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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 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.

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 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 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

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 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 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

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.

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.

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.

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.

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.

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 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.

In this paper, we study a hydrodynamic system modeling the evolution of a plasma subject to a self-induced electromagnetic Lorentz force in incompressible viscous fluids. The system consists of the Navier–Stokes equations coupled with a Maxwell equation. In the three dimensional case, we show that every weak solution verifies the energy equality for the incompressible Navier–Stokes–Maxwell equations with damping. We also establish some non-explosion criteria in terms of the velocity and magnetic of local strong solution for standard Navier–Stokes–Maxwell system.

The shear mechanical parameters of coal are important parameters for analyzing the deformation and stability of coal. In order to study the shear characteristics of straight joints of coal under different normal stress and shear rate conditions, the shear numerical simulation and laboratory test were carried out to study the influence of normal stress and shear rate on the shear characteristics of straight joints of coal. The results show that the shear strength of joints decreases with the increase of shear rate, and increases with the increase of normal stress. The higher the normal stress, the greater the influence of shear rate on the shear strength of joints. Shear stiffness is positively correlated with normal stress and negatively correlated with shear rate. When the shear rate reaches a certain value, the influence of shear stiffness is not obvious. The increase of shear rate makes the simulated joints more prone to shear slip, which is easy to cause coal and rock dynamic disasters. This phenomenon is more serious in high normal stress.

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

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 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.

Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity.

In this short note, we provide a self-contained proof for the criterion $\nabla u\in L^\frac{5}{2}(0, T; L^2(\mathbb{R}^3))$ to Navier–Stokes equations energy balance, which improves some recent results on this problem.

Abstract Aims Surveys and research on the applications of the hepatic venous pressure gradient (HVPG) are important for understanding the current status and future development of this technology in China. This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. Methods We investigated the overall status of HVPG technology in China—including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications, and current challenges by using online questionnaire. By counting the number and percentages of cases of these results, we hope to clarify the current status of HVPG measurements in China. Results According to the survey, 85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces. A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022, of which 2813 cases (56.4%) were measured alone. The average cost of HVPG measurement was 5646.8 ± 2327.9 CNY. Of the clinical teams who performed the measurements (sometimes multiple per hospital), 94.3% (82/87) used the balloon method, and the majority of the teams (72.4%, 63/87) used embolectomy catheters. Conclusions This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology. It is still necessary to continue promoting and popularizing this technology in the future.

Abstract Background The risk of asthma in patients with psoriasis has been identified in previous studies, but the bidirectional association between the two has not been fully explored. Methods We thoroughly searched PubMed, Embase, and the Cochrane Library to find relevant observational studies published from the inception of these databases to October 2023. All the risk and bias assessments were analyzed by STATA 16.0. Where the heterogeneity was less than 50%, the fixed effect model was utilized. While where the level of heterogeneity was more than 50%, the random effect model was applied. Moreover, to identify publication bias, a visual funnel chart, and Egger’s test were applied. Results A total of 12,396,911 participants from 16 studies, published between 2011 and 2023 were included in this meta-analysis. We found that psoriasis patients had a higher risk of developing asthma (OR = 1.48, 95%CI 1.28–1.68). Meanwhile, asthma patients also had a higher overall risk of developing psoriasis (OR = 1.33, 95%CI 1.23–1.44). In the subgroup analysis, we found that the type of study, age, and severity of the psoriasis were significant factors in the survey of asthma risk in psoriasis patients. Conclusions In the present systematic review and meta-analysis, we found a bidirectional association between psoriasis and asthma with significantly increased risk. As a result, clinicians should make patients aware of the connection between the two, particularly adolescents or patients with moderate to severe psoriasis who need to be informed about the rising likelihood of developing asthma. Trial registration Registration number CRD42023390111 .

