajectory of frailty were evaluated using Cox regression/logistic regression, and linear mixed models. Restricted Cubic Splines(RCS) models were utilized to detect potential non-linear associations. Results A higher MetS score was significantly associated with an increased risk of frailty(HR per 1 SD increase = 1.205; 95%CI: 1.14 to 1.273) and an accelerated FI trajectory(β per 1 SD increase = 0.113 per year; 95%CI: 0.075 to 0.15 per year). Evaluating changes in MetS score using a Cumulative MetS score indicated that each 1 SD increase in the Cumulative MetS score increased the risk of frailty by 22.2%(OR = 1.222; 95%CI: 1.133 to 1.319) and accelerated the rate of increase in FI(β = 0.098 per year; 95%CI: 0.058 to 0.138 per year). RCS model results demonstrated a dose-response curve relationship between MetS score and Cumulative MetS score with frailty risk. Stratified analysis showed consistency across subgroups. The interaction results indicate that in males and individuals under aged 60, MetS score may accelerate the increase in FI, a finding consistent across both models. Conclusions Our findings underscore the positive correlation between the severity of MetS and frailty progression in the middle-aged and elderly, highlighting the urgent need for early identification of MetS and targeted interventions to reduce the risk of frailty.

Abstract Pressure-induced phase transformations (PTs) in Si, the most important electronic material, have been broadly studied, whereas strain-induced PTs have never been studied in situ. Here, we reveal in situ various important plastic strain-induced PT phenomena. A correlation between the direct and inverse Hall-Petch effect of particle size on yield strength and pressure for strain-induced PT is predicted theoretically and confirmed experimentally for Si-I→Si-II PT. For 100 nm particles, the strain-induced PT Si-I→Si-II initiates at 0.3 GPa under both compression and shear while it starts at 16.2 GPa under hydrostatic conditions. The Si-I→Si-III PT starts at 0.6 GPa but does not occur under hydrostatic pressure. Pressure in small Si-II and Si-III regions of micron and 100 nm particles is ∼5–7 GPa higher than in Si-I. For 100 nm Si, a sequence of Si-I → I + II → I + II + III PT is observed, and the coexistence of four phases, Si-I, II, III, and XI, is found under torsion. Retaining Si-II and single-phase Si-III at ambient pressure and obtaining reverse Si-II→Si-I PT demonstrates the possibilities of manipulating different synthetic paths. The obtained results corroborate the elaborated dislocation pileup-based mechanism and have numerous applications for developing economic defect-induced synthesis of nanostructured materials, surface treatment (polishing, turning, etc.), and friction.

Abstract Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

Microwave-assisted mechanical excavation has great application prospects in mines and tunnels, but there are few field experiments on microwave-assisted rock breaking. This paper takes the Sishanling iron mine as the research object and adopts the self-developed high-power microwave-induced fracturing test system for hard rock to conduct field experiments of microwave-induced fracturing of iron ore. The heating and reflection evolution characteristics of ore under different microwave parameters (antenna type, power, and working distance) were studied, and the optimal microwave parameters were obtained. Subsequently, the ore was irradiated with the optimal microwave parameters, and the cracking effect of the ore under the action of the high-power open microwave was analyzed. The results show that the reflection coefficient (standing wave ratio) can be rapidly (

Abstract Background Platinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the treatment of OC patients. Our previous studies identified cell surface CD55, a member of the complement regulatory proteins, drives chemoresistance and maintenance of cancer stem cells (CSCs). CSCs are implicated in tumor recurrence and metastasis in multiple cancers. Methods Protein localization assays including immunofluorescence and subcellular fractionation were used to identify CD55 at the cell surface and nucleus of cancer cells. Protein half-life determinations were used to compare cell surface and nuclear CD55 stability. CD55 deletion mutants were generated and introduced into cancer cells to identify the nuclear trafficking code, cisplatin sensitivity, and stem cell frequency that were assayed using in vitro and in vivo models. Detection of CD55 binding proteins was analyzed by immunoprecipitation followed by mass spectrometry. Target pathways activated by CD55 were identified by RNA sequencing. Results CD55 localizes to the nucleus of a subset of OC specimens, ascites from chemoresistant patients, and enriched in chemoresistant OC cells. We determined that nuclear CD55 is glycosylated and derived from the cell surface pool of CD55. Nuclear localization is driven by a trafficking code containing the serine/threonine (S/T) domain of CD55. Nuclear CD55 is necessary for cisplatin resistance, stemness, and cell proliferation in OC cells. CD55 S/T domain is necessary for nuclear entry and inducing chemoresistance to cisplatin in both in vitro and in vivo models. Deletion of the CD55 S/T domain is sufficient to sensitize chemoresistant OC cells to cisplatin. In the nucleus, CD55 binds and attenuates the epigenetic regulator and tumor suppressor ZMYND8 with a parallel increase in H3K27 trimethylation and members of the Polycomb Repressive Complex 2. Conclusions For the first time, we show CD55 localizes to the nucleus in OC and promotes CSC and chemoresistance. Our studies identify a therapeutic mechanism for treating platinum resistant ovarian cancer by blocking CD55 nuclear entry.

Abstract Objective Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. Method Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1β, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. Results CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1β, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. Conclusion CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.

Exercise prescriptions play a vital role in the prevention and treatment of chronic diseases. A consensus regarding exercise prescription is important for physical health. The “Consensus statement of Chinese experts on exercise prescription” (hereinafter referred to as “Expert Consensus”) divides exercise prescription into two categories: fitness exercise prescription and medical exercise prescription. Traditional Chinese fitness exercises, exercise risk, exercise prescription, and basic precautions for exercise prescription are explained.

The effect of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) therapy on knee osteoarthritis (KOA) has been contradictory in previous meta-analyses. This umbrella review on published meta-analyses aimed to investigate the effect of MSCs and PRP on KOA. We systematically searched Scopus, PubMed, and Cochrane databases to include related meta-analyses. The outcome included studies reporting visual analog scale scores, the Western Ontario and McMaster Universities Osteoarthritis Index, Whole-Organ Magnetic Resonance Imaging Scores, International Knee Documentation Committee scores, and the Knee injury and Osteoarthritis Outcome Score. A total of 28 meta-analyses with 32 763 participants. MSCs and PRP therapies were significantly associated with an improvement in KOA scores. This umbrella meta-analysis supports the beneficial health effects of MSCs and PRP in KOA.

