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Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell-derived sarcomas that are sporadic or associated with Neurofibromatosis 1 (NF1) gene mutations. Traditional therapies are usually ineffective for treating MPNSTs, so new targets need to be identified for the treatment of MPNSTs. In the present study, the role of the mitochondrial translocator protein (TSPO) in the regulation of cell proliferation and the cell cycle in MPNSTs was investigated. TSPO expression was lower in MPNSTs than in NFs. Loss-of-function experiments revealed that TSPO deficiency promoted MPNST cell growth, migration, and invasion and influenced the cell cycle in vitro and in vivo. In addition, TSPO depletion suppressed cell apoptosis by downregulating the expression of caspase-3, caspase-8, HSP60, p27, p53, and BCL-2 and suppressed the cell cycle by upregulating CDK1, CDK2, CCNB1 and CCNA2. Furthermore, CDK1 was determined to be an upstream target of TSPO-mediated regulation via RNA-seq, qPCR, and Western blotting. Specifically, depletion of CDK1 weakened the effect of TSPO deficiency on cell proliferation and migration. More importantly, CDK1 knockdown induced significant cell cycle arrest in the G2/M phase. In summary, TSPO deficiency regulates the cell cycle in MPNSTs by targeting CDK1, which may be an effective molecular target for prognosis evaluation and treatment.

Abstract Pilocytic astrocytoma (PA) is classified as a Grade I benign neuroglial tumor. The extent of surgical resection is a critical factor influencing the prognosis for patients with PA. In prior researches of PA, the extent of surgical resection is generally categorized into GTR, STR and biopsy. In some researches on brain tumor surgeries, the extent of resection also includes GTL. There is no existing research specifically comparing the efficacy of GTR versus GTL in PA treatment. In this study, the data we used are from the SEER database. We categorized the extent of resection into GTL, GTR, STL, STR, biopsy, and no surgery based on SEER classification of surgical procedures, to investigate the impact of extent of resection on PA patient survival. A multivariate logistic regression model was utilized to acquire odds ratios (OR) for different extent of resection. Survival outcomes across different extent of resection (GTL, GTR, STL, STR, biopsy, no surgery) were assessed using Kaplan–Meier survival curve analysis, with curve comparisons conducted via log-rank tests. The impact of various risk factors on survival was assessed using the Cox proportional hazards model. The hazard ratio (HR) was employed to quantify the influence of one or more factors on overall survival throughout the follow-up period. Multivariate Cox analysis revealed that age, tumor location, extent of resection, as well as the application of radiotherapy and chemotherapy, all significantly impacted prognosis. Compared to GTL, GTR did not significantly increase the risk of mortality (HR 1.17; 95% CI 0.73–1.86, p = 0.5). Furthermore, there was no statistically significant difference between the Kaplan–Meier survival curves of the two groups (p = 0.18). We employed propensity score matching (PSM) to balance the differences in baseline characteristics of patients receiving chemotherapy or radiotherapy. A total of 4429 patients were included in this study. Age, diagnosis period, race, tumor size, and tumor location as influential on the extent of resection. Age, tumor location, extent of resection, and application of radiotherapy and chemotherapy influenced the survival of PA patients. The Kaplan–Meier survival curves revealed that the long-term survival rate for GTR is slightly higher than that for GTL. The PSM analysis revealed that the application of radiotherapy and chemotherapy was associated with the reduction of overall survival in PA patients. In conclusion, there was no significant difference in survival between GTR and GTL, so GTR with less damage was preferred. The application of radiotherapy and chemotherapy can reduce overall survival of patients with PA.

Abstract The incidence of multiple primary lung cancer (MPLC) is increasing, with some of our surgical patients exhibiting numerous lesions. We defined lung cancer with five or more primary lesions as super MPLCs. Elucidating the genomic characteristics of this special MPLC subtype can help reduce disease burden and understand tumor evolution. In our cohort of synchronous super early-stage MPLCs (PUMCH-ssesMPLC), whole-exome sequencing on 130 resected malignant specimens from 18 patients provided comprehensive super-MPLC genomic landscapes. Mutations are enriched in PI3k-Akt and MAPK pathways. Their BRAF mutation frequency (31.5%) is significantly higher than MPLC with fewer lesions and early-stage single-lesion cancer, while EGFR mutations are significantly fewer (13.8%). As lesion counts increase, BRAF mutations gradually become dominant. Also, invasive lesions more tend to have classic super-MPLC mutation patterns. High-frequency BRAF mutations, especially Class II, and low-frequency EGFR mutations could be a reason for the limited effectiveness of targeted therapy in super-MPLC patients.

In this paper, we introduced the gradient-enhanced fractional physics-informed neural networks (gfPINNs) for solving the forward and inverse problems of the multiterm time-fractional Burger-type equation. The gfPINNs leverage gradient information derived from the residual of the fractional partial differential equation and embed the gradient into the loss function. Since the standard chain rule in integer calculus is invalid in fractional calculus, the automatic differentiation of neural networks does not apply to fractional operators. The automatic differentiation for the integer order operators and the finite difference discretization for the fractional operators were used to construct the residual in the loss function. The numerical results demonstrate the effectiveness of gfPINNs in solving the multiterm time-fractional Burger-type equation. By comparing the experimental results of fractional physics-informed neural networks (fPINNs) and gfPINNs, it can be seen that the training performance of gfPINNs is better than fPINNs.

Abstract Background Lung adenocarcinoma (LUAD) is the most common type of lung cancer and closely associated with the immune system. Emerging evidence suggests that blood immune cell phenotypes in patients with LUAD may undergo alterations. Nevertheless, the limited amount of relevant research makes it difficult to understand the causal links between LUAD and changes in the immune cells. This study aimed to reveal the potential causal relationships between 731 immune cell phenotypes and LUAD. Methods A bidirectional two‐sample Mendelian randomization (MR) analysis was used to clarify causal relationships. Four types of immune phenotypes, absolute cell counts, relative cell counts, median fluorescence intensities (MFIs) of surface antigens, and morphological parameters, were investigated in this study. Heterogeneity tests, horizontal pleiotropy tests, and leave‐one‐out analyses were performed to validate the reliability of our study. Results A total of 26 immune cell characteristics were identified as contributing to the occurrence of LUAD. Memory B cells, IgD−CD38br cells, CD4+ regulatory T cells (Tregs), and plasmacytoid dendritic cells (DCs) may play a role in the development of LUAD. Through reverse MR, our study discovered that the presence of LUAD also induced changes in the expression levels of 16 immune cell traits involving specific surface markers and various types of immune cells, some of which pertain to antigen presentation and immune activation processes. Conclusion Our study demonstrated causal links between several immune cell phenotypes and LUAD, thereby providing indications of the potentially oncogenic physiological state and early screening biomarkers for future research.

