Search

Abstract Background The etiology of depression involves many biological and environmental factors, among which the inflammatory process is an important contributor. However, the role of pro-inflammatory cytokines in postmenopausal depression is unclear. Therefore, we aimed to explore the association between the serum concentrations of four pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and depressive symptoms in postmenopausal women who had been receiving menopause hormone therapy (MHT) for at least 6 months and postmenopausal women who had not received MHT. Methods This study included a total of 136 Chinese postmenopausal women aged 40 to 65 years who visited the gynecology outpatient department between June 2020 and December 2022. They were divided into the POST group (n = 94) and the POST + MHT (n = 42) group. Demographic information was collected, and the Hamilton Rating Scale for Depression (HAMD) was used to assess depression. The circulating levels of IL-1β, IL-6, IL-18, and TNF-α were determined using ELISA kits. Results According to the HAMD score, 39.36% of the participants in the POST group and 14.29% in the POST + MHT group were considered to have depression. The POST + MHT group had significantly lower serum concentrations of IL-18 and TNF-α than the POST group. Multiple linear regression analysis showed that the serum IL-18 (β = 3.996, 95% CI = 0.508–7.484), and TNF-α levels (β = 4.784, 95% CI = 0.939–8.629) were significant predictors of the HAMD-24 scores in women in the POST group. In addition, age was found to be positively related with the level of depression (β = 0.531, 95% CI = 0.063–0.999). Conclusions Postmenopausal women who received MHT had a lower HAMD-24 score as well as lower serum TNF-α and IL-18 levels than women who did not receive MHT. Further, the TNF-α and IL-18 level were positively associated with the HAMD-24 score in women who had not received MHT.

Abstract Schwannomas are tumors that originate from the glial cells of the nervous system and can occur on myelinated nerve fibers throughout the body, especially in the craniofacial region. However, pancreatic schwannomas are extremely rare. We report a case of a pancreatic schwannoma that was difficult to differentiate from other pancreatic tumors preoperatively. A 44-year-old female patient was found to have a pancreatic mass on Computed Tomography imaging and the preoperative diagnosis was a pancreatic solid pseudopapillary neoplasm. Meanwhile, the patient had type 2 diabetes and the blood glucose was controlled at 8-15mmol/L by taking oral antidiabetic drugs. During exploratory laparotomy, an 8 cm × 7 cm × 4 cm mass was discovered in the middle part of the pancreas. Considering the preoperative diabetes, the patient underwent a central pancreatectomy (CP) and Roux-en-Y pancreaticojejunostomy. Postoperative histopathological examination confirmed the diagnosis of a pancreatic epitheloid schwannoma. After surgery, the patient developed Grade B pancreatic fistula, which disappeared after treatment. At the same time, the patient’s blood glucose remained basically stable by insulin therapy, which was adjusted to oral antidiabetic medications in about 40 days after surgery. At a 32-month follow-up after discharge, no tumor recurrence was observed, and the patient’s blood glucose was controlled below 11.1mmol/L with only oral antidiabetic drugs. The radiological diagnosis of pancreatic schwannomas lacks specific features, and diagnosis primarily relies on histopathological examination and immunohistochemical testing. Although pancreatic schwannomas are extremely rare, they must be differentiated from other solid or cystic pancreatic lesions. For patients with pancreatic schwannoma and diabetes, CP may represent a favorable surgical option.

Abstract Background Obesity and insulin resistance (IR) may be risk factors for thyroid disease, but there is no clinical-based consensus on this topic. Therefore, this study aims to evaluate the associations between the triglyceride-glucose index (TyG) and its derivatives and Hashimoto thyroiditis (HT) in type 2 diabetes mellitus (T2DM) patients, and explore the relationships between the central obesity indicators and HT risk to provide a reliable basis for the early prevention of HT. Methods A total of 1071 T2DM patients aged ≥ 20 years were selected from a tertiary hospital in Tianjin, all of them had normal thyroid function (including free triiodothyronine, free thyroxine, total triiodothyronine, total thyroxine, and thyroid-stimulating hormone). HT was assessed via thyroid-associated antibodies and thyroid colour Doppler ultrasound. TyG and its derivatives were measured via IR. Restricted cubic spline (RCS) models, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis were used to explore the correlations and predict HT. Mediation analysis explored the mediating role of TyG and its derivatives in the associations between the central obesity indicators and HT. Results RCS models revealed that increases in waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), TyG-WC, TyG-WHR, and TyG-WHtR were associated with increased HT risk. Logistic regression revealed that participants in the fourth quartile of TyG-WC, TyG-WHR, and TyG-WHtR had approximately 3.38 times greater HT risk (odds ratio range: 2.807 to 3.375). ROC analysis revealed that WC, WHtR, WHR, TyG-WC, TyG-WHtR and TyG-WHtR could distinguish the presence of HT. In females, the WHR had the highest predictive power, with an area under the ROC curve of 0.651 (95% confidence interval 0.611–0.691, P

Abstract To mitigate the safety risks and economic losses caused by wheel damage, this paper proposes an interval valued fuzzy inference-based sound analysis method for wheel damage detection. Firstly, interval valued fuzzy sets are defined to represent various levels of damage severity. A similarity calculation method is then designed, based on the defined interval valued fuzzy sets, to assess the damage level of wheel components. Moreover, the OWA operator is employed to assign higher weights to key features while reducing the influence of noise or redundant features. Finally, a double-threshold interval valued fuzzy inference approach is proposed for comprehensive decision-making regarding the wheel damage degree. The proposed method is applied to wheel damage sound analysis, and a corresponding detection system is developed. Experimental results demonstrate that the proposed method outperforms existing techniques in detection accuracy, response speed, and robustness, and it is adaptable to various wheel operating environments.

Abstract Background Although symptoms of depressive episodes in patients with bipolar depressive episodes (BDE) and major depressive disorder (MDD) are similar, the treatment strategies for these disorders are completely different, suggesting that BDE and MDD have different neurobiological backgrounds. In this study, we examined the relationship between brain function and clinical symptoms, particularly cognitive function, in female individuals with bipolar disorder and MDD experiencing depressive episodes. Methods Regional homogeneity (ReHo) was analyzed in 51 medication-free female patients with BDE, 63 medication-free female patients with MDD, and 45 female healthy controls (HCs). Depressive symptom severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and multidimensional cognitive function was evaluated using the MATRICS Consensus Cognition Battery. Partial correlation analysis was used to explore the links between the brain regions and clinical characteristics. A support vector machine (SVM) was used to assess the classification accuracy. Results Compared with HCs, patients with BDE and MDD had decreased ReHo in the left lobule VI of the cerebellum and increased ReHo in the left precuneus. Patients with BDE also had reduced ReHo in the left lobules IV–V of the cerebellum and increased ReHo in the right putamen, unlike patients with MDD who had no significant differences in these regions. Patients with BDE exhibited more severe cognitive deficits in processing speed, attention, word learning, and overall cognitive function than those with MDD. In patients with BDE, a significant negative correlation was found between the right putamen and HAMD-24 scores. However, no significant association was observed between abnormal ReHo levels and cognitive function. The SVM effectively differentiated between patients with BDE, MDD, and HCs. Conclusion Cognitive impairment was more severe in female patients with BDE than in those with MDD. Changes in the ReHo values of the right putamen and left lobules IV–V may serve as unique neuroimaging markers for BDE. Alterations in the ReHo values of the left precuneus and left lobule VI could serve as common pathophysiological mechanisms for BDE and MDD in women and indicate depressive states.