Abstract Tafamidis is the world's first and only oral drug approved to treat the rare disease transthyretin amyloid cardiomyopathy (ATTR-CM). Medicines are known to have different adverse reactions during the course of treatment. However, the current limited clinical studies did not identify significant adverse drug reactions to tafamidis. Tafamidis has been on the market for 5 years now, a large number of adverse drug event (ADE) reports with tafamidis as the primary suspected drug have been reported in the United Food and Drug Administration's adverse event reporting system (FAERS). We retrieved 8170 adverse event reports in FAERS with tafamidis as the first suspected drug, and mined these reports for positive signals to perform risk warnings for potentially possible adverse events with tafamidis. We found that a large number of adverse events associated with the primary disease were reported due to insufficient awareness of ATTR among the reporters, leading to a large number of positive signals reported in the cardiac disorders system. We also found that tafamidis has the potential to cause an adverse event risks of ear and labyrinth disorders system and urinary tract infection bacterial, which deserve continued clinical attention.

Abstract The Omicron subvariants BQ.1.1, XBB.1.5, and XBB.1.16 of SARS-CoV-2 are known for their adeptness at evading immune responses. Here, we isolate a neutralizing antibody, 7F3, with the capacity to neutralize all tested SARS-CoV-2 variants, including BQ.1.1, XBB.1.5, and XBB.1.16. 7F3 targets the receptor-binding motif (RBM) region and exhibits broad binding to a panel of 37 RBD mutant proteins. We develop the IgG-like bispecific antibody G7-Fc using 7F3 and the cross-neutralizing antibody GW01. G7-Fc demonstrates robust neutralizing activity against all 28 tested SARS-CoV-2 variants and sarbecoviruses, providing potent prophylaxis and therapeutic efficacy against XBB.1 infection in both K18-ACE and BALB/c female mice. Cryo-EM structure analysis of the G7-Fc in complex with the Omicron XBB spike (S) trimer reveals a trimer-dimer conformation, with G7-Fc synergistically targeting two distinct RBD epitopes and blocking ACE2 binding. Comparative analysis of 7F3 and LY-CoV1404 epitopes highlights a distinct and highly conserved epitope in the RBM region bound by 7F3, facilitating neutralization of the immune-evasive Omicron variant XBB.1.16. G7-Fc holds promise as a potential prophylactic countermeasure against SARS-CoV-2, particularly against circulating and emerging variants.

Abstract Background Melilotus, a member of the Fabaceae family, is a pivotal forage crop that is extensively cultivated in livestock regions globally due to its notable productivity and ability to withstand abiotic stress. However, the genetic attributes of the chloroplast genome and the evolutionary connections among different Melilotus species remain unresolved. Results In this study, we compiled the chloroplast genomes of 18 Melilotus species and performed a comprehensive comparative analysis. Through the examination of protein-coding genes, we successfully established a robust phylogenetic tree for these species. This conclusion is further supported by the phylogeny derived from single-nucleotide polymorphisms (SNPs) across the entire chloroplast genome. Notably, our findings revealed that M. infestus, M. siculus, M. sulcatus, and M. speciosus formed a distinct subgroup within the phylogenetic tree. Additionally, the chloroplast genomes of these four species exhibit two shared inversions. Moreover, inverted repeats were observed to have reemerged in six species within the IRLC. The distribution patterns of single-nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) within protein-coding genes indicated that ycf1 and ycf2 accumulated nonconservative alterations during evolutionary development. Furthermore, an examination of the evolutionary rate of protein-coding genes revealed that rps18, rps7, and rpl16 underwent positive selection specifically in Melilotus. Conclusions We present a comparative analysis of the complete chloroplast genomes of Melilotus species. This study represents the most thorough and detailed exploration of the evolution and variability within the genus Melilotus to date. Our study provides valuable chloroplast genomic information for improving phylogenetic reconstructions and making biogeographic inferences about Melilotus and other Papilionoideae species.