Abstract Objectives Thoracic surgery is a complex field requiring advanced technical skills and critical decision-making. Surgical education must evolve to equip trainees with proficiency in new techniques and technologies. Methods This bibliometric analysis systematically reviewed 113 articles on thoracic surgery skills training published over the past decade, retrieved from databases including Web of Science. Publication trends, citation analysis, author and journal productivity, and keyword frequencies were evaluated. Results The United States contributed the most publications, led by pioneering institutions. Simulation training progressed from basic to sophisticated modalities and virtual reality emerged with transformative potential. Minimally invasive techniques posed unique learning challenges requiring integrated curricula. Conclusion Ongoing investments in educational research and curriculum innovations are imperative to advance thoracic surgery training through multidisciplinary strategies. This study provides an evidentiary foundation to optimize training and address the complexities of modern thoracic surgery.

Abstract Background The treatment for bilateral synchronous multiple primary lung cancers (MPLC) remains challenging. Simultaneous bilateral video-assisted thoracic surgery (VATS) may be an optimal treatment with curative intent, but its safety and feasibility are controversial. Methods One hundred and fifty-eight patients who underwent simultaneous bilateral VATS (simultaneous group) and 79 who underwent two-staged bilateral VATS (two-staged group) were included in this study. Their medical records were retrospectively reviewed and analyzed. Results The majority of patients were female and non-smokers. The most common surgical plan was lobectomy and contralateral wedge resection in both groups. There was no significant difference in the postoperative complication rate between the simultaneous groups and two-staged group (13.3% vs. 11.4%, p = 0.73). Patients who underwent simultaneous bilateral resection had shorter hospital stays, shorter anesthesia time and less chest drainage compared with those who underwent two-staged resection. Advanced TNM stage, complicated surgical plan and aggressive lymph node resection were risk factors for postoperative complications in simultaneous bilateral VATS. Patients in two groups had similar overall survival and disease free survival (p = 0.2). Conclusions Simultaneous bilateral VATS for bilateral lung nodule resection is as safe and feasible as two-staged bilateral VATS. Patients who underwent simultaneous bilateral resection had similar or even better outcomes compared to that of the two-staged group. Simultaneous bilateral VATS is potentially an optimal treatment option for patients with erarly cTNM stage and good physical condition.

Lightweight refractory high-entropy alloy (LRHEA) is one of potential structural materials in aerospace industry for its excellent high-temperature comprehensive properties and low density. In this work, a new high-throughput method to develop LRHEAs was proposed. The equimolar HfNbTaTiZr alloy was immersed with melting pure aluminum for a given time, and a thick layer with composition gradient was obtained. Further characterizations of the layer result in relations between composition and nanohardness or Young's modulus, which facilitate the selection of the optimal composition with desired properties. Finally, three LRHEAs were designed and casted into bulk samples with arc-melting method. The alloys show superhigh Vickers hardness of 8.29–9.56 GPa and low densities of 6.27–7.08 g/cm3, showing great potentials in applications as wear-resistant materials. The high-throughput method developed here may also accelerate the development of new LRHEAs.

Abstract Objectives The goal of this research is to pinpoint the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer. Methods We identified the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer by searching the Web of Science database. We extracted key information from the selected studies, including the author, journal, impact factor, type of article, year of publication, country, organization, and keyword. Results To the best of our understanding, this is the inaugural bibliometric study on sublobectomy for non-small cell lung cancer. The publication years of the top 100 most frequently referenced studies span from 1994 to 2022, with citation counts ranging from 51 to 795. The majority of the included studies are original (93/100) and primarily retrospective studies (82/93). The United States leads in terms of published articles and citations, with the Annals of Thoracic Surgery being the most frequently sourced journal (n = 27). High-density keywords primarily originate from limited resection, lobectomy, survival, carcinoma, recurrence, randomized trial, radiotherapy, lung cancer, outcome, 2 cm, as revealed by CiteSpace analysis. Conclusions Our research compiles and analyzes the top 100 most frequently referenced studies in the field of sublobectomy for non-small cell lung cancer. The United States has the most published and cited works on this topic. Currently, the hot keywords for sublobectomy research are gradually shifting towards prognosis and obtaining better evidence-based medical evidence to demonstrate its value in the treatment of non-small cell lung cancer.

Abstract Background Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables. Methods This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001–2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools. Results Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p

Objective: The present study aims to evaluate the impact of Astilbin (AST) on cortical neuron survival in vitro under conditions of oxygen-glucose deprivation and reoxygenation (OGD/R) and determine the role of NF-E2-related factor 2 (Nrf2) in this process. Methods: Primary neurons were pre-treated with various concentrations of AST for 8 h before OGD induction. Cell viability and lactate dehydrogenase (LDH) leakage were assessed to determine the optimal concentration. Biomarkers related to oxidative stress, antioxidant enzyme activities, and apoptosis were evaluated at 24 h post-OGD/R. To investigate the involvement of Nrf2 in AST-mediated neuroprotection, we conducted molecular docking and microscale thermophoresis analyses, as well as examined the expression levels of Nrf2 and its regulatory genes including heme oxygenase-1(HO-1), (NAD(P)H: quinone oxidoreductase 1 (NQO-1), and peroxiredoxin 1 (Prdx1). Additionally, lentivirus-mediated knockdown of Nrf2 and overexpression of Nrf2 with L-sulforaphane (SFN) were performed, followed by an assessment of cell viability, oxidative stress, antioxidant enzyme activities and apoptosis. Results: Pre-treatment with AST reduced oxidative stress levels while increasing antioxidant enzyme activities and mitigating neuronal apoptosis. After OGD/R exposure, AST upregulated nuclear Nrf2 expression and increased the expression of HO-1, NQO-1 and Prdx1 in the cytoplasm. However, the knockdown of Nrf2 abolished the antioxidative and protective effects exerted by AST treatment. Conversely, combining AST with the Nrf2 agonist SFN demonstrated an enhancement in the protective effects provided by AST. These results demonstrate that Nrf2-dependent antioxidant responses contribute to AST-induced tolerance against neuronal injury caused by OGD/R injury. Conclusions: Overall findings support the ability of AST to protect primary neurons from OGD/R-induced damage through activation of Nrf2-dependent antioxidant responses.

Abstract Background We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. Methods Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan–Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. Results A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. Conclusions Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Abstract Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 min). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post-tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.