Abstract Erythropoiesis is a crucial process in hematopoiesis, yet it remains highly susceptible to disruption by various diseases, which significantly contribute to the global challenges of anemia and blood shortages. Current treatments like erythropoietin (EPO) or glucocorticoids often fall short, especially for hereditary anemias such as Diamond-Blackfan anemia (DBA). To uncover new erythropoiesis-stimulating agents, we devised a screening system using primary human hematopoietic stem and progenitor cells (HSPCs). We discovered that BRAF inhibitors (BRAFi), commonly used to treat BRAFV600E melanoma, can unexpectedly and effectively promote progenitor cell proliferation by temporarily delaying erythroid differentiation. Notably, these inhibitors exhibited pronounced efficacy even under cytokine-restricted conditions and in patient samples of DBA. Mechanistically, although these BRAFi inhibit the MAPK cascade in BRAFV600E mutant cells, they paradoxically act as amplifiers in wild-type BRAF cells, potently enhancing the cascade. Furthermore, we found that while the oncogenic BRAFV600E mutation disrupts hematopoiesis and erythropoiesis through AP-1 hyperactivation, BRAFi minimally impact HSPC self-renewal and differentiation. In vivo studies have shown that BRAFi can enhance human hematopoiesis and erythropoiesis in severe immunodeficient mouse models and alleviate anemia in the Rpl11 haploinsufficiency DBA model, as well as other relevant anemia models. This discovery underscores the role of the MAPK pathway in hematopoiesis and positions BRAFi as a promising therapeutic option for improving hematopoietic reconstitution and treating anemias, including DBA.

To evaluate the protective effects of sodium butyrate (SB) on intestinal morphology, anti-oxidant status, inflammatory response and barrier integrity in male broilers under heat stress. A total of 180 21-d-old male Arbour Acres broilers with similar body weight were used for this 21-d experiment. Broilers were randomly allocated to three groups: CON group, basal diet and raised under 24 °C; HS group, basal diet and raised under heat stress condition (34 °C from 10:00 to 18:00 and 24 °C for the rest time); HS-SB group, basal diet with 1200 mg/kg SB and raised under heat stress condition. Compared to the HS group, SB supplementation increased average daily gain (ADG), villus height: crypt depth ratio (VH: CD), VH, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, and interleukin-10 (IL-10) level, decreased feed conversion ratio (FCR), CD, reactive oxygen species (ROS), IL-1β and tumour necrosis factor-alpha (TNF-α) level, up-regulated the mRNA expression of nuclear factor erythroid 2-related factor 2, haem oxygenase 1, GSH 1 (GPX1), SOD and CAT, down-regulated the mRNA expression of toll-like receptor 4 (TLR4), nuclear transcription factors, IL-1β, and TNF-α in jejunum of heat-stressed broilers. Furthermore, SB supplementation up-regulated the mRNA expression of occluding, claudin-1 and zona occludens-1 (ZO-1) in jejunum of heat-stressed broilers, accompanied with decreasing serum endotoxin and D-lactic acid concentration, and diamine oxidase (DAO) activity. There results suggested that SB supplementation could alleviate heat stress-induced jejunal tight junction structure dysfunction by up-regulated the expression of occluding, claudin-1 and ZO-1, presumably through alleviating oxidative stress and inflammatory response.HIGHLIGHTS Sodium butyrate alleviated heat stress-induced jejunal morphology damage. Sodium butyrate alleviated heat stress-induced jejunal oxidative damage. Sodium butyrate alleviated heat stress-induced jejunal inflammatory response. Sodium butyrate alleviated heat stress-induced tight junction structure dysfunction.

This research is to explore the impacts of irisin on hyperalgesia and behavioral deficits caused by chronic constriction injury (CCI) and the underlying mechanisms. The CCI mice model was used in this study. The experimental mice were assigned into sham, sham + irisin (3 μg/kg), CCI, CCI + irisin (0.1, 1, and 3 μg/kg), and CCI + irisin (3 μg/kg) + ML385 (30 mg/kg) groups. The results showed that after CCI injury, the mice exhibited hyperalgesia, depression, and anxiety. In addition, the levels of inflammatory cytokines NF-κB, IL-1β, IL-6, TNF-α, and iNOS increased in the mice hippocampus, frontal cortex, and spinal cord. Moreover, oxidative stress relevant factor MDA increased, while GSH and SOD decreased in the mice hippocampus, frontal cortex, and spinal cord. However, irisin treatment ameliorated CCI-induced mechanical allodynia, thermal hyperalgesia, depressive, and anxiety behaviors, and reversed the abnormal expressions of inflammatory and oxidative stress relevant cytokines. Interestingly, these therapeutic effects of irisin were partly abolished by ML385, a specific Nrf2 antagonist. Taken together, irisin may be an effective therapeutic agent for CCI-induced neuralgia and the affective disorders, and the mechanisms may be associated with the anti-neuroinflammation mediated by NF-κB and the anti- oxidative stress function regulated by Nrf2.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract Nanometal-based composite fibers have been widely explored in flexible sensors due to their outstanding optical and electrical properties. However, the weak binding force between metallic nanomaterial and fiber greatly limits the real application. In this work, nano silver (Ag) are strongly bonded with poly(3,4-ethylenedioxythiophene)-poly (styrene sulfonate) (PEDOT: PSS) fiber by the wet-spun process. Ag-S chemical bonds are formed by the interaction of Ag and PEDOT. The Ag/PEDOT: PSS composite fiber shows excellent surface-enhanced Raman scattering (SERS) sensitivity on Rhodamine 6G (R6G) molecules. The detection limit can reach 10–11 M and Raman enhancement factor (EF) is of 1.3 × 107. The high-sensitive SERS activity of Ag/PEDOT: PSS composite fiber mainly results from PEDOT: PSS, and the enhancement factor is 3 orders of magnitude better than that of other PEDOT: PSS based SERS substrates. Moreover, the composite fiber has metal-level conductivity of 1019 S/cm. This is 5 times higher than the conductivity of PEDOT: PSS fiber and a two-fold improvement over the reported values for nanometal/PEDOT: PSS based fabrics. The composite fiber has electric stability under bending test with bending speeds of 2 Hz indicating the composite fiber has good structural stability. In addition, the temperature of the composite fiber with 7 cm length can reach 76.5 °C at a voltage of 18 V. Additionally, the composite fiber shows anti-bacterial property and melting drop resistance, which pave the way for the integration of fiber-based optical and electrical sensors in the future multifunctional flexible devices.

Abstract Owing to the presence of exceptional points (EPs), non-Hermitian (NH) systems can display intriguing topological phenomena without Hermitian analogs. However, experimental characterizations of exceptional topological invariants have been restricted to second-order EPs (EP2s) in classical or semiclassical systems. We here propose an NH multi-mode system with higher-order EPs, each of which is underlain by a multifold-degenerate multipartite entangled eigenstate. We implement the NH model by controllably coupling a Josephson-junction-based electronic mode to two microwave resonators. We experimentally quantify the topological invariant for an EP3, by mapping out the complex eigenspectra of the tripartite system along a loop surrounding this EP3 in the parameter space. The nonclassicality of the realized topology is manifested by the observed quantum correlations in the corresponding eigenstates. Our results extend research of exceptional topology to fully quantum-mechanical models with multipartite entangled eigenstates.