Abstract The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0–95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Abstract In 2008, sorafenib became the first approved systemic therapeutic agent for advanced HCC. Although its pharmacological efficacy has been established, reimbursement for such a new, high‐cost drug, as well as physicians' awareness and prescription practice, likewise contribute to its clinical effectiveness. We therefore conducted a retrospective study using 38 sorafenib‐eligible, advanced HCC patients when sorafenib was approved but not yet reimbursed as a control and 216 patients during the reimbursed era. Study group showed longer survival at 8.2 months versus the control's 4.9 months (p = 0.0063 hazard ratio: 0.612 [0.431 ~ 0.868], p = 0.0059). Among the 42 (19.4%) patients who survived more than 2 years, 50% had tumor rupture, and all 32 patients with portal vein tumor thrombus and/or extrahepatic metastasis received sorafenib (p = 0.003). Furthermore, during their first 2 years of HCC management, sorafenib had been given in 29.1% of the treatment courses among survivors between 2 and 5 years while it was prescribed in 55.8% among the more than 5 years survivor group (p

Extraction of built-up areas from polarimetric synthetic aperture radar (PolSAR) images plays a crucial role in disaster management. The polarimetric orientation angles (POAs) of built-up areas exhibit diversity, and built-up areas with POA close to 45° are often misclassified as vegetation. To address this problem, a polarimetric feature suitable for the extraction of built-up areas with large POAs is first designed, and a mixed real-complex-valued polarimetric feature combination is constructed. Then, a real-complex and spatial feature fusion classification network (RCSFFCNet) is designed. In which the proposed mixed real-complex-valued residual structure can efficiently extract mixed numerical features. Additionally, a multi-local spatial convolutional attention module is designed and embedded to efficiently fuse mixed numerical features, as well as superpixel multi-local spatial features. Experiments were conducted using PolSAR images from Gaofen-3, Radarsat-2, and ALOS-2/PALSAR-2. The experimental results show that the feature combination proposed in this paper increases the F1 score of built-up areas by approximately 2%-3%, and the F1 score of built-up areas extracted using the RCSFFCNet also improves by about 2%-3%, with F1 scores exceeding 95%. On all three datasets, the proposed method achieves the best performance in extracting built-up areas with various POAs, indicating overall superiority from feature selection to model implementation.

The term “NEET” refers to individuals aged 15 to 34 years who are not involved in education, employment, or training programs. Recent studies have shown that NEET individuals are at a high risk of experiencing lower well-being and mental health issues. This study aimed to examine the relationship between intolerance of uncertainty (IU), meme use (MU), depression emoticon empathy (DEE), and career indecisiveness and anxiety (CIA) in NEETs who were locked down during the COVID-19 pandemic in China. We hypothesize positive interrelations among study variables. Then, mediation path models were carried out to study the relationship between IU and CIA through MU and DEE. We collected data through an online survey from NEETs (N = 1,404) in China, using questionnaires assessing IU, MU, DEE, and CIA, and Structural Equation Modeling analyses were performed to explore the interrelations among them. We found that IU influenced NEET’s CIA primarily through the independent intermediaries of MU and DEE. Additionally, the chain intermediary of MU → DEE was significant. Our study indicated that MU and DEE partially mediated the relationship between IU and CIA, respectively. Digital communications through MU and DEE are playing an important role in the relationship between IU and CIA, respectively. Therefore, MU and DEE as studied in this research may work as alarm to foretell early of the CIA among NEET. Moreover, our findings could be used as a reference for promoting employment and increasing the employment rate among NEET population and might be a potential target for intervention or service delivery.