Abstract Objective To compare neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal for treatment of hypertensive cerebral hemorrhage. Method Ninety-one patients with hypertensive cerebral hemorrhage admitted to our neurosurgery department from June 2022 to May 2023 were selected: 47 patients who underwent endoscopic hematoma removal with the aid of neuronavigation in observation Group A and 44 who underwent intracerebral hematoma puncture and drainage in control Group B. The duration of surgery, intraoperative bleeding, hematoma clearance rate, pre- and postoperative GCS score, National Institutes of Health Stroke Scale (NIHSS) score, mRS score and postoperative complications were compared between the two groups. Results The duration of surgery, intraoperative bleeding and hematoma clearance were significantly lower in Group B than in Group A (p

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.

Background Major depressive disorders (MDDs) impose substantial burdens on individuals and society; however, further detailed analysis is still needed for its long-term trends.Aims This study aimed to analyse the gender-specific temporal trends and cohort variations of MDD incidence among Chinese residents over the past three decades.Methods Employing the age-period-cohort-interaction model and leveraging data from the Global Burden of Disease Study 2019, this research identified and analysed incidence trends of MDD among Chinese males and females aged 5–94 years from 1990 to 2019 across three dimensions, encompassing age, period and birth cohort.Results The analysis reveals age-related effects, indicating heightened MDD risk among adolescents and older adults. Specifically, individuals entering the older adulthood at the age of 65–69 significantly increased the risk of MDD by 64.9%. People aged 90–94 years witnessed a 105.4% increase in MDD risk for the overall population, with females and males in this age group experiencing a 75.1% and 103.4% increase, respectively. In terms of period effects, the risk of MDD displayed a decline from 1990 to 1994, followed by a rebound in 2008. Cohort effects demonstrated diverse generational patterns, with generation I and generation III manifesting opposing ‘age-as-level’ trends. Generation II and generation IV exhibited ‘cumulative disadvantage’ and ‘cumulative advantage’ patterns, respectively. Age effects indicated an overall higher risk of MDD incidence in females, while cohort effects showed greater variations of MDD incidence among females.Conclusions The study underscores the substantial effects of age, period and cohort on MDD across genders in China. Priority interventions targeting vulnerable populations, including children, adolescents, older adults, females and the post-millennium birth cohort, are crucial to mitigate the impact of MDD.

Objective The objective is to explore the impact of the pandemic shock on the unmet medical needs of middle-aged and older adults worldwide.Methods The COVID-19 pandemic starting in 2020 was used as a quasiexperiment. Exposure to the pandemic was defined based on an individual’s context within the global pandemic. Data were obtained from the Integrated Values Surveys. A total of 11 932 middle-aged and older adults aged 45 years and above from 10 countries where the surveys conducted two times during 2011 and 2022 were analysed. We used logistic regression models with the difference-in-difference method to estimate the impact of pandemic exposure on unmet medical needs by comparing differences before and after the pandemic across areas with varying degrees of severity.Results Among the 11 932 middle-aged and older adults, 3647 reported unmet medical needs, with a pooled unmet rate of 30.56% (95% CI: 29.74% to 31.40%). The pandemic significantly increased the risk of unmet medical needs among middle-aged and older adults (OR: 2.33, 95% CI: 1.94 to 2.79). The deleterious effect of the pandemic on unmet medical needs was prevalent among middle-aged adults (2.53, 2.00 to 3.20) and older adults (2.00, 1.48 to 2.69), as well as among men (2.24, 1.74 to 2.90) and women (2.34, 1.82 to 3.03). The results remained robust in a series of sensitivity analyses.Conclusion These findings suggest that efforts should be made by policymakers and healthcare professionals to balance healthcare resources to adequately address the comprehensive healthcare demands of individuals regarding multiple health issues, taking into account the challenges posed by pandemics.

Safety is a top concern for the civil aviation industry, and the risk of safety accidents will increase due to pilot fatigue. To ensure the safety of civil aviation, this paper proposes a method to solve the crew scheduling problem considering pilot fatigue. In order to reflect individual differences and fatigue levels of pilots, an improved three-stage alertness calculation model is first proposed based on subjective and objective perspectives to represent pilots’ alertness levels and fatigue working duration quantitatively. Then, for the crew scheduling problem considering pilot fatigue, a mixed integer programming model is constructed to simultaneously achieve the optimization objectives of reducing the overall scheduling cost and crew fatigue working duration. Next, since the actual crew scheduling problem is large-scale, a solution algorithm based on a column generation framework is developed to improve the quality and efficiency of solving the large-scale crew scheduling problem. Furthermore, in the case study, we collected actual data from an airline company to validate the effectiveness of our proposed method. Finally, through multiple experimental comparisons and analyses, to balance the two optimization objectives mentioned above, it is more reasonable to handle pilot fatigue working duration with soft constraints. Sensitivity analysis reveals the variation rules of the crew cost and fatigue, providing some valuable managerial insights for the crew scheduling problem considering pilot fatigue.

Abstract Objective To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model. Methods A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression. Results A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1–128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p

Objectives: Amid the challenges posed by the global COVID-19 pandemic, understanding how the crisis shapes people' environmental behaviours and consciousness becomes paramount. This study aimed to unravel the implications of the global pandemic on individuals' environmental protection activities, environmentally prioritized attitudes, and confidence in future environmental protection movements. Methods: By combing detailed COVID-19 surveillance data from the World Health Organization and the Integrated Values Surveys, this study analysed information from 54,951 participants aged 15 years and above across 18 countries spanning 6 continents. Utilizing the global pandemic as a natural experiment, Logistic regressions with Difference-in-Difference (DID) models were employed for a robust estimation of the pandemic's effects on environmental outcomes. Results: The findings revealed a notable reduction in the likelihood of environmental protection activities among individuals (adjusted OR: 0.34, 95% CI: 0.23–0.51). However, pandemic exposure was linked to an increased environmentally prioritized attitude (1.35, 1.18–1.54) and enhanced confidence in environmental protection movements (1.16, 1.01–1.32). Notably, the beneficial effects of the pandemic on environmental attitudes (1.42, 1.21–1.67) and confidence (1.19, 1.01–1.39) were significantly observed exclusively among younger individuals and women exhibited heightened sensitivity to the pandemic's positive impact on environmental attitudes (1.55, 1.30–1.86), while men displayed increased sensitivity in confidence regarding future environmental movements (1.23, 1.00–1.50). Conclusions: This study contributes valuable insights to the existing literature by elucidating the intricate relationship between global crises and individual environmental protection. The evidence generated provides policymakers with essential information for formulating comprehensive post-pandemic strategies aimed at jointly promoting and achieving high-quality development of the population and the environmental dimension of SDGs.