Abstract Background Fixation instability serves as an initial trigger for femoral head necrosis in patients with femoral neck fractures undergoing internal fixation. The configuration of screw trajectories is critical in determining the stability of the fixation. Our previously published study indicates that abduction of screw trajectories may enhance postoperative angular stability. However, the effectiveness of a wider screw distribution on the sagittal plane in optimizing fixation stability and reducing the risk of femoral head necrosis remains uncertain. Methods This retrospective study reviewed imaging data from patients with femoral neck fractures who were treated with inverse triangle cannulated screw fixation. Postoperative lateral radiographs were used to evaluate the screw configuration strategy. The distance between the two cranial screws and the femoral neck width at its narrowest point were measured. The ratio of these two measurements was calculated to represent the screw spread grade. Demographic and imaging parameters were compared between patients who developed femoral head necrosis and those who did not. Regression analysis was conducted to identify potential risk factors associated with femoral head necrosis. Additionally, numerical models were employed to simulate the biomechanical impact of variations in screw spread grade. Results The clinical analysis revealed that a lower screw distance-to-femoral width ratio was associated with a higher incidence of femoral head necrosis. This ratio was also identified as an independent risk factor for femoral head necrosis. Biomechanical simulations corroborated these findings, demonstrating that models with a lower screw-to-femoral width ratio exhibited reduced fixation stability and increased stress distribution. Conclusions Wider distribution of screws along the sagittal plane may significantly mitigate the risk of femoral head necrosis by enhancing fixation stability. The optimization of screw trajectories, particularly through broader screw spacing facilitated by a navigation system, emerges as a promising strategy for improving the local biomechanical environment and reducing the likelihood of femoral head necrosis.

Abstract Background The aim of this study was to evaluate the inter-fraction reproducibility and intra-fraction stability of breast radiotherapy using voluntary deep-inspiration breath hold (DIBH) and free breathing (FB) based on an optical surface imaging system (OSIS). Methods Seventeen patients (510 breath-hold sessions) treated using a field-in-field (FiF) technique and twenty patients (600 breath-free sessions) treated with a volume-modulated arc therapy (VMAT) technique were included in this retrospective study. All the patients were positioned with the guidance of CBCT and OSIS, and also monitored with OSIS throughout the whole treatment session. Eight setup variations in three directions were extracted from the treatment reports of OSIS for all sessions and were subsequently manually introduced to treatment plans, resulting in a total of 296 perturbed plans. All perturbed plans were recalculated, and the dose volume histograms (DVH) for the target and organs at risk (OAR) were analyzed. Results The OSIS and CBCT for both DIBH and FB treatments showed a good agreement of less than 0.30 cm in each direction. The intra-fraction respiratory motion data during DIBH were −0.06 ± 0.07 cm, 0.12 ± 0.15 cm, and 0.12 ± 0.12 cm in the lateral, longitudinal, and vertical directions, respectively; for FB, the respiratory motion data were −0.02 ± 0.12 cm, 0.08 ± 0.18 cm, and 0.14 ± 0.20 cm, respectively. For the target, DIBH plans were more sensitive to setup errors; the mean deviations in D95 for CTV were 39.78 Gy–40.17 Gy for DIBH and 38.46 Gy–40.52 Gy for FB, respectively. For the OARs, the mean deviations of V10, V20, and Dmean to the heart; V5, V20, and Dmean to the ipsilateral lung; and Dmean to the breast were lower for the FB plan compared with the DIBH plan. Conclusion Based on OSIS, our results indicate that both DIBH and FB can provide good reproducibility in the inter-fractions and stability in the intra-fractions. When the patient respiratory motion is large, the FB technology has greater possibility for the undercoverage of the target volume, while DIBH technology is more likely to result in increases in dose to OARs (the lung, heart, and contralateral breast).

Abstract Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells. Our approach leverages the ECM-degrading enzyme collagenase, integrated with dsMNs, to enhance drug penetration by reducing matrix stiffness. Furthermore, the innovative use of a pancreatic cancer cell membrane coating on the nanoparticles enhances tumor targeting and stability (dsMCu-D@M-Co). The multifunctional platform not only facilitates deep drug penetration and triggers cuproptosis effectively but also utilizes the inherent properties of Cu to serve as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vitro and in vivo assessments demonstrate significant tumor size reduction in PDAC-bearing mice, highlighting the dual functionality of our platform in improving therapeutic efficacy and diagnostic precision. This integrated strategy represents a significant advancement in the management of PDAC, offering a promising new direction for overcoming one of the most lethal cancers. Graphical Abstract

Abstract Objective This study investigated the association of Time In Range (TIR) obtained from Blood Glucose Monitoring (BGM) with Cognitive Impairment (CI) inpatients with middle-aged Type 2 Diabetes Mellitus (T2DM) and further explored whether a TIR goal for T2DM in adults with > 70% possess a protective effect on cognitive function. Research design and methods A total of 274 inpatients with T2DM aged 40–64 years, who underwent seven-point BGM ( pre meals and 120 min post meals and at bedtime) were recruited in this cross-sectional study. TIR was defined as the percentage of blood glucose within the target range of 3.9-10.0mmol/L. Subjects were divided into Normal Cognitive Function (NCF) (n = 160) and CI (n = 114) groups according to the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The association of TIR and other glycemic metrics, calculated from seven-point BGM data, with cognitive dysfunction was analyzed. Results The prevalence of CI was 41.6% in patients with middle-aged T2DM (median age 58 years). TIR was lower in CI group than in NCF group (28.6% vs. 42.9%, P = 0.004). The prevalence of CI decreased with ascending tertiles of TIR (p for trend 70% probably possessed independent protective effect on cognitive function (OR = 0.25, p = 0.001) after controlling for confounders above. Conclusions TIR obtained from BGM was related to CI in middle-aged T2DM individuals and a TIR goal of > 70% probably possessed a protective effect on cognitive function for middle-aged T2DM .

Abstract Purpose Lympho-vascular invasion (LVI) and perineural invasion (PNI) have been established as prognostic factors in various types of cancers. The preoperative prediction of LVI and PNI has the potential to guide personalized medicine strategies for patients with esophageal squamous cell cancer (ESCC). This study investigates whether radiomics features derived from preoperative contrast-enhanced CT could predict LVI and PNI in ESCC patients. Methods and materials A retrospective cohort of 544 ESCC patients who underwent esophagectomy were included in this study. Preoperative contrast-enhanced CT images, pathological results of PNI and LVI, and clinical characteristics were collected. For each patient, the gross tumor volume (GTV-T) and lymph nodes volume (GTV-N) were delineated and four categories of radiomics features (first-order, shape, textural and wavelet) were extracted from GTV-T and GTV-N. The Mann–Whitney U test was used to select significant features associated with LVI and PNI in turn. Subsequently, radiomics signatures for LVI and PNI were constructed using LASSO regression with ten-fold cross-validation. Significant clinical characteristics were combined with radiomics signature to develop two nomogram models for predicting LVI and PNI, respectively. The area under the curve (AUC) and calibration curve were used to evaluate the predictive performance of the models. Results The radiomics signature for LVI prediction consisted of 28 features, while the PNI radiomics signature comprised 14 features. The AUCs of the LVI radiomics signature were 0.77 and 0.74 in the training and validation groups, respectively, while the AUCs of the PNI radiomics signature were 0.69 and 0.68 in the training and validation groups. The nomograms incorporating radiomics signatures and significant clinical characteristics such as age, gender, thrombin time and D-Dimer showed improved predictive performance for both LVI (AUC: 0.82 and 0.80 in the training and validation group) and PNI (AUC: 0.75 and 0.72 in the training and validation groups) compared to the radiomics signature alone. Conclusion The radiomics features extracted from preoperative contrast-enhanced CT of gross tumor and lymph nodes have demonstrated their potential in predicting LVI and PNI in ESCC patients. Furthermore, the incorporation of clinical characteristics has shown additional value, resulting in improved predictive performance.