Abstract Background The positive impacts of work engagement among specialist nurses on retention, organizational commitment, and quality of care are well-documented. However, there is a lack of research on the specific differences in work engagement among specialist nurses. Therefore, the purpose of this study is to assess the level of work engagement among specialist nurses in China and identify its influencing factors. Methods A descriptive cross-sectional study was conducted in China from April to July, 2023, with 724 nurses selected from 22 hospitals through convenience sampling involved. The survey was conducted by using self-administered general information questionnaires and work engagement scales. Questionnaire Star was employed as the online data collection tool. The collected data was analyzed by using descriptive statistics and stepwise regression analysis to draw meaningful conclusions from the study. Results Among specialist nurses in Xiamen, China, who had a response rate of 97.10%, an average work engagement score is 140.35 (SD=18.17), with the highest score for the work attitude at 4.65 (SD=0.52) and the lowest score for the work recognition at 4.09 (SD=0.85). It was shown through regression analysis that factors such as career satisfaction, involvement in challenging case discussions, marital status, gender, presence of promotion advantage and title accounted for 14.5% of the total variance in the model and were significant explanatory variables that could predict work engagement. Conclusion It is shown that specialist nurses in Xiamen, China have a high level of work engagement. It is imperative for nursing managers to prioritize the work engagement of specialist nurses, provide the specialist nurses with ample development opportunities and room for growth, and effectively promote the overall development of specialist nurses by improving work engagement in various aspects.

Abstract Background There is a scarcity of studies that quantitatively assess the difficulty and importance of knowledge points (KPs) depending on students’ self-efficacy for learning (SEL). This study aims to validate the practical application of psychological measurement tools in physical therapy education by analyzing student SEL and course conceptual structure. Methods From the “Therapeutic Exercise” course curriculum, we extracted 100 KPs and administered a difficulty rating questionnaire to 218 students post-final exam. The pipeline of the non-parametric Item Response Theory (IRT) and parametric IRT modeling was employed to estimate student SEL and describe the hierarchy of KPs in terms of item difficulty. Additionally, Gaussian Graphical Models with Non-Convex Penalties were deployed to create a Knowledge Graph (KG) and identify the main components. A visual analytics approach was then proposed to understand the correlation and difficulty level of KPs. Results We identified 50 KPs to create the Mokken scale, which exhibited high reliability (Cronbach’s alpha = 0.9675) with no gender bias at the overall or at each item level (p > 0.05). The three-parameter logistic model (3PLM) demonstrated good fitness with questionnaire data, whose Root Mean Square Error Approximation was

Abstract Based on the WBS-RBS method, in this study, the risk factors corresponding to the construction risk events of an offshore tunnel foundation pit in Ningbo were identified, and the fuzzy comprehensive evaluation method was used to evaluate the construction safety risk of the project. The system-level risk value was obtained by using the risk event deformation resulting from changes in two factors, namely, “mechanical property of soil” and “stiffness of the envelope structure”, to calculate the new event-level risk value corresponding to the deformation using a finite element numerical model. The findings indicate that the tunnel project has a risk evaluation score of 62.78 and thus falls within the category of high-risk projects. A change in risk factors will alter the likelihood that risk events will occur, which affects the safety risk status of the entire project. When two factors are coupled, a project’s system-level risk can increase dramatically.

Abstract Background Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. Case presentation H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient’s anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient’s body temperature gradually returned to the normal range and her mood improved significantly. Conclusion Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.

Abstract Non-oxidative methane dehydro-aromatization reaction can co-produce hydrogen and benzene effectively on a molybdenum-zeolite based thermochemical catalyst, which is a very promising approach for natural-gas upgrading. However, the low methane conversion and aromatics selectivity and weak durability restrain the realistic application for industry. Here, a mechanism for enhancing catalysis activity on methane activation and carbon-carbon bond coupling has been found to promote conversion and selectivity simultaneously by adding platinum–bismuth alloy cluster to form a trimetallic catalyst on zeolite (Pt-Bi/Mo/ZSM-5). This bimetallic alloy cluster has synergistic interaction with molybdenum: the formed CH3 * from Mo2C on the external surface of zeolite can efficiently move on for C-C coupling on the surface of Pt-Bi particle to produce C2 compounds, which are the key intermediates of oligomerization. This pathway is parallel with the catalysis on Mo inside the cage. This catalyst demonstrated 18.7% methane conversion and 69.4% benzene selectivity at 710 °C. With 95% methane/5% nitrogen feedstock, it exhibited robust stability with slow deactivation rate of 9.3% after 2 h and instant recovery of 98.6% activity after regeneration in hydrogen. The enhanced catalytic activity is strongly associated with synergistic interaction with Mo and ligand effects of alloys by extensive mechanism studies and DFT calculation.

Abstract Background Glioblastoma (GBM) presents as an aggressive brain cancer, notorious for its recurrence and resistance to conventional treatments. This study aimed to assess the efficacy of the EMulate Therapeutics Voyager®, a non-invasive, non-thermal, non-ionizing, battery-operated, portable experimental medical device, in treating GBM. Using ultra-low radiofrequency energy (ulRFE) to modulate intracellular activity, previous preliminary results in patients have been encouraging. Now, with a focus on murine models, our investigation seeks to elucidate the device's mechanistic impacts, further optimizing its therapeutic potential and understanding its limitations. Methods The device employs a silicone over molded coil to deliver oscillating magnetic fields, which are believed to interact with and disrupt cellular targets. These fields are derived from the magnetic fluctuations of solvated molecules. Xenograft and syngeneic murine models were chosen for the study. Mice were injected with U-87 MG or GL261 glioma cells in their flanks and were subsequently treated with one of two ulRFE cognates: A1A, inspired by paclitaxel, or A2, based on murine siRNA targeting CTLA4 + PD1. A separate group of untreated mice was maintained as controls. Results Mice that underwent treatments with either A1A or A2 exhibited significantly reduced tumor sizes when compared to the untreated cohort. Conclusion The EMulate Therapeutics Voyager® demonstrates promising potential in inhibiting glioma cells in vivo through its unique ulRFE technology and should be further studied in terms of biological effects in vitro and in vivo.