BackgroundWith the penetration of the “Internet+” into social life, the digitization of education has become a trend and national demand. Alongside the rise of the “Everyone Live Streaming” era, online live streaming class platforms have rapidly grown due to favorable user experiences.MethodsGrounded in the Expectation Confirmation Theory, this study employed questionnaire surveys to investigate the influence mechanism of perceived quality, flow experience, and perceived usefulness on individuals’ continuance usage intention of online live streaming class platforms.ResultsThrough the analysis of 773 survey responses, this study reveals several key findings. Firstly, perceived quality significantly and positively affects users’ intention to continue using the online live streaming class platforms. Secondly, flow experience partially mediates the relationship between perceived quality and continuance usage intention, underscoring its significance in user decision-making. Additionally, Perceived usefulness negatively moderates the relationship between perceived quality and flow experience, demonstrating varied effects.ConclusionOn the one hand, online live streaming platforms should actively invest in improving the quality of user perception, as this can lead to a better user flow experience and continued willingness to use. On the other hand, they should also pay more attention to the user’s flow experience, which has a direct impact on the user’s propensity to continue to use. Besides, the perceived usefulness of the online live class by the user should also be taken seriously.

BackgroundPreeclampsia (PE) poses significant diagnostic and therapeutic challenges. This study aims to identify novel genes for potential diagnostic and therapeutic targets, illuminating the immune mechanisms involved.MethodsThree GEO datasets were analyzed, merging two for training set, and using the third for external validation. Intersection analysis of differentially expressed genes (DEGs) and WGCNA highlighted candidate genes. These were further refined through LASSO, SVM-RFE, and RF algorithms to identify diagnostic hub genes. Diagnostic efficacy was assessed using ROC curves. A predictive nomogram and fully Connected Neural Network (FCNN) were developed for PE prediction. ssGSEA and correlation analysis were employed to investigate the immune landscape. Further validation was provided by qRT-PCR on human placental samples.ResultFive biomarkers were identified with validation AUCs: CGB5 (0.663, 95% CI: 0.577-0.750), LEP (0.850, 95% CI: 0.792-0.908), LRRC1 (0.797, 95% CI: 0.728-0.867), PAPPA2 (0.839, 95% CI: 0.775-0.902), and SLC20A1 (0.811, 95% CI: 0.742-0.880), all of which are involved in key biological processes. The nomogram showed strong predictive power (C-index 0.873), while FCNN achieved an optimal AUC of 0.911 (95% CI: 0.732-1.000) in five-fold cross-validation. Immune infiltration analysis revealed the importance of T cell subsets, neutrophils, and NK cells in PE, linking these genes to immune mechanisms underlying PE pathogenesis.ConclusionCGB5, LEP, LRRC1, PAPPA2, and SLC20A1 are validated as key diagnostic biomarkers for PE. Nomogram and FCNN could credibly predict PE. Their association with immune infiltration underscores the crucial role of immune responses in PE pathogenesis.

BackgroundSubstantial studies reveal that tertiary lymphoid structure (TLS) correlate with prognosis and immunotherapy response in various types of cancers. However, the predictive value of TLS, the specific immune cell subtype within TLS and their anti-tumor mechanisms remain unclear.MethodsBased on 23 TLS-related genes (TLSRGs), we utilized bioinformatics methods to construct a scoring system, named TLSscore. By integrating RNA and single-cell sequencing data, we assessed the utility of TLSscore in head and neck squamous cell carcinoma (HNSCC). Flow cytometric sorting was used to isolate specific T cells subtypes, in vivo and in vitro experiments were conducted to demonstrate its anti-tumor effects.ResultsThe TLSscore model was constructed and specific TLSscore-genes were found to consistently align with the spatial location of TLS. TLSscore has proven to be a robust predictive model for predicting survival prognosis, immune cell infiltration, somatic mutation and immunotherapy response. Notably, a specific PD1+CXCL13+CD8+T cell subtype was identified within TLS. Both in vivo and in vitro experiments demonstrated that PD1+CXCL13+CD8+T cell might represent a functional cell subtype exerting anti-tumor effects during the process of immune surveillance.ConclusionsOur study presents a predictive model for TLS, which can evaluate its presence and predicts survival prognosis and immunotherapy response in HNSSC patients. Additionally, we identify a specific subtype of T cells that might elucidate the mechanism of TLS function in anti-tumor activities. This T cell subtype holds the potential to be a prognostic marker and a target for adoptive cell therapy (ACT) in the future.