Abstract The incidence of thyroid cancer (TC) is increasing annually worldwide, with a growing burden. This study aims to analyze temporal trends in the burden of TC by age and sex in China and globally from 1990 to 2021, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates, and to predict future trends. We obtained data on TC in China and globally from 1990 to 2021 from the Global Burden of Disease (GBD) database. Using the Joinpoint regression model, we calculated and analyzed the trends in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). Specifically, we estimated the annual percent change (APC), the average annual percent change (AAPC), and the corresponding 95% confidence intervals (95% CI) for each metric. Additionally, we conducted a decomposition analysis to investigate the impact of aging, population growth, and epidemiological factors on the incidence and mortality rates of TC. Furthermore, the autoregressive integrated moving average (ARIMA) model was employed to predict the burden of TC from 2022 to 2036. From 1990 to 2021, the ASIR for TC in China increased from 1.249 (95% uncertainty interval [UI]: 1.009–1.473) per 100,000 to 2.473 (95% UI: 1.993–3.088) per 100,000. Conversely, the ASMR decreased from 0.473 (95% UI: 0.403–0.550) per 100,000 to 0.387 (95% UI: 0.307–0.472) per 100,000. Both males and females demonstrated an upward trajectory in ASIR. However, while the ASMR for females decreased, that for males showed an overall increase despite a decline in the last decade. The age of peak onset for TC ranged from 30 to 79 years, whereas the age of peak mortality was between 50 and 89 years. The analysis using the AAPC indicates that the growth in the ASIR (AAPC = 2.242, 95% CI: 2.112–2.371) and ASPR (AAPC = 2.975, 95% CI: 2.833–3.117) in China exceeds the global rate. Furthermore, the reduction in ASMR (AAPC = -0.651, 95% CI: -0.824 - -0.479) and ASDR (AAPC = -0.590, 95% CI: -0.787 - -0.392) in China is also more pronounced than globally. Decomposition analysis indicates that the increasing TC burden in China is primarily driven by population aging, whereas globally, population growth plays a more significant role. Projections based on predictive models suggest that from 2021 to 2036, the ASIR for both China and the global population is expected to continue rising, while the ASMR is anticipated to decline further. The incidence rates of TC in China and globally have shown a continuous upward trend, which is expected to persist over the next 15 years. Additionally, although the number of male TC cases is relatively lower compared to females, the overall ASMR and ASDR for males have shown an upward trend, despite a slight decline in recent years. This highlights the need to enhance prevention, diagnosis, and treatment measures, and to develop differentiated screening and treatment strategies based on age and sex.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Abstract Background Magnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient’s daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy. Methods Nineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan ( $$\:{\text{T}\text{P}}_{\text{a}\text{d}\text{a}\text{p}}$$ ), a second plan ( $$\:{\text{T}\text{P}}_{\text{I}\text{G}\text{R}\text{T}}$$ ) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of $$\:{\text{T}\text{P}}_{\text{a}\text{d}\text{a}\text{p}}$$ and $$\:\:{\text{T}\text{P}}_{\text{I}\text{G}\text{R}\text{T}}$$ was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters. Results Ninety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median $$\:{\text{D}}_{15\text{c}\text{c}}$$ values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median $$\:{\text{D}}_{5\text{c}\text{c}}$$ values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements. Conclusions MRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Abstract Background Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. Methods A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. Results WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261–1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032–4.371, P for trend

Abstract This study aimed to assess the potential of home monitoring using a monitoring application for the early prediction of acute exacerbations (AEs) in patients with fibrosing interstitial lung diseases (F-ILDs) by tracking symptoms, peripheral blood oxygen saturation (SpO2), and heart rate (HR). Data on symptoms, SpO2, and HR before and after a 1-min sit-to-stand test (1STST) were collected using an online home monitoring application. Symptoms were recorded at least 3 times a week, including cough intensity and frequency (Cough Assessment Test scale (COAT) score), breathlessness grade (modified Medical Research Council (mMRC) score), and SpO2 and HR before and after 1STST. Eighty-five patients with stable F-ILDs were enrolled. We observed a significant increase in COAT and mMRC scores, alongside a significant decrease in SpO2 before and after 1STST, 2 weeks before the first recorded AE. Furthermore, a combination of variables-an increase in COAT (≥ 4) and mMRC(≥ 1) scores, a decrease in SpO2 at rest (≥ 5%), and a decrease in SpO2 after 1STST (≥ 4%)- proved the most effective in predicting AE onset in patients with F-ILDs at 2 weeks before the first recorded AE. Home telemonitoring of symptoms, SpO2 holds potential value for early AE detection in patients with F-ILDs.

Abstract Background The impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC) remains uncertain given the lack of sufficient evidence. Aim To investigate the impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC). Methods Patients who were pathologically diagnosed with HCC and underwent elective partial hepatectomy in Guangdong Provincial People’s Hospital between January 2022 and April 2023 were enrolled in this retrospective cohort study. The patients were divided into two groups based on their history of SARS-CoV-2 infection. Rehabilitation parameters, including postoperative liver function, incidence of complications, and hospitalization expenses, were compared between the two groups. Propensity score matching (PSM) was performed to reduce confounding bias. Results We included 172 patients (58 with and 114 without prior SARS-CoV-2 infection) who underwent liver resection for HCC. No significant differences in the rehabilitation parameters were observed between the two groups. After PSM, 58 patients were selected from each group to form the new comparative groups. Similar results were obtained within the population after PSM. Conclusion Prior SARS-CoV-2 infection does not appear to affect postoperative rehabilitation, including liver function, postoperative complications, or hospitalization expenses among patients with HCC after elective partial hepatectomy.