AbstractContext Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear.Objective To elucidate styrax’s anti-ischemic stroke protective effects and underlying mechanisms.Materials and methods An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax’s cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify.Results The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1β, and increase SOD and GSH-Px in ischemic-stroke rats (p

A stable and robust odometry system is essential for autonomous robot navigation. The 4D millimeter-wave radar, known for its resilience in harsh weather conditions, has attracted considerable attention. As the latest generation of FMCW radar, 4D millimeter-wave radar provides point clouds with both position and Doppler velocity information. However, the increased uncertainty and noise in 4D radar point clouds pose challenges that prevent the direct application of LiDAR-based SLAM algorithms. To address this, we propose a SLAM framework that fuses 4D radar data with gyroscope readings using graph optimization techniques. Initially, Doppler velocity is employed to estimate the radar’s ego velocity, with dynamic points being removed accordingly. Building on this, we introduce a pre-integration factor that combines ego-velocity and gyroscope data. Additionally, leveraging the stable RCS characteristics of radar, we design a corresponding point selection method based on normal direction and propose a scan-to-submap point cloud registration technique weighted by RCS intensity. Finally, we validate the reliability and localization accuracy of our framework using both our own dataset and the NTU dataset. Experimental results show that the proposed DGRO system outperforms traditional 4D radar odometry methods, especially in environments with slow speeds and fewer dynamic objects.

Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising the quality of life for affected individuals. Nevertheless, the precise underlying mechanism remains elusive. Here, we report for the first time that the accumulation of iron within the hippocampus, distal to the site of ICH in the striatum, is causally linked to the observed cognitive impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) demonstrated significant iron accumulation in the hippocampus of ICH patients, which is far from the actual hematoma. Logistical regression analysis and multiple linear regression analysis identified iron level as an independent risk factor with a negative correlation with post-ICH cognitive impairment. Using a mouse model of ICH, we demonstrated that iron accumulation triggers an excessive activation of neural stem cells (NSCs). This overactivation subsequently leads to the depletion of the NSC pool, diminished neurogenesis, and the onset of progressive cognitive dysfunction. Mechanistically, iron accumulation elevated the levels of reactive oxygen species (ROS), which downregulated the expression of Itga3. Notably, pharmacological chelation of iron accumulation or scavenger of aberrant ROS levels, as well as conditionally overexpressed Itga3 in NSCs, remarkably attenuated the exhaustion of NSC pool, abnormal neurogenesis and cognitive decline in the mouse model of ICH. Together, these results provide molecular insights into ICH-induced cognitive impairment, shedding light on the value of maintaining NSC pool in preventing cognitive dysfunction in patients with hemorrhagic stroke or related conditions.

Abstract The immune-related microenvironment of thymic carcinoid has rarely been reported. We analyzed the expression of PD-L1 and VISTA, and the distribution of CD4+ T cells, CD8+ T cells and CD68+ macrophages in the thymic carcinoid by immunohistochemical staining, and showed the correlation between these markers and clinical survival, indicating the potential therapeutic prospects.

Abstract Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

Abstract Objective Adopting a healthy lifestyle, including regular physical activity, is widely believed to decrease cancer risk. This study aimed to quantitatively establish the dose‐response relationships between total physical activity and the risk of breast, colon, lung, gastric, and liver cancers. Methods A systematic review and dose‐response analysis were conducted using PubMed and Embase from January 1, 1980 to March 20, 2023. Prospective cohort studies that examined the association between physical activity and the risks of any of the 5 outcomes were included. The search was confined to publications in the English language with a specific focus on human studies. Physical activity is standardized by using the data from US National Health and Nutrition Examination Surveys (NHANES) and the Global Burden of Disease 2019 database. Results A total of 98 studies, involving a combined population of 16,418,361 individuals, were included in the analysis. Among the included studies, 57 focused on breast cancer, 17 on lung cancer, 23 on colon cancer, 5 on gastric cancer, and 7 on liver cancer. Overall, elevated levels of physical activity exhibited an inverse correlation with the risk of cancer. The dose‐response curve for lung cancer exhibited a non‐linear pattern, with the greatest benefit risk reduction observed at 13,200 MET‐minutes/week of physical activity, resulting in a 14.7% reduction in risk (relative risk 0.853, uncertainty interval 0.798 to 0.912) compared to the inactive population. In contrast, the dose‐response curves for colon, gastric, breast, and liver cancers showed linear associations, indicating that heightened levels of total physical activity were consistently associated with reduced cancer risks. However, the increase in physical activity yielded a smaller risk reduction for colon and gastric cancers compared to breast and liver cancers. Compared to individuals with insufficient activity (total activity level < 600 MET‐minutes/week), individuals with high levels of activity (≥ 8,000 MET‐minutes/week) experienced a 10.3% (0.897, 0.860 to 0.934) risk reduction for breast cancer; 5.9% (0.941, 0.884 to 1.001) for lung cancer; 7.1% (0.929, 0.909 to 0.949) for colon cancer; 5.1% (0.949, 0.908 to 0.992) for gastric cancer; 17.1% (0.829, 0.760 to 0.903) for liver cancer. Conclusions This study demonstrated a significant inverse relationship between total physical activity and the risk of breast, gastric, liver, colon, and lung cancers.

Multi-layer satellite network (MLSN) is an important part of the Space-Air-Ground Integrated Network (SAGIN), it has obvious advantages in coverage density, business processing, service efficiency and other comprehensive capabilities compared with ordinary single-layer satellite networks. However, due to the fact that many space nodes, highly dynamic topology changes and wireless links scattered in free space, MLSNs are facing the dual challenges of inefficient organization and lack of security. In this case, this paper considers providing secure encryption decision support for the return of data obtained by low earth orbit (LEO) observation satellites relying on the local autonomous region of multi-layer satellite space. By quantifying the security strength of encryption algorithms, the work to be optimized is described as the problem of maximizing the security strength under the constraint of return delay of the data. This paper thus proposes a solution based on deep reinforcement learning (DRL), which relies on reasonably setting the key supporting elements such as state, action and reward closely related to the problem to achieve fast and reliable decision output, and the simulation results show that the proposed method has better performance than many comparison methods.