In this paper, we investigate the BKM type blowup criterion applied to 3D double-diffusive magneto convection systems. Specifically, we demonstrate that a unique local strong solution does not experience blow-up at time T, given that ). To prove this, we employ the logarithmic Sobolev inequality in the Besov spaces with negative indices and a well-known commutator estimate established by Kato and Ponce. This result is the further improvement and extension of the previous works by O (2021) and Wu (2023).

Abstract This research delves into the effects of 2D layers on the functionality of 3D perovskite using lock‐in amplifier‐based in situ surface photovoltage (SPV) and its phase spectroscopy, with an emphasis on elucidating the connection between the tuning of dipole moments and the photocurrent hysteresis. Conventionally, the SPV of a perovskite/hole transport layer is observed to diminish as positive bias escalates. However, this trend is reversed in the case of 3D perovskite samples, where an augmentation in SPV is noted under positive bias. Notably, 3D/2D perovskite structures initially show a decrease, then an increase in SPV as bias intensifies, a phenomenon more pronounced with larger dipole moments in 2D. However, there is no linear relationship between the dipole moment and the hysteresis factor. Furthermore, using in situ light‐chopping‐frequency‐modulated SPV and Kelvin Probe Force Microscopy, it is revealed that the dipole fields of 2D layers can hinder ion migration. This leads to efficient hole transfer and minimal photocurrent hysteresis in 3D/2D perovskites, providing strong evidence for the underlying cause of hysteresis. Additionally, these findings suggest intricate interplays among the external electric field, interface dipole moments, and surface photovoltaics, offering significant insights into perovskite optoelectronics.

Background We aimed to investigate the associations of long‐term exposure to ambient formaldehyde with hypertension and angina pectoris symptoms in Chinese adults. Methods and Results Participants' information was obtained from the WHO SAGE (World Health Organization Study on Global Aging and Adult Health) study. The Cox proportional hazards regression model was applied to estimate the associations of formaldehyde with hypertension and angina pectoris symptoms. Mediating effect analysis was used to investigate the mediating effect of hypertension between formaldehyde exposure and angina pectoris symptoms. Long‐term exposure to formaldehyde was positively associated with the risk of angina pectoris symptoms (hazard ratio [HR], 1.66 [95% CI, 1.29–2.13], per interquartile range [IQR], 3.33, 1015 molecules/cm2) and hypertension (HR, 1.17 [95% CI, 1.02–1.34], per IQR, 3.34, 1015 molecules/cm2). The associations between formaldehyde and angina pectoris symptoms were greater in participants aged ≥65 years (HR, 1.90 [95% CI, 1.29–2.80]) and in rural areas (HR, 2.71 [95% CI, 1.54–4.77]), whereas the associations of formaldehyde with hypertension were stronger in men (HR, 1.27 [95% CI, 1.02–1.58]), rural areas (HR, 1.22 [95% CI, 0.94–1.59]), and in ever smokers (HR, 1.33 [95% CI, 1.02–1.72]). The mediation effect analysis indicated that 18.44% (95% CI, 2.17–37.65) of the association between formaldehyde exposure and angina pectoris symptoms was mediated by hypertension. Conclusions Long‐term exposure to ambient formaldehyde was positively associated with hypertension and angina pectoris symptoms. The effects of formaldehyde may be modified by age, sex, urbanicity, and smoking status. Hypertension might play a mediating effect in formaldehyde‐induced angina pectoris symptoms.