Abstract Background The prognosis of breast cancer patients with visceral metastasis (VM) is significantly worse than that of patients without VM. We aimed to evaluate EZH2 (enhancer of zeste homolog 2) mutation as a biomarker associated with VM. Methods Data from forty-nine patients with metastatic breast cancer (MBC) pathologically confirmed at our hospital between March 2016 and September 2018 were collected. Metastatic tissue samples were obtained via ultrasound-guided needle biopsy, and paired peripheral blood samples were also collected. Tissue and blood samples were subjected to targeted next-generation sequencing via a 247-gene panel. Stably transfected MDA-MB-231 cells expressing wild-type EZH2 (EZH2WT) or a mutant form of EZH2 (EZH2K515R) were generated. Cell proliferation, colony formation ability, migration and invasion abilities and apoptosis were assessed using CCK-8 assays, plate colony formation assays, Transwell chamber assays and flow cytometry. Results The incidence of EZH2 mutations in the VM subgroup was greater than that in the non-VM subgroup in the entire cohort (n = 49, 42.3% vs. 13.0%, p = 0.024) and in the triple-negative breast cancer (TNBC) subgroup (n = 20, 50.0% vs. 10.0%, p = 0.05). Patients carrying EZH2 mutations had a significantly greater risk of developing VM than did those in the non-EZH2 mutation group in the entire cohort (HR 2.9) and in the TNBC subgroup (HR 6.45). Multivariate analysis revealed that EZH2 mutation was an independent prognostic factor for VM (HR 2.99, p = 0.009) in the entire cohort and in the TNBC subgroup (HR 10.1, p = 0.006). Data from cBioPortal also showed that patients with EZH2 mutations had a significantly greater risk of developing VM (HR 3.1), and the time to develop VM was significantly earlier in the EZH2 mutation group (31.5 months vs. 109.7 months, p = 0.008). Multivariate analysis revealed that EZH2 mutation (HR 2.73, p = 0.026) was an independent factor for VM after breast cancer surgery. There was no correlation between EZH2 mutations and BRCA1/2 mutations. Most of the patients (81.8%) in our cohort who developed VM carried the “c.1544A > G (p.K515R)” mutation. Compared with EZH2WT MDA-MB-231 cells, EZH2K515R MDA-MB-231 cells had greater colony formation rates (p

Abstract Bioaerosols in public transportation systems raise critical environmental concerns, seriously threatening passenger health and safety. In this study, we investigate the spread characteristics of bioaerosols in a standard type-B subway compartment using both air sampling and sediment sampling methods. Additionally, without compromising indoor passenger comfort, two self-designed air purification devices, based on intense field dielectric (IFD) and dielectric barrier discharge (DBD) technologies, respectively, are successfully applied for the improvement of the subway air quality. The results show that bioaerosols can propagate rapidly throughout the entire compartment in 5 min via airborne transmission. Under the effect of the symmetric air ducts and compartment structure, the difference in bioaerosol concentration in the air is less than 10% between both ends of the compartment. Concurrent substantial bioaerosol deposition on the ground, seats, and windows underscores the risk of contact transmission. Furthermore, the real-time purification rates of the two devices integrated into the air conditioning system reach 59.40% and 44.98%, respectively. With their demonstrated high efficiency in purifying bioaerosols and modular design featuring low energy consumption, easy cleaning, and reusability, these devices stand out as viable long-term solutions for large traffic vehicles. These research findings provide practical equipment recommendations and installation strategies for optimizing indoor air quality in subways and are applicable to other similar transportation systems.

Abstract The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS). AcpS is a highly conserved enzyme essential for bacterial survival that catalyzes the first step in lipid synthesis. To the best of our knowledge, there are no current antibiotics targeting AcpS making this drug development program of high interest. We synthesize a library of > 700 novel compounds targeting AcpS, from which 33 inhibit bacterial growth in vitro at ≤ 2 μg/mL. We demonstrate that compounds from this class have stand-alone activity against a broad spectrum of Gram-positive organisms and synergize with colistin to enable coverage of Gram-negative species. We demonstrate efficacy against clinically relevant multi-drug resistant strains in vitro and in animal models of infection in vivo including a difficult-to-treat ischemic infection exemplified by diabetic foot ulcer infections in humans. This antibiotic family could form the basis for several multi-drug-resistant antimicrobial programs.

Abstract Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio

Hepatocellular carcinoma (HCC) is typically diagnosed at intermediate to advanced stage, making surgical treatment unfeasible. Conversion therapy aims to reduce tumor stage, improve hepatic resection feasibility, and lower recurrence rates. Since traditional therapies are often accompanied by uncertainty of efficacy, there is an urgent need to explore new treatment strategies. Near-infrared phototheranostics technology provides a new way for HCC diagnosis and treatment by its excellent optical properties. However, complex preparation and poor biocompatibility of phototheranostics probes limit clinical application. In this study, we developed a fluorescence/magnetic resonance dual-modality imaging (FLI/MRI) as well as photothermal/photodynamic therapy (PTT/PDT) GPC3-targeted multifunctional phototheranostics probe, IR820-GPC3-Gd NPs (IGD NPs), to improve the efficiency of conversion therapy for HCC. The IGD NPs were simply prepared with the IR820 as the core. Conjugating the HCC-specific targeting molecule GPC3 peptide and the MRI agent DOTA-Gd through click chemistry. IGD NPs target HCC cells through GPC3, releasing heat and reactive oxygen species (ROS) under noninvasive 808 nm laser irradiation to reduce tumor size and achieve downstaging. High-sensitivity FLI/MRI precisely delineates tumor boundaries, providing real-time surgical navigation and prognosis assessment. This novel probe offers a feasible and effective treatment option for advanced HCC.

ObjectiveKnee osteoarthritis (KOA) is a degenerative joint condition, leading to disability and diminished quality of life. Molecular hydrogen has been proven to have antioxidant and anti-inflammatory properties, but few studies have investigated its effects on osteoarthritis. Our study aims to assess the therapeutic potential of hydrogen-oxygen mixture (H2-O2) inhalation for KOA.MethodsIn this randomized controlled trial, eligible elderly KOA patients were randomly assigned to either Group H or Group C. Both groups participated in a 12-week home-based exercise (HBE) program, which included knee-joint exercises and health education. Group H additionally received H2-O2 inhalation for 60 min per day over 2 weeks, while Group C did not. The primary outcome was measured using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included inflammation levels (hs-CRP, NLR, PLR, LMR), Chair Stand Test (CST), Timed Up and Go (TUG), 36-item short-form health survey (SF-36), Exercise Adherence Rating Scale (EARS), and adverse events.ResultsA total of 121 subjects were enrolled, with an average age of 81.2 years, and 80.2% were female. The between-group mean difference in the WOMAC total score was −5.2 (95% CI −12.1 to 1.7, P = 0.140) at week 12, with Group H showing an improvement of −22.9 (95% CI −26.3 to −19.6, P < 0.001) and Group C showing an improvement of −19.4 (95% CI −22.7 to −16.0, P < 0.001) compared to baseline, revealing a significant group × time interaction (F (3, 356.034) = 14.425, P < 0.001). No significant differences were observed between both groups at week 12 in CST, TUG, SF-36 scores, EARS scores, or the incidence of adverse events.ConclusionAlthough clinical significance was not achieved, H2-O2 inhalation alleviated KOA symptoms and enhanced functional activity in elderly patients undergoing the HBE program during the initial 2 weeks. However, its sustained effects on improving KOA symptoms were not observed.

Prostate cancer is one of the most prevalent malignant tumors in men, particularly in regions with a high Human Development Index. While the long-term survival rate for localized prostate cancer is relatively high, the mortality rate remains significantly elevated once the disease progresses to advanced stages, even with various intensive treatment modalities. The primary obstacle to curing advanced prostate cancer is the absence of comprehensive treatment strategies that effectively target the highly heterogeneous tumors at both genetic and molecular levels. Prostate cancer development is a complex, multigenic, and multistep process that involves numerous gene mutations, alteration in gene expression, and changes in signaling pathways. Key genetic and pathway alterations include the amplification and/or mutation of the androgen receptor, the loss of Rb, PTEN, and p53, the activation of the WNT signaling pathway, and the amplification of the MYC oncogene. This review summarizes the mechanisms by which these genes influence the progression of prostate cancer and highlights the interactions between multiple genes and their relationship with prostate cancer. Additionally, we reviewed the current state of treatments targeting these genes and signaling pathways, providing a comprehensive overview of therapeutic approaches in the context of prostate cancer.

