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Abstract The switch from oxidative phosphorylation to glycolysis is crucial for microglial activation. Recent studies highlight that histone lactylation promotes macrophage homeostatic gene expression via transcriptional regulation, but its role in microglia activation in Parkinson’s disease (PD) remains unclear. Here, we demonstrated that inhibiting glycolysis with 2-deoxy-d-glucose alleviates microgliosis, neuroinflammation and dopaminergic neurons damage by reducing lactate accumulation in PD mice. Notably, we observed a marked increase in histone lactylation, particularly H3K9 lactylation, in microglia in the substantia nigra of PD mice. Mechanistically, CUT&Tag and Chip-qPCR analyses revealed that H3K9 lactylation enriched at the SLC7A11promoter and activated its expression. Importantly, inhibiting SLC7A11 by sulfasalazine mitigated microglia-mediated neuroinflammation and improved motor function in PD mice. Moreover, we found that lactate-induce histone lactylation is dependent on P300/CBP. Collectively, our findings demonstrate that glycolysis-derived lactate promotes microglial activation via histone lactylation and provide a potential therapeutic strategy for PD.

Abstract Objective To examine the mid-term efficacy and imaging results of using the Mobi-C and Bryan implants after cervical hybrid surgery for 2-level cervical spondylolisthesis, and to observe their postoperative changes and differences in the flexion-extension center of rotation (FE-COR) for the anterior cervical disc replacement (ACDR) segment. Methods Patients who underwent cervical hybrid surgery between June 2014 and June 2019 were included in this study. The mJOA, NDI, and VAS scores were used to assess clinical outcomes, and the FE-COR of the ACDR segment was measured. Pre-operative and 36-month radiographs were collected to compare the range of motion (ROM) in the total cervical spine, ACDR segmental ROM, and operated adjacent segmental ROM. Translation distances for the Mobi-C and Bryan devices were measured. The degree of disc degeneration in the adjacent segment and bony fusion of the ACDF segment were observed. Results Eighty-one patients were included (40 in the Mobi-C group and 41 in the Bryan group). All patients showed improvements in their postoperative mJOA, NDI, and VAS scores (P 0.05). No significant differences were found between the two groups in the above ROM measurements (P > 0.05). For the Mobi-C group, the follow-up compared with pre-surgery showed statistical significance in both FE-COR-X (44.86 ± 7.70% vs. 57.13 ± 8.45%, P 0.05). No significant difference in translation distance between the two groups was observed (P > 0.05). All ACDF segments were in a stable condition. Twenty-two out of 162 adjacent segments showed imaging ASD (9 cases in the Mobi-C group and 13 cases in the Bryan group). In the Mobi-C group, there were mild cases in 6 instances and moderate cases in 3 instances. In the Bryan group, there were mild cases in 8 instances and moderate cases in 5 instances. Conclusions Cervical hybrid surgery using either the Mobi-C or Bryan artificial cervical discs can achieve satisfactory results. The FE-COR of the Mobi-C segment shifts forward and downward, while the FE-COR of the Bryan segment is relatively closer to the pre-operative condition. Changes in the FE-COR after hybrid surgery in both the Mobi-C and Bryan segments might not affect clinical outcomes.

Abstract Objective To investigate the correlation between the implantation status of the ROI-C cervical cage plates and the Hounsfield unit(HU) value of the target vertebral endplate during anterior cervical decompression and fusion (ACDF)surgery. Methods Review of patient data undergoing ACDF from January 2018 to December 2021. Data on gender, age, body mass index, history of hypertension, diabetes, hyperlipidemia, smoking, alcohol consumption, cervical cage plates status, and HU values of the cervical vertebral endplate. Logistic regression analysis was used to evaluate the relationship between the HU values and the plates status. Results A total of 17 cases (12.1%) had misplaced implants during surgery. There were statistical differences in gender, long-term smoking history, drinking history, and cervical vertebral endplate HU values between the abnormal implantation group and the normal implantation group (P

Abstract Background This study aims to identify risk factors associated with Methicillin-resistant Staphylococcus aureus (MRSA) infection in children diagnosed with acute osteomyelitis (AO) and to elucidate the laboratory characteristics of these MRSA-infected children to enhance early targeted therapeutic interventions. Methods We conducted a retrospective analysis involving 123 children with acute osteomyelitis treated at our hospital. Upon admission, we measured white blood cell (WBC) counts, C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), and platelet counts. Patients were categorized into two groups: the non-MRSA group (n = 73) and the MRSA group (n = 50), with values assigned as follows (non-MRSA group = 0, MRSA group = 1). Results The MRSA group had a significantly higher average age compared to the non-MRSA group (P 10.95 × 10^9/L, CRP > 49.56 µg/mL, age > 3.5 years, and the absence of suppurative arthritis suggests a heightened risk of MRSA infection.