Photodynamic therapy (PDT), employing photosensitizers to induce formation of reactive oxygen species (ROS) for tumor elimination, is emerging as a promising treatment modality in oncology due to its unique benefits. However, the PDT application in ovarian cancer, the most prevalent and lethal type of gynecological malignancy with a severe hypoxic microenvironment, remains unknown. This study revealed that photosensitizer TMPyP4 exhibited enhanced efficacy under H2O2 stimulation, with minimal change in cytotoxicity compared to TMPyP4 alone. The results showed that H2O2 increased ROS production induced by TMPyP4, leading to exacerbated mitochondrial dysfunction and DNA damage, ultimately inhibiting proliferation and inducing apoptosis in ovarian cancer cells. Mechanistically, H2O2 primarily enhanced the therapeutic efficacy of PDT with TMPyP4 against ovarian cancer cells by degrading HIF-1α, which subsequently modulated the HIF-1 signaling pathway, thereby alleviating the hypoxic environment in ovarian cancer cells. Our findings underscore the therapeutic potential of targeting HIF-1α within the hypoxic microenvironment for PDT in ovarian cancer and propose a novel integrated strategy for PDT treatment of this malignancy in vitro.

Purposes Increasing the permeability of coal reservoirs is a key technology to improve the recovery rate of coalbed methane, and in-situ thermal injection mining is an effective method to enhance coalbed methane production. Methods In order to explore the change rule of coal reservoir permeability under the coupling of heat, fluid, and solid, pyrolysis seepage experiments of anthracite with different burial depths and temperatures were conducted, and theoretical analysis and research were conducted on the experimental results. Findings The results showed that: 1) Under three-dimensional effective stress, the permeability of pyrolysis anthracite varies with temperature and pore pressure in a "V" shape, with a significant rebound phenomenon, which decreases with the increase of burial depth. When the pore pressure is less than the critical pore pressure and the temperature is lower than 70 ℃, the permeability of the coal body mainly depends on the slippage effect. When the pore pressure is greater than the critical pore pressure and the temperature is higher than 70 ℃, the permeability mainly depends on thermal expansion and the opening degree of pore pressure on the fracture, and the impact of thermal stimulation on the permeability is much greater than that of pore pressure. 2) The critical pore pressure is between 1 and 1.5 MPa, the influence of slippage effect on permeability gradually decreases with the increase of temperature, and the gradient of influence reduction increases with the increase of burial depth. 3) The fracture opening coefficient increases with the increase of temperature and burial depth, but the higher the temperature, the smaller the change in the sensitivity of permeability to pore pressure under different burial depths. Conclusions These research results further enrich the theory of in-situ thermal injection mining of coalbed methane, and provide valuable data reference for enhanced permeability of coalbed methane.

Abstract In situ profiling of subcellular proteomics in primary living systems, such as native tissues or clinic samples, is crucial for understanding life processes and diseases, yet challenging due to methodological obstacles. Here we report CAT-S, a bioorthogonal photocatalytic chemistry-enabled proximity labeling method, that expands proximity labeling to a wide range of primary living samples for in situ profiling of mitochondrial proteomes. Powered by our thioQM labeling warhead development and targeted bioorthogonal photocatalytic chemistry, CAT-S enables the labeling of mitochondrial proteins in living cells with high efficiency and specificity. We apply CAT-S to diverse cell cultures, dissociated mouse tissues as well as primary T cells from human blood, portraying the native-state mitochondrial proteomic characteristics, and unveiled hidden mitochondrial proteins (PTPN1, SLC35A4 uORF, and TRABD). Furthermore, CAT-S allows quantification of proteomic perturbations on dysfunctional tissues, exampled by diabetic mouse kidneys, revealing the alterations of lipid metabolism that may drive disease progression. Given the advantages of non-genetic operation, generality, and spatiotemporal resolution, CAT-S may open exciting avenues for subcellular proteomic investigations of primary samples that are otherwise inaccessible.

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. To identify additional genetic factors, we analyzed exome sequences in a large cohort of Chinese ALS patients and found a homozygous variant (p.L700P) in PCDHA9 in three unrelated patients. We generated Pcdhα9 mutant mice harboring either orthologous point mutation or deletion mutation. These mice develop progressive spinal motor loss, muscle atrophy, and structural/functional abnormalities of the neuromuscular junction, leading to paralysis and early lethality. TDP-43 pathology is detected in the spinal motor neurons of aged mutant mice. Mechanistically, we demonstrate that Pcdha9 mutation causes aberrant activation of FAK and PYK2 in aging spinal cord, and dramatically reduced NKA-α1 expression in motor neurons. Our single nucleus multi-omics analysis reveals disturbed signaling involved in cell adhesion, ion transport, synapse organization, and neuronal survival in aged mutant mice. Together, our results present PCDHA9 as a potential ALS gene and provide insights into its pathogenesis.

Abstract Media convergence works by processing information from different modalities and applying them to different domains. It is difficult for the conventional knowledge graph to utilise multi‐media features because the introduction of a large amount of information from other modalities reduces the effectiveness of representation learning and makes knowledge graph inference less effective. To address the issue, an inference method based on Media Convergence and Rule‐guided Joint Inference model (MCRJI) has been proposed. The authors not only converge multi‐media features of entities but also introduce logic rules to improve the accuracy and interpretability of link prediction. First, a multi‐headed self‐attention approach is used to obtain the attention of different media features of entities during semantic synthesis. Second, logic rules of different lengths are mined from knowledge graph to learn new entity representations. Finally, knowledge graph inference is performed based on representing entities that converge multi‐media features. Numerous experimental results show that MCRJI outperforms other advanced baselines in using multi‐media features and knowledge graph inference, demonstrating that MCRJI provides an excellent approach for knowledge graph inference with converged multi‐media features.

