Search

Background: In past studies, non-medical factors in the social-healthcare-patient triad associated with the prevalence of COVID-19 have led to delays in the presentation of patients with acute appendicitis and an increase in complications. However, as research progresses, there is increasing evidence of a clinical association between COVID-19 and the development of acute appendicitis. Methods: The effect of COVID-19 prevalence and associated factors on acute appendicitis in the control (2016–2019) and exposed (2020−2023) groups was derived from a retrospective study of 3070 patients with acute appendicitis from 2016 to 2023. Results: After the implementation of the restrictions, the rate of acute appendicitis visits in the exposed group compared to the control group dropped sharply in the initial period (P = 0.047) and recovered gradually with the relaxation of the restrictions. Similar changes occurred in the number of acute complicated appendicitis visits. In addition, after the lifting of restrictions and the COVID-19 outbreak, the proportion of acute complicated appendicitis in the exposed group increased significantly (P

This study delved into the potential application of Platanus acerifolia leaf extract (PALE) as an environmentally benign corrosion inhibitor. Evaluation of corrosion inhibition was conducted using electrochemical methods, field emission scanning electron microscopy equipped with energy dispersive spectrometer. The results reveal that PALE offers efficient protection for Q235 steel across the temperature range of 298 K–318 K, achieving a maximum corrosion inhibition efficiency of approximately 93%. Furthermore, Density functional theory (DFT) calculations and molecular dynamics (MD) simulations were performed to elucidate the spontaneous and stable adsorption of PALE molecules onto the surface of Q235 steel. This adsorption impedes the diffusion of corrosive substances towards the steel surface, thereby endowing Q235 steel with robust corrosion resistance.

Purpose: To develop and validate deep learning algorithms that can identify and classify angle-closure (AC) mechanisms using anterior segment optical coherence tomography (AS-OCT) images. Methods: This cross-sectional study included participants of the Handan Eye Study aged ≥35 years with AC detected via gonioscopy or on the AS-OCT images. These images were classified by human experts into the following to indicate the predominant AC mechanism (ground truth): pupillary block, plateau iris configuration, or thick peripheral iris roll. A deep learning architecture, known as comprehensive mechanism decision net (CMD-Net), was developed to simulate the identification of image-level AC mechanisms by human experts. Cross-validation was performed to optimize and evaluate the model. Human-machine comparisons were conducted using a held-out and separate test sets to establish generalizability. Results: In total, 11,035 AS-OCT images of 1455 participants (2833 eyes) were included. Among these, 8828 and 2.207 images were included in the cross-validation and held-out test sets, respectively. A separate test was formed comprising 228 images of 35 consecutive patients with AC detected via gonioscopy at our eye center. In the classification of AC mechanisms, CMD-Net achieved a mean area under the receiver operating characteristic curve (AUC) of 0.980, 0.977, and 0.988 in the cross-validation, held-out, and separate test sets, respectively. The best-performing ophthalmologist achieved an AUC of 0.903 and 0.891 in the held-out and separate test sets, respectively. And CMD-Net outperformed glaucoma specialists, achieving an accuracy of 89.9 % and 93.0 % compared to 87.0 % and 86.8 % for the best-performing ophthalmologist in the held-out and separate test sets, respectively. Conclusions: Our study suggests that CMD-Net has the potential to classify AC mechanisms using AS-OCT images, though further validation is needed.

Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.

Summary: Background: The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape. Methods: This retrospective multicenter study enrolled 6315 patients with nonmetastatic NPC from nonendemic and endemic regions of China from 2007 to 2020. We applied mixture and nonmixture cure models to estimate the cure probabilities and cure times by incorporating background mortality for the general population, matching by gender, age, and diagnosed year. Findings: With death as the uncured event, the probability of patients with NPC achieving a life expectancy at par with the general population was 78.1%. Considering progression as the uncured event, the likelihood of patients attaining a life expectancy without progression equivalent to that of the general population was 72.4%. For individuals, the probabilities of achieving cure were conditional and time-dependent, requiring approximately 7.1 and 4.7 years with 95% certainty, respectively. The corresponding cure times for uncured patients were 8.9 and 6.8 years, respectively. The cure probability was correlated with age, Eastern Cooperative Oncology Group score, TNM staging, Epstein–Barr virus DNA copies, and lactate dehydrogenase. The correlation was excellent between 5-year overall survival/progression-free survival and cure fractions. Interpretation: Statistical cure is potentially achievable among patients with NPC undergoing contemporary treatment modalities. The results hold significant potential implications for both clinical practice and patient perspectives. Funding: National High Level Hospital Clinical Research Funding; Beijing Xisike Clinical Oncology Research Foundation; Beijing hope run fund.

Aims and objectives: During the new coronavirus disease 2019 (COVID-19) outbreak period, there was increasing presentation in the number of patients with acute primary angle closure (APAC). This study aimed to report the occurrence of APAC during the COVID-19 post-restriction period and investigate the related characteristics of these patients with APAC. Methods: This retrospective, multi-center study included consecutive patients seeking APAC treatment at two eye centers in China from December 7, 2022 to January 13, 2023 (post-restriction period) and from December 7, 2021 to January 13, 2022 (control period). Electronic medical records were reviewed, and ocular data of the affected eye(s) were analyzed for patients with unilateral or bilateral APAC. Information including COVID-19 related symptoms, medications used for COVID-19 infection, and living habits and emotions related to the COVID-19 outbreak during the post restriction period were collected using a questionnaire. Results: Overall, 189 (219 APAC eyes) and 51 (54 APAC eyes) patients with APAC were identified during the post-restriction and control periods, respectively. The patients identified during the post-restriction period were younger (P = 0.043) and had a longer duration from symptoms to treatment (P = 0.039), shorter axial length (P = 0.002), larger pupil diameter (P = 0.004), larger vertical cup disc ratio (P = 0.004), poorer mean deviation values (P = 0.003), and more glaucomatous optic neuropathy diagnoses (P = 0.032) compared with the patients with APAC identified during the control period. Among 151 included patients with APAC who completed the questionnaires, 130 patients with APAC were diagnosed with concurrent COVID-19 infection, of which 54 (41.5 %) had coughing and/or vomiting as the main symptoms. Of these, 89.2 % spent 0 h per day on outdoor activity; 44.6 % drank more water than usual, with 14.6 % drinking more than twice the amount of water than usual; 91.5 % used antipyretics; and 20.0 % had mood swings, including anxiety, depression, and tension, during the concurrent COVID-19 infection. Conclusion: In our study, a significant increase in the number of patients presenting with APAC with certain characteristics was observed during the COVID-19 post-restriction period. And whether COVID-19 symptoms, such as coughing and vomiting, and behavioral and psychological changes caused by COVID-19 infection contributing to the concurrence of APAC and COVID-19 recurrence require further investigation.