Recent advancements in the mechanistic comprehension of vascular biology have concentrated on METTL3-mediated N6-methyladenosine modification of RNA, which modulates a spectrum of RNA functionalities with precision. Despite extensive investigations into the roles and mechanisms of METTL3 within vascular biology, a holistic review elucidating their interconnections remains absent. This analysis endeavors to meticulously scrutinize the involvement of METTL3 in both the physiological and pathological paradigms of vascular biology. The findings of this review indicate that METTL3 is indispensable for vascular development and functionality, predominantly through its regulatory influence on pericytes, endothelial cells, vascular smooth muscle cells, and hematopoietic stem cells. Conversely, aberrant METTL3 activity is implicated as a risk factor, diagnostic biomarker, and therapeutic target for vascular pathologies. This comprehensive review offers an exhaustive synthesis of METTL3’s role in vascular biology, addressing existing knowledge gaps and serving as an essential reference for future research and potential clinical applications.

As a mechanism of cell death, ferroptosis has gained popularity since 2012. The process is distinguished by iron toxicity and phospholipid accumulation, in contrast to autophagy, apoptosis, and other cell death mechanisms. It is implicated in the advancement of multiple diseases across the body. Researchers currently know that osteosarcoma, osteoporosis, and other orthopedic disorders are caused by NRF2, GPX4, and other ferroptosis star proteins. The effective relief of osteoarthritis symptoms from deterioration has been confirmed by clinical treatment with multiple ferroptosis inhibitors. At the same time, it should be reminded that the mechanisms involved in ferroptosis that regulate orthopedic diseases are not currently understood. In this manuscript, we present the discovery process of ferroptosis, the mechanisms involved in ferroptosis, and the role of ferroptosis in a variety of orthopedic diseases. We expect that this manuscript can provide a new perspective on clinical diagnosis and treatment of related diseases.

The hydrological environment of wetlands is vital for ensuring the stable development of their ecological functions. However, previous sample-scale studies have failed to capture the spatial heterogeneity of the hydrology-function relationship. The objective of this study is to elucidate the hydrological driving mechanisms responsible for the formation of and changes in the spatial patterns of wetland functions at different spatial and time scales. This study established a multi-dimensional hydrological element and wetland function index system through space technology and multi-source remote sensing images and proposed a multi-scale hydrology-function relationship analysis framework to reveal the relationships between hydrological elements and wetland function spatial patterns at different spatial and temporal scales. The final results demonstrated that, at different spatial and time scales, increasing water coverage contributes greatly to the improvement of habitat, soil conservation, and water supply functions, and increasing the flooding frequency and connectivity structure are more effective at improving the water purification function. At the grid scale, the proportion of grids with medium or strong correlations ranges from 26.63 % to 51.19 %, whereas with respect to temporal correlations, the proportion of grids with medium or strong correlations ranges from 50.67 % to 92.76 %, indicating a pronounced scale effect and spatial heterogeneity of the hydrology-function relationship. The opposite relationships between hydrological elements and functions in some grids (with proportions ranging from 9.89 % to 37.38 %) may result from geographical, environmental constraints, which disrupt the normal correlation between hydrological elements and wetland functions. This study contributes to a deep understanding of the hydrological driving mechanism of wetland functional patterns and provides guidance for wetland protection and restoration planning and hydrological condition regulation by developing specific strategies for improving ecological function.

Consumers have begun to move their attention away from product functioning and toward value probably extracted from items. Companies have begun to use customer service systems (CSS) in response to this trend, which are business models that give clients with not solitary tangible items as well as intangible facilities. Even with substantial investigation on Smart CSS frameworks, rare of this frameworks considered customers active data producers actively creating data for the Smart CSS. Furthermore, the majority of them offered a generic remedy rather than a personalized one. To classify customer service systems, performance metrics, such as precision, accuracy, F1-score, Recall (Sensitivity), Specificity, Error rate, Computation time, and RoC are considered. The performance of AETGCN-NGOA-CSS approach attains 19.11%, 24.12% and 28.13% high specificity, 24.93%, 23.04%, and 9.51% lower computation time, 15.2%, 25.45% and 13.91% higher ROC and 8.45%, 20.98%, and 27.55% higher accuracy compared with existing methods, such as developing personalized recommendation system in smart product service system depend on unsupervised learning model (CSS-BERT), Cognitive Decision-Making approaches in Data-driven Retail Intelligence: Consumer Sentiments, Choices, Shopping Behaviors (CSS-CDMA), e-Commerce Online Intelligent Customer Service System under Fuzzy Control (CSS-FFNN), respectively.

Abstract Background Immune checkpoint inhibitors (ICIs) are rapidly evolving in the management of bladder cancer (BLCA). Nevertheless, effective biomarkers for predicting immunotherapeutic outcomes in BLCA are still insufficient. Ferroptosis, a form of immunogenic cell death, has been found to enhance patient sensitivity to ICIs. However, the underlying mechanisms of ferroptosis in promoting immunotherapy efficacy in BLCA remain obscure. Methods Our analysis of The Cancer Genome Atlas (TCGA) mRNA data using single sample Gene Set Enrichment Analysis (ssGSEA) revealed two immunologically distinct subtypes. Based on these subtypes and various other public cohorts, we identified Apolipoprotein L6 (APOL6) as a biomarker predicting the efficacy of ICIs and explored its immunological correlation and predictive value for treatment. Furthermore, the role of APOL6 in promoting ferroptosis and its mechanism in regulating this process were experimentally validated. Results The results indicate that APOL6 has significant immunological relevance and is indicative of immunologically hot tumors in BLCA and many other cancers. APOL6, interacting with acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), mediates immunotherapy efficacy by ferroptosis. Additionally, APOL6 is regulated by signal transducer and activator of transcription 1 (STAT1). Conclusions To conclude, our findings indicate APOL6 has potential as a predictive biomarker for immunotherapy treatment success estimation and reveal the STAT1/APOL6/GPX4 axis as a critical regulatory mechanism in BLCA.