BackgroundGaussian signals have symmetry and completeness, hence, the Gaussian filtering method is widely used in nuclear signal processing and radiation energy spectrum analysis. The mathematical description of Gaussian signals is relatively complex, which makes it difficult to construct digital Gaussian pulse shaping filters for nuclear pulse signal real-time processing. The commonly used digital quasi-Gaussian shaping algorithm in radiation measurement systems is derived from the differential equations of Sallen-Key and CR-(RC)n filters in analog nuclear electronics. However, its output shaping pulse signals have poor symmetry and problems such as undershoot occur when used in a single stage.PurposeThis study aims to explore the convolutional quasi-Gaussian pulse shaping filter algorithm and apply it to the processing of X-ray fluorescence measurement system experimental platform to obtain measured nuclear pulse data.MethodsFirstly, a convolutional quasi-Gaussian pulse shaping algorithm was implemented based on trapezoidal pulse signals, and bipolar pulse shaping was achieved after the initial convolution. Then, the second convolution was accumulated and summed to obtain left and right symmetric quasi-Gaussian shaping pulses. The digital recursive formula of the quasi-Gaussian pulse shaping algorithm was obtained using the Z-transform method, and the effectiveness of the algorithm and the influence of shaping parameters on the amplitude frequency characteristics were studied through simulation. Finally, quasi-gaussian shaping algorithm and trapezoidal shaping algorithm were applied separately to the offline process of measured nuclear pulse data from the X-ray fluorescence measurement system experimental platform.ResultsThe quasi-Gaussian pulse shaping filter has better high-frequency noise suppression performance compared to trapezoidal pulse shaping filters. With the increase of the values of shaping parameters na and nc, the filter passband decreases whilst the low-frequency amplitude relatively increases, and the high-frequency noise suppression effect is enhanced. However, this also leads to shaping pulse broadening and increases the probability of pulse pile-up.ConclusionsThe experimental results demonstrate that the quasi-Gaussian pulse shaping algorithm has better pile-up pulse separation ability. Under identical X-ray tube voltage and current conditions and peaking time, the energy resolution of the energy spectra obtained by both algorithms is fundamentally equivalent. However, the energy spectrum with quasi-Gaussian pulse shaping has a higher characteristic peak area.

Abstract Background Metabolic syndrome (MetS) is a pathological condition characterized by the abnormal clustering of several metabolic components and has become a major public health concern. We aim to investigate the potential link of Systemic immunity-inflammation index (SII) on MetS and its components. Methods and result Weighted multivariable logistic regression was conducted to assess the relationship between SII and MetS and its components. Restricted cubic spline (RCS) model and threshold effect analysis were also performed. A total of 6,999 U.S. adults were enrolled. Multivariate model found that SII were positively associated with MetS (OR = 1.18;95CI%:1.07–1.30) and hypertension (OR = 1.22; 95CI%:1.12–1.34) in a dose-dependent manner. When SII was converted into a categorical variable, the risk of MetS increased by 36% and the risk of hypertension increased by 53% in the highest quantile of SIIs. The RCS model confirmed linear associations between SII and MetS, as well as a non-linear association between SII and certain components of MetS, including hypertension, hyperglycemia, low HDL, and hyperlipidemia. Meanwhile, the relationship between SII and hypertension presents a J-shaped curve with a threshold of 8.27, above which the risk of hypertension increases. Furthermore, in MetS and hypertension, age, sex, body mass index (BMI), and race were not significantly associated with this positive association based on subgroup analyses and interaction tests(p for interaction > 0.05). Conclusions The present study indicated that there was a higher SII association with an increased risk of MetS and hypertension in adults. However, further prospective cohort studies are required to establish a causal relationship between SII and MetS, as well as its components.

ObjectiveExploring the Incidence, Epidemic Trends, and Spatial Distribution Characteristics of Sporadic Hepatitis E in Hainan Province from 2013 to 2022 through four major tertiary hospitals in the Province.MethodsWe collected data on confirmed cases of hepatitis E in Hainan residents admitted to the four major tertiary hospitals in Haikou City from January 2013 to December 2022. We used SPSS software to analyze the correlation between incidence rate and economy, population density and geographical location, and origin software to draw a scatter chart and SAS 9.4 software to conduct a descriptive analysis of the time trend. The distribution was analyzed using ArcMap 10.8 software (spatial autocorrelation analysis, hotspot identification, concentration, and dispersion trend analysis). SAS software was used to build an autoregressive integrated moving average model (ARIMA) to predict the monthly number of cases in 2023 and 2024.ResultsFrom 2013 to 2022, 1,922 patients with sporadic hepatitis E were treated in the four hospitals of Hainan Province. The highest proportion of patients (n = 555, 28.88%) were aged 50–59 years. The annual incidence of hepatitis E increased from 2013 to 2019, with a slight decrease in 2020 and 2021 and an increase in 2022. The highest number of cases was reported in Haikou, followed by Dongfang and Danzhou. We found that there was a correlation between the economy, population density, latitude, and the number of cases, with the correlation coefficient |r| value fluctuating between 0.403 and 0.421, indicating a linear correlation. At the same time, a scatter plot shows the correlation between population density and incidence from 2013 to 2022, with r2 values fluctuating between 0.5405 and 0.7116, indicating a linear correlation. Global Moran’s I, calculated through spatial autocorrelation analysis, showed that each year from 2013 to 2022 all had a Moran’s I value >0, indicating positive spatial autocorrelation (p

The rail transit system plays a crucial role in modern transportation. With the increasing demand for clean and green energy in the transport sector, its energy system is expected to achieve low-carbon and highly efficient energy utilization in rail transit. However, the gradual development of the rail transport energy system has led to an increase in its complexity, and the rising difficulty of system assessment has faced the limitations of traditional assessment methods. Hence, it is essential to develop effective assessment methods. This paper begins by providing a systematic review of the development status of Reliability, Availability, Maintainability and Safety (RAMS) assessment and analyzing the shortcomings of traditional RAMS assessment technology in the context of rail transit energy systems. Subsequently, based on the four fundamental properties of RAMS, it summarizes the current state of key assessment technologies in the field of rail transit. Moreover, the paper delves into the challenges and potential solutions concerning the implementation of RAMS assessment technology for rail transit energy systems. Finally, the paper offers an outlook on the future development of RAMS assessment for rail transport energy systems. By comprehensively analyzing these aspects, the paper aims to contribute valuable insights into optimizing the rail transit energy system, promoting its sustainable and efficient operation in the context of clean and green energy utilization.