BackgroundThis study investigates the relationship between basal metabolic rate (BMR), body composition, obesity indices, and cognitive impairment (CI) in middle-aged and older type 2 diabetes mellitus (T2DM) patients, assessing their potential role in CI screening.MethodsA cross-sectional study included 1243 T2DM patients over 45 years old. CI was assessed using the Montreal Cognitive Assessment. BMR and body composition indices were measured through bioelectrical impedance analysis. The associations and predictions related to CI were explored using multivariable-adjusted logistic regression, restricted cubic spline (RCS) models, and receiver operating characteristic (ROC) curve analyses. Mediation analysis explored the role of BMR adjusted by body surface area (BMR/BSA) in CI risk.ResultsPatients with CI showed significantly lower BMR, BMR adjusted for height squared (BMR/Height²), BMR/BSA, appendicular skeletal muscle mass (ASM), and fat-free mass (FFM), alongside higher waist circumference (WC) and percentage of body fat. Logistic regression showed that participants in the fourth quartile of BMR, BMR/Height2, and BMR/BSA had approximately a 54% reduced risk of CI (odds ratio range 0.457 to 0.463). RCS analysis indicated a linear decrease in CI risk with increasing BMR metrics. ROC analysis indicated high predictive efficacy for CI with combined indicators, particularly BMR and FFM (area under the curve 0.645). Mediation analysis suggested that BMR/BSA played a significant mediating role in WC, ASM and FFM on CI risk, with a mediation proportion ranging from 45.73% to 50.87%.ConclusionLow energy expenditure assessed by BMR/BSA is an independent risk factor for increased CI risk in middle-aged and elderly T2DM patients. Central obesity, low muscle mass, and low energy expenditure significantly elevate CI risk in this population.

BackgroundAnticoagulants are the primary means for the treatment and prevention of venous thromboembolism (VTE), but their clinical standardized application still remains controversial. The present study intends to comprehensively compare the efficacy and safety of various anticoagulants in VTE.MethodsMedline, Embase, and Cochrane Library from their inception up to August 2023 were searched to compare the efficacy and safety of various anticoagulants in VTE. We extracted data on study settings, baseline characteristics, interventions, and outcomes, applying the intention-to-treat principle. Two researchers assessed study bias using the Cochrane tool, resolving disagreements through discussion or third-party adjudication. Network meta-analyses were performed based on Bayesian generalized linear models, and a frequentist framework with multivariate random effects was used to fit the model.ResultsIn terms of treatment, 58 trials with 119,417 patients proved eligible, while 125 trials with 225,414 patients were included in terms of prevention. All anticoagulants were found to reduce the recurrence or incidence of VTE compared with Placebo, of which high-level evidence indicated that direct thrombin inhibitors (TIs) and novel oral anticoagulants (NOACs) were the two most effective drugs. For treatment, low molecular weight heparin (LMWH), unfractionated heparin (UFH), and vitamin K antagonists (VKAs) significantly increased the risk of major bleeding in comparison to Placebo. For prevention, only UFH (OR 2.0, 95% CI 1.2–3.3) and NOACs (OR 1.8, 95% CI 1.2–2.6) showed significant increased risks in major bleeding. Additionally, after an exhaustive analysis of NOACs, analysis showed that apixaban (RR 0.5, 95%CI 0.17–1.46) had a superior performance in major bleeding compared to rivaroxaban (RR 3.87, 95%CI 1.48–10.09).ConclusionTIs and NOACs were superior in efficacy with minimal side effects, making them pivotal choices for both prevention and treatment of VTE. Clinical practitioners must carefully weigh drug characteristics, indications, and contraindications to optimize treatment outcomes.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=466775.

Background Resistance to existing therapies is a major cause of treatment failure in patients with refractory and relapsed B-cell non-Hodgkin’s lymphoma (r/r B-NHL). Therapy-induced senescence (TIS) is one of the most important mechanisms of drug resistance.Methods This study used single-cell RNA sequencing to analyze doxorubicin-induced senescent B-NHL cells. C-C chemokine receptor 7 (CCR7) expression in patients with aggressive B-NHL was assessed using immunohistochemistry and flow cytometry. Lentiviral transfection was used to target CCR7 expression in Raji and SU-DHL-2 cells. Protein localization was visualized through immunofluorescence, while western blotting and co-immunoprecipitation were used to analyze protein expression and interactions. Cell proliferation was measured with the Cell Counting Kit-8 assay, and senescent cells were detected using senescence-associated β-galactosidase staining. The stemness of cells was evaluated through colony and sphere formation assays. Transwell assays assessed cell migration and invasion. Finally, inhibitors GS143 and Y27632 were used to examine the effect of IKBα and ARHGAP/RhoA inhibition on B-NHL-TIS.Results Here we identified a distinct group of TIS, composed of memory B-cell population characterized by strong positive expression of CCR7, which was significantly elevated in TIS population compared with normal proliferating and autonomously senescent lymphoma cell populations. Additionally, CCR7 expression was significantly upregulated in patients with r/r B-NHL, and was an independent prognostic factor in B-NHL, with high CCR7 expression being strongly associated with poor prognosis. In vitro results indicated that CCL21 induced migration and invasion of B-NHL cells via CCR7, while blocking CCR7 reduced doxorubicin-induced migration and invasion of these cells. Furthermore, B-NHL-TIS regulated by CCR7 and exhibited enhanced phenotypic and functional stemness features, including the upregulation of stemness markers, increased colony-forming, invasive and migratory capabilities. Mechanistically, blocking CCR7 reversed the stemness characteristics of senescent B-NHL cells by inhibiting the activation of ARHGAP18/IKBα signaling.Conclusions Together, TIS promotes the stemness of B-NHL cells via CCR7/ARHGAP18/IKBα signaling activation and targeting CCR7/ARHGAP18 might overcome the chemoresistance of senescent B-NHL cells by inhibiting stemness acquisition and maintenance.

Background and hypothesis: Treatment-resistant schizophrenia (TR-SZ) and non-treatment-resistant schizophrenia (NTR-SZ) lack specific biomarkers to distinguish from each other. This investigation aims to identify consistent dysfunctional brain connections with different atlases, multiple feature selection strategies, and several classifiers in distinguishing TR-SZ and NTR-SZ. Study design: 55 TR-SZs, 239 NTR-SZs, and 87 healthy controls (HCs) were recruited from the Affiliated Brain Hospital of Nanjing Medical University. Resting-state functional connection (FC) matrices were constructed from automated anatomical labeling (AAL), Yeo-Networks (YEO) and Brainnetome (BNA) atlases. Two feature selection methods (Select From Model and Recursive Feature Elimination) and four classifiers (Adaptive Boost, Bernoulli Naïve Bayes, Gradient Boosting and Random Forest) were combined to identify the consistent FCs in distinguishing TR-SZ and HC, NTR-SZ and HC, TR-SZ and NTR-SZ. Study results: The whole brain FCs, except the temporal-occipital FC, were consistent in distinguishing SZ and HC. Abnormal frontal-limbic, frontal-parietal and occipital-temporal FCs were consistent in distinguishing TR-SZ and NTR-SZ, that were further correlated with disease progression, symptoms and medication dosage. Moreover, the frontal-limbic and frontal-parietal FCs were highly consistent for the diagnosis of SZ (TR-SZ vs. HC, NTR-SZ vs. HC and TR-SZ vs. NTR-SZ). The BNA atlas achieved the highest classification accuracy (>90 %) comparing with AAL and YEO in the most diagnostic tasks. Conclusions: These results indicate that the frontal-limbic and the frontal-parietal FCs are the robust neural pathways in the diagnosis of SZ, whereas the frontal-limbic, frontal-parietal and occipital-temporal FCs may be informative in recognizing those TR-SZ in the clinical practice.