Abstract Background Sacral screw loosening is a typical complication after internal fixation surgery through the vertebral arch system. Bicortical fixation can successfully prevent screw loosening, and how improving the rate of bicortical fixation is a challenging clinical investigation. Objective To investigate the feasibility of improving the double corticality of sacral screws and the optimal fixation depth to achieve double cortical fixation by combining the torque measurement method with bare hands. Methods Ninety-seven cases of posterior lumbar internal fixation with pedicle root system were included in this study. Based on the tactile feedback of the surgeon indicating the expected penetration of the screw into the contralateral cortex of the sacrum, the screws were further rotated by 180°, 360°, or 720°, categorized into the bicortical 180° group, bicortical 360° group, and bicortical 720° group, respectively. Intraoperatively, the torque during screw insertion was recorded. Postoperatively, the rate of double-cortex engagement was evaluated at 7 days, and screw loosening was assessed at 1 year follow-up. Results The bicortical rates of the 180° group, 360° group, and 720° group were 66.13%, 91.18% and 93.75%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P 0.05).The rates of loosening of sacral screws in the 180° group, 360° group, and 720° group were 20.97%, 7.35% and 7.81%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P 0.05). The bicortical 360° group achieved a relatively satisfactory rate of dual cortical purchase while maintaining a lower rate of screw loosening. Conclusion Manual insertion of sacral screws with the assistance of a torque measurement device can achieve a relatively satisfactory dual cortical purchase rate while reducing patient hospitalization costs.

Abstract Background Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, effective biomarkers for accurate prediction and personalized treatment remain an urgent clinical need. Methods In this study, we analyzed the microbial contents of 453 ovarian serous cystadenocarcinoma and 68 adjacent non-cancerous samples. A univariate Cox regression model was used to identify microorganisms significantly associated with survival and a prognostic risk score model constructed using LASSO Cox regression analysis. Patients were subsequently categorized into high-risk and low-risk groups based on their risk scores. Results Survival analysis revealed that patients in the low-risk group had a higher overall survival rate. A nomogram was constructed for easy visualization of the prognostic model. Analysis of immune cell infiltration and immune checkpoint gene expression in both groups showed that both parameters were positively correlated with the risk level, indicating an increased immune response in higher risk groups. Conclusion Our findings suggest that microbial profiles in ovarian serous cystadenocarcinoma may serve as viable clinical prognostic indicators. This study provides novel insights into the potential impact of intratumoral microbial communities on disease prognosis and opens avenues for future therapeutic interventions targeting these microorganisms.

Abstract Breast cancer (BC) is a highly prevalent malignancy worldwide, with complex pathogenesis and treatment challenges. Research reveals that methyltransferase-like 3 (METTL3) is widely involved in the pathogenesis of several tumors through methylation of its target RNAs, and its role and mechanisms in BC are also extensively studied. In this review, we aim to provide a comprehensive interpretation of available studies and elucidate the relationship between METTL3 and BC. This review suggests that high levels of METTL3 are associated with the pathogenesis, poor prognosis, and drug resistance of BC, suggesting METTL3 as a potential diagnostic or prognostic biomarker and therapeutic target. Collectively, this review provides a comprehensive understanding of how METTL3 functions through RNA methylation, which provides a valuable reference for future fundamental studies and clinical applications.