In the enhancement of Novel Sorghum bicolor × S. propinquum Hybrid utilization, optimal planting densities and silage methods remain elusive. This study assesses the effects of planting densities, cellulase (CE), Lactobacillus buchneri (LAB), and their combination (LC) on fermentation quality and bacterial diversity of the hybrid silage. The experiment was carried out in a completely random block design with four additives and five planting densities (M1, M2, M3, M4, M5) as follows (4 additives × 5 planting densities): a control group without additives (CK), a group treated with Lactobacillus buchneri (LAB), a group with cellulase (CE), and a group treated with a combination of LAB and CE (LC), maintaining triplicates per treatment. In this study, the additive treatment improved the fermentation quality of silage compared with the control. In the M2-LC group, the contents of crude protein (CP; 7.88%), ether extract (EE; 1.91%), and ash (7.76%) were the highest, while the pH (3.30) was the lowest. The water-soluble carbohydrate (WSC; 11.28%) content was the highest in the M3-CE group, the lactic acid (LA; 6.79%) content was the highest in the M4-CE group, and the acetic acid (AA; 7.71%) content was the highest in the M2-LAB group. Meanwhile, the neutral washing fiber (NDF; 53.17%) content was the lowest in the M5-CE group, the acid detergent fiber (ADF; 41.01%) content was the lowest in the M2-CE group, and the propionic acid (PA; 0.26%) content was the lowest in the M1-LAB group. Adding LC notably reduced bacterial diversity, boosted Lentilactobacillus, and curbed Proteobacteria. LAB and LC markedly improved amino acid metabolism over CE and CK. Conversely, beta-lactam resistance, flagellar assembly, and ascorbate/aldarate metabolism pathways were suppressed. In the future, we will explore a variety of additives and adjust the cutting height to improve its comprehensive quality, create an innovative path for silage production, promote the efficient use of agricultural resources, and provide high-quality feed for animal husbandry.

Background: Rapid progression of coronary non-target lesions is essential for the determination of future cardiovascular events. Clinical factors that predict rapid progression of non-target lesions are unclear. The purpose of this study was to identify the clinical predictors of rapid progression and revascularization of coronary non-target lesions. Methods: Consecutive patients with coronary heart disease who had undergone two serial coronary angiograms were enrolled. All coronary non-target lesions were identified and evaluated at both procedures. Multivariable Cox regression analysis was used to investigate the clinical risk factors associated with rapid progression or revascularization of coronary non-target lesions. Results: A total of 1255 patients and 1670 lesions were enrolled. In this cohort of patients, 239 (19%) had rapid progression and 186 (14.8%) underwent revascularization. At the lesion level, 251 (15.0%) had rapid progression and 194 (11.6%) underwent revascularization. The incidence of lesion revascularization and myocardial infarction was significantly higher in patients with rapid progression. In multivariable analyses, hypertension (hazard ratio [HR], 0.76; 95% confidence interval [95% CI], 0.58–1.00; p = 0.049), ST-segment elevation myocardial infarction (STEMI) (HR, 1.46; 95% CI, 1.03–2.07; p = 0.035), glycosylated hemoglobin (HR, 1.16; 95% CI, 1.01–1.33; p = 0.039) and lesion classification (B2/C versus A/B1) (HR, 1.73; 95% CI, 1.27–2.35; p = 0.001) were significant factors associated with rapid progression. The level of triglycerides (HR, 1.10; 95% CI, 1.00–1.20; p = 0.040) and lesion classification (B2/C versus A/B1) (HR, 1.53; 95% CI, 1.09–2.14; p = 0.014) were predictors of lesion revascularization. Conclusions: Hypertension, STEMI, glycosylated hemoglobin and lesion classification may be used as predictors of rapid progression of coronary non-target lesions. The level of triglyceride and lesion classification may predict the revascularization of non-target lesions. In order to prevent future cardiovascular events, increased attention should be paid to patients with these factors.

Abstract The construction and operation of the Three Gorges Reservoir and the cascade reservoirs upstream have significantly altered the processes of flow and sediment in the main and tributary channels of the Yangtze River. This has led to substantial adjustments in the riverbed through erosion and deposition, thereby impacting flood protection, water resource utilization, navigation, and the aquatic environment in the Yangtze River basin. In this study, prototype measurements were used to analyze the variations in runoff and sediment load in the main channel of the Yangtze River, as well as the changes and evolution of the riverbed. Mathematical modeling was done to predict the trends in reservoir sedimentation and riverbed adjustments. The results indicate that, apart from the significantly increased runoff and sediment load in the river source region (Zhimenda station) over the past two decades, there is no clear unidirectional trend of increasing or decreasing in the main and tributary annual runoff of the Yangtze River. However, the release of reservoir outflows undergoes significant changes throughout the year due to reservoir regulation. Suspended sediment load in the upper Yangtze River has been decreasing since the 1990s, especially after the operation of the Three Gorges Reservoir and the four cascade reservoirs in the lower reach of the Jinsha River. The factors influencing flow and sediment variations include mainly climate change and human activities such as reservoir operation and soil and water conservation. The significant changes in flow and sediment conditions have disrupted the original relative equilibrium state of the main channel of the Yangtze River, leading to riverbed adjustments. The river sections in the upper reach, located within reservoir areas, have shifted from erosional state under natural conditions to accumulative state, while the middle and lower reaches have transitioned from a relatively equilibrium state to a process dominated by erosion and reconstruction. Overall, the river regime in the reservoir area and downstream of the Three Gorges Dam remains relatively stable, but there have been adjustments in some local river sections, for example, in the curved sections, particularly in the sharply curved sections downstream of the Three Gorges Dam, where gradual or abrupt chute cutoff has occurred. In the foreseeable future, the river channel downstream of the Three Gorges Dam will remain in an unsaturated state regarding sediment transport. The process of river channel erosion will persist for a long time and have far‐reaching consequences. Some long straight sections, multiple bifurcation sections, and sections with large curvature are expected to undergo certain adjustments in the river regime, necessitating continuous observation, long‐term monitoring, and timely river management and channel governance.

Abstract Chinese health system remains the crucial one for understanding the wider healthcare landscape across the Global South and in particular the leading Emerging Markets. Purpose of our observation was to understand the inner dynamics of mainland Chinese health reforms adopting a lengthy time horizon. We have analysed the public reports and seminal evidence on Chinese of multiple waves of national health reforms taking place since 1980s in terms of medical care and pharmaceuticals provision and financing. Chinese international trade with ASEAN nations and wider South-East Asia is accelerating its growth after the recovery of trade routes. In terms of health sector this means that global demand and supply of medical goods, services and pharmaceuticals remains largely driven by Chinese domestic developments. Furthermore, Chinese domestic manufacturing and sales of decent quality medical devices and services have grown exponentially. Some temporary pitfalls and increasing in rural–urban inequalities in equity of access and affordability of medical care and pharmaceuticals did take place. Despite these difficulties to generate a balanced development strategy for the largest global market, this is a clear path upwards. Further upcoming improvements expanding health insurance coverage are in strong demand for certain layers of the society. Domestic bottleneck weaknesses yet remain manufacturing, import and market penetration of cutting-edge pharmaceuticals such as monoclonal antibodies and targeted oncology agents. Yet some of these obstacles are likely to be overcome in foreseeable future with the adoption of responsible strategies by governmental agencies in health care arena.