Luteolin, a monomeric substance, is a natural product of the Brucea javanica (BJ) plant. Brucea javanica oil emulsion injection (BJOEI) is a proprietary Chinese medicine purified from BJ that is widely used clinically as an anti-tumor treatment. Although a growing body of research suggests that luteolin and BJOEI have anti-tumor effects, the molecular mechanism of action has not been fully elucidated. In this study, through molecular docking technology, we found that luteolin can interact directly with GPSM2 and regulate the FoxO signaling pathway through GPSM2. In addition, the inhibitory effect of luteolin on colon adenocarcinoma (COAD) cells was found to be offset by knockdown of GPSM2. In contrast, the anti-proliferative effects of luteolin could be notably reversed by overexpression of GPSM2. The results reveal that GPSM2 is crucial in luteolin-mediated anti-proliferative effects. The mediation of anti-proliferative effects by GPSM2 has also been indirectly demonstrated in RKO and SW480 xenograft mice models. In addition, we verified that BJOEI inhibits the progression of COAD by mediating GPSM2 and regulating the FoxO signaling pathway. We also found that BJOEI achieved a better anti-tumor effect when combined with fluorouracil injection. Collectively, our data show that the anti-tumor effects of BJOEI and luteolin on COAD are GPSM2-dependent and downregulating the expression of GPSM2 to regulate the FoxO signaling pathway may be an effective way to treat COAD.

Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.

Neuroimmune and neurodegenerative ailments impose a substantial societal burden. Neuroimmune disorders involve the intricate regulatory interactions between the immune system and the central nervous system. Prominent examples of neuroimmune disorders encompass multiple sclerosis and neuromyelitis optica. Neurodegenerative diseases result from neuronal degeneration or demyelination in the brain or spinal cord, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The precise underlying pathogenesis of these conditions remains incompletely understood. Ferroptosis, a programmed form of cell death characterised by lipid peroxidation and iron overload, plays a pivotal role in neuroimmune and neurodegenerative diseases. In this review, we provide a detailed overview of ferroptosis, its mechanisms, pathways, and regulation during the progression of neuroimmune and neurodegenerative diseases. Furthermore, we summarise the impact of ferroptosis on neuroimmune-related cells (T cells, B cells, neutrophils, and macrophages) and neural cells (glial cells and neurons). Finally, we explore the potential therapeutic implications of ferroptosis inhibitors in diverse neuroimmune and neurodegenerative diseases.

Objectives: This study aims to assess the efficacy of narrow band imaging (NBI) endoscopy in utilizing radiomics for predicting radiosensitivity in nasopharyngeal carcinoma (NPC), and to explore the associated molecular mechanisms. Materials: The study included 57 NPC patients who were pathologically diagnosed and underwent RNA sequencing. They were categorized into complete response (CR) and partial response (PR) groups after receiving radical concurrent chemoradiotherapy. We analyzed 267 NBI images using ResNet50 for feature extraction, obtaining 2048 radiomic features per image. Using Python for deep learning and least absolute shrinkage and selection operator for feature selection, we identified differentially expressed genes associated with radiomic features. Subsequently, we conducted enrichment analysis on these genes and validated their roles in the tumor immune microenvironment through single-cell RNA sequencing. Results: After feature selection, 54 radiomic features were obtained. The machine learning algorithm constructed from these features showed that the random forest algorithm had the highest average accuracy rate of 0.909 and an area under the curve of 0.961. Correlation analysis identified 30 differential genes most closely associated with the radiomic features. Enrichment and immune infiltration analysis indicated that tumor-associated macrophages are closely related to treatment responses. Three key NBI differentially expressed immune genes (NBI-DEIGs), namely CCL8, SLC11A1, and PTGS2, were identified as regulators influencing treatment responses through macrophages. Conclusion: NBI-based radiomics models introduce a novel and effective method for predicting radiosensitivity in NPC. The molecular mechanisms may involve the functional states of macrophages, as reflected by key regulatory genes.

This work characterized the structural features and investigated the immunomodulatory activity of an alkaline-precipitated polysaccharide fraction produced by Chaetomium globosum CGMCC 6882 (CGP-AP) in RAW 264.7 macrophages. The CGP-AP yield was 0.93 ± 0.08 g/L, which contained 98.33% ± 2.04% (w/w) carbohydrate and 1.52% ± 0.26% (w/w) protein. Structural analysis showed that CGP-AP comprised glucose (99.51%) and arabinose (0.49%), its weight (Mw) and number (Mn) average molecular weights were 0.948 and 0.55 kDa, and its polydispersity (Mw/Mn) was 1.724. In vitro immunomodulatory results show that CGP-AP stimulated nitric oxide production and tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-8 secretion via upregulation of the expression levels of related genes in RAW 264.7 macrophages. Meanwhile, CGP-AP upregulated the expression levels of proinflammatory genes (inducible nitric oxide synthase and cyclooxygenase-2 COX-2). Furthermore, CGP-AP improved the antioxidant status of RAW 264.7 cells by increasing antioxidase (superoxide dismutase, catalase, and glutathione peroxidase) levels and enhancing the mRNA expression of nuclear factor erythroid-2 related factor 2. The above results indicate that CGP-AP may be used as a potential immunomodulator in the pharmaceutical industry.

Objective: Accurate prognostic predictions and personalized decision-making on induction chemotherapy (IC) for individuals with locally advanced nasopharyngeal carcinoma (LA-NPC) remain challenging. This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival (OS) and their value in guiding treatment in patients with LA-NPC. Methods: Individuals with LA-NPC were reviewed retrospectively. Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods, the interpretable eXtreme Gradient Boosting (XGBoost) risk prediction model, and DeepHit time-to-event neural network. The models' prediction performances were compared using the concordance index (C-index) and the area under the curve (AUC). The patients were divided into two cohorts based on the risk predictions of the most successful model. The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone. Results: The 1 221 eligible individuals, assigned to the training (n = 813) or validation (n = 408) set, showed significant respective differences in the C-indices of the XGBoost, DeepHit, and nomogram models (0.849 and 0.768, 0.811 and 0.767, 0.730 and 0.705). The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS (0.881 and 0.760, 0.845 and 0.776, and 0.764 and 0.729, P < 0.001). IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group. Conclusion: This research used machine-learning algorithms to create and verify a comprehensive model integrating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC. This model could be valuable for delivering patient counseling and conducting clinical evaluations.

The unique structure and complex deformation characteristics of concrete face rockfill dams (CFRDs) create safety monitoring challenges. This study developed an improved random forest (IRF) model for dam health monitoring modeling by replacing the decision tree in the random forest (RF) model with a novel M5' model tree algorithm. The factors affecting dam deformation were preliminarily selected using the statistical model, and the grey relational degree theory was utilized to reduce the dimensions of model input variables. Finally, a deformation prediction model of CFRDs was established using the IRF model. The ten-fold cross-validation method was used to quantitatively analyze the parameters affecting the IRF algorithm. The performance of the established model was verified using data from three specific measurement points on the Jishixia dam and compared with other dam deformation prediction models. At point ES-10, the performance evaluation indices of the IRF model were superior to those of the M5' model tree and RF models and the classical support vector regression (SVR) and back propagation (BP) neural network models, indicating the satisfactory performance of the IRF model. The IRF model also outperformed the SVR and BP models in settlement prediction at points ES2-8 and ES4-10, demonstrating its strong anti-interference and generalization capabilities. This study has developed a novel method for forecasting and analyzing dam settlements with practical significance. Moreover, the established IRF model can also provide guidance for modeling health monitoring of other structures.