Hexavalent chromium [Cr(VI)] is a widely distributed carcinogen in industrial contexts and general environmental contexts. Emerging research highlights the central role of ribosomal DNA (rDNA) in DNA Damage Responses (DDRs). However, there remains a lack of investigation into the potential dose-dependent relationship between exposure to Cr(VI) and alterations in rDNA copy number (CN), as well as the related mechanisms underlying these effects. A molecular epidemiological investigation involving 67 workers exposed to Cr(VI) and 75 unexposed controls was conducted. There was a notable increase in ZNF385A expression, variations in rDNA CN, and elevated γH2AX levels in the peripheral blood of Cr(VI)-exposed workers. Restricted cubic spline (RCS) models showed that blood Cr levels in the exposed population exhibited non-linear dose-dependent relationships with γH2AX, rDNA CN, and ZNF385A. Of considerable interest, there were robust and positive associations between ZNF385A and both γH2AX and rDNA CN. Further in vitro experiments provided concrete evidence that Cr(VI) simultaneously caused an increase in ZNF385A expression and variations in rDNA CN. ZNF385A-depleted cells showed increased sensitivity to Cr(VI)-mediated DDRs and alterations in rDNA CN. This study indicated that ZNF385A played a highly significant role in the rDNA CN variation in response to Cr(VI)-induced DNA damage.

Purpose To investigate the association between the Dietary Inflammatory Index (DII) and disease severity as well as complications in children diagnosed with Henöch-Schönlein purpura (HSP), shedding light on the potential influence of dietary factors on HSP. Methods A retrospective cohort study was conducted, enrolling children aged 2–14 years diagnosed with HSP. Participants were divided into low and Pro-inflammatory dietary groups based on their DII scores. Biomarkers, nutrient intake, blood lipid profiles and disease complications were compared between the two groups. Spearman correlation analysis was performed to assess the relationship between DII and complications. Results A total of 115 patients, including 56 patients with anti-inflammatory dietary and 59 with pro-inflammatory dietary, were included. The pro-inflammatory dietary group demonstrated significantly elevated of C-reactive protein, tumor necrosis factor-α, interleukin-6, erythrocyte sedimentation rate, white blood cell count, eosinophils, IgE, consumption of total calories, protein, carbohydrates, fiber, fat intake, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, VLDL cholesterol, complications of renal, skin, gastrointestinal, coagulation and respiratory in comparison to the anti-inflammatory dietary group. DII was positively correlated with renal, skin, gastrointestinal, coagulation and respiratory complications. Conclusion The study highlights the potential influence of dietary inflammatory potential, as quantified by the DII, on disease severity and complications in children with HSP. Understanding the interplay between dietary patterns and inflammatory responses in pediatric vasculitis has implications for the management of HSP, emphasizing the relevance of considering dietary interventions to optimize clinical outcomes and improve the overall well-being of affected children.

High agility, maneuverability, and payload capacity, combined with small footprints, make legged robots well-suited for precision agriculture applications. In this study, we introduce a novel bionic hexapod robot designed for agricultural applications to address the limitations of traditional wheeled and aerial robots. The robot features a terrain-adaptive gait and adjustable clearance to ensure stability and robustness over various terrains and obstacles. Equipped with a high-precision Inertial Measurement Unit (IMU), the robot is able to monitor its attitude in real time to maintain balance. To enhance obstacle detection and self-navigation capabilities, we have designed an advanced version of the robot equipped with an optional advanced sensing system. This advanced version includes LiDAR, stereo cameras, and distance sensors to enable obstacle detection and self-navigation capabilities. We have tested the standard version of the robot under different ground conditions, including hard concrete floors, rugged grass, slopes, and uneven field with obstacles. The robot maintains good stability with pitch angle fluctuations ranging from −11.5° to 8.6° in all conditions and can walk on slopes with gradients up to 17°. These trials demonstrated the robot’s adaptability to complex field environments and validated its ability to maintain stability and efficiency. In addition, the terrain-adaptive algorithm is more energy efficient than traditional obstacle avoidance algorithms, reducing energy consumption by 14.4% for each obstacle crossed. Combined with its flexible and lightweight design, our robot shows significant potential in improving agricultural practices by increasing efficiency, lowering labor costs, and enhancing sustainability. In our future work, we will further develop the robot’s energy efficiency, durability in various environmental conditions, and compatibility with different crops and farming methods.