The paper presents a novel approach to enhancing the accuracy of turbulence modeling in nuclear reactor simulations, specifically addressing secondary flow in the fuel assembly of pressurized water reactors. The accurate prediction of secondary flow in the rod bundle channels of pressurized water reactors is crucial for the design and performance evaluation of nuclear fuel assemblies. Traditional numerical simulation methods have difficulty in striking a balance between computational cost and prediction accuracy. This paper addressed this challenge by calibrating the constants of the nonlinear eddy viscosity model (NLEVM) based on the high-fidelity flow field measurement data from a 5×5 rod bundle with a split mixing vaned spacer grid using a novel data assimilation strategy that incorporated the ensemble Kalman filter (EnKF) algorithm. This study enhanced the overall data assimilation strategy and the EnKF algorithm by introducing sensitivity-based deterministic sampling and correlation-length-based local adjustment, respectively. These modifications aimed to accelerate convergence and reduce residuals in the model constant calibration process. Besides, this study adopted the correlation coefficient between the predicted and measured flow fields as a criterion for judging whether the calibrated model constants improve the prediction accuracy of the secondary flow in the rod bundle channel, which is more in line with the actual phenomenon than the traditional relative error criterion. The calibrated NLEVM significantly improves the prediction accuracy of secondary flow in the rod bundle channels compared to the standard NLEVM. The similarity between the predicted flow field of the calibrated model and the experimentally observed flow field is improved, with the correlation coefficients of the full cross-section flow field improving to a greater extent the further away from the localized grids. The secondary flow structure of the subchannels predicted by the calibrated model agrees well with the experimental observations and can successfully predict the cross-sectional vortex structure that is not accurately predicted by the original model. These results demonstrate effectiveness in refining turbulence model predictions through the novel data assimilation strategy and the modified EnKF algorithm. This research represents a substantial contribution to computational fluid dynamics, particularly in the context of nuclear reactor applications. The innovative approach to calibrating turbulence models using data assimilation strategies paves the way for more accurate and reliable predictions of turbulent flows in complex geometries, with broad-reaching implications for various scientific and engineering disciplines. The study’s findings could be instrumental in enhancing the safety and efficiency of nuclear reactor operations and potentially applicable in other fields requiring precise turbulence modeling, such as aerospace engineering, climate modeling, and industrial process optimization. The integration of data assimilation strategies with traditional turbulence models opens new avenues for improving the fidelity of simulations in complex flow scenarios.

Abstract High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual dysregulation of MYC and BCL2 is one of the important pathogenic mechanisms. Thus, combined targeting of MYC and BCL2 appears to be a promising strategy. Dihydroorotate dehydrogenase (DHODH) is the fourth rate-limiting enzyme for the de novo biosynthesis of pyrimidine. It has been shown to be a potential therapeutic target for multiple diseases. In this study, the DHODH inhibitor brequinar exhibited growth inhibition, cell cycle blockade, and apoptosis promotion in HGBCL cell lines with MYC and BCL2 rearrangements. The combination of brequinar and BCL2 inhibitors venetoclax had a synergistic inhibitory effect on the survival of DHL cells through different pathways. Venetoclax could upregulate MCL-1 and MYC expression, which has been reported as a resistance mechanism of BCL2 inhibitors. Brequinar downregulated MCL-1 and MYC, which could potentially overcome drug resistance to venetoclax in HGBCL cells. Furthermore, brequinar could downregulate a broad range of genes, including ribosome biosynthesis genes, which might contribute to its anti-tumor effects. In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2.

Objective To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. Methods A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). Results A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). Conclusion The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.

Methyltransferase-like 3(METTL3), recognized as the primary N6-methyladenosine methyltransferase, influences cellular functions such as proliferation, migration, invasion, differentiation, and fate determination by regulating gene expression post-transcriptionally. Recent studies have highlighted the indispensability of METTL3 in various immune cells such as hematopoietic stem/progenitor cells, innate immune cells (monocytes, macrophages, dendritic cells), and adaptive immune cells (thymic epithelial cell, T cells, natural killer cells). However, a comprehensive summary and analysis of these findings to elucidate the relationship between METTL3 and the immune system is yet to be undertaken. Therefore, in this review, we systematically collate reports detailing the mechanism underlying the role of METTL3 in regulating various immune processes and examine the modification of METTL3 and its potential implications. This review suggests that METTL3 plays an essential role in the immune system, ranging from maintaining homeostasis to regulating functions. Collectively, this review provides a comprehensive analysis of the relationship between METTL3 and the immune system, serving convenient researchers to understand the frontiers of immunological research and facilitate future clinical applications.

Extracorporeal membrane oxygenation (ECMO), as an extracorporeal life support technique, can save the lives of reversible critically ill patients when conventional treatments fail. However, ECMO-related acute organ injury is a common complication that increases the risk of death in critically ill patients, including acute kidney injury, acute brain injury, acute lung injury, and so on. In ECMO supported patients, an increasing number of studies have shown that activation of the inflammatory response plays an important role in the development of acute organ injury. Cross-cascade activation of the complement system, the contact system, and the coagulation system, as well as the mechanical forces of the circuitry are very important pathophysiological mechanisms, likely leading to neutrophil activation and the production of neutrophil extracellular traps (NETs). NETs may have the potential to cause organ damage, generating interest in their study as potential therapeutic targets for ECMO-related acute organ injury. Therefore, this article comprehensively summarized the mechanism of neutrophils activation and NETs formation following ECMO treatment and their actions on acute organ injury.

Abstract N6‐methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A is pivotal in diverse diseases especially cancer. m6A corelates with the initiation, progression, resistance, invasion, and metastasis of cancer. However, despite these insights, a comprehensive understanding of its specific roles and mechanisms within the complex landscape of cancer is still elusive. This review begins by outlining the key regulatory proteins of m6A modification and their posttranslational modifications (PTMs), as well as the role in chromatin accessibility and transcriptional activity within cancer cells. Additionally, it highlights that m6A modifications impact cancer progression by modulating programmed cell death mechanisms and affecting the tumor microenvironment through various cancer‐associated immune cells. Furthermore, the review discusses how microorganisms can induce enduring epigenetic changes and oncogenic effect in microorganism‐associated cancers by altering m6A modifications. Last, it delves into the role of m6A modification in cancer immunotherapy, encompassing RNA therapy, immune checkpoint blockade, cytokine therapy, adoptive cell transfer therapy, and direct targeting of m6A regulators. Overall, this review clarifies the multifaceted role of m6A modification in cancer and explores targeted therapies aimed at manipulating m6A modification, aiming to advance cancer research and improve patient outcomes.