Objectives: To investigate prognostic factors in patients with head and neck Mucoepidermoid Carcinoma (MEC), especially the impact of treatment modalities on survival. Methods: Patients with primary head and neck MEC between 2000 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic factors related to Overall Survival (OS) and Cancer-Specific Survival (CSS), as well as the impact of treatments, were evaluated by multivariable Cox regression analysis. Results: We identified 2692 patients diagnosed with head and neck MEC, of whom 1397 (51.89%) had a parotid gland primary, 569 (22.14%) died, and 341 (12.67%) died of MEC. Older age (≥53 years), males, unmarried, lower income, tumor site in other head and neck areas, higher tumor grade, larger tumor size, and higher stage were related to poorer OS and CSS. Patients who did not undergo surgery (HR = 3.20, 95% CI 2.45‒4.18) had worse OS, while no significant difference was detected between partial and total organ excision on patients’ OS (p = 0.729). For combination therapy, patients who received radiotherapy only (HR = 3.21, 95% CI 2.27–4.53) or no surgery and no radiotherapy (HR = 2.59, 95% CI 1.83–3.67) were correlated with worse OS (vs. surgery only), but no significant difference was detected between surgery only and surgery combined with radiotherapy on patients’ OS (p = 0.218). For CSS, the corresponding results were consistent with OS. Conclusion: Surgical resection only may be a better survival option for head and neck MEC.

Leaves of Melaleuca alternifolia are abundant in essential oils comprising terpenoids and volatile organic compounds, which play an important role in plant abiotic stress response. However, the molecular mechanisms underlying terpenoid biosynthesis in M. alternifolia remain poorly understood. To fill this knowledge gap, we profiled terpenoid content and composition across four distinct growth phases using gas chromatography-mass spectrometry (GC/MS). We also performed an integrated analysis of gene expression in leaf tissues through full-length transcriptome sequencing combined with high throughput RNA sequencing. We identified 46,313 transcripts, 99 % (45,848 transcripts) of which were annotated using existing databases. Our study also revealed 2,792 transcription factors (TFs) and 1,812 alternative splicing (AS) events. Through weighted gene co-expression network analysis (WGCNA), we clustered these identified genes into 11 co-expressed modules. Notably, two modules—designated as blue and brown—were significantly correlated with essential oil content. Homologous annotation with the Arabidopsis database revealed that genes within the blue module are largely involved in the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, suggesting its pivotal role in essential oil synthesis in M. alternifolia. Furthermore, elevated expression levels of VAMP72 and DGK1 in the brown module indicate their potential function as negative regulators of essential oil synthesis. Our findings unveil key differentially expressed genes (DEGs) and pathways that can be targeted to enhance essential oil production in M. alternifolia. The identified TFs may serve as potential candidates for genetic modification through genome editing technologies. This research provides valuable insights into the processes involved in essential oil biosynthesis and highlights key genes for functional characterization in M. alternifolia.

The numerical shock instability problem significantly limits the application of the finite volume method in hypersonic flow simulations, especially for high-order schemes, which will encounter more severe shock instability problems. In the previous work, the MSAT (matrix stability analysis tool) was introduced to quantitatively analyze the numerical shock instability problem. However, the utilization of the three-point reconstruction stencil in the original version of MSAT presents challenges in conducting investigations into high-order schemes. The current work provides an extension of MSAT by extending the reconstruction stencil to five points, a challenging but necessary endeavor for high-order schemes. This extension enables MSAT to provide analyses for schemes with high-order reconstruction methods. Furthermore, the updated MSAT can be utilized to investigate the impact of characteristic variable reconstruction on the shock instability problem. Results demonstrate the reliability of the updated MSAT and reveal novel characteristics in the shock instability of high-order schemes. Consequently, the updated MSAT will contribute to the investigation of shock instabilities for high-order schemes, ultimately aiding in mitigating this challenging problem.

Background: As a marker of the GABAergic system, the expression of glutamate decarboxylase 1 (GAD1) is mainly restricted to the central nervous system. Emerging studies have shown that aberrant expression of GAD1 in tumor tissues may promote tumor cell growth. The role of GAD1 in the development of osteosarcoma (OS) remains unclear, so this study sought to investigate the expression status of GAD1 and the effect of its specific inhibitor 3-mercaptopropionic acid (3-MPA) on OS. Methods: The R2 database was used to analyze the relationship between the expression of GAD1 and clinical prognosis in OS patients. Immunohistochemistry was used to compare the expression profile of GAD1 between OS and matched neighboring tissues. The potential antitumor effects of 3-MPA on cell viability, colony formation and the cell cycle were examined. Moreover, the in vivo effect of 3-MPA on tumor growth was investigated using tumor-bearing nude mice. Results: The expression level of GAD1 was aberrantly upregulated in OS tissues, but almost no expression of GAD1 was found in matched neighboring tissues. Western blotting analyses showed upregulation of GAD1 in OS cells compared to human osteoblast cells. In vitro and in vivo, 3-MPA significantly suppressed the growth of OS. Regarding the mechanism, 3-MPA inhibited β-catenin and cyclin D1 in OS cells, thereby inactivating the Wnt/β-catenin pathway. Conclusions: OS displays increased expression of the GABAergic neuronal marker GAD1, and 3-MPA significantly reduces OS growth by inhibiting the Wnt/β-catenin pathway.

Objective: Although the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Materials and methods: Twenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. Results: After the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. Conclusion: Parietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal–parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients with heart disease worldwide. It is characterized by fibroblast activation, abnormal proliferation, excessive deposition, and abnormal distribution of extracellular matrix (ECM) proteins. The maladaptive process of cardiac fibrosis is complex and often involves multiple mechanisms. With the increasing research on cardiac fibrosis, redox has been recognized as an important part of cardiac remodeling, and an imbalance in redox homeostasis can adversely affect the function and structure of the heart. The metabolism of metal ions is essential for life, and abnormal metabolism of metal ions in cells can impair a variety of biochemical processes, especially redox. However, current research on metal ion metabolism is still very limited. This review comprehensively examines the effects of metal ion (iron, copper, calcium, and zinc) metabolism-mediated redox homeostasis on cardiac fibrosis, outlines possible therapeutic interventions, and addresses ongoing challenges in this rapidly evolving field.