Abstract Estimation of Remaining Useful Lifetime (RUL) of discrete power electronics is important to enable predictive maintenance and ensure system safety. Conventional data-driven approaches using neural networks have been applied to address this challenge. However, due to ignoring the physical properties of the target RUL function, neural networks can result in unreasonable RUL estimates such as going upwards and wrong endings. In the paper, we apply the fundamental principle of Physics-Informed Neural Network (PINN) to enhance Recurrent Neural Network (RNN) based RUL estimation methods. Through formulating proper constraints into the loss function of neural networks, we demonstrate in our experiments with the NASA IGBT dataset that PINN can make the neural networks trained more realistically and thus achieve performance improvements in estimation error and coefficient of determination. Compared to the baseline vanilla RNN, our physics-informed RNN can improve Mean Squared Error (MSE) of out-of-sample estimation on average by 24.7% in training and by 51.3% in testing; Compared to the baseline Long Short Term Memory (LSTM, a variant of RNN), our physics-informed LSTM can improve MSE of out-of-sample estimation on average by 15.3% in training and 13.9% in testing.

Passive Containment Cooling Systems (PCCSs) have attracted wide attention to improve the inherent safety of nuclear power plants. This study summarizes a system analysis method of a closed-loop natural circulation of the PCCS via separately evaporation and condensation. A lumped-parameter model is built using SPRUCE, a code of system simulation of severe accidents, to investigate the natural circulation characteristics and heat-removal efficiency of the PCCS. The analysis of heat-removal capacity of the PCCS is carried out under typically thermal conditions of the containment, such as pressure from 0.28 to 0.4 MPa, and the results are validated by comparison with the experimental data obtained from a single-loop testing facility of the PCCS in full scale. The SPRUCE model agrees with the data, despite slightly underestimating the rate of condensation heat transfer. It conservatively satisfies the requirement of design capacity. To further verify the effectiveness of mitigation on containment overpressure, a representative scenario of LBLOCA (Large Break Loss of Coolant Accident) is implemented using the code. Meanwhile, the effects of non-condensable gas are also presented, as a reference for optimization of PCCS design.

Background: Glioma is the most frequent type of malignancy that may damage the brain with high morbidity and mortality rates and patients' prognoses are still dismal. Ferroptosis, a newly uncovered mode of programmed cell death, may be triggered to destroy glioma cells. Nevertheless, the significance of ferroptosis-related genes (FRGs) in predicting prognosis in glioma individuals is still a mystery. Methods: The CGGA (The Chinese Glioma Atlas), GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas) databases were all searched to obtain the glioma expression dataset. First, TCGA was searched to identify differentially expressed genes (DEGs). This was followed by a machine learning algorithm-based screening of the glioma's most relevant genes. Additionally, these genes were subjected to Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analyses. The chosen biological markers were then submitted to single-cell, immune function, and gene set enrichment analysis (GSEA). In addition, we performed functional enrichment and Mfuzz expression profile clustering on the most promising biological markers to delve deeper into their regulatory mechanisms and assess their clinical diagnostic capacities. Results: We identified 4444 DEGs via differential analysis and 564 FRGs from the FerrDb database. The two were subjected to intersection analysis, which led to the discovery of 143 overlapping genes. After that, glioma biological markers were identified in fourteen genes by the use of machine learning methods. In terms of its use for clinical diagnosis, SMG9 stands out as the most significant among these biomarkers. Conclusion: In light of these findings, the identification of SMG9 as a new biological marker has the potential to provide information on the mechanism of action and the effect of the immune milieu in glioma. The promise of SMG9 in glioma prognosis prediction warrants more study.

BackgroundDescending Necrotizing Mediastinitis (DNM) is an acute and often fatal infection that affects the neck and mediastinum. DNM treatment consists of broad-spectrum antibiotics, early diagnosis, and surgical debridement with multidisciplinary cooperation. However, owing to the rarity and complexity of this disease, the mortality rate is high. This retrospective study analyzed a single-center experience of managing DNM in Chinese patients over the last 10 years.MethodsA single-center, retrospective, observational, and descriptive study was conducted on 31 patients with DNM at Peking Union Medical College Hospital from 2012 to 2022. Case report forms were used to collect data which were then analyzed with a focus on surgical management and outcomes.ResultsThis study examined the outcomes of 31 patients diagnosed with DNM at our hospital. The most common comorbidities on admission were hypertension (48%) and diabetes mellitus (42%). The degree of diffusion of DNM according to Endo’s classification was classified as follows: type I in 7 patients (22.6%), type IIA in 5 (16.1%), and type IIB in 19 patients (61.3%). Among these patients, 13 (41.9%) were found to have a single microbial infection, while 16 (51.6%) were found to have polymicrobial infections. In all cases, neck drainage was performed via cervicotomy, with multiple drains (64.5%) and vacuum sealing drainage (VSD) (35.5%). Mediastinal drainage was performed via a cervical mediastinotomy (51.6%), video-assisted thoracic surgery (VATS) (41.9%), or thoracotomy (6.5%). The 30-day mortality rate was 25.8% and 24.0 days of the average length of hospital stay.ConclusionEarly accurate diagnosis and timely intervention have been shown to be correlated with a positive prognosis. Cervicothoracic CT (computed tomography) is essential for the diagnosis, staging, and evaluation of the optimal surgical treatment. Cervicotomy and video-assisted thoracoscopic surgery with percutaneous drainage is effective, even in advanced cases. Additionally, the application of VSD in cervical incision did not improve prognosis but may shorten the length of ICU (intensive care unit) and hospital stays.

All-fiber coherent beam combiners based on the self-imaging effect can achieve a near-perfect single laser beam, which can provide a promising way to overcome the power limitation of a single-fiber laser. One of the key points is combining efficiency, which is determined by various mismatches during fabrication. A theoretical model has been built, and the mismatch error is analyzed numerically for the first time. The mismatch errors have been numerically studied with the beam quality and combining efficiency being chosen as the evaluation criteria. The tolerance of each mismatch error for causing 1% loss is calculated to guide the design of the beam combiners. The simulation results are consistent with the experimental results, which show that the mismatch error of the square-core fiber is the main cause of the efficiency loss. The results can provide useful guidance for the fabrication of all-fiber coherent beam combiners.