Abstract To reduce the occurrence of information loss and distortion in image style transfer, a method is proposed for researching and designing image style transfer technology based on multi‐scale convolutional neural networks (CNNs) feature fusion. Initially, the VGG19 model is designed for coarse and fine‐scale networks to achieve multi‐scale CNN feature extraction of target image information. Subsequently, while setting the corresponding feature loss function, an additional least‐squares penalty parameter is introduced to balance the optimal total loss function. Finally, leveraging the characteristics of stochastic gradient descent iteration, image features are fused and reconstructed to obtain better style transfer images. Experimental evaluations utilize peak signal‐to‐noise ratio (PSNR), structural similarity index (SSIM), information entropy (IE), and mean squared error (MSE) as metrics for assessing the transferred images, comparing them with three typical image style transfer methods. Results demonstrate that the proposed method achieves optimal performance across all metrics, realizing superior image style transfer effects.

Clonal plants are widely distributed in the riparian zone and play a very important role in the maintenance of wetland ecosystem function. Flooding is an environmental stress for plants in the riparian zone, and the response of plants varies according to the depth and duration of flooding. However, there is a lack of research on the growth response of clonal plants during flooding, and the endogenous hormone response mechanism of clonal plants is still unclear. In the present study, Alternanthera philoxeroides, a clonal plant in the riparian zone, was used to investigate the time-dependent stem elongation, the elongation of different part of the immature internodes, and the relationship between growth elongation and the phytohormone gibberellin (GA) under a series of submergence depths (0 m, 2 m, 5 m, and 9 m). The results showed that stem elongation occurred under all treatments, however, compared to 0 m (control), plants grew more under 2 m and 5 m submergence depth, while grew less under 9 m water depth. Additionally, basal part elongation of the immature internode was the predominant factor contributing to the stem growth of A. philoxeroides under different submergence depths. The phytohormone contents in basal part of the mature and immature internodes showed that GA induced the differential elongation of internode. Plant submerged at depth of 2 m had the highest GA accumulation, but plant submerged at depth of 9 m had the lowest GA concentration. These data suggested that GA biosynthesis are essential for stem elongation in A. philoxeroides, and the basal part of the immature internode was the main position of the GA biosynthesis. This study provided new information about the rapid growth and invasion of the clonal plant A. philoxeroides around the world, further clarified the effects of submergence depth and duration on the elongation of the stem, and deepened our understanding of the growth response of terrestrial plants in deeply flooded environments.

Tobacco (Nicotiana tabacum L.) use is the leading cause of preventable death, due to deleterious chemical components and smoke from tobacco products, and therefore reducing harmful chemical components in tobacco is one of the crucial tobacco breeding targets. However, due to complexity of tobacco smoke and unavailability of high-density genetic maps, the genetic architecture of representative hazardous smoke has not been fully dissected. The present study aimed to explore the genetic architecture of nine hazardous component traits of mainstream smoke through QTL mapping using 271 recombinant inbred lines (RILs) derived from K326 and Y3 in multiple environments. The analysis of genotype and genotype by environment interaction (GE) revealed substantially greater heritability over 95% contributed mostly by GE interaction effects. We also observed strong genetic correlations among most studied hazardous smoke traits, with the highest correlation coefficient of 0.84 between carbon monoxide and crotonaldehyde. Based on a published high-density genetic map, a total of 19 novel QTLs were detected for eight traits using a full QTL model, of which 17 QTLs showed significant additive effects, six showed significant additive-by-environment interaction effects, and one pair showed significant epistasis-by-environment interaction effect. Bioinformatics analysis of sequence in QTL region predicted six genes as candidates for four traits, of which Nt21g04598.1, Nt21g04600.1, and Nt21g04601.1 had pleiotropic effects on PHE and TAR.

Summary: Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified intention-to-treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088). Findings: Between Dec 19, 2022, and May 4, 2023, 1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% confidence interval 12.0–15.0] vs. 15.0 days [14.0–15.0], P = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred. Interpretation: Treatment with GST-HG171 plus Ritonavir has demonstrated benefits in symptom recovery and viral clearance among low-risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, confirming the potential benefits of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real-world studies. Funding: Fujian Akeylink Biotechnology Co., Ltd.

Aim: The objectives were to investigate the differences in per patient per month (PPPM) healthcare resource utilization (HCRU) and costs among commercially insured and Medicare Advantage patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) who experience disease progression in 12 months compared with those who don’t investigate the impact of progression timing on cumulative healthcare costs. Patients & methods: This claims-based study included patients diagnosed with mBC between 1 January 2013 and 30 April 2020 and received HER2-targeted therapy. Patients were categorized as progressed or nonprogressed. For objective one, monthly HCRU and costs were assessed for up to two lines of therapy (LOTs). Data were summarized descriptively and compared using a generalized linear model (GLM). For objective two, patients with at least 6 months of follow-up were assessed and cumulative healthcare costs were estimated in the 3 years following the start of LOT1 or LOT2 using a GLM and Kaplan–Meier weighting. Results: Among the 4113 patients in the study sample, 3406 had at least 12 months of follow-up (or less if due to death). Compared with nonprogressed patients, progressed patients had higher mean PPPM healthcare costs (LOT1: $22,014 vs $18,372, p < 0.001; LOT2: $19,643 vs $16,863, p = 0.001), and HCRU, including number of emergency room visits and inpatient stays (both p < 0.001) in the 12 months following LOT start. Progressed patients had higher 3-year mean cumulative healthcare costs than nonprogressed patients following LOT1 and LOT2 and this difference was greater for patients who progressed earlier. Conclusion: Disease progression was associated with significant increases in HCRU and costs. Delays in progression were associated with lower cumulative healthcare costs. Earlier use of more clinically effective treatments to delay progression may reduce the economic burden among these patients.