Purpose: This study aimed to investigate the performance of deep learning algorithms in the opportunistic screening for primary angle-closure disease (PACD) using combined anterior segment parameters. Methods: This was an observational, cross-sectional hospital-based study. Patients with PACD and healthy controls who underwent comprehensive eye examinations, including gonioscopy and anterior segment optical coherence tomography (ASOCT) examinations under both light and dark conditions, were consecutively enrolled from the Department of Ophthalmology at the Beijing Tongren Hospital between November 2020 and June 2022. The anterior chamber, anterior chamber angle, iris, and lens parameters were assessed using ASOCT. To build the prediction models, backward logistic regression was utilized to select the variables to discriminate patients with PACD from normal participants, and the area under the receiver operating characteristic curve was used to evaluate the efficacy of the opportunistic screening. Results: The data from 199 patients (199 eyes) were included in the final analysis and divided into two groups: PACD (109 eyes) and controls (90 eyes). Angle opening distance at 500 μm, anterior chamber area, and iris curvature measured in the light condition were included in the final prediction models. The area under the receiver operating characteristic curve was 0.968, with a sensitivity of 91.74 % and a specificity of 91.11 %. Conclusion: ASOCT-based algorithms showed excellent diagnostic performance in the opportunistic screening for PACD. These results provide a promising basis for future research on the development of an angle-closure probability scoring system for PACD screening.

Purpose: To investigate the proportion of zonulopathy in patients with age-related cataract, and further explore demographics and ocular characteristics, as well as potential risk factors. Methods: Hospital-based, observational, cross-sectional study. We enrolled consecutive patients who were 45 years or older and diagnosed with age-related cataract and underwent surgery between October 2022 and April 2023 at the Division of Cataract, Beijing Tongren Hospital. Zonulopathy was diagnosed based on intraoperative signs. We calculated the total proportion, age, and gender specific proportions of zonulopathy. We compared the demographic and ocular characteristics between the cases with and without zonulopathy. Univariate and multivariate logistic regression analyses were employed to determine the risk factors associated with the presence of zonulopathy in patients with age-related cataract. Results: A total of 640 age-related cataract patients with a median age of 70.0 (64.0–77.0) were enrolled. Zonulopathy was diagnosed intraoperatively in 70 patients (10.9%). Compared with the patients having no zonulopathy, those with zonulopathy were likely to be older (P

Popliteal cysts, also termed Baker's cysts, are clinically common cystic lesions in the popliteal fossa. Typically, the contents of a ruptured cyst tend to spread into the myofascial interfaces in any direction, most commonly inferomedially or into a palpable superficial position. However, to our knowledge, reports of Baker's cysts dissecting into the deep intermuscular septum of the lower calf are extremely rare. We present here the details of the successful treatment through arthroscopy combined with lower calf incision of a patient who sustained hematoma of the knee and lower calf secondary to Baker's cyst rupture. Given the rarity of this disease in China, we present this case report to improve our understanding of the disease and avoid misdiagnosis and provide evidence for its clinical treatment, management, and prognosis.

Background: Since the first human infection with H9N2 virus was reported in 1998, the number of cases of H9N2 infection has exceeded one hundred by 2021. However, there is no systematic description of the biological characteristics of H9N2 viruses isolated from humans. Methods: Therefore, this study analyzed the pathogenicity in mice of all available H9N2 viruses isolated from human cases in China from 2013 to 2021. Results: Although most of the H9N2 viruses analyzed showed low or no pathogenicity in mice, the leucine to glutamine substitution at residue 226 (L226Q) in the hemagglutinin (HA) protein rapidly emerged during the adaptation of H9N2 viruses, and was responsible for severe infections and even fatalities. HA amino acid 226Q conferred a remarkable competitive advantage on H9N2 viruses in mice relative to viruses containing 226L, increasing their virulence, infectivity, and replication. Conclusion: Thus, our study demonstrates that the adaptive substitution HA L226Q rapidly acquired by H9N2 viruses during the course of infection in mice contributed to their high pathogenicity.

Introduction: The typical functionality of astrocytes was previously shown to be disrupted by Parkinson's disease (PD), which actively regulates synaptic neurotransmission. However, the morphological changes in astrocytes wrapping glutamatergic synapses in the striatum after dopamine (DA) neuronal degeneration is unclear. Methods: We utilized a range of methodologies, encompassing the 6-hydroxydopamine (6OHDA)-induced PD model, as well as techniques such as immunohistochemistry, Western blotting, immunofluorescence and immunoelectron microscopy (IEM) to delve into the consequences of DA neuronal degeneration on the morphological attributes of perisynaptic astrocytes. Results: Our findings demonstrated a notable rise in glial fibrillary acidic protein (GFAP) + astrocyte density and an upregulation in GFAP protein expression within the striatum due to DA neuronal degeneration, coincided with the enlargement, elongation, and thickening of astrocyte protuberances. However, the expression levels of glutamate transporter 1 (GLT1) and glutamine synthetase (GS), which are related to glutamate–glutamine cycle, were significantly reduced. Double immunofluorescence and IEM results indicated that different proportions of vesicular glutamate transporter 1 (VGlut1)+ and vesicular glutamate transporter 2 (VGlut2) + terminals were wrapped by astrocytes. Additionally, DA neuronal degeneration increased the percentage and area of VGlut1+ and VGlut2+ terminals wrapped by GFAP + astrocytes in the striatum. Furthermore, we noted that DA neuronal degeneration increased the percentage of VGlut1+ and VGlut2+ axo-spinous synapses wrapped by astrocytes but had no effect on axo-dendritic synapses. Conclusion: Hence, perisynaptic astrocytes wrapping striatal glutamatergic synapses exhibit substantial morphological and functional alterations following DA neuronal degeneration making them a potential target for therapeutic interventions in PD.

Green tea has great potential to enhance the quality of beer. In this study, green tea was added at different stages of beer brewing, and evaluated the antioxidant capacity, volatile components, as well as sensory quality. The results showed that the addition of green tea during the start of boiling has great potential for application, and the green tea beer (GTB) had remarkable antioxidant properties (ABTS radical scavenging ability, 8.67 mmol TE/L; DPPH radical scavenging ability, 3.97 mmol TE/L; reducing power, 3.28 mmol TE/L), and an excellent sensory quality (acceptance, 6.09/9). HPLC analysis indicated that the principal phenolics in GTB were catechin and caffeic acid, in addition, the relative amounts of ferulic acid, gallic acid can be used to differentiate between GTB and beer. HS-SPME-GC–MS analyses showed that ethyl caprylate, ethyl nonanoate, ethyl caprate, linalool, and phenethyl alcohol were potentially significant for the aroma profile of GTB.

Introduction: Baidu San mainly treats viral colds and relieves muscle pain. They are widely used in clinical practice, but their therapeutic effects and anti-inflammatory mechanisms against influenza are unknown. Methods: Active compounds and targets were mined with the help of TCMSP platform, OMIM database and Gene Cards database. Protein-protein interaction networks and component-target networks were established to screen core targets and components, and GO and KEGG enrichment analyses were performed in the DAVID database and visualized by the Microbiology Letter Platform. Finally, the binding affinity between potential targets and active compounds was assessed by molecular docking. Results: Baidu San is effective in the treatment of influenza. network pharmacology studies have shown that TNF, AKT1 and EGFR are the core targets of action of Baidu San in the treatment of influenza. Luteolin, quercetin and kaempferol are the key compounds. GO and KEGG enrichment analyses suggest that the mechanism of action of Baidu San is related to antiviral, anti-inflammatory and modulation of immune function are closely related. Conclusion: This study highlights the potential of combining in vitro experiments and network pharmacology as a promising strategy to explore the potential mechanism of TCMs.

We generated PUMCi005-A, an induced pluripotent stem cell (iPSC) line, from dermal fibroblasts of a 32-year-old female Perrault syndrome patient with double heterozygous (794 G > A and 1181 G > A) mutations in the TWNK gene using Sendai viral delivery of OCT4, SOX2, KLF4, and c-MYC. The PUMCi005-A iPSC line carried the TWNK mutations, displayed typical iPSC morphology, expressed pluripotent stem cell markers, did not have integration of Sendai virus, and exhibited a normal karyotype and differentiation into three germ layers.

Objective: We evaluated the utility of concurrent chemoradiotherapy (CCRT) compared to surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT) in terms of improving the life expectancy and quality-of-life (QOL) of patients with stage III/IV hypopharyngeal squamous cell carcinomas (HPSCCs). Methods: From January 2010 to July 2018, a total of 299 patients with stage III/IV HPSCC who received surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT, n = 111), or concurrent chemoradiotherapy (CCRT, n = 188) in our hospital were included. We measured overall survival (OS) and disease-free survival (DFS). We used the EORTC QLQ-C30, QLQ-H&N35, and Voice handicap index-30 (VHI-30) instruments to assess the long-term QOL. Results: The OS and DFS afforded by SRT were significantly better than those associated with CCRT (p = 0.039; p = 0.048 respectively), especially for stage N2–N3 patients. CCRT patients experienced better speech outcomes. Conclusion: For resectable stage III/IV HPSCC patients, appropriate treatment plans should be selected comprehensively considering survival rate, QOL, patient preference and multidisciplinary treatment.

Summary: Background: Liver disease is linked to series of extrahepatic multisystem manifestations. However, little is known about the associations between liver and eye diseases, especially cataract, the global leading cause of blindness. We aimed to investigate whether severe liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, and liver fibrosis and cirrhosis, were associated with an increased risk of the cataract. Methods: A total of 326,558 participants without cataract at baseline enrolled in the UK Biobank between 2006 and 2010 were included in this prospective study. The exposures of interest were severe liver diseases (defined as hospital admission), including NAFLD, ALD, viral hepatitis and liver fibrosis and cirrhosis. The outcome was incident cataract. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Each liver disease was first treated as a binary time-varying variable to investigate its association with cataract, and then was treated as a ternary time-varying variable to examine the recent (liver disease within 0–5 years) vs. long-term (liver disease > 5 years) state associations with the risk of cataract. Findings: After a median follow-up of 13.3 years (interquartile range, 12.5–14.0 years), 37,064 individuals were documented as developing cataract. Higher risk of cataract was found in those with severe NAFLD (HR, 1.47; 95% CI, 1.33–1.61), ALD (HR, 1.57; 95% CI, 1.28–1.94) and liver fibrosis and cirrhosis (HR, 1.58; 95% CI, 1.35–1.85), but not in individuals with viral hepatitis when exposure was treated as a binary time-varying variable (P = 0.13). When treating exposure as a ternary time-varying variable, an association between recently diagnosed viral hepatitis and cataract was also observed (HR, 1.55; 95% CI, 1.07–2.23). Results from the combined model suggested they were independent risk factors for incident cataract. No substantial changes were found in further sensitivity analyses. Interpretation: Severe liver diseases, including NAFLD, ALD, liver fibrosis and cirrhosis and recently diagnosed viral hepatitis, were associated with cataract. The revelation of liver-eye connection suggests the importance of ophthalmic care in the management of liver disease, and the intervention precedence of patients with liver disease in the early screening and diagnosis of cataract. Funding: National Natural Science Foundation of China, Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission, Clinical Research Plan of Shanghai Shenkang Hospital Development Center, Shanghai Municipal Key Clinical Specialty Program, the Guangdong Basic and Applied Basic Research Foundation and Shenzhen Science and Technology Program.

Background: Widespread functional alterations have been implicated in patients with generalized anxiety disorder (GAD). However, most studies have primarily focused on static brain network features in patients with GAD. The current research focused on exploring the dynamics within functional brain networks among individuals diagnosed with GAD. Methods: Seventy-five participants were divided into patients with GAD and healthy controls (HCs), and resting-state functional magnetic resonance imaging data were collected. The severity of symptoms was measured using the Hamilton Anxiety Scale and the Patient Health Questionnaire. Co-activation pattern (CAP) analysis, centered on the bed nucleus of the stria terminalis, was applied to explore network dynamics. The capability of these dynamic characteristics to distinguish between patients with GAD and HCs was evaluated using a support vector machine. Results: Patients with GAD exhibited disruptions in the limbic-prefrontal and limbic-default-mode network circuits. Particularly noteworthy was the marked reduction in dynamic indicators such as occurrence, EntriesFromBaseline, ExitsToBaseline, in-degree, out-degree, and resilience. Moreover, these decreased dynamic features effectively distinguished the GAD group from the HC in this study. Conclusions: The current findings revealed the underlying brain networks associated with compromised emotion regulation in individuals with GAD. The dynamic reduction in connectivity between the limbic-default mode network and limbic-prefrontal networks could potentially act as a biomarker and therapeutic target for GAD in the future.

Background: According to the World Health Organization (WHO), healthy aging is the process of developing and maintaining the functional capacity for health in old age. A rapidly growing number of research studies on healthy aging have been conducted worldwide. The purpose of this research work is to explore global scientific landscape of healthy aging research over the last 22 years. Methods: Scientific publications on healthy aging from January 1, 2000 to October 11, 2022 were retrieved from the Web of Science Core Collection (WoSCC) on October 11, 2022. A total of 6420 publications were included in the scientometric analysis. VOSviewer (1.6.18) was used to conduct scientometric and visualized analysis. Results: The publication growth rate was 35.68 from 2000 to 2021. The United States of America (USA) led in both productivity and citations. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA was prominent in terms of both the highest citation count and the highest average citation count. The National Institute on Aging (NIA) and Evans, Michele K. were the most influential organization and author, respectively. Research hotspots in healthy aging were identified based on the co-occurrence analysis of keywords: (1) physical activity and mental health of older adults; (2) diseases impacting the health and lifespan of older adults; and (3) neuroscience. Our analysis indicates that gut microbiota, loneliness, frailty, mitochondria and resilience were the emerging themes in healthy aging research. Conclusions: The quantity of annual publications on healthy aging has rapidly increased over the past 22 years, especially during 2018–2021. This analysis identified the status, trends, hot topics, and frontiers of healthy aging research. These findings will help researchers quickly understand the global representation of healthy aging research, influence resource dissemination, promote international collaborations, guide policy formulation, and improve health services for older adults.

Background: Mpox, one of the most serious threats to global health, is now being seen in small but rising numbers in Beijing, China. Our study aimed to investigate healthcare workers’ (HCWs) knowledge of Mpox and to explore reasons associated with their hesitancy to vaccinate against Mpox in Beijing, China. Methods: A cross-sectional study was conducted among HCWs in Beijing from July 24 to August 2, 2023, through an online questionnaire. Participants answered questions about sociodemographic characteristics, Mpox information sources, Mpox knowledge, perception of vaccines, and attitudes toward Mpox vaccination. We used Chi-squared test to compare difference in Mpox vaccination hesitancy between different groups. Multivariable logistic regression models were applied to analyze correlates of vaccination hesitancy among HCWs. Results: A total of 2331 HCWs completed the questionnaire, with an effective response rate of 92.45 % (2155/2331). Most of the HCWs in this study worked at tertiary hospitals (89.65 %), with a mean age of 36.69 ± 9.08 years. Among the 2155 participants, 52.99 % had over ten years of working experience, and 16.66 % were from high-risk departments relevant to Mpox treatment. Approximately 84.41 % knew about Mpox before this study, 80.79 % exhibited a high level of knowledge about Mpox, whereas 42.37 % were hesitant to be vaccinated against Mpox. Moreover, the hesitancy rate of HCWs in high-risk departments (47.91 %) was higher than in lower-risk departments (41.26 %). Higher educational level (aOR = 1.75, 95 %CI: 1.17–2.62), longer working years (1.71, 1.32–2.22), working at high-risk departments (1.34, 1.05–1.71), and lower level of knowledge about Mpox (1.78, 1.13–2.85) appeared as the most significant determinants of Mpox vaccination hesitancy among HCWs who knew about Mpox. For the HCWs who did not know about Mpox, longer working years (1.96, 1.02–3.78) were significant factors associated with their hesitancy. The predominant reason for hesitancy toward Mpox vaccination among HCWs encompassed apprehensions about vaccine side effects. Conclusion: HCWs had good knowledge of Mpox, whereas their Mpox vaccination hesitancy was also relatively high in Beijing, China. Increasing HCWs’ vaccination confidence and knowledge level about Mpox, especially for those working in high-risk departments, may be an essential way of reducing their hesitancy.

Background and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments. Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic. Results: Available technological capabilities for motion surveillance and compensation determined the course of each 4D particle treatment. 4D motion management, delivery techniques and strategies including imaging were diverse and depended on many factors. These included aspects of motion amplitude, tumour location, as well as accelerator technology driving the necessity of centre-specific dosimetric validation. Novel methodologies for X-ray based image processing and MRI for real-time tumour tracking and motion management were shown to have a large potential for online and offline adaptation schemes compensating for potential anatomical changes over the treatment course. The latest research developments were dominated by particle imaging, artificial intelligence methods and FLASH adding another level of complexity but also opportunities in the context of 4D treatments. Conclusion: This review showed that the rapid technological advances in radiation oncology together with the available intrafractional motion management and adaptive strategies paved the way towards clinical implementation.

Climate change and human activities have markedly altered flow regimes, leading to deleterious consequences for riverine ecosystems. The widely employed hydrological modeling restoration method for conducting flow regime attribution often tends to underemphasize the impact of simulation errors on attribution outcomes. Moreover, the issue of ambiguous attribution targets in flow regime attribution remains a critical concern. This study presented a flow regime attribution framework integrated the hydrological model error correction. Indicators of hydrologic alteration (IHA) simulated by the XAJ and GR4J hydrological models and corrected using the quantile-mapping (QM) and convolutional neural network-long short term memory (CNN-LSTM) error correction methods, were employed to create 6 scenarios for assessing the impacts of climate change and human activities on flow regime changes. A case study was conducted in the Xitiaoxi basin, located in the upper reaches of Lake Tai in China. The results demonstrated that CNN-LSTM's superior performance over QM in correcting IHA metrics simulated by both XAJ and GR4J. The mean flow regime attribution results obtained from XAJ and GR4J simulations following the application of CNN-LSTM correction, mitigated the underestimation of contributions from the primary driving factors, in contrast to uncorrected or QM-corrected IHA metrics attribution results. Additionally, the regime attribution findings revealed all 33 IHA metrics experienced changes, with 73 % of them attributing human activities as the predominant driving forces. Substantial variations in IHA metrics exerted a certain degree of pressure on riverine habitats, particularly impacting the spawning and reproductive activities of piscine species.

The simulation of supersonic or hypersonic flows often suffers from numerical shock instabilities if the flow field contains strong shocks, limiting the further application of shock-capturing schemes. In this paper, we develop the unified matrix stability analysis method for schemes with three-point stencils and present MSAT (matrix stability analysis tool), an open-source tool to quantitatively analyze the shock instability problem. Based on the finite-volume approach on the structured grid, MSAT can be employed to investigate the mechanism of the shock instability problem, evaluate the robustness of numerical schemes, and then help to develop robust schemes. Also, MSAT has the ability to analyze the practical simulation of supersonic or hypersonic flows, evaluate whether it will suffer from shock instabilities, and then assist in selecting appropriate numerical schemes accordingly. As a result, MSAT is a helpful tool that can investigate the shock instability problem and help to cure it.

Summary: Dysregulated lipid metabolism occurs in pathological processes characterized by cell proliferation and migration. Nonetheless, the mechanism of increased mitochondrial lipid oxidation is poorly appreciated in diabetic cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. Herein, increased WTAP expression promotes cardiac fibroblast proliferation and migration, contributing to diabetic cardiac fibrosis. Knockdown of WTAP suppresses mitochondrial lipid oxidation, fibroblast proliferation and migration to ameliorate diabetic cardiac fibrosis. Mechanistically, WTAP-mediated m6A methylation of AR induced its degradation, dependent on YTHDF2. Additionally, AR directly interacts with mitochondrial lipid oxidation enzyme Decr1; overexpression of AR-suppressed Decr1-mediates mitochondrial lipid oxidation, inhibiting cardiac fibroblast proliferation and migration. Knockdown of AR produced the opposite effect. Clinically, increased WTAP and YTHDF2 levels correlate with decreased AR expression in human DCM heart tissue. We describe a mechanism wherein WTAP boosts higher mitochondrial lipid oxidation, cardiac fibroblast proliferation, and migration by enhancing AR methylation in a YTHDF2-dependent manner.

The bio-inertness of titanium (Ti) and accompanying severe inflammation can extremely inhibit the coupled osteogenesis-angiogenesis regulation and result in an undesirable osseointegration of peri-implant during the implantation process. Herein, three types of TiO2 nanotubes (TNT) were prepared on native Ti substrate using an anodic oxidation approach, including TNT with a diameter of 30 nm (TNT-30), 70 nm (TNT-70), or 110 nm (TNT-110). Among the four substrates, TNT-70 was the most prominent to induce the differentiation of macrophages to the pro-healing M2 phenotype via significant down-regulation of pro-inflammation genes (CD86, iNOS, CD11c) and cytokines (TNF-α, IL-6), as well as up-regulation of anti-inflammation genes (CD206, Arg-1, IL-10) and cytokines (TGF-β, IL-10). Furthermore, TNT-70 could stimulate the osteogenic potential of mesenchymal stem cells (MSCs) and the angiogenic ability of human umbilical vein endothelial cells (HUVECs) via multiple paracrine signaling. In vivo experiments suggested that TNT-70 significantly relieved early inflammatory response around the implant, facilitated coupled osteogenesis and angiogenesis, and effectively promoted the osseointegration of peri-implant. This study provided a reference for fabricating surface topography on Ti implant for improving osseointegration and relieving associated excessive inflammatory response.

With the in-depth investigation of cardiac fibrosis, oxidative stress (OS) has been recognized as a significant pathophysiological pathway involved in cardiac remodeling and progression. OS is a condition characterized by the disruption of equilibrium between reactive oxygen species (ROS) produced by the organism and the antioxidant defense system, resulting in adverse effects on the structure and function of the heart. The accumulation of reactive substances beyond cellular thresholds disrupts the normal physiology of both cardiomyocytes and non-cardiomyocytes, leading to OS, inflammation, hypertrophy, and cardiac fibrosis. Furthermore, cardiac OS also modulates several crucial genes involved in maintaining cellular homeostasis, including those associated with mitochondrial biogenesis, injury, and antioxidant defense, which are inevitably associated with concurrent epigenetic changes. Multiple studies have demonstrated the crucial role of epigenetic modifications in regulating cardiac OS. Consequently, modulating OS through targeted epigenetic modifications emerges as a potentially promising therapeutic strategy for managing cardiac fibrosis. This article provides a new review of current research on this subject and proposes that epigenetics may improve OS-induced cardiac fibrosis.

All forms of life produce nanosized extracellular vesicles called exosomes, which are enclosed in lipid bilayer membranes. Exosomes engage in cell-to-cell communication and participate in a variety of physiological and pathological processes. Exosomes function via their bioactive components, which are delivered to target cells in the form of proteins, nucleic acids, and lipids. Exosomes function as drug delivery vehicles due to their unique properties of innate stability, low immunogenicity, biocompatibility, biodistribution, accumulation in desired tissues, low toxicity in normal tissues, and the stimulation of anti-cancer immune responses, and penetration capacity into distance organs. Exosomes mediate cellular communications by delivering various bioactive molecules including oncogenes, oncomiRs, proteins, specific DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), and circular RNA (circRNA). These bioactive substances can be transferred to change the transcriptome of target cells and influence tumor-related signaling pathways. After considering all of the available literature, in this review we discuss the biogenesis, composition, production, and purification of exosomes. We briefly review exosome isolation and purification techniques. We explore great-length exosomes as a mechanism for delivering a variety of substances, including proteins, nucleic acids, small chemicals, and chemotherapeutic drugs. We also talk about the benefits and drawbacks of exosomes. This review concludes with a discussion future perspective and challenges. We hope that this review will provide us a better understanding of the current state of nanomedicine and exosome applications in biomedicine.

Dysregulated mitochondrial metabolism occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the role of mitochondrial fission is not well appreciated in cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. We investigated the causes and consequences of mitochondrial fission in cardiac fibrosis using cultured cells, animal models, and clinical samples. Increased METTL3 expression caused excessive mitochondrial fission, resulting in the proliferation and migration of cardiac fibroblasts that lead to cardiac fibrosis. Knockdown of METTL3 suppressed mitochondrial fission, inhibiting fibroblast proliferation and migration for ameliorating cardiac fibrosis. Elevated METTL3 and N6-methyladenosine (m6A) levels were associated with low expression of long non-coding RNA GAS5. Mechanistically, METTL3-mediated m6A methylation of GAS5 induced its degradation, dependent of YTHDF2. GAS5 could interact with mitochondrial fission marker Drp1 directly; overexpression of GAS5 suppressed Drp1-mediated mitochondrial fission, inhibiting cardiac fibroblast proliferation and migration. Knockdown of GAS5 produced the opposite effect. Clinically, increased METTL3 and YTHDF2 levels corresponded with decreased GAS5 expression, increased m6A mRNA content and mitochondrial fission, and increased cardiac fibrosis in human heart tissue with atrial fibrillation. We describe a novel mechanism wherein METTL3 boosts mitochondrial fission, cardiac fibroblast proliferation, and fibroblast migration: METTL3 catalyzes m6A methylation of GAS5 methylation in a YTHDF2-dependent manner. Our findings provide insight into the development of preventative measures for cardiac fibrosis.

Aiming at solving the challenges of the Internet of Vehicles (IoV), such as privacy sensitive data exposing, data being vulnerable to unauthorized access and tampered with and the single point of failure of the cloud server, this paper introduces a blockchain-enabled data access method based on attribute-based encryption. To enhance the privacy protection, the attributes are hidden and all generated transactions are recorded on the blockchain for auditing. Even if it is untrusted to a third party, it can guarantee the user’s control over his own data. To reduce the computation cost, decentralized edge nodes jointly maintain the blockchain and assist users with limited resources to complete most of the calculations. Meanwhile, the use of smart contracts not only reduces the verification workload, but also evaluates multiple factors such as the communication range, communication time, and calculation overhead of the roadside unit (RSU) to ensure that the vehicle can receive messages in a timely manner. In addition, timely updating the attributes can reduce the user’s computational burden and increase the flexibility of the system. Numeral experiments to show the proposed scheme has many advantages of over others such as the storage cost, the whole time consume of the proposed algorithms and the proxy computation cost.

Drought stress is one of the major environmental factors affecting crop growth and productivity. Cuticular wax plays essential roles in protecting plants from environmental stress via forming a hydrophobic barrier on leaf epidermis. In this study, we analyzed nine members (OsCUT1‒OsCUT9) of β-ketoacyl-CoA synthase, the rate-limiting key enzyme for cuticular wax synthesis in rice by homology search and domain prediction. The expression levels of OsCUT genes under different abiotic stresses were investigated and OsCUT1 down-regulated by abiotic stress was selected for further function validation. Compared to the wild type, overexpression of OsCUT1 (OX-OsCUT1) exhibited significantly increased drought resistance. Epicuticular wax was increased on the leaf surface of OX-OsCUT1 and the chlorophyll leaching experiment showed that the cuticular permeability was decreased in the OX-OsCUT1 plants. Moreover, overexpression of OsCUT1 didn’t result in the significant changes of major agronomic traits. In total, these results suggested that OsCUT1 is a promising gene for engineering rice plants with enhanced drought tolerance.

The transmission line is an important channel for the electric energy transmission in the power system. Whether the stable transmission of electric energy is related to key issues such as people’s livelihood and industry, so it is of great significance to evaluate the operation status of the transmission line. Aiming at the shortcomings of the current evaluation methods for the operation status of transmission lines, this paper proposes a comprehensive evaluation method for the operation status of transmission lines based on the improved combination weighting evaluation model. By constructing a transmission line status indication system based on transmission line standards and specifications, comprehensively considering subjective weights and objective weights, the operational health status of the 6 transmission lines in actual operation is calculated, and the calculation results are compared with the evaluation results of the national grid industry standards. In contrast, this method fully combines the advantages of the improved AHP method and the CRITIC method. While retaining the subjective opinions of experts, it can well avoid the phenomenon of unbalanced weights. Compared with the traditional standard evaluation method, it is more in line with objective reality. The evaluation and early warning of the operation status of transmission lines are of great guiding significance.

Background and purpose: Anatomical changes may compromise the planned target coverage and organs-at-risk dose in particle therapy. This study reports on the practice patterns for adaptive particle therapy (APT) to evaluate current clinical practice and wishes and barriers to further implementation. Materials and methods: An institutional questionnaire was distributed to PT centres worldwide (7/2020–6/2021) asking which type of APT was used, details of the workflow, and what the wishes and barriers to implementation were. Seventy centres from 17 countries participated. A three-round Delphi consensus analysis (10/2022) among the authors followed to define recommendations on required actions and future vision. Results: Out of the 68 clinically operational centres, 84% were users of APT for at least one treatment site with head and neck being most common. APT was mostly performed offline with only two online APT users (plan-library). No centre used online daily re-planning. Daily 3D imaging was used for APT by 19% of users. Sixty-eight percent of users had plans to increase their use or change their technique for APT. The main barrier was “lack of integrated and efficient workflows”. Automation and speed, reliable dose deformation for dose accumulation and higher quality of in-room volumetric imaging were identified as the most urgent task for clinical implementation of online daily APT. Conclusion: Offline APT was implemented by the majority of PT centres. Joint efforts between industry research and clinics are needed to translate innovations into efficient and clinically feasible workflows for broad-scale implementation of online APT.

Background and purpose: Organ motion compromises accurate particle therapy delivery. This study reports on the practice patterns for real-time intrafractional motion-management in particle therapy to evaluate current clinical practice and wishes and barriers to implementation. Materials and methods: An institutional questionnaire was distributed to particle therapy centres worldwide (7/2020–6/2021) asking which type(s) of real-time respiratory motion management (RRMM) methods were used, for which treatment sites, and what were the wishes and barriers to implementation. This was followed by a three-round DELPHI consensus analysis (10/2022) to define recommendations on required actions and future vision. With 70 responses from 17 countries, response rate was 100% for Europe (23/23 centres), 96% for Japan (22/23) and 53% for USA (20/38). Results: Of the 68 clinically operational centres, 85% used RRMM, with 41% using both rescanning and active methods. Sixty-four percent used active-RRMM for at least one treatment site, mostly with gating guided by an external marker. Forty-eight percent of active-RRMM users wished to expand or change their RRMM technique. The main barriers were technical limitations and limited resources. From the DELPHI analysis, optimisation of rescanning parameters, improvement of motion models, and pre-treatment 4D evaluation were unanimously considered clinically important future focus. 4D dose calculation was identified as the top requirement for future commercial treatment planning software. Conclusion: A majority of particle therapy centres have implemented RRMM. Still, further development and clinical integration were desired by most centres. Joint industry, clinical and research efforts are needed to translate innovation into efficient workflows for broad-scale implementation.

Purpose: To report the anterior segment measurements and investigate the determinants of angle width with short, medium, and long axial length (AL) in a rural Chinese population. Design: Observational, population-based, cross-sectional study. Methods: Subjects aged ≥35 years who underwent complete ocular examinations during the follow-up of the Handan Eye Study were included. Ocular data of the right eye were analyzed. Anterior segment parameters were obtained and stratified by age and sex. AL was categorized into short (23.5 mm) subgroups. Linear regression analyses were performed to identify the parameters associated with angle width (angle opening distance at 500 μm from the scleral spur (SS) [AOD500]). Results: The final analysis included 4435 subjects (58.0 [49.0, 64.0] years old, 44.1% males). Smaller AOD500 was significantly associated with female sex (P = 0.032), larger iris thickness at 750 μm from the SS (IT750) (P

Sleep and stress have complex interactions that are implicated in both physical diseases and psychiatric disorders. These interactions can be modulated by learning and memory, and involve additional interactions with the neuroimmune system. In this paper, we propose that stressful challenges induce integrated responses across multiple systems that can vary depending on situational variables in which the initial stress was experienced, and with the ability of the individual to cope with stress- and fear-inducing challenges. Differences in coping may involve differences in resilience and vulnerability and/or whether the stressful context allows adaptive learning and responses. We provide data demonstrating both common (corticosterone, SIH and fear behaviors) and distinguishing (sleep and neuroimmune) responses that are associated with an individual's ability to respond and relative resilience and vulnerability. We discuss neurocircuitry regulating integrated stress, sleep, neuroimmune and fear responses, and show that responses can be modulated at the neural level. Finally, we discuss factors that need to be considered in models of integrated stress responses and their relevance for understanding stress-related disorders in humans.

Objective: This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index (SII) in non-metastatic nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed the data of 839 patients with non-metastatic NPC recruited from two independent institutions. The training-set cohort and the external validation-set cohort was comprised of 459 and 380 patients from each institution, respectively. The optimal cut-off value of SII was determined, and a prognostic risk stratification model was developed based on the training cohort and further assessed in the validation cohort. The propensity score matching (PSM) method was applied to minimize the confounding effects of unbalanced covariables. Results: The optimal cut-off value of the SII in the training cohort was 686, which was confirmed using the validation cohort. Multivariate analysis showed that both before and after PSM, SII values > 686 were independently associated with worse progression-free survival (PFS) ratio in both cohorts (before PSM, P = 0.008 and P = 0.008; after PSM, P = 0.008 and P = 0.007, respectively). Based on the analysis of independent prognostic factors of SII and N stage, we developed a categorical risk stratification model, which achieved significant discrimination among risk indexes associated with PFS and distant metastasis-free survival (DMFS) in the training cohort. There was no significant difference in PFS between RT alone and combined therapies within the low- and intermediate-risk groups (5-year PFS, 77.5% vs. 75.3%, P = 0.275). Patients in the high-risk group who received concurrent chemoradiotherapy experienced superior PFS compared with those who received other therapies (5-year PFS, 64.9% vs. 40.3%, P = 0.003). Conclusion: Pretreatment SII predicts PFS of patients with non-metastatic NPC. Prognostic risk stratification incorporating SII is instructive for selecting individualized treatment.

A KD-control human induced pluripotent stem cells (iPSCs) line (PUMCi002-A) was generated from dermal fibroblasts of a Krabbe patient’s father with a c.461C>A mutation in Galactocerebrosidase (GALC) gene. The pluripotency, in vitro differentiation potential and karyotype stability of generated iPSC line were analyzed and confirmed. This cell line can be exploited as a control iPSC line to better understand the mechanisms involved in GALC-associated Krabbe disease and provide plausible new therapeutic directions.