Immunosenescence impacts both the innate and adaptive immune systems, predominantly affecting certain immune cell types. A notable manifestation of immunosenescence is the diminished efficacy of adaptive immunity. The excessive senescence of immune cells, particularly T cells, leads to marked immune deficiency, consequently escalating the risk of infections, tumors, and age-associated disorders. Lymphocytes, especially T cells, are subject to both replicative and premature senescence. Telomerase reverse transcriptase (TERT) and telomerase have multifaceted roles in regulating cellular behavior, possessing the ability to counteract both replicative and premature senescence in lymphocytes. This review encapsulates recent advancements in understanding immunosenescence, with a focus on T cell senescence, and the regulatory mechanisms involving TERT/telomerase. Additionally, it comprehensively discusses strategies aimed at inhibiting immunosenescence by augmenting TERT/telomerase activity.

Abstract Introduction The aim of this work was to compare the prognosis and characteristics of patients with Cytomegalovirus (CMV) infection (CMV+) with those of patients without virus infection (Virus–) undergoing repeat keratoplasty. Methods This prospective propensity score-matched cohort study enrolled patients who underwent repeat keratoplasty for graft failure at the Peking University Third Hospital between January 2016 and May 2022. Patients with prior viral keratitis before the first keratoplasty were excluded. The primary outcome measure was the graft failure rate. The secondary outcome measures included the anterior segment characteristics, intraocular pressure (IOP), and endothelial cell density. Results Ninety-four matched patient pairs were included. The graft failure rate in the CMV+ group (71%) was higher than that in the Virus– group (29%) (P

Abstract Background The detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molecular events during human SN development process. Methods A fifth Ewing variant (FEV)-EGFP reporter system was established by CRISPR/Cas9 technology to indicate SN since postmitotic stage. FACS was performed to purify SN from the heterogeneous cell populations. RNA-sequencing analysis was performed for cells at four key stages of differentiation (pluripotent stem cells, serotonergic neural progenitors, purified postmitotic SN and purifed mature SN) to explore the transcriptomic dynamics during SN differentiation. Results We found that human serotonergic fate specification may commence as early as day 21 of differentiation from human pluripotent stem cells. Furthermore, the transcriptional factors ZIC1, HOXA2 and MSX2 were identified as the hub genes responsible for orchestrating serotonergic fate determination. Conclusions For the first time, we exposed the developmental transcriptomic profiles of human SN via FEV reporter system, which will further our understanding for the development process of human SN. Graphical Abstract

Abstract Background Studies has suggested that receiving social support improves the professional identity of health professional students. According to the two-way social support theory, social support includes receiving social support and giving social support. However, the effect of the two-way social support on health professional students’ professional identity has not been clarified yet. Methods To explore the mechanism of how two-way social support affects health professional students’ professional identity, an observational, cross-sectional study was conducted among a convenience and cluster sample of 1449 health professional students from two medical schools in western China. Measures included a short version of the two-way social support scale, a health professional students’ professional identity questionnaire, an achievement motivation scale, and a meaning in life scale. (Data were analyzed by use of SPSS26.0 software, Amos 28.0 software, and PROCESSv4.0 plug-in.). Results Receiving social support, giving social support, achievement motivation, meaning in life, and professional identity were positively correlated with each other. Receiving and giving social support not only directly predicted health professional students’ professional identity, but also indirectly predicted health professional students’ professional identity through the mediating roles of achievement motivation and meaning in life, and the chain mediating roles of achievement motivation and meaning in life, respectively. The effectiveness of predicting health professional students’ professional identity varied among different types of two-way social support, which could be depicted as two-way social support > mainly giving social support > mainly receiving social support > low two-way social support. Conclusion In the medical education, the awareness and ability of health professional students to receive and give social support should be strengthened. More attention should be drawn on the chain mediating effect of achievement motivation and meaning in life between two-way social support and professional identity. The current results shed new light on exploring effective ways of improving health professional students’ professional identity, which suggested that more attention should be paid to the positive effects of mainly giving social support and two-way social support rather than only on the effects of receiving social support.

Nervous system diseases represent a significant global burden, affecting approximately 16% of the world’s population and leading to disability and mortality. These conditions, encompassing both central nervous system (CNS) and peripheral nervous system (PNS) disorders, have substantial social and economic impacts. Metformin, a guanidine derivative derived from a plant source, exhibits therapeutic properties in various health conditions such as cancer, aging, immune-related disorders, polycystic ovary syndrome, cardiovascular ailments, and more. Recent studies highlight metformin’s ability to cross the blood–brain barrier, stimulate neurogenesis, and provide beneficial effects in specific neurological disorders through diverse mechanisms. This review discusses the advancements in research on metformin’s role and mechanisms in treating neurological disorders within both the central and peripheral nervous systems, aiming to facilitate further investigation, utilization, and clinical application of metformin in neurology.