Abstract Exosomes are small membrane vesicles that are released by cells into the extracellular environment. Tumor‐associated exosomes (TAEs) are extracellular vesicles that play a significant role in cancer progression by mediating intercellular communication and contributing to various hallmarks of cancer. These vesicles carry a cargo of proteins, lipids, nucleic acids, and other biomolecules that can be transferred to recipient cells, modifying their behavior and promoting tumor growth, angiogenesis, immune modulation, and drug resistance. Several potential therapeutic targets within the TAEs cargo have been identified, including oncogenic proteins, miRNAs, tumor‐associated antigens, immune checkpoint proteins, drug resistance proteins, and tissue factor. In this review, we will systematically summarize the biogenesis, composition, and function of TAEs in cancer progression and highlight potential therapeutic targets. Considering the complexity of exosome‐mediated signaling and the pleiotropic effects of exosome cargoes has challenge in developing effective therapeutic strategies. Further research is needed to fully understand the role of TAEs in cancer and to develop effective therapies that target them. In particular, the development of strategies to block TAEs release, target TAEs cargo, inhibit TAEs uptake, and modulate TAEs content could provide novel approaches to cancer treatment.

Environmental heavy metals pollution have seriously threatened the health of human beings. An increasing number of researches have demonstrated that environmental heavy metals can influence the telomere length of Peripheral Blood Mononuclear Cells (PBMCs), which implicate biological aging as well as predicts diseases. Our previous study has shown that methylmercury (MeHg)-induced telomere shortening in rat brain tissue was associated with urinary melatonin metabolite 6-sulfatoxymelatonin (aMT6s) levels. Here, we aimed to further elucidate the impact of 4 typical heavy metals (As, Hg, Cd and Pb) on telomere length of PBMCs and their association with urinary aMT6s in rats. In this study, eighty-eight male Sprague-Dawley rats were randomized grouped into eleven groups. Among them, forty 3-month-old (young) and forty 12-month-old (middle-aged) rats were divided into young or middle-aged control groups as well as typical heavy metals exposed groups, respectively. Eight 24-month-old rats (old) was divided into aging control group. The results showed that MeHg exposure in young rats while sodium arsenite (iAs), MeHg, cadmium chloride (CdCl2), lead acetate (PbAc) exposure in middle-aged rats for 3 months significantly reduced the levels of and urinary aMT6s, as well as telomere length of PBMCs. In addition, they also induced abnormalities in serum oxidative stress (SOD, MDA and GPx) and inflammatory (IL-1β, IL-6 and TNF-α) indicators. Notably, there was a significant positive correlation between declined level of urinary aMT6s and the shortening of telomere length in PBMCs in rats exposed to 4 typical heavy metals. These results suggested that 4 typical heavy metals exposure could accelerate the reduction of telomere length of PBMCs partially by inducing oxidative stress and inflammatory in rats, while ageing may be an important synergistic factor. Urinary aMT6s detection may be a alternative method to reflect telomere toxic effects induced by heavy metal exposure.

Large amounts of CO2 were discharged into the atmosphere, resulting in a severe greenhouse effect and inducing ecological environmental problems that threaten human survival. Integrated carbon dioxide capture and conversion (ICCC) with Dual Functional Materials (DFMs) was a promising process to capture CO2 emission in flue gas and convert it into value-added chemicals, reducing energy consumption and economic cost. The catalytic component of DFMs enhances hydrogen source activation and promotes carbonate hydrogenation to produce high value-added chemicals. The hydrogenation process achieved the regeneration of bifunctional materials, which is the key to realizing the ICCC process. This research focuses on DFMs development with different hydrogen sources (hydrogen or light alkanes) for the ICCC process in recent years. In addition, the reaction mechanism and catalytic components modification were discussed to improve the in-situ conversion activity of the ICCC process. Finally, future prospects were anticipated to guide the development and application scenarios of DFMs in the ICCC process.