Distractor suppression (DS) is crucial in goal-oriented behaviors, referring to the ability to suppress irrelevant information. Current evidence points to the prefrontal cortex as an origin region of DS, while subcortical, occipital, and temporal regions are also implicated. The present study aimed to examine the contribution of communications between these brain regions to visual DS. To do it, we recruited two independent cohorts of participants for the study. One cohort participated in a visual search experiment where a salient distractor triggering distractor suppression to measure their DS and the other cohort filled out a Cognitive Failure Questionnaire to assess distractibility in daily life. Both cohorts collected resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate function connectivity (FC) underlying DS. First, we generated predictive models of the DS measured in visual search task using resting-state functional connectivity between large anatomical regions. It turned out that the models could successfully predict individual's DS, indicated by a significant correlation between the actual and predicted DS (r = 0.32, p < 0.01). Importantly, Prefrontal-Temporal, Insula-Limbic and Parietal-Occipital connections contributed to the prediction model. Furthermore, the model could also predict individual's daily distractibility in the other independent cohort (r = –0.34, p < 0.05). Our findings showed the efficiency of the predictive models of distractor suppression encompassing connections between large anatomical regions and highlighted the importance of the communications between attention-related and visual information processing regions in distractor suppression. Current findings may potentially provide neurobiological markers of visual distractor suppression.

Microwave pre-treatment is considered as a promising technique for alleviating cutter wear. This paper introduces a high-power microwave-induced fracturing system for hard rock. The test system consists of a high-power microwave subsystem (100 kW), a true triaxial testing machine, a dynamic monitoring subsystem, and an electromagnetic shielding subsystem. It can realize rapid microwave-induced fracturing, intelligent tuning of impedance, dynamic feedback under strong microwave fields, and active control of microwave parameters by addressing the following issues: the instability and insecurity of the system, the discharge breakdown between coaxial lines during high-power microwave output, and a lack of feedback of rock-microwave response. In this study, microwave-induced surface and borehole fracturing tests under true triaxial stress were carried out. Experimental comparisons imply that high-power microwave irradiation can reduce the fracturing time of hard rock and that the fracture range (160 mm) of a 915-MHz microwave source is about three times that of 2.45 GHz. After microwave-induced borehole fracturing, many tensile cracks occur on the rock surface and in the borehole: the maximum reduction of the P-wave velocity is 12.8%. The test results show that a high-power microwave source of 915 MHz is more conducive to assisting mechanical rock breaking and destressing. The system can promote the development of microwave-assisted rock breaking equipment.

Abstract To improve lithium-ion battery technology, it is essential to probe and comprehend the microscopic dynamic processes that occur in a real-world composite electrode under operating conditions. The primary and secondary particles are the structural building blocks of battery cathode electrodes. Their dynamic inconsistency has profound but not well-understood impacts. In this research, we combine operando coherent multi-crystal diffraction and optical microscopy to examine the chemical dynamics in local domains of layered oxide cathode. Our results not only pinpoint the asynchronicity of the lithium (de)intercalation at the sub-particle level, but also reveal sophisticated diffusion kinetics and reaction patterns, involving various localized processes, e.g., chemical onset, reaction front propagation, domains equilibration, particle deformation and motion. These observations shed new lights onto the activation and degradation mechanisms of state-of-the-art battery cathode materials.

Background: The diagnostic and prognostic value of the leucine-rich alpha-2-glycoprotein 1 (LRG1) gene in thyroid cancer remains unclear. Using the Cancer Genome Atlas (TCGA) database, we conducted a bioinformatics analysis to determine the role of LRG1 in thyroid cancer. Methods: Data from 512 patients with thyroid cancer and 59 normal individuals were collected from TCGA database. The Kruskal–Wallis test and logistic analysis were used to examine the relationship between LRG1 expression and clinicopathologic characteristics. Cox regression and Kaplan–Meier analysis were used to determine the predictive value of LRG1 on clinical outcomes. Single-sample gene set enrichment analysis (ssGSEA) was used to reveal associations between LRG1 expression and immune infiltration levels in thyroid cancer. Results: LRG1 was highly expressed in thyroid cancer (P < 0.001) and could effectively distinguish tumor tissue (area under the curve = 0.875) from normal tissue. Moreover, LRG1 was significantly correlated with pathological N stage (odds ratio (OR) = 2.411 (1.659–3.505), P < 0.001). Kaplan–Meier survival analysis revealed that patients with high LRG1 expression had better overall survival (hazard ratio (HR) = 0.30, P = 0.038). Cox regression analysis indicated that pathological M stage was a risk factor for progression-free interval (HR = 5.964 (2.010–17.694), P < 0.001). Using ssGSEA, we found that LRG1 expression was positively correlated with the number of T helper 1 cells (R = 0.435, P < 0.001), dendritic cells (R = 0.442, P < 0.001), and macrophages (R = 0.459, P < 0.001). Conclusion: LRG1 may be an important biomarker for predicting the prognosis of thyroid cancer and represent a suitable target for immunotherapy associated with immune infiltration.

Under the combined effects of inventory-level-dependent demand (ILDD) and trade credit, the retailer is able to order more quantities to stimulate market demand. However, from the supplier's perspective, two important issues are lacking sufficient attention. First, during the credit period, the retailer's higher order quantities imply increases in both the retailer's account payable and the supplier's opportunity cost of capital. Second, given the supplier's fixed production rate, the increased market demand may drive the capacity utilization to be variable. Thus, by formulating a supplier-dominated system, this paper incorporates trade credit limit (TCL) to address its effects on optimal policies vis-à-vis the item with ILDD. Specifically, three indicators can be proposed to reveal which type of financing policy the retailer should choose. Moreover, based on TCL, the supplier can effectively manage the retailer's order quantity and the corresponding account payable. Additionally, the retailer's maximum allowable order quantity is developed to ensure that the supplier can supply the retailer's order quantity on time. Furthermore, when the effects of ILDD become more significant, the manufacturer will reduce the maximum allowable order quantity to control the retailer's order incentive.