With the deployment of renewable energy and the increasing demand for power grid modernization, redox flow battery has attracted a lot of research interest in recent years. Among the available energy storage technologies, the redox flow battery is considered the most promising candidate battery due to its unlimited capacity, design flexibility, and safety. In this review, we summarize the latest progress and improvement strategies of common inorganic redox flow batteries, such as vanadium redox flow batteries, iron-chromium redox flow batteries, and zinc-based redox flow batteries, including electrolyte, membrane, electrode, structure design, etc. In addition, we introduce the latest progress in aqueous and non-aqueous organic redox flow batteries. We also focus on the modification mechanism, optimization design, improvement strategy, and modeling method of the redox flow battery reaction. Finally, this review presents a brief summary, challenges, and perspectives of the redox flow battery.

ABSTRACTBalancing the potentially serious outcomes of asymptomatic brucellosis and “waiting” for treatment in clinical practice is an urgent issue. Therefore, we assessed the follow-up outcomes and epidemiological characteristics of asymptomatic brucellosis in the absence of treatment to provide evidence-based clinical clues. We searched eight databases in which 3610 studies from 1990 to 2021 were related to the follow-up outcomes of asymptomatic brucellosis. Thirteen studies, involving 107 cases, were finally included. Regarding the follow-up outcomes, we examined the presence or absence of symptoms and decreased serum agglutination test (SAT) titre. During the 0.5–18 months follow-up period, the pooled prevalence of appearing symptomatic was 15.4% (95% CI 2.1%–34.3%), cases that remained asymptomatic were 40.3% (95% CI 16.6%–65.8%), and decreased SAT titre was observed in 36.5% (95% CI 11.6%–66.1%). Subgroup analysis indicated that the pooled prevalence of appearing symptomatic with follow-up times of less than 6 months, 6–12 months, and 12–18 months was 11.5%, 26.4%, and 47.6%, respectively. The student subgroup had a higher prevalence of symptoms (46.6%) than the occupational and family populations. In conclusion, asymptomatic brucellosis has a high likelihood of appearing symptomatic and its severity may be underestimated. Active screening of occupational and family populations should be enhanced, and special attention should be paid to high-titre students for early intervention, if necessary. Additionally, future prospective, long-term, and large-sample follow-up studies are essential.

Abstract Background This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma. Methods We conducted a retrospective analysis of the results of 39 patients with type B2 + B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3 thymoma. The Kaplan–Meier technique was used to generate survival curves. For multivariate analysis, the Cox proportional hazard model was applied. Results With a median follow‐up of 60 months (range: 1–128 months), the percentage of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2, B2 + B3, and B3, respectively, p = 0.045. Twenty‐three patients experienced recurrence or metastasis. The total 10‐year progression‐free survival (PFS) rates were 86.0% overall (85.0% in type B2, 87.2% in type B2 + B3, and 87.5% in type B3). Age, R0 resection, and Masaoka–Koga stage were found to have a significant on PFS in all patients. There was no statistically significant difference in PFS between different histotypes of thymoma, p = 0.650. PFS was predicted by R0 resection in all histotypes and by the Masaoka–Koga stage in the type B2 subgroup. Conclusion Combining the two staging methods to guide the diagnosis and treatment of patients with B2 + B3 thymoma is recommended. R0 resection is recommended to reduce recurrence. Patients with B2 + B3 thymoma have a prognosis similar to those with a B2 thymoma or a B3 thymoma alone.

Aiming at the problem of integrating optimization of worker fatigue and learning effects faced by human and machine dual-resource scheduling in large equipment manufacturing workshops, a mixed-integer programming model was constructed based on exponential fatigue characterization and DeJong learning curves. In accordance with the coding characteristics of the dual-resource scheduling problem, an initial scheduling scheme was generated based on sorting rules, and an adaptive large neighborhood search algorithm was designed by combining removal and insertion operations to solve sub-problems, such as the allocation of human and machine resources, job sequencing and dynamic scheduling. A rescheduling strategy was also designed to address disturbances such as urgent job insertions, machine failures and worker absences. Based on the original algorithm, dynamic scheduling was implemented and tested. The results show that compared with solvers, rules, genetic algorithms and other methods, the proposed algorithm can find scheduling solutions with shorter completion times, and it also performs better in dynamic scheduling scenarios such as urgent orders insert, machine breakdowns and worker absences. The proposed equipment manufacturing workshop scheduling problem takes into account worker fatigue and learning effects, and the corresponding algorithm can provide reference for the development of large-scale equipment manufacturing production scheduling systems.

Abstract Background With the rapidly increasing morbidity and mortality, lung cancer has been considered one of the serious malignant tumors, affecting millions of patients globally. Currently, the pathogenesis of lung cancer remains unclear, hindering the development of effective treatment. This study aims to investigate the mechanisms of lung cancer and develop an effective therapeutic approach for intervention in preventing lung cancer progress. Methods The USP5 levels are detected in lung cancerous and paracancerous tissue by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to explore their roles in lung cancer progression. MTT, colony assay, and transwell chamber approaches are employed to measure cell viability, proliferation, and migration, respectively. Further, flow cytometry experiments are performed to examine the effect of USP5 on lung cancer. Finally, the investigations in vivo are executed using the mice subcutaneous tumor model to identify the effect of USP5 in promoting lung cancer development. Results Notably, USP5 is highly expressed in lung cancer, USP5 overexpression promoted the proliferation and migration in the lung cancer cell lines, H1299 and A549, while knockdown of USP5 inhibited these via regulating the PARP1-mediated mTOR signaling pathway. Furthermore, the subcutaneous tumors model was established in C57BL/6 mice, and the volume of subcutaneous tumors was significantly reduced after silencing USP5, while increased after USP5 overexpression and decreased significantly with shRARP1 treatment at the same time. Conclusions Together, USP5 could promote the progression of lung cancer cells by mTOR signaling pathway and interacting with PARP1, indicating that USP5 may become a new target for lung cancer treatment.