We observed tunable characteristics of optical frequency combs (OFCs) generated from InGaAs/GaAs double quantum wells (DQWs) asymmetric waveguide two-section mode-locked lasers (TS-MLLs). This involves an asymmetric waveguide mode-locked semiconductor laser (AWML-SL) operating at a center wavelength of net modal gain of approximately 1.06 µm, which indicates a stable pulse shape, with the power-current(P-I) characteristic curve revealing a small difference between forward and reverse drive currents in the gain region. Under different operating conditions, the laser exhibits the characteristics of OFCs. And the pulse interval in the timing and the peak interval in the frequency domain show a periodic alternating change trend with the increase in the gain current. This tunable characteristic is reported for the first time. The study demonstrates the feasibility of generating tunable optical combs using a monolithic integrated two-section mode-locked semiconductor laser (MI-TS-MLL). This has important reference value for the application of OFCs generated from MI-TS-MLLs or integrated optical chips.

Fiber Bragg gratings (FBGs) are widely used in stress and temperature sensing due to their small size, light weight, high resistance to high temperatures, corrosion, electromagnetic interference, and low cost. In recent years, various structural enhancements and sensitization to FBGs have been explored to improve the performance of ocean temperature and depth sensors, thereby enhancing the accuracy and detection range of ocean temperature and depth data. This paper reviews advancements in temperature, pressure, and dual-parameter enhancement techniques for FBG-based sensors. Additionally, the advantages and disadvantages of each method are compared and analyzed, providing new directions for the application of FBG sensors in marine exploration.

Cancer cell line is commonly used for discovery and development of anti-cancer drugs. It is generally considered that drug response remains constant for a certain cell line due to the identity of genetics thus protein patterns. Here, we demonstrated that cancer cells continued dividing even after reaching confluence, in that the proteomics was changed continuously and dramatically with strong relevance to cell division, cell adhesion and cell metabolism, indicating time-dependent intrinsically reprogramming of cells during expansion. Of note, the inhibition effect of most anti-cancer drugs was strikingly attenuated in culture cells along with cell expansion, with the strongest change at the third day when cells were still expanding. Profiling of an FDA-approved drug library revealed that attenuation of response with cell expansion is common for most drugs, an exception was TAK165 that was a selective inhibitor of mitochondrial respiratory chain complex I. Finally, we screened a panel of natural products and identified four pentacyclic triterpenes as selective inhibitors of cancer cells under prolonged growth. Taken together, our findings underscore that caution should be taken in evaluation of anti-cancer drugs using culture cells, and provide agents selectively targeting overgrowth cancer cells.

With the swift advancement of online teaching in vocational education, an increasing number of web-based course materials are being made available to students, granting them the freedom to select resources that suit their personal needs. To optimize the effectiveness of artificial intelligence-enabled smart vocational education, this study presents a course recommendation model centered on learning behaviors and interests. The model utilizes short-term preferences reconstruction behavior contribution to identify fluctuations in learners' interests in real-time. A model for recommending courses is proposed based on short-term preferences and enhancements to learning behavior. Its purpose is to tackle the issue of generalization arising from sparsity and weak correlation in learning behavior. The outcomes demonstrated the model put forth in the study achieved higher Hit Rate (HR) and Normalized Discounted Cumulative Gain (NDCG) values in comparison experiments with multiple models. Hence, this suggested that creating a novel component of historical learning behavior, powered by dynamic interest factors, could resolve the issue of changing learning interests and enhance the efficacy of course recommendation models. Furthermore, the introduction of a correlation mapping network enables the forward mapping transformation from weak to strong learning behavior, thus improving and optimizing input for the agent strategy, reducing data sparsity, and enhancing the performance and generalization of the course recommendation model.

Abstract Early-life human gut microbiome is a pivotal driver of gut homeostasis and infant health. However, the viral component (known as “virome”) remains mostly unexplored. Here, we establish the Early-Life Gut Virome (ELGV), a catalog of 160,478 non-redundant DNA and RNA viral sequences from 8130 gut virus-like particles (VLPs) enriched or bulk metagenomes in the first three years of life. By clustering, 82,141 viral species are identified, 68.3% of which are absent in existing databases built mainly from adults, and 64 and 8 viral species based on VLPs-enriched and bulk metagenomes, respectively, exhibit potentials as biomarkers to distinguish infants from adults. With the largest longitudinal population of infants profiled by either VLPs-enriched or bulk metagenomic sequencing, we track the inherent instability and temporal development of the early-life human gut virome, and identify differential viruses associated with multiple clinical factors. The mother-infant shared virome and interactions between gut virome and bacteriome early in life are further expanded. Together, the ELGV catalog provides the most comprehensive and complete metagenomic blueprint of the early-life human gut virome, facilitating the discovery of pediatric disease-virome associations in future.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Microglia-mediated neuroinflammation has been largely considered one of main factors to the PD pathology. MicroRNA-218-5p (miR-218-5p) is a microRNA that plays a role in neurodevelopment and function, while its potential function in PD and neuroinflammation remains unclear. Methods We explore the involvement of miR-218-5p in the PD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. The miR-218-5p agomir used for overexpression was delivered into the substantia nigra (SN) by bilateral stereotaxic infusions. The loss of dopaminergic (DA) neurons and microglial inflammation in the SN was determined using Western blotting and immunofluorescence. Motor function was assessed using the rotarod test. RNA sequencing (RNA-seq) was performed to explore the pathways regulated by miR-218-5p. The target genes of miR-218-5p were predicted using TargetScan and confirmed using dual luciferase reporter assays. The effects of miR-218-5p on microglial inflammation and related pathways were verified in murine microglia-like BV2 cells. To stimulate BV2 cells, SH-SY5Y cells were treated with 1-methyl-4-phenylpyridinium (MPP+) and the conditioned media (CM) were collected. Results MiR-218-5p expression was reduced in both the SN of MPTP-induced mice and MPP+-treated BV2 cells. MiR-218-5p overexpression significantly alleviated MPTP-induced microglial inflammation, loss of DA neurons, and motor dysfunction. RNA sequence and gene set enrichment analysis showed that type I interferon (IFN-I) pathways were upregulated in MPTP-induced mice, while this upregulation was reversed by miR-218-5p overexpression. A luciferase reporter assay verified that Ddx41 was a target gene of miR-218-5p. In vitro, miR-218-5p overexpression or Ddx41 knockdown inhibited the IFN-I response and expression of inflammatory cytokines in BV2 cells stimulated with MPP+-CM. Conclusions MiR-218-5p suppresses microglia-mediated neuroinflammation and preserves DA neurons via Ddx41/IFN-I. Hence, miR-218-5p-Ddx41 is a promising therapeutic target for PD.

Abstract Introduction Neurotrophic keratopathy (NK) is a rare degenerative ocular disease that can be difficult to treat. There were no effective resolutive treatments for severe NK caused by ocular graft-versus-host disease (oGVHD) along with virus infection. To address this question, we designed a prospective cohort study to evaluate the efficacy and safety of topical recombinant human nerve growth factor (rhNGF) in patients with recalcitrant NK of oGVHD and viral infection. Methods This prospective cohort study enrolled patients with recalcitrant NK diagnosed with oGVHD and treated with rhNGF. Clinical evaluations included the range of epithelial defects, best corrected visual acuity, intraocular pressure, slit-lamp examination, and corneal fluorescein staining. Examinations of the central corneal thickness, corneal sensitivity, and nerve fiber regeneration were performed at each visit at 4, 8, 12, 20 weeks and 6 months, respectively, after initiating rhNGF treatment. Results All enrolled patients were diagnosed with NK at stage 2 (7 eyes, 63.6%) or stage 3 (4 eyes, 36.4%) and responded to rhNGF treatment. Five of 11 (45.5%) and 9 of 11 eyes (81.8%) achieved complete corneal epithelial healing after 4 and 8 weeks, respectively. All 11 eyes (100%) achieved complete corneal healing after 12 weeks. There was also a significant reduction in the corneal ulcer area during each visit (P

Lactate, an important metabolic product, provides energy to neural cells during energy depletion or high demand and acts as a signaling molecule in the central nervous system. Recent studies revealed that lactate-mediated protein lactylation regulates gene transcription and influences cell fate, metabolic processes, inflammation, and immune responses. This review comprehensively examines the regulatory roles and mechanisms of lactylation in neurodevelopment, neuropsychiatric disorders, brain tumors, and cerebrovascular diseases. This analysis indicates that lactylation has multifaceted effects on central nervous system function and pathology, particularly in hypoxia-induced brain damage. Highlighting its potential as a novel therapeutic target, lactylation may play a significant role in treating neurological diseases. By summarizing current findings, this review aims to provide insights and guide future research and clinical strategies for central nervous system disorders.

Abstract. Background:. Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein. Methods:. Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis. Results:. A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04–1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to

Abstract Background Previous studies have explored the stress and turnover intention of healthcare workers, but as important backup talents in the healthcare system, resident physicians have received little attention from researchers, especially after experiencing COVID-19. Therefore, this study aims to evaluate the chronic stress and turnover intention of resident physicians after experiencing COVID-19. Methods From June to August 2022, we conducted a questionnaire survey on resident physicians in the Children's Hospital of Hebei Province through the online platform (Wenjuanxing) to evaluate their chronic stress and turnover intention after experiencing COVID-19. For the collected data, we used frequency and percentage to make the statistical description, the Chi-square test to make a univariate analysis on the scores of chronic stress and turnover intention scale, and binary logistic regression analysis to explore the influencing factors of turnover intention. Results Out of 143 respondents, we finally received 127 questionnaires, with a response rate of 88.81%. Among 127 respondents, 80.31% of resident physicians experienced varying degrees of chronic stress (mild: 36.22%, moderate: 35.43%, severe: 8.66%), and 74.80% of resident physicians showed varying degrees of turnover intention (mild: 23.62%, moderate: 37.79%, severe: 13.39%). Moreover, age (OR = 0.772, P = 0.042), identity (OR = 8.648, P = 0.021), and chronic stress levels (mild: OR = 6.938, P = 0.003; moderate: OR = 44.049, P

Abstract Background The mental health and living arrangements of older adults are worthy of attention. Previous studies have pointed out that the living arrangements may be related to older adults’ depression. However, it has not been found that studies concern the relationship between actual living arrangements, living arrangement preferences, and the fit between living arrangement preferences and reality and depression in older adults, so we carried out this study. Methods The data from the Chinese longitudinal healthy longevity survey were used in this study. With the older adults’ depression as the dependent variable and the living arrangement related variables as the independent variable, we constructed three binary-logistic regression analysis models to explore the potential relationship between living arrangement related variables and depression in older adults. Results We found that the actual living arrangements, living arrangement preferences, and the fit between living arrangement preferences and reality are significantly correlated with depression in older adults. Specifically, older adults living alone or only with the spouse are at greater risk of depression. Older adults who prefer living alone or only with the spouse are at relatively low risk of depression. Older adults whose living arrangement preferences do not match reality have a higher risk of depression. Conclusion The living arrangement related variables are significantly correlated with depression in older adults. In addition to the actual living arrangements, living arrangement preferences and whether the living arrangement preferences fit with reality are also related to the depression of older adults.

Background and purposeMyelin oligodendrocyte glycoprotein (MOG) IgG is frequently elevated in pediatric patients with acquired demyelinating syndrome (ADS). However, no specific biomarkers exist for phenotype classification, symptom severity, prognosis, and treatment guidance of MOG-IgG-associated disease (MOGAD). This study evaluated neurofilament light chain (NfL) and endothelial growth factor receptor (EGFR) mRNA expression levels in serum and cerebrospinal fluid (CSF) as potential biomarkers for MOGAD in Chinese children.MethodsThis was a cross-sectional and single-center study. We enrolled 22 consecutive pediatric patients hospitalized with MOGAD and 20 control pediatric patients hospitalized for noninflammatory neurological diseases in Hebei Children’s Hospital. Serum and CSF were collected from MOGAD patients within 3 days before immunotherapy. The mRNA levels of NfL and EGFR in serum and CSF were measured by real-time polymerase chain reaction (qPCR), and the EGFR/NfL ratio mRNA was calculated. These measurement values were then compared between disease groups and among MOGAD phenotypes. In addition, the correlations between the mRNAs of three markers (NfL, EGFR, EGFR/NfL ratio), extended disability status scale (EDSS) scores, and clinical phenotypes were analyzed.ResultsSerum and CSF NfL mRNA levels were significantly higher of acute-stage MOGAD patients than those of control patients (p< 0.05 and p< 0.01, respectively), while the mRNA levels of serum EGFR and EGFR/NfL ratio were significantly lower of MOGAD patients than those of controls (p < 0.05, p < 0.0001). Serum NfL mRNA was significantly correlated with mRNA of serum EGFR (r =0.480, p < 0.05). Serum and CSF NfL mRNA levels in MOGAD patients with the ADEM-like phenotype were also significantly higher than those in control patients (p < 0.01, p < 0.01) and optic neuritis (ON) phenotype (p < 0.05, p < 0.05). Both mRNAs of NfL in CSF and EGFR/NfL ratio in serum were correlated with EDSS scores (p < 0.05, r = 0.424; p < 0.05, r= -0.521).ConclusionThe mRNA levels of elevated NfL in serum and CSF as well as lower EGFR and EGFR/NfL ratio in serum could help distinguish acute-phase MOGAD. Higher mRNA levels of NfL in serum and CSF of MOGAD patients help distinguish ADEM-like phenotype. In addition, serum EGFR/NfL mRNA ratio is indicative of disease severity in pediatric patients with MOGAD. Further investigations are warranted to elucidate the pathological mechanisms underlying these associations.

The direct utilization of low-light images hinders downstream visual tasks. Traditional low-light image enhancement (LLIE) methods, such as Retinex-based networks, require image pairs. A spiking-coding methodology called intensity-to-latency has been used to gradually acquire the structural characteristics of an image. convLSTM has been used to connect the features. This study introduces a simplified DCENet to achieve unsupervised LLIE as well as the spiking coding mode of a spiking neural network. It also applies the comprehensive coding features of convLSTM to improve the subjective and objective effects of LLIE. In the ablation experiment for the proposed structure, the convLSTM structure was replaced by a convolutional neural network, and the classical CBAM attention was introduced for comparison. Five objective evaluation metrics were compared with nine LLIE methods that currently exhibit strong comprehensive performance, with PSNR, SSIM, MSE, UQI, and VIFP exceeding the second place at 4.4% (0.8%), 3.9% (17.2%), 0% (15%), 0.1% (0.2%), and 4.3% (0.9%) on the LOL and SCIE datasets. Further experiments of the user study in five non-reference datasets were conducted to subjectively evaluate the effects depicted in the images. These experiments verified the remarkable performance of the proposed method.