This research is devoted to simulating the flight characteristics of real butterflies, and a small remote-controlled bionic butterfly flying machine is designed and manufactured. We analyze the principle of butterfly wing flight, which provides a theoretical basis for bionic design. Then, through 3D modeling and finite element analysis, an innovative design scheme of small bionic butterfly flight vehicle was proposed and verified, and its lift force was analyzed after assembly. This study not only demonstrates the feasibility of the design and implementation of small bionic butterfly aircraft, but also emphasizes its potential application value in the execution of small space missions, providing a new perspective for the design and optimization of bionic aircraft in the future.

BackgroundBronchopulmonary Dysplasia (BPD) is a chronic lung disease affecting preterm infants, with limited prevention and treatment options. Inhaled Nitric Oxide (iNO) is sometimes used to treat Persistent Pulmonary Hypertension of the Newborn (PPHN) and Hypoxemic Respiratory Failure (HRF), and its impact on BPD development remains debated.ObjectiveTo assess whether iNO-related factors are potential contributors to the development of BPD Grade Ⅱ-Ⅲ in very premature infants (VPI) diagnosed with PPHN or HRF at birth using Propensity Score Matching (PSM).MethodsWe conducted a retrospective cohort study of infants born at 22–32 weeks gestation with PPHN or HRF, treated with iNO for over 3 h. PSM matched groups by gestational age, birth weight, and gender, etc. Multivariate logistic regression evaluated the association between iNO treatment and BPD outcomes to identify influencing factors, while Restricted Cubic Spline (RCS) and mediation analysis examined iNO dose effects and potential mediators like mechanical ventilation time and oxygenation index (OI).ResultsA higher initial iNO dose was significantly associated with a reduced risk of BPD Grade Ⅱ-Ⅲ (adjusted OR = 0.68, 95% CI: 0.52–0.89, p < 0.01). Additionally, administration of iNO within the first 7 days of life was identified as an important influencing factor No significant mediation effects were observed for factors such as mechanical ventilation time and OI.ConclusionA higher initial iNO dose within the first 7 days was associated with a reduced risk of BPD Grade Ⅱ-Ⅲ in VPI with PPHN or HRF.

Aging, marked by a gradual decline in physiological functions, presents significant global health challenges. While royal jelly (RJ) is known for its biological activities, its anti-aging mechanisms require further investigation. Using a D-galactose (D-gal)-induced aging mouse model, this study applied untargeted serum metabolomics to explore RJ's effects. RJ administration significantly (P

Objectives Gentamicin is one of the most common ototoxic drugs that can lower patients' quality of life. Oxidative stress is a key factors inducing sensory hair cell death during gentamicin administration. So far, there are no effective drugs to prevent or treat gentamicin- induced hearing loss. A recent study found cystic fibrosis transmembrane conductance regulator (CFTR) as a new target to modulate cellular oxidative balance. The objective of this study was to estimate the effect of the CFTR activator ivacaftor on gentamicin-induced ototoxicity and determine its mechanism.Methods The hair cell count was analyzed by Myosin 7a staining. Apoptosis was analyzed by TUNEL Apoptosis Kit. Cellular reactive oxygen species (ROS) level was detected by DCFH-DA probes. The Nrf2 related proteins expression levels were analyzed by western blot.Results An in vitro cochlear explant model showed that gentamicin caused ROS accumulation in sensory hair cells and induced apoptosis, and this effect was alleviated by pretreatment with ivacaftor. Western blotting showed that ivacaftor administration markedly increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO1), and NAD(P)H:quinone oxidoreductase 1 (NQO1). The protective effect of ivacaftor was abolished by the Nrf2 inhibitor ML385.Discussion Our results indicate the protective role of the CFTR-Nrf2-HO1/NQO1 pathway in gentamicin-induced ototoxicity. Ivacaftor may be repositioned or repurposed towards aminoglycosides-induced hearing loss.

Cisplatin is widely employed in clinical oncology as an anticancer chemotherapy drug in clinical practice and is known for its severe ototoxic side effects. Prior research indicates that the accumulation of reactive oxygen species (ROS) plays a pivotal role in cisplatin's inner ear toxicity. Hesperidin is a flavanone glycoside extracted from citrus fruits that has anti-inflammatory and antioxidant effects. Nonetheless, the specific pharmacological actions of hesperidin in alleviating cisplatin-induced ototoxicity remain elusive. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical mediator of the cellular oxidative stress response, is influenced by hesperidin. Activation of Nrf2 was shown to have a protective effect against cisplatin-induced ototoxicity. The potential of hesperidin to stimulate Nrf2 in attenuating cisplatin's adverse effects on the inner ear warrants further investigation. This study employs both in vivo and in vitro models of cisplatin ototoxicity to explore this possibility. Our results reveal that hesperidin mitigates cisplatin-induced ototoxicity by activating the Nrf2/NQO1 pathway in sensory hair cells, thereby reducing ROS accumulation, preventing hair cell apoptosis, and alleviating hearing loss.

Fusion-based welding and additive manufacturing are two key pillars of manufacturing. Rapidly evolving melt pools are associated with both of these processing approaches. Understanding and controlling the evolution of the melt pools are critical for optimization of such processes. Flow and interface oscillation during those processes are closely linked to the final fusion zone and microstructure formation. Synchrotron X-ray radiography enables observation of transient melt pools in additive manufacturing and welding processes in real time. However, analysis of the large amount of data generated in such experiments are cumbersome. Thus, we have examined the potential to analyse fast time-resolved X-ray image sequences of melt pools with image-based convolutional neural networks. The results demonstrate successful recognition of changes in the fluctuations of melt-pool interfaces associated with rapid-flow evolution.

Favipiravir is a nucleobase analogue that exhibits antiviral activities against a variety of RNA viruses. Due to the lack of antivirals to combat SFTS, an emerging tickborne epidemic caused by a RNA virus belonging to the Phenuividae family within Bunyavirales, Favipiravir has been put brand new attention as optimal SFTS clinical candidate. We here disclose chemical synthesis of novel derivatives of Favipiravir. All derivatives showed favorable inhibitory effect on SFTSV replication in vitro. The 50 % effective concentration (EC50) of the most active compound H3 was 12.06 μM, better than that of Favipiravir (15.51 μM). Most importantly, compared with the clinical candidate Favipiravir, pharmacokinetic studies conducted on rats demonstrated enhanced pharmacokinetic properties for H2 and H3 including parameters of T1/2, Cmax and AUC. These combined attributes identified novel promising drug candidates for the treatment of SFTSV infection.