Abstract Objectives The aim of this bibliometric analysis was twofold: to identify the 100 most cited research articles on thymoma and to highlight future research opportunities in light of past and current research efforts. Methods The Web of Science database was queried to identify the 100 most cited articles on thymoma. Imformations relevant to scientific research were extracted and analyzed: first author, journal, impact factor, type of article, year of publication, country, organization and keywords. Results The publication year of the top 100 most cited articles ranged from 1981 to 2018, and the number of citations ranged from 97 to 1182. Most of the included articles are original (75/100) and are mainly retrospective studies (52/75). The United States has the most published articles and citations, and the Annals of Thoracic Surgery is the most sourced journal (n = 16). Through VOSviewer analysis, high-density keywords mainly come from thymic carcinoma/invasive thymoma management, immune-related diseases, and laboratory research. Conclusions To our knowledge, this is the first bibliometric study on thymoma. We found most of the top 100 most cited articles are original and retrospective research. The United States has the published and cited works. Presently, the hot keywords for thymoma research has gradually tilted towards immune-related diseases and laboratory research.

Biomedical degradable materials would be subjected to different degrees and forms of static stress after being implanted in the human body. In this work, the biocorrosion behaviors of AZ31B magnesium alloy under different stress forms with different magnitudes (20 ∼ 150 MPa) were studied. It was found that the corrosion behaviors at stressed conditions were severer than those at unstressed conditions and corrosion rates were obviously accelerated. The biocorrosion behaviors are more sensitive to the effects of tensile loads than to compressive loads. A biocorrosion numerical model on the degradation process of Mg alloy under static loads was established. The corrosion current density (icorr) of Mg alloy and the applied static stress (σ) matches a linear relationship of ln icorr ∼ σ well during the early stage (within 24 hrs) while deviated gradually in the latter period of corrosion. This work could provide a guidance and theoretical reference for further researches on the biocorrosion behaviors and practical clinical applications of the biomedical materials subjected to physiological loads.

Abstract The advent of cloud computing, 5G, and artificial intelligence technology has spurred the exponential growth of big data and the need for data compression. To alleviate the CPU burden, computational engines for data compression integrated into network cards and storage devices, giving rise to computational storage. However, computational storage faces several challenges, such as limited memory resources for large hash tables, data dependency for parallel encoding and decoding, and stringent requirements for bandwidth, latency, and power efficiency. Here, an application‐specific integrated circuit‐based LZ77 solution that aims to address these challenges is proposed. Our solution reduces the hash table resource consumption and the bandwidth fluctuations, while achieving high compression ratios. The solution is implemented using Taiwan Semiconductor Manufacturing Company Limited 12 nm technology and demonstrate that a single LZ77 engine can achieve a 4 GB/s throughput at 1 GHz clock frequency. By using four engines, a computational storage drive to achieve 16 GB/s compression bandwidth is enabled. The solution achieves a comparable compression ratio as the standard LZ77 algorithm with a negligible compression ratio loss of 5%, balancing efficiency and effectiveness.

The effects of different processing methods on the nutritional components of sea cucumber (Apostichopus japonicus) are of concern to consumers who select sea cucumber products. This study employed liquid chromatography tandem mass spectrometry to examine the metabolites in fresh, unsoaked salted, soaked salted, and instant sea cucumber body wall samples sourced from Dalian, China. Metabolites were evaluated utilizing partial least squares discriminant analysis (PLS-DA) and subsequently subjected to KEGG metabolic pathway analysis for further investigation. PLS-DA effectively discriminated the body wall metabolites of sea cucumbers obtained via various processing techniques. The differential metabolites identified predominantly encompassed amino acids, lipids, and carbohydrates. Subsequent KEGG metabolic pathway analysis demonstrated a significant association between lipid, carbohydrate, and amino acid metabolism and the specific processing methods employed. The assessment of nutritional differences corresponding to the various A. japonicus processing methods was conducted. The findings of this study can assist in the choice of sea cucumber products and the selection of suitable processing methods.

Background: For prediction on leukemic transformation of MDS patients, emerging model based on transcriptomic datasets, exhibited superior predictive power to traditional prognostic systems. While these models were lack of external validation by independent cohorts, and the cell origin (CD34+ sorted cells) limited their feasibility in clinical practice.Methods: Transformation associated co-expressed gene cluster was derived based on GSE58831 (‘WGCNA’ package, R software). Accordingly, the least absolute shrinkage and selection operator algorithm was implemented to establish a scoring system (i.e., MDS15 score), using training set (GSE58831 originated from CD34+ cells) and testing set (GSE15061 originated from unsorted cells).Results: A total of 68 gene co-expression modules were derived, and the ‘brown’ module was recognized to be transformation-specific (R2 = 0.23, p = 0.005, enriched in transcription regulating pathways). After 50,000-times LASSO iteration, MDS15 score was established, including the 15-gene expression signature. The predictive power (AUC and Harrison’s C index) of MDS15 model was superior to that of IPSS/WPSS in both training set (AUC/C index 0.749/0.777) and testing set (AUC/C index 0.933/0.86).Conclusion: By gene co-expression analysis, the crucial gene module was discovered, and a novel prognostic system (MDS15) was established, which was validated not only by another independent cohort, but by a different cell origin.

The present-day topography of Tianshan is the product of repeated phases of Meso-Cenozoic intracontinental deformation and reactivation, whereas the long-term Mesozoic topographic evolution and the timing of the onset of Cenozoic deformation remain debated. New insights into the Meso-Cenozoic geodynamic evolution and related basin-range interactions in the Tianshan were obtained based on new detrital single-grain apatite U-Pb, fission-track, and trace-element provenance data from Mesozoic sedimentary sequences on the northern margin of the Tarim Basin. Detrital apatite U-Pb age data from Early-Middle Triassic clastic rocks show two prominent age populations at 500–390 Ma and 330–260 Ma, with a paucity of ages between 390 and 330 Ma, suggesting that sediment source is predominantly from the northern Tarim and South Tianshan. From the Late Triassic to Early Jurassic, the first appearance of populations in the 390–330 Ma and 260–220 age ranges indicates that the Central Tianshan-Yili Block and Western Kunlun Orogen were source regions for the northern margin of Tarim Basin. In the Cretaceous strata, south-directed paleocurrents combined with the decrease in the 390–330 Ma age population from the Central Tianshan-Yili Block imply that South Tianshan was uplifted and again became the main source region to the Baicheng-Kuqa depression during the Cretaceous. Our new apatite fission-track data from the southern Chinese Tianshan suggest that rapid cooling commenced at c. 30 Ma along the southern margin, and the Early Mesozoic strata exposed on the southern flank of the Tianshan underwent c. 4–5 km of late Cenozoic exhumation during this period. This age is approximately synchronous with the onset of exhumation/deformation not only in the whole Tianshan but also in the interior of the Tibetan Plateau and its margins. It suggests that far-field, N-directed shortening resulting from the India-Asia collision was transmitted to the Tianshan at that time.