Abstract Interferon-gamma (IFN-γ) signaling is necessary for the proinflammatory activation of macrophages but IFN-γ-independent pathways, for which the initiating stimuli and downstream mechanisms are lesser known, also contribute. Here we identify, by high-content screening, SEPTIN2 (SEPT2) as a negative regulation of IFN-γ-independent macrophage autoactivation. Mechanistically, endoplasmic reticulum (ER) stress induces the expression of SEPT2, which balances the competition between acetylation and ubiquitination of heat shock protein 5 at position Lysine 327, thereby alleviating ER stress and constraining M1-like polarization and proinflammatory cytokine release. Disruption of this negative feedback regulation leads to the accumulation of unfolded proteins, resulting in accelerated M1-like polarization, excessive inflammation and tissue damage. Our study thus uncovers an IFN-γ-independent macrophage proinflammatory autoactivation pathway and suggests that SEPT2 may play a role in the prevention or resolution of inflammation during infection.

Abstract Advancing personalized medicine in brain cancer relies on innovative strategies, with mRNA vaccines emerging as a promising avenue. While the initial use of mRNA vaccines was in oncology, their stunning success in COVID-19 resulted in widespread attention, both positive and negative. Regardless of politically biased opinions, which relate more to the antigenic source than form of delivery, we feel it is important to objectively review this modality as relates to brain cancer. This class of vaccines trigger robust immune responses through MHC-I and MHC-II pathways, in both prophylactic and therapeutic settings. The mRNA platform offers advantages of rapid development, high potency, cost-effectiveness, and safety. This review provides an overview of mRNA vaccine delivery technologies, tumor antigen identification, combination therapies, and recent therapeutic outcomes, with a particular focus on brain cancer. Combinatorial approaches are vital to maximizing mRNA cancer vaccine efficacy, with ongoing clinical trials exploring combinations with adjuvants and checkpoint inhibitors and even adoptive cell therapy. Efficient delivery, neoantigen identification, preclinical studies, and clinical trial results are highlighted, underscoring mRNA vaccines' potential in advancing personalized medicine for brain cancer. Synergistic combinatorial therapies play a crucial role, emphasizing the need for continued research and collaboration in this area.

Abstract Background Limb-girdle muscular dystrophies (LGMDs) are a group of heterogeneous inherited diseases predominantly characterized by limb-girdle muscle weakness and dystrophic changes on histological analysis. The frequency of LGMD subtypes varies among regions in China and ethnic populations worldwide. Here, we analyzed the prevalence of LGMD subtypes, their corresponding clinical manifestations, and molecular data in a cohort of LGMD patients in Southeast China. Methods A total of 81 consecutive patients with clinically suspected LGMDs from 62 unrelated families across Southeast China were recruited for targeted next-generation sequencing and whole-exome sequencing from July 2017 to February 2020. Results Among 50 patients (41 families) with LGMDs, the most common subtypes were LGMD-R2/LGMD2B (36.6%) and LGMD-R1/LGMD2A (29.3%). Dystroglycanopathies (including LGMD-R9/LGMD2I, LGMD-R11/LGMD2K, LGMD-R14/LGMD2N and LGMD-R20/LGMD2U) were the most common childhood-onset subtypes and were found in 12.2% of the families. A total of 14.6% of the families had the LGMD-R7/LGMD2G subtype, and the mutation c.26_33dupAGGTGTCG in TCAP was the most frequent (83.3%). The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal‒distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. A total of 22.0% of the patients had cardiac abnormalities, and one patient with LMNA-related muscular dystrophy/LGMD1B experienced sudden cardiac death at 37 years of age. A total of 15.4% of the patients had restrictive respiratory insufficiency. Muscle imaging in patients with LGMD-R1/LGMD2A and LGMD-R2/LGMD2B showed subtle differences, including more severe fatty infiltration of the posterior thigh muscles in those with LGMD-R1/LGMD2A and edema in the lower leg muscles in those with LGMD-R2/LGMD2B. Conclusion We determined the prevalence of different LGMD subtypes in Southeast China, described the detailed clinical manifestations and distinct muscle MRI patterns of these LGMD subtypes and reported the frequent mutations and the cardiorespiratory involvement frequency in our cohort, all of which might facilitate the differential diagnosis of LGMDs, allowing more timely treatment and guiding future clinical trials.

Abstract Background Elliptical excision is the most commonly used method for small benign tumour excision and primary closure. However, elliptical excision remains the topic of debate. The aim of this study was to explore the relationship among postoperative incision, vertex angle, and the length and width of fusiform excision through a mathematical model. Methods We collected data from fusiform circle excisions performed at the author’s hospital (101 cases). The measured values were applied to the mathematical model formula for statistical analysis. Results The functional relationships among the length, width, arc, and angle of the fusiform circle were obtained. The mean apical tangent angle was 100.731°±15.782°, and the mean apical inner angle was 50.366°±7.891°. There was no significant difference between the preoperatively designed arc length preoperative and the postoperative incision length (P

Abstract Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis. In vivo, the rabbits with osteochondral critical-size defects receiving the ultrasound-activated piezoelectric hydrogel show increased subchondral bone formation, improved hyaline-cartilage structure, and good mechanical properties, close to healthy native cartilage. This piezoelectric hydrogel is not only useful for cartilage healing but also potentially applicable to other tissue regeneration, offering a significant impact on the field of regenerative tissue engineering.

Abstract Hypoxic-ischemic encephalopathy (HIE) at high-altitudes leads to neonatal mortality and long-term neurological complications without effective treatment. Acer truncatum Bunge Seed extract (ASO) is reported to have effect on cognitive improvement, but its molecular mechanisms on HIE are unclear. In this study, ASO administration contributed to reduced neuronal cell edema and improved motor ability in HIE rats at a simulated 4500-meter altitude. Transcriptomics and WGCNA analysis showed genes associated with lipid biosynthesis, redox homeostasis, neuronal growth, and synaptic plasticity regulated in the ASO group. Targeted and untargeted-lipidomics revealed decreased free fatty acids and increased phospholipids with favorable ω-3/ω-6/ω-9 fatty acid ratios, as well as reduced oxidized glycerophospholipids (OxGPs) in the ASO group. Combining multi-omics analysis demonstrated FA to FA-CoA, phospholipids metabolism, and lipid peroxidation were regulated by ASO treatment. Our results illuminated preliminary metabolism mechanism of ASO ingesting in rats, implying ASO administration as potential intervention strategy for HIE under high-altitude.

The phenomenon of Asaro–Tiller–Grinfeld (ATG) instability is common in the molecular beam epitaxy (MBE) process. In order to investigate the ATG instability, a two-dimensional mathematical model is established, which considers elastic stress. The phase-field method is utilized to simulate the interface evolution and the stress distribution. Furthermore, the Allen–Cahn approach, coupled with the motion of the interface, is used to investigate the morphology evolution. The results show that the thin film becomes unstable when it reaches a critical value. The critical thickness of the thin film is about 5.08 nm. The interface breaks into several parts due to the effect of elastic stress. The validity and correctness of the model are verified by the relevant theoretical results. Moreover, the numerical model can provide the basis for optimizing the ATG instability phenomenon in the MBE process.

Introduction: Aortic dissection (AD) is often fatal, and its pathogenesis involves immune infiltration and pyroptosis, though the molecular pathways connecting these processes remain unclear. This study aimed to investigate the role of immune infiltration and pyroptosis in AD pathogenesis using bioinformatics analysis.Methods: Two Gene Expression Omnibus datasets and a Gene Cards dataset of pyroptosis-related genes (PRGs) were utilized. Immunological infiltration was assessed using CIBERSORT, and AD diagnostic markers were identified through univariate logistic regression and least absolute shrinkage and selection operator regression. Interaction networks were constructed using STRING, and weighted gene correlation network analysis (WGCNA) was employed to identify important modules and essential genes. Single-sample gene set enrichment analysis determined immune infiltration, and Pearson correlation analysis assessed the association of key genes with infiltrating immune cells.Results: Thirty-one PRGs associated with inflammatory response, vascular epidermal growth factor receptor, and Rap1 signaling pathways were identified. WGCNA revealed seven important genes within a critical module. CIBERSORT detected immune cell infiltration, indicating significant changes in immune cell infiltration and pyroptosis genes in AD and their connections.Discussion: Our findings suggest that key PRGs may serve as indicators for AD or high-risk individuals. Understanding the role of pyroptosis and immune cell infiltration in AD pathogenesis may lead to the development of novel molecular-targeted therapies for AD.Conclusion: This study provides insights into the molecular mechanisms underlying AD pathogenesis, highlighting the importance of immune infiltration and pyroptosis. Identification of diagnostic markers and potential therapeutic targets may improve the management of AD and reduce associated morbidity and mortality.

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear.ObjectivesThis study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms.MethodsIn this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention.ResultsThe VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV.ConclusionThe combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Complete submergence, especially deep submergence, poses a serious threat to the growth and survival of plants. One study previously showed that Alternanthera philoxeroides (a herbaceous perennial plant) submerged at depth of 2 m presented fast stem elongation and reduced stem elongation as water depth increased. In the present study, we aimed to figure out from the morphological and anatomical perspective how the differential growth response of the plant to water depth was achieved. We investigated the elongation of different stem parts and the relationship of stem elongation to cell size and number in A. philoxeroides by conducting experiments using a series of submergence depths (0 m, 2 m, 5 m, and 9 m). The results showed that, in comparison with unsubmerged plants, completely submerged plants exhibited enhanced elongation at depths of 2 m and 5 m but suppressed elongation at depth of 9 m in immature stem internodes, and displayed very little elongation in mature stem internodes at any depths. The stem growth of A. philoxeroides at any submergence depth was chiefly caused by the elongation of the basal parts of immature internodes. The elongation of the basal parts of immature internodes was highly correlated to both cell proliferation and cell enlargement, but the elongation of the middle and upper parts of immature internodes correlated nearly only with cell enlargement. This study provided new information on the growth responses of A. philoxeroides to heterogeneous submergence environments and deepened our understanding of the growth performance of terrestrial plants in habitats prone to deep floods.

Purpose: To investigate the rate of vault changes after implantation of ICL V4c and the correlation with anterior segment parameters. Methods: A total of 64 eyes were studied from the 37 myopic subjects recruited. CASIA2 was used to record the vault at 1 week, 1 month, 3 months and 6 months after the operation as well as the preoperative anterior segment parameters including pupil diameter, lens vault, anterior chamber depth, anterior chamber width, iris area (IA), iris thickness, angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle. The rates of vault change in different time intervals were compared and the correlations between the rates and anterior segment parameters were analyzed. P 0.05). Conclusion: The rate of decreasing vault significantly slowed down from 3 months post-operation. A larger IA may imply a lower decreasing rate of vault change.

Miscanthus lutarioriparia is a promising energy crop that is used for abandoned mine soil phytoremediation because of its high biomass yield and strong tolerance to heavy metals. However, the biological mechanism of heavy metal resistance is limited, especially for applications in the soil restoration of mining areas. Here, through the investigation of soil cadmium(Cd) in different mining areas and soil potted under Cd stress, the adsorption capacity of Miscanthus lutarioriparia was analyzed. The physiological and transcriptional effects of Cd stress on M. lutarioriparia leaves and roots under hydroponic conditions were analyzed. The results showed that M. lutarioriparia could reduce the Cd content in mining soil by 29.82%. Moreover, different Cd varieties have different Cd adsorption capacities in soils with higher Cd concentration. The highest cadmium concentrations in the aboveground and belowground parts of the plants were 185.65 mg/kg and 186.8 mg/kg, respectively. The total chlorophyll content, superoxide dismutase and catalase activities all showed a trend of increasing first and then decreasing. In total, 24,372 differentially expressed genes were obtained, including 7735 unique to leaves, 7725 unique to roots, and 8912 unique to leaves and roots, which showed differences in gene expression between leaves and roots. These genes were predominantly involved in plant hormone signal transduction, glutathione metabolism, flavonoid biosynthesis, ABC transporters, photosynthesis and the metal ion transport pathway. In addition, the number of upregulated genes was greater than the number of downregulated genes at different stress intervals, which indicated that M. lutarioriparia adapted to Cd stress mainly through positive regulation. These results lay a solid foundation for breeding excellent Cd resistant M. lutarioriparia and other plants. The results also have an important theoretical significance for further understanding the detoxification mechanism of Cd stress and the remediation of heavy metal pollution in mining soil.

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.