Accurate population mapping is crucial for disaster management, urban planning, etc. However, current methods using nighttime light (NTL) and gridded population datasets are limited by low spatial resolution and insufficient training data for complex models such as deep learning. These models do not adequately utilize spatial information in population mapping. To address these limitations, this study proposes a high-resolution population mapping method using the Sustainable Development Goals Science Satellite 1 (SDGSAT-1) glimmer imager data and deep learning. The method includes a sample generation strategy with multiple regression and multilevel screening to provide sufficient, high-quality samples for deep learning. A Fine Population mapping network (FinePop-net) is also developed to train regression models using image samples, capturing multi-scale features for model training. When applied to the Guangdong-Hong Kong-Macao Greater Bay Area with 40-meter resolution SDGSAT 1 glimmer imagery, the method significantly reduced the average absolute error and root-mean-square error by 9.35% and 11.44%, respectively, compared with those of the pixel-level learning methods. It also outperformed other population spatialization datasets and NTL data by over 30% and 10%, respectively, in terms of error reduction. The results highlight the method’s effectiveness and the value of SDGSAT-1 glimmer imagery for fine population spatialization.

Abstract The paper suggests a design and optimisation approach for a consequent‐pole line‐start permanent magnet motor (CPLSPM) with flexible pole arc coefficients and high utilisation of rare‐earth (RE) materials, without the need for a variable frequency drive. The presence of dual‐sided slots and adjustable pole arc coefficient sets CPLSPM apart from other types of motors, making the analysis of its cogging torque more complex. Taking into account the double‐sided slotted and flexible adjustable pole arc coefficient, a cogging torque and airgap flux density model was established, and the influence of the pole arc coefficient on the characteristics of the cogging torque and airgap flux density of CPLSPM was analysed. The authors conduct multidimensional optimisation considering the coupling of multiple parameters to obtain a CPLSPM with minimal RE material usage, low cogging torque and excellent start‐up and steady‐state performance. Finite element simulation data are presented to validate the factors affecting the cogging torque and the feasibility of the proposed less‐magnetic CPLSPM design. Finally, a prototype of a 750 rpm/2.2 kW CPLSPM is built, and performance testing is carried out for comparison, and applied to submersible mixers.

Abstract Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion. Furthermore, our investigations reveal that this compact antibody displays enhanced permeability across the blood-brain barrier (BBB) and demonstrates superior efficacy in eliminating pseudovirus within the brain in a murine model of Nipah virus infection, particularly compared to the well-characterized antibody m102.4 in an IgG1 format. Consequently, this single-domain antibody holds promise as a therapeutic candidate to prevent Nipah virus infections and has potential implications for vaccine development.

Abstract The development of drug resistance remains a major challenge in cancer treatment. Ferroptosis, a unique type of regulated cell death, plays a pivotal role in inhibiting tumour growth, presenting new opportunities in treating chemotherapeutic resistance. Accumulating studies indicate that epigenetic modifications by non-coding RNAs (ncRNA) can determine cancer cell vulnerability to ferroptosis. In this review, we first summarize the role of chemotherapeutic resistance in cancer growth/development. Then, we summarize the core molecular mechanisms of ferroptosis, its upstream epigenetic regulation, and its downstream effects on chemotherapeutic resistance. Finally, we review recent advances in understanding how ncRNAs regulate ferroptosis and from such modulate chemotherapeutic resistance. This review aims to enhance general understanding of the ncRNA-mediated epigenetic regulatory mechanisms which modulate ferroptosis, highlighting the ncRNA-ferroptosis axis as a key druggable target in overcoming chemotherapeutic resistance.

Highlights Polysaccharide-based microneedles are novel and emerging tools for ocular drug delivery and the research on the diagnosis and treatment of eye diseases is advancing at a fast pace. Microneedle devices constructed from polysaccharide molecules derived from ocular tissue have the potential to significantly enhance the efficiency of clinical treatments and improve patient compliance with therapeutic regimens. Guided by our vast clinical experience, this is the first review collates the cutting-edge scientific findings from the interdisciplinary field combining natural macromolecules and ophthalmology.

Abstract Friction as a fundamental physical phenomenon dominates nature and human civilization, among which the achievement of molecular rolling lubrication is desired to bring another breakthrough, like the macroscale design of wheel. Herein, an edge self-curling nanodeformation phenomenon of graphite nanosheets (GNSs) at cryogenic temperature is found, which is then used to promote the formation of graphite nanorollers in friction process towards molecular rolling lubrication. The observation of parallel nanorollers at the friction interface give the experimental evidence for the occurrence of molecular rolling lubrication, and the graphite exhibits abnormal lubrication performance in vacuum with ultra-low friction and wear at macroscale. The molecular rolling lubrication mechanism is elucidated from the electronic interaction perspective. Experiments and theoretical simulations indicate that the driving force of the self-curling is the uneven atomic shrinkage induced stress, and then the shear force promotes the intact nanoroller formation, while the constraint of atomic vibration decreases the dissipation of driving stress and favors the nanoroller formation therein. It will open up a new pathway for controlling friction at microscale and nanostructural manipulation.

The distribution of the deep geothermal field and the tectonic thermal control mode in the Yingshan area were not understood systematically, which would bring in constraints to the sustainable exploration of local geothermal resources. Based on the field survey on continuous temperature, fracture measurements in the outcrops of granite rock, slug-test, and pumping test in the boreholes, a three-dimensional model coupling fluid flow and heat transfer process in fractured rock reservoir was established. Then the distribution of fluid pressure temperature and the Darcy velocity in the whole geothermal reservoir were calculated considering different treatment combinations of main faults. The results show that the deep temperature field and fluid pressure distribution are greatly affected by the faults system. At the location of bedrock and impermeable fault, the fluid movement is very weak, and the heat transfer is mainly controlled by heat conduction, while in the high permeable fault, it is mainly controlled by heat convection. Low temperature and fluid pressure occurred in the deep, high-permeable fault zone whereas high fluid pressure occurred in the impermeable fault zone. At a depth larger than 2000 m, the zones with high temperatures and intense hydraulic exchange coincide with the conductive fault zones, which indicates that the high-permeable faults are the most important channel for seepage and heat transfer in the reservoir. Therefore, the northeast faults are the dominant channel for fluid migration and heat conduction in the Yinshan area. Hot water migrates upward along the northeast faults and is blocked by the north-south fault. The hot spring is formed at the intersecting position of two groups of faults. This study is helpful for scientific, sustainable exploration of geothermal resources in the Yingshan area.

Abstract The Tibetan Plateau (TP) is crucial for global climate change and China’s ecological security. Given recent drastic changes in vegetation from climate change and human activities, long-term vegetation monitoring is urgently required. This study produced the vegetation maps of the TP from 1990 to 2020 every ten years using random forest classifier and Landsat imagery. We selected the same stable samples and features for mapping to reduce errors between years and proposed spatial filtering to further improve the accuracy. The overall accuracy surpassed 95.00%, with all Kappa coefficients exceeding 0.95. A further assessment based on sampling sites from literature and field survey was higher than 80%. The importance ranking results indicated that in the TP, climate factors and terrain factors are the most important factors in the vegetation mapping. This study provides a method for mapping vegetation in alpine areas and data support for researching the dynamic change of vegetation on the TP and evaluating its response to climate change.

Abstract Background The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking. Results In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn’s disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models. Conclusions Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract