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Low socioeconomic status (SES) is a well-recognized risk factor for depression. However, the relationship between the timing of exposure to disadvantaged SES in childhood and depression in adolescence remains to be explored. We examined the differential influence of SES in early childhood, late childhood and adolescence on adolescent depression by modeling life course models. We used longitudinal data from the China Family Panel Studies (N = 2245). SES was measured using average household income (objective SES) and maternal subjective SES and grouped into three time points: 5–8 years, 9–12 years, and 13–16 years of age. The main outcome was depression at 13–16 years of age. Structured linear regression analysis was used to predict depression by low SES over the three time periods. A partial F test was used to compare the nested life course models to the saturated model. Among objective SES permutations, approximately 24.63 % of the adolescents had low SES in all periods, and 73.63 % had low SES in at least one period. Among subjective SES permutations, approximately 5.48 % of the adolescents had low SES in all periods, and 54.65 % had low SES in at least one period. Regardless of objective SES or subjective SES, the accumulation of risk (relaxed) model was the best-fit model. In this model, chronic low SES exposure in late childhood was the best predictor. We suggest that interventions targeting the late childhood period may have a practical effect on reducing depression in adolescents. • The accumulation of risk (relaxed) model best explains how socioeconomic status relates to depression. • The duration of low socioeconomic status during childhood increased the risk of depression in adolescence. • Persistent low socioeconomic status in late childhood best predicts adolescent depression. [ABSTRACT FROM AUTHOR]

Background: Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. Methods: In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. Results: The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. Conclusions: Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population. [ABSTRACT FROM AUTHOR]

Quantifying the activity and seismic recurrence behavior of active faults is essential for assessing seismic risk. A reliable chronology of faulting events is necessary, and optically stimulated luminescence (OSL) dating is a robust technique that offers advantages for situations where materials for radiocarbon dating are unavailable. However, OSL dating of young events (<5 kyr) can be challenging due to a variety of reasons, incomplete signal resetting, low OSL grain sensitivity, and signal instability, particularly in fluvial, colluvial, and alluvial settings. These factors also limit broader applications of OSL technique in Late Quaternary geology studies. Recent efforts to overcome these limitations have included modified protocols and statistical approaches, such as pulsed infrared stimulated luminescence (IRSL) signal method and the modified unlogged three- and four-parameter minimum age (MAM) models. The agreement of OSL dating results with independent age control, such as 14C dating, verifies its effectiveness and reliability in providing timing constraints of faulting events. New techniques and methods, such as pulsed photon-stimulated luminescence (PPSL) and rock surface luminescence dating (RSLD), are gaining momentum, expanding the horizon of conventional OSL dating as a significant tool for the Late Quaternary timescale. Future development of OSL techniques for dating active faults and paleo-earthquakes will prioritize the accuracy and precision of OSL results for short time scales and the development of new softwares for analyzing OSL datasets in complex settings. [ABSTRACT FROM AUTHOR]

Geometric complexities play an important role in the nucleation, propagation, and termination of strike-slip earthquake ruptures. The 2021 Mw7.4 Maduo earthquake rupture initiated at a large releasing stepover with a complex fault intersection. In the epicentral region, we conducted detailed mapping and classification of the surface ruptures and slip measurements associated with the earthquake, combining high-resolution uncrewed aerial vehicle (UAV) images and optical image correlation with field investigations. Our findings indicate that the coseismic ruptures present discontinuous patterns mixed with numerous lateral spreadings due to strong ground shaking. The discontinuous surface ruptures are uncharacteristic in slip to account for the large and clear displacements of offset landforms in the epicentral region. Within the releasing stepovers, the deformation zone revealed from the optical image correlation map indicates that a fault may cut diagonally across the pull-apart basin at depth. The left-lateral horizontal coseismic displacements from field measurements are typically ≤0.6 m, significantly lower than the 1–2.7 m measured from the optical image correlation map. Such a discrepancy indicates a significant proportion of off-fault deformation or the possibility that the rupture stopped at a shallow depth during its initiation phase instead of extending to the surface. The fault network and multi-fault junctions west and south of the epicenter suggest a possible complex path, which retarded the westward propagation at the initial phase of rupture growth. A hampered initiation might enhance the seismic ground motion and the complex ground deformation features at the surface, including widespread shaking-related fissures. [ABSTRACT FROM AUTHOR]

Incorporating heteroatoms can effectively modulate the molecular optoelectronic properties. However, the fundamental understanding of BN doping effects in BN‐embedded polycyclic aromatic hydrocarbons (PAHs) is underexplored, lacking rational guidelines to modulate the electronic structures through BN units for advanced materials. Herein, a concise synthesis of novel B2N2‐perylenes with BN doped at the bay area is achieved to systematically explore the doping effect of BN position on the photophysical properties of PAHs. The shift of BN position in B2N2‐perylenes alters the π electron conjugation, aromaticity and molecular rigidness significantly, achieving substantially higher electron transition abilities than those with BN doped in the nodal plane. It is further clarified that BN position dominates the photophysical properties over BN orientation. The revealed guideline here may apply generally to novel BN‐PAHs, and aid the advancement of BN‐PAHs with highly‐emissive performance. [ABSTRACT FROM AUTHOR]

Sarcoma is a malignant tumor that originates from mesenchymal tissue. The common treatment for sarcoma is surgery supplemented with radiotherapy and chemotherapy. However, patients have a 5-year survival rate of only approximately 60%, and sarcoma cells are highly resistant to chemotherapy. Ferroptosis is an iron-dependent nonapoptotic type of regulated programmed cell death that is closely related to the pathophysiological processes underlying tumorigenesis, neurological diseases and other conditions. Moreover, ferroptosis is mediated via multiple regulatory pathways that may be targets for disease therapy. Recent studies have shown that the induction of ferroptosis is an effective way to kill sarcoma cells and reduce their resistance to chemotherapeutic drugs. Moreover, ferroptosis-related genes are related to the immune system, and their expression can be used to predict sarcoma prognosis. In this review, we describe the molecular mechanism underlying ferroptosis in detail, systematically summarize recent research progress with respect to ferroptosis application as a sarcoma treatment in various contexts, and point out gaps in the theoretical research on ferroptosis, challenges to its clinical application, potential resolutions of these challenges to promote ferroptosis as an efficient, reliable and novel method of clinical sarcoma treatment. [ABSTRACT FROM AUTHOR]

There is an urgent need for new CO2 adsorbents to overcome the rapidly increasing CO2 pollution. New CuO@UiO-67 composites were prepared by encapsulating CuO nanoparticles (NPs) in the shallow pore channels of UiO-67 through postsynthetic exchange (PSE) to form a core–shell structure. The composites were characterized via TEM, XRD, and BET analyses, and single component adsorption isotherm measurements of CO2, CH4 and N2 were performed at different temperatures. The selectivities of CO2/CH4 and CO2/N2 and the isosteric heats of CO2 adsorption were estimated based on the ideal adsorption solution theory (IAST) and the Clausius–Clapeyron equation, respectively. The highest CO2 uptake of CuO@UiO-67 was achieved at 273 K and 100 kPa with 61.9 cc g−1, which was twice that of parent UiO-67. The significant increase in CO2 uptake was not only due to the introduction of CuO NPs in the pore channel of CuO@UiO-67, but also due to the new open nitrogen sites due to ligand substitution. The adsorption selectivities of CO2/CH4 and CO2/N2 at 298 K and 100 kPa were 9.2 and 54.3, respectively. Furthermore, CuO@UiO-67 could efficiently separate the CO2/N2 mixture under a dynamic flow condition. These excellent properties suggest that the CuO@UiO-67 composite is a promising and efficient CO2 adsorbent material. This study lays a solid foundation for metal oxide-modified MOFs and is a great contribution to the preparation of new adsorbents. [ABSTRACT FROM AUTHOR]

Sufficient dimension reduction (SDR) methods target finding lower-dimensional representations of a multivariate predictor to preserve all the information about the conditional distribution of the response given the predictor. The reduction is commonly achieved by projecting the predictor onto a low-dimensional subspace. The smallest such subspace is known as the Central Subspace (CS) and is the key parameter of interest for most SDR methods. In this article, we propose a unified and flexible framework for estimating the CS in high dimensions. Our approach generalizes a wide range of model-based and model-free SDR methods to high-dimensional settings, where the CS is assumed to involve only a subset of the predictors. We formulate the problem as a quadratic convex optimization so that the global solution is feasible. The proposed estimation procedure simultaneously achieves the structural dimension selection and coordinate-independent variable selection of the CS. Theoretically, our method achieves dimension selection, variable selection, and subspace estimation consistency at a high convergence rate under mild conditions. We demonstrate the effectiveness and efficiency of our method with extensive simulation studies and real data examples. for this article are available online. [ABSTRACT FROM AUTHOR]

Background: Graves' disease increases bone resorption in hyperthyroidism, leading to elevated serum calcium levels and a negative bone balance. Thymic hyperplasia is observed in some Graves' disease patients. What's more, there have been a few reports of increased serum calcium and severe osteoporosis induced by Graves' disease with thymic hyperplasia. It remains unclear whether Graves' disease with thymic hyperplasia is associated with higher serum calcium levels. Our study aimed to investigate the possibility of elevated serum calcium levels and aggravated bone mobilization in Graves' disease patients with thymic hyperplasia. Methods: Newly diagnosed and untreated patients with Graves' disease (n = 96) were enrolled. They were divided into two groups based on the incidental detection of thymic hyperplasia during imaging. Albumin, alkaline phosphatase, calcium, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, and thyrotrophin receptor antibody (TRAb) were measured, and a computerized tomography of the chest was obtained. Results: Patients with Graves' disease who had thymic hyperplasia were notably younger (P=0.018) and exhibited higher serum calcium levels (P=0.001) compared to those with Graves' disease without thymic hyperplasia. In the multiple regression analysis, thymic hyperplasia, TRAb, and female gender were significant variables associated with elevated serum calcium levels in patients with Graves' disease, collectively accounting for 31.7% of the variation in serum calcium. Conclusions: Graves' disease patients with thymic hyperplasia showed higher serum calcium levels. thymic hyperplasia, TRAb, and female gender were found to be correlated with increased serum calcium levels in Graves' disease, suggesting a potential association between thymic hyperplasia and bone mobilization in Graves' disease. [ABSTRACT FROM AUTHOR]

Introduction: Intimate partner violence (IPV) is associated with multiple adverse health consequences. Nurses (including midwives) are well positioned to identify patients subjected to IPV, and provide care, support, and referrals. However, studies about nursing response to IPV are limited especially in low‐ and middle‐income countries (LMICs). The study aimed to examine nurses' perceived preparedness and opinions toward IPV and to identify barriers and facilitators in responding to IPV. Design: An explanatory sequential mixed‐methods study was conducted by collecting quantitative data first and explaining the quantitative findings with qualitative data. Methods: The study was conducted in two tertiary general hospitals in northeastern (Shenyang city) and southwestern (Chengdu city) China with 1500 and 1800 beds, respectively. A total of 1071 survey respondents (1039 female [97.0%]) and 43 interview participants (34 female [79.1%]) were included in the study. An online survey was administered from September 3 to 23, 2020, using two validated scales from the Physician Readiness to Manage Intimate Partner Violence Survey. In‐depth, semistructured interviews were conducted from September 15 to December 23, 2020, guided by the Consolidated Framework for Implementation Research. Results: The survey respondents largely agreed with feeling prepared to manage IPV, e.g., respond to discourses (544 [50.8%] of 1071) and report to police (704 [65.7%] of 1071). The findings of surveyed opinions (i.e., Response competencies; Routine practice; Actual activities; Professionals; Victims; Alcohol/drugs) were mixed and intertwined with social desirability bias. The quantitative and qualitative data were consistent, contradicted, and supplemented. Key qualitative findings were revealed that may explain the quantitative results, including lack of actual preparedness, absence of IPV‐related education, training, or practice, and socially desirable responses (especially those pertaining to China's Anti‐domestic Violence Law). Commonly reported barriers (e.g., patients' reluctance to disclose; time constraints) and facilitators (e.g., patients' strong need for help; female nurses' gender advantage), as well as previously unreported barriers (e.g., IPV may become a workplace taboo if there are healthcare professionals known as victims/perpetrators of IPV) and facilitators (e.g., nurses' responses can largely meet the first‐line support requirements even without formal education or training on IPV) were identified. Conclusions: Nurses may play a unique and important role in responding to IPV in LMICs where recognition is limited, education and training are absent, policies are lacking, and resources are scarce. Our findings support World Health Organization recommendations for selective screening. Clinical Relevance: The study highlights the great potential of nurses for IPV prevention and intervention especially in LMICs. The identified barriers and facilitators are important evidence for developing multifaceted interventions to address IPV in the health sector. [ABSTRACT FROM AUTHOR]

A novel chamfered V-shaped microstrip meander line (MML) slow-wave structure (SWS) based on the V-shaped MML SWS for W-band traveling-wave tube (TWT) is proposed to decrease the transmission loss and thus to improve the output power and beam-wave interaction efficiency. The high-frequency characteristics, transmission characteristics, and the beam-wave interaction processes of the novel structure are investigated by simulations. The simulation results show that the S21 parameters of the chamfered V-shaped MML SWS are improved by 4.3 dB for 100 periods compared with that of the traditional V-shaped MML SWS at 95 GHz. Besides, the particle-in-cell simulations indicate that the output power of the TWT with the novel structure is 30% higher than the V-shaped MML SWS in W-band. Finally, two types of SWSs with 100 periods are fabricated, assembled, and experimentally tested. According to the experimental test results, while the S11 parameters are below − 20 dB, the “cold” S21 parameters are − 17.04 dB vs − 20.74 dB at 95 GHz, which shows potential advantages of the proposed novel SWS in millimeter wave and even terahertz spectrum. [ABSTRACT FROM AUTHOR]

We seek to investigate the multifaceted factors influencing secondary infections in patients with multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization or infection post-hospitalization. A total of 100 patients with MDR-GNB colonization or infection were retrospectively reviewed, encompassing those admitted to both the general ward and intensive care unit of our hospital from August 2021 to December 2022. Patients were categorized into the control group (non-nosocomial infection, n = 56) and the observation group (nosocomial infection, n = 44) based on the occurrence of nosocomial infection during hospitalization. Clinical data were compared between the two groups, including the distribution and antibiotic sensitivity of MDR-GNB before nosocomial infection. Significant differences were observed between the two groups in terms of age, underlying diseases, immune status, length of stay, and invasive medical procedures (P < 0.05). The observation group also had fewer patients practicing optimized hygiene, strict isolation, and antibiotic control than the control group (P < 0.05). Factors influencing the risk of secondary infection after hospitalization in patients colonized or infected with MDR-GNB included patient age, underlying diseases, immune status, length of hospitalization, medical invasive procedures, optimized hygiene, strict isolation, and antibiotic control (P < 0.05). The length of hospitalization and treatment cost in the observation group were higher than those in the control group (P < 0.05). This study comprehensively analyzes the intricate mechanisms of secondary infections in patients with MDR-GNB infections post-hospitalization. Key factors influencing infection risk include patient age, underlying diseases, immune status, length of hospitalization, medical invasive procedures, optimized hygiene, strict isolation, and antibiotic control. • Insights into the mechanisms of MDR-GNB infection. • Immunocompromised elderly patients are vulnerable for MDR-GNB infection. • Strengthening isolation, antibiotic control reduce incidence of MDR-GNB infection. • The long term MDR-GNB infections lead to escalated treatment costs. [ABSTRACT FROM AUTHOR]

[Display omitted] • SAR of VEGFR small molecule inhibitors under patents (2021–2023) are discussed. • In vitro and in vivo pharmacological evaluation demonstrate anticancer potential. • Quinoline derivatives are a predominant structural class among anti-VEGFR agents. VEGFR, a receptor tyrosine kinase inhibitor (TKI), is an important regulatory factor that promotes angiogenesis and vascular permeability. It plays a significant role in processes such as tumor angiogenesis, tumor cell invasion, and metastasis. VEGFR is mainly composed of three subtypes: VEGFR-1, VEGFR-2, and VEGFR-3. Among them, VEGFR-2 is the crucial signaling receptor for VEGF, which is involved in various pathological and physiological functions. At present, VEGFR-2 is closely related to a variety of cancers, such as non-small cell lung cancer (NSCLC), Hepatocellular carcinoma, Renal cell carcinoma, breast cancer, gastric cancer, glioma, etc. Consequently, VEGFR-2 serves as a crucial target for various cancer treatments. An increasing number of VEGFR inhibitors have been discovered to treat cancer, and they have achieved tremendous success in the clinic. Nevertheless, VEGFR inhibitors often exhibit severe cytotoxicity, resistance, and limitations in indications, which weaken the clinical therapeutic effect. In recent years, many small molecule inhibitors targeting VEGFR have been identified with anti-drug resistance, lower cytotoxicity, and better affinity. Here, we provide an overview of the structure and physiological functions of VEGFR, as well as some VEGFR inhibitors currently in clinical use. Also, we summarize the in vivo and in vitro activities, selectivity, structure–activity relationship, and therapeutic or preventive use of VEGFR small molecule inhibitors reported in patents in the past three years (2021–2023), thereby presenting the prospects and insights for the future development of targeted VEGFR inhibitors. [ABSTRACT FROM AUTHOR]

The propagation of the 2021 M w 7.4 Maduo earthquake rupture from the central Jiangcuo fault (JCF) onto its eastern terminus, in the northern Tibetan Plateau, exhibits a complex surface geometry with conjugate faults, bends, and stepovers. About 50 km east of the 2021 earthquake epicenter, which is located at Maduo County within the Tibetan plateau, the surface rupture along the Jiangcuo eastern fault (JCEF), deviating <20° anticlockwise from the general strike, provides a valuable chance for understanding rupture processes through a geometrically complex fault network where ≥4 interactional faults come together. Using orthophotos derived from an unmanned aerial vehicle (UAV) survey with a ground resolution of 6 cm, complemented by field investigations, we mapped the surface rupture in detail and measured the coseismic slip distribution of the JCEF. Our mapping illuminates sporadic breaks of tectonic origin in the sand dune area immediately near the branching point and a more simple, linear rupture trace eastward of the junction. The high-resolution slip measurements along the JCEF follow approximately a dogtail shape to the eastern termination with a maximum left-lateral coseismic slip of 2.9 m at a fault bend. We found linear surface ruptures along the NW-strike geologic faults, indicating triggered coseismic slip on conjugate faults. The intersections with conjugate faults overlap with discontinuities in rupture geometry and interference of surface slip on the main fault. We propose that triggered slip on pre-mapped Quaternary faults impacted the rupture propagation onto the JCEF. The complexity in rupture geometry suggests fault interaction in the eastern tip zone of the Maduo rupture. • The 2021 Maduo M w7.4 earthquake rupture broke the most complex fault network to the east terminus. • Sporadic breaks in the sand dune may suggest fast eastward propagation of the 2021 Maduo rupture. • The slip distribution exhibits a dogtail shape with a maximum left-lateral slip of 2.9 m. • Our results indicate discontinuities in rupture geometry and strong dynamic fault interaction. [ABSTRACT FROM AUTHOR]

The high-speed train wheel wear problem persists throughout the whole service cycle, including the traction-braking stage, constant-speed stage, acceleration and deceleration stage, and so on. This article focuses on the wheel wear of high-speed trains under various braking modes. Firstly, high-speed motor cars and trailers are created, and the two are linked by the coupler buffer device, and the former considers detailed gear transmission system. A comprehensive wheel wear prediction process is then established based on the vehicle model, wheel-rail contact model, wear model, and wheel tread update strategy. Secondly, vehicle model and wheel wear prediction procedure are validated using the measured dynamic data and worn wheel profile. Thirdly, common braking modes and emergency braking modes are used for the braking process of high-speed trains. Finally, wheel wear and wear mechanism of high-speed trains during braking process is revealed. The results demonstrate that with the increase of braking mode level, the amplitude of longitudinal creepage also increases synchronously, while lateral creepage and spin creepage do not change significantly. According to wheel wear depth under different braking processes, the order from large to small is emergency braking mode >8-level common braking mode >6-level common braking mode >4-level common braking mode >3-level common braking mode >B1-level common braking mode. Furthermore, with the increase of rail slope, wheel wear is increasing during braking process. With the increase of friction coefficient, wheel wear depth decreases gradually during braking process. • The thesis focuses on wheel wear of high-speed trains during different braking modes. • The wear evolution and wear mechanism of high-speed trains during braking process is revealed. • The wheel wear law of high-speed trains during braking process on tracks with different rail slopes and friction coefficients is analyzed. [ABSTRACT FROM AUTHOR]

Herein, the effects of different bulking agents (sawdust and mushroom residue), on compost quality and the environmental benefits of semipermeable film composting with poultry manure were investigated. The results show that composting with sawdust as the bulking agent resulted in greater efficiency and more cost benefits than composting with mushroom residue, and the cost of sawdust for treating an equal volume of manure was only 1/6 of that of mushroom residue. Additionally, lignin degradation and potential carbon emission reduction in the sawdust group were better than those in the mushroom residue group, and the lignin degradation efficiency of the bottom sample in the sawdust group was 48.57 %. Coupling between lignin degradation and potential carbon emission reduction was also closer in sawdust piles than in mushroom residue piles, and sawdust is more environmentally friendly. The abundance of key functional genes was higher at the bottom of each pile relative to the top and middle. Limnochordaceae , Lactobacillus and Enterococcus were the core microorganisms involved in coupling between lignin degradation and potential carbon emission reduction, and the coupled relationship was influenced by electric conductivity, ammonia nitrogen and total nitrogen in the compost piles. This study provides important data for supporting bulking agent selection in semipermeable film composting and for improving the composting process. The results have high value for compost production and process application. [Display omitted] • The efficiency and cost advantages of sawdust as the bulking agent is better. • The use of sawdust in film composting is more environmentally friendly. • The abundance of functional genes was higher at the bottom of the pile. • Bacteria with both lignin degradation and carbon retention functions were screened. [ABSTRACT FROM AUTHOR]

Bogie hunting instability is one of the common faults in railway vehicles. It not only affects ride comfort but also threatens operational safety. Due to the lower operating speed of metro vehicles, their bogie hunting stability is often overlooked. However, as wheel tread wear increases, metro vehicles with high conicity wheel–rail contact can also experience bogie hunting instability. In order to enhance the operational safety of metro vehicles, this paper conducts field tests and simulation calculations to study the bogie hunting instability behavior of metro vehicles and proposes corresponding solutions from the perspective of wheel–rail contact relationships. Acceleration and displacement sensors are installed on metro vehicles to collect data, which are processed in real time in 2 s intervals. The lateral acceleration of the frame is analyzed to determine if bogie hunting instability has occurred. Based on calculated safety indicators, it is determined whether deceleration is necessary to ensure the safety of vehicle operation. For metro vehicles in the later stages of wheel wear (after 300,000 km), the stability of their bogies should be monitored in real time. To improve the stability of metro vehicle bogies while ensuring the longevity of wheelsets, metro vehicle wheel treads should be reprofiled regularly, with a recommended reprofiling interval of 350,000 km. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationship between serum α-Klotho levels and insulin resistance (IR), a precursor to type 2 diabetes. The study analyzed data from 4,758 adult participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. The relationship between α-Klotho concentration and IR was assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and odds ratios (OR) derived from logistic regression models. Results showed that every 1-ln increase in α-Klotho concentration raised the HOMA-IR value by 0.55 (95% confidence interval 0.35–0.74) and the odds of IR by 64% (odds ratio 1.64; 95% confidence interval 1.28–2.1). The odds of IR was 40% greater in highest tertile than in the lowest tertile. The findings of this study underscore a significant correlation between increased serum α-Klotho levels and the prevalence of IR. [ABSTRACT FROM AUTHOR]

Background: Huanglian (HL), also known as Coptis chinensis Franch., was initially documented in "Sheng Nong's Herbal Classic" as a high-quality product used to cure ailments such as fever, indigestion, bloating, nausea, dysentery, diarrhea, abdominal pain, and tuberculosis. Nowadays, it is extensively employed in clinical settings to alleviate pulmonary diseases, like tuberculosis, lobular lung disease, and pulmonary abscess, and is worth exploring further. Nevertheless, there is limited research on the precise advancements of anti-lung adenocarcinoma (LUAD). Objectives: Using biological experiments and network pharmacology, the objective of this research was to investigate the most effective parts and chemical constituents of C. chinensis against LUAD and ascertain the probable targets and pathways. Materials and Methods: First, an MTT experiment verified the impact of each part on A549 and BEAS-2B cells. High performance liquid chromatography (HPLC) was then used to identify the chemical components of the effective substance in C. chinensis against LUAD. Then, network pharmacology was used to screen potential pathways and binding target proteins. Finally, a subcutaneous tumor model was established in mice using LLC cells to observe the effects of the effective components of C. chinensis against LUAD in tumor-bearing mice. Results: The MTT assay demonstrated the efficacy of oxyepiberberine (OPB) as an anti-LUAD compound with minimal toxicity and side effects. According to the results of network pharmacology and molecular docking, SRC appears to be the primary target of C. chinensis active substance against LUAD. In vivo experiments revealed that the OPB group exhibited lowered toxicity and side effects. Additionally, the density of tumor cells decreased and the nuclei were destroyed in OPB groups of tumor tissues. Finally, OPB could regulate apoptosis, migration, and protein expression significantly related to the SRC pathway in tumor cells. Conclusion: Our research reveals the anti-LUAD properties of C. chinensis through a combination of experimentation and network analysis. These findings establish a theoretical foundation for C. chinensis as a clinical antitumor agent. Furthermore, our work provided an essential groundwork for further investigations into the medicinal properties of C. chinensis. [ABSTRACT FROM AUTHOR]

Few studies have focused on the spatially clustered regions in the association between short-term exposure to temperature and mortality, which is important for identifying high-susceptibility population and enhancing the prevention of high/low temperatures. Previous studies have explored the association inequality, but no study has evaluated the inequalities of temperature-attributable burdens, which may be more meaningful for reducing temperature-related regional inequality. Taking the Sichuan Basin (SCB), an economically imbalanced area with high humidity and four distinctive seasons, as an example, we used a novel multi-stage strategy to investigate the two issues. First, distributed lag nonlinear models were independently constructed to obtain the county-level associations between daily temperature and cardiorespiratory mortality. Then, an estimation-error-based spatial scan statistic was used to detect the association-clustered regions. Third, multivariate meta-regression incorporating the identified clustered regions and socioeconomic and natural factors was used to obtain stable county-specific associations, based on which the heat- and cold-attributable deaths were mapped and their inequalities were evaluated using concentration indices and Lorenz curves. On average, a U-shaped temperature-mortality association was examined. A significantly association-clustered region was detected (P = 0.017), in which heat and cold temperatures presented significantly stronger associations than those in the non-clustered region, particularly for heat temperatures. The cold-attributable deaths (3.5%) were substantially more than the heat-attributable deaths (0.5%). Both presented severe inequalities over counties. Significant temperature-attributable inequalities were also found over per-capital public budget, urbanization rate, employment rate and per-capital GDP. The directions of inequalities over GDP and urbanization rate were opposite between heat and cold temperatures. Our analysis provided the first evidence about the clustering of temperature-mortality associations and the inequality of cold- and heat-attributable burdens. Significantly association-clustered regions and heavy temperature-attributable inequalities were found in the SCB. Rural people bore heavier cold-attributable but less heat-attributable mortality risk than urban people, suggesting that different policies should be designed to reduce the temperature-attributable inequalities for heat and cold temperatures and different regions. This novel strategy can provide an interesting new perspective in the association between environmental exposure and human health. [Display omitted] • A significantly association-clustered region was detected in the SCB. • People in the clustered region are significantly more susceptible to heat. • Inequality of temperature-attributable burdens is first evaluated. • Temperature-attributable inequality over public budget is strong in the SCB. • Heat and cold have opposite inequality directions over GDP and urbanization rate. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ordered porous WO 3 films were prepared using polystyrene as template. • Ordered porous stacked WO 3 films were fabricated by electrodeposition-assisted sol-gel. • The deposition time has effect on the microstructure of ordered porous stacked WO 3 films. • The ECD assembled with ordered porous stacked WO 3 films exhibited good performance. WO 3 is currently the most widely used and promising electrochromic material, but the preparation of WO 3 thin films with excellent optoelectronic properties is a formidable challenge. The amorphous WO 3 /ordered porous crystalline WO 3 stacked films (a-WO 3 /OP-c-WO 3) were prepared by electrodeposition-assisted sol–gel method with polystyrene (PS) spheres as the templates. The microstructure and properties of a-WO 3 /OP-c-WO 3 films were significantly influenced by electrodeposition time (150 s ∼ 300 s). The optimized a-WO 3 /OP-c-WO 3 films exhibited even better electrochromic properties (at 633 nm) with high cycling stability, superior optical modulation (53.9 %), fast response time (3.9 s/6.1 s for bleaching /coloration), and especially high coloration efficiency (51.3 cm2/C), compared with OP-c-WO 3 film (25.1 cm2/C) and a-WO 3 film (35.2 cm2/C), which is unique synergistic effect between the top layer of a-WO 3 and the bottom layer of OP-c-WO 3 film. The ordered porous structure allows the film to fully contact with the electrolyte, thereby providing a greater specific surface area and more active sites for the electrochemical reaction. The electrochromic device (EDC) prototype assembled with a-WO 3 /OP-c-WO 3 laminated film as the electrochromic layer has better electrochromic properties. [ABSTRACT FROM AUTHOR]

Hydrogen is not only an important energy carrier needed to achieve the global goal of carbon neutrality, but also an important way of international energy trade in the future. This research analyzes the advantages and challenges of China's participation in international hydrogen trade in detail, proposes the possible routes of China's international hydrogen trade, and proposes specific measures to enhance China's participation in international hydrogen trade. This paper proposes that China should take green hydrogen as its development direction, and guide the development of China's hydrogen trade with the principle of blue green cooperation and gray hydrogen withdrawal. In the future, China's hydrogen trade forms will be diversified, and the types of trade will cover the entire hydrogen energy industry chain. Therefore, China should accelerate the overall deployment of hydrogen trade and the construction of hydrogen trade infrastructure, and build a more sophisticated hydrogen economy. [Display omitted] • The advantages of China's international hydrogen trade are analyzed. • Discussed China's possible international hydrogen trade routes in the future. • The obstacles affecting China's hydrogen competitiveness are analyzed. • Put forward suggestions to promote China's international hydrogen trade. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to explore the effect of Baduanjin qigong on improving lung function and postoperative quality of life of patients with non-small cell lung cancer (NSCLC) and to find an effective home-based pulmonary rehabilitation method. Methods: A randomised controlled trial was carried out from July 2019 to October 2021, which included 216 NSCLC postoperative participants from Beijing China-Japan Friendship Hospital and Cancer Hospital of Chinese Academy of Medical Science. Participants were randomly divided into two groups, including the observation (n = 108) group and the control group (n = 108). The control group was given routine lung rehabilitation training, while the observation group was given Baduanjin qigong. Both groups were trained for 12 weeks.The patient's age, sex, smoking history, lung cancer stage, pathological type were recorded. Related indicators of lung function, 6-min walk distance(6MWD), Piper fatigue Scale, and Borg dyspnea score before and after intervention were recorded. Results: Compared with these indicators before indicators, lung function, 6MWD, Piper fatigue Scale score and Borg score were significantly better in the two groups after intervention (P < 0.05). There were no significant differences in FVC%, 6MWD and Borg score between the two groups (P > 0.05), whereas FEV1% and Piper fatigue Scale scores in the observation group were better than that in the control group (P < 0.05). Conclusion: Both Baduanjin qigong and traditional pulmonary rehabilitation methods can improve the postoperative lung function and quality of life of patients with NSCLC; and compared with traditional pulmonary rehabilitation training, Baduanjin Qigong may have certain advantages in relieving cancer-related fatigue and FEV1%, and may be another new method of home-based pulmonary rehabilitation for patients with NSCLC. Trial registration: Clinical Trial No.: ChiCTR1900025121. [ABSTRACT FROM AUTHOR]

A two-degree-of-freedom nonlinear high-speed railway wheelset model with two time delays in the lateral and yaw dampers is studied. The aim is to investigate the effect of time delays on stability and Hopf bifurcation characteristics of the wheelset model. The local stability of the trivial equilibrium under different time delay conditions is qualitatively analyzed. Analytical studies reveal that the wheelset model undergoes stability switches with the variation of the time delays. The stability switches correspond to Hopf bifurcations that occur when the time delays cross critical values. Furthermore, properties of Hopf bifurcation including direction and stability of bifurcating limit cycles are studied by using the normal form theory and the center manifold theorem. Our findings indicate that time delays in both lateral dampers and yaw dampers influence the stability and direction of Hopf bifurcation. Additionally, the numerical results show that time delays in the lateral and yaw dampers not only affect the amplitude of the hunting motion of the wheelset but also the periodic and chaotic motions. If the time delays gradually increase, the wheelset will vibrate irregularly with large lateral displacements. The analytical results presented in this paper offer a theoretical reference for the stability design of wheelsets. [ABSTRACT FROM AUTHOR]

This article discusses the diagnostic challenges associated with pediatric central nervous system (CNS) tumors that have CIC::LEUTX gene fusions. Recent studies have identified pediatric high-grade neuroepithelial tumors with CIC fusions, suggesting that CNS tumors with CIC gene fusions may encompass various tumor types and have different clinical outcomes. The article describes a multicenter study that aims to deepen the understanding of CIC-fused CNS tumors through comprehensive histological, molecular, and clinical analysis. The document provides a summary of clinical findings for a cohort of patients with CIC-fused CNS tumors, including age, sex, location, histology, fusion, therapy, follow-up, and status. It also provides information on the histological and immunohistochemical characteristics of CIC and CIC::LEUTX fused tumors, as well as detailed descriptions of four cases of CIC::LEUTX fused CNS tumors. The study suggests that these tumors may represent a heterogeneous group, including CIC-rearranged sarcomas, high-grade neuroepithelial tumors, and rare lower-grade neuroepithelial tumors. The article also presents a study on the survival rates of CNS tumors with CIC:LEUTX and non-LEUTX fusions, finding that the presence of CIC:LEUTX fusions is associated with a higher overall survival rate and longer progression-free survival in CNS tumors. These findings provide valuable insights for further research and potential treatment strategies for CNS tumors [Extracted from the article]

Ex vivo resting culture is a standard procedure following genome editing in hematopoietic stem and progenitor cells (HSPCs). However, prolonged culture may critically affect cell viability and stem cell function. We investigated whether varying durations of culture resting times impact the engraftment efficiency of human CD34+ HSPCs edited at the BCL11A enhancer, a key regulator in the expression of fetal hemoglobin. We employed electroporation to introduce CRISPR-Cas9 components for BCL11A enhancer editing and compared outcomes with nonelectroporated (NEP) and electroporated-only (EP) control groups. Post-electroporation, we monitored cell viability, death rates, and the frequency of enriched hematopoietic stem cell (HSC) fractions (CD34+CD90+CD45RA- cells) over a 48-hour period. Our findings reveal that while the NEP group showed an increase in cell numbers 24 hours post-electroporation, both EP and BCL11A -edited groups experienced significant cell loss. Although CD34+ cell frequency remained high in all groups for up to 48 hours post-electroporation, the frequency of the HSC-enriched fraction was significantly lower in the EP and edited groups compared to the NEP group. In NBSGW xenograft mouse models, both conditioned with busulfan and nonconditioned, we found that immediate transplantation post-electroporation led to enhanced engraftment without compromising editing efficiency. Human glycophorin A+ (GPA+) red blood cells (RBCs) sorted from bone marrow of all BCL11A edited mice exhibited similar levels of γ-globin expression, regardless of infusion time. Our findings underscore the critical importance of optimizing the culture duration between genome editing and transplantation. Minimizing this interval may significantly enhance engraftment success and minimize cell loss without compromising editing efficiency. These insights offer a pathway to improve the success rates of genome editing in HSPCs, particularly for conditions like sickle cell disease. [ABSTRACT FROM AUTHOR]

Aims Design Methods Results Conclusion Implications for the Profession and/or Patient Care Patient or Public Contribution This study aimed to explore the mediating effect of self‐management (SM) on the relationship between illness perception and quality of life (QOL) among Human immunodeficiency virus (HIV)‐positive men who have sex with men (MSM).A cross‐sectional study.We explored the effect of illness perception and self‐management on QOL using the multiple regression model. Moreover, we conducted a simple mediation analysis to examine the role of SM in the relationship between illness perception and QOL. In addition, a parallel mediation analysis was performed to investigate the differences in domains of SM on the relationship between illness perception and QOL.Among 300 Chinese HIV‐positive MSM, the mean score of SM was 39.9 ± 6.97, with a range of 14.0–54.0. The higher score in SM indicated a higher level of HIV SM. SM was negatively related to illness perception (r = −0.47) while positively related to QOL (r = 0.56). SM partially mediated the relationship between illness perception and QOL, accounting for 25.3% of the total effect. Specifically, both daily self‐management health practices and the chronic nature of the self‐management domain played a parallel role in mediating the relationship between illness perception and QOL.Our study demonstrated that SM was a significant factor influencing QOL among HIV‐positive MSM. Focusing on daily self‐management health practices and the chronic nature of self‐management could be the potential key targets for enhancing HIV self‐management strategies.This study emphasized the role of SM in the well‐being of HIV‐positive MSM and underscored the importance of developing interventions that integrate SM strategies to improve QOL in this population.No patient or public contribution. [ABSTRACT FROM AUTHOR]

This study aimed to predict the probability of grade ≥2 pneumonitis or dyspnea within 12 months of receiving conventionally fractionated or mildly hypofractionated proton beam therapy for locally advanced lung cancer using machine learning. Demographic and treatment characteristics were analyzed for 965 consecutive patients treated for lung cancer with conventionally fractionated or mildly hypofractionated (2.2-3 Gy/fraction) proton beam therapy across 12 institutions. Three machine learning models (gradient boosting, additive tree, and logistic regression with lasso regularization) were implemented to predict Common Terminology Criteria for Adverse Events version 4 grade ≥2 pulmonary toxicities using double 10-fold cross-validation for parameter hyper-tuning without leak of information. Balanced accuracy and area under the curve were calculated, and 95% confidence intervals were obtained using bootstrap sampling. The median age of the patients was 70 years (range, 20-97), and they had predominantly stage IIIA or IIIB disease. They received a median dose of 60 Gy in 2 Gy/fraction, and 46.4% received concurrent chemotherapy. In total, 250 (25.9%) had grade ≥2 pulmonary toxicity. The probability of pulmonary toxicity was 0.08 for patients treated with pencil beam scanning and 0.34 for those treated with other techniques (P = 8.97e-13). Use of abdominal compression and breath hold were highly significant predictors of less toxicity (P = 2.88e-08). Higher total radiation delivered dose (P =.0182) and higher average dose to the ipsilateral lung (P =.0035) increased the likelihood of pulmonary toxicities. The gradient boosting model performed the best of the models tested, and when demographic and dosimetric features were combined, the area under the curve and balanced accuracy were 0.75 ± 0.02 and 0.67 ± 0.02, respectively. After analyzing performance versus the number of data points used for training, we observed that accuracy was limited by the number of observations. In the largest analysis of prospectively enrolled patients with lung cancer assessing pulmonary toxicities from proton therapy to date, advanced machine learning methods revealed that pencil beam scanning, abdominal compression, and lower normal lung doses can lead to significantly lower probability of developing grade ≥2 pneumonitis or dyspnea. [ABSTRACT FROM AUTHOR]

Hunting stability is a critical aspect of the dynamic performance of high-speed trains. However, the current evaluation criteria only address heavy hunting motion, and they require supplementation and improvement to meet the increasing requirements of dynamic performance. Therefore, a study was conducted to develop an identification method for small-amplitude bogie hunting (SABH) motion. A total of 39,816 samples were obtained from field-measured bogie lateral acceleration and manually labelled as normal and SABH. The distribution comparison, Pierce coefficient, and importance ranking showed that harmonic character-related features (the autocorrelation coefficient, approximate entropy and etc.) should be considered more for SABH identification than amplitude-related features (maximum and RMS). The most critical features for SABH identification were the autocorrelation coefficient and spectral frequency spread. The classifier performance comparison showed that the decision tree was the best-performing classifier, followed by the support vector machine, while the linear discriminant, K-nearest neighbour, and naive Bayes classifiers were less effective. Sensitivity analysis indicated that the proposed method worked well with a sampling frequency of 50–200 Hz and a window length of 5–10 s. This research provides theoretical support for hunting instability monitoring and real-time active control studies for high-speed trains. [ABSTRACT FROM AUTHOR]

Mechanisms behind the impaired response of antigen-specific B cells to therapeutic vaccination in chronic hepatitis B virus (HBV) infection remain unclear. The development of vaccines or strategies to overcome this obstacle is vital for advancing the management of chronic hepatitis B. A mouse model, denominated as E6F6-B, was engineered to feature a knock-in of a B-cell receptor (BCR) that specifically recognizes HBsAg. This model served as a valuable tool for investigating the temporal and spatial dynamics of humoral responses following therapeutic vaccination under continuous antigen exposure. Using a suite of immunological techniques, we elucidated the differentiation trajectory of HBsAg-specific B cells post-therapeutic vaccination in HBV carrier mice. Utilizing the E6F6-B transfer model, we observed a marked decline in antibody-secreting cells 2 weeks after vaccination. A dysfunctional and atypical pre-plasma cell population (BLIMP-1+ IRF4+ CD40- CD138- BCMA-) emerged, manifested by sustained BCR signaling. By deploying an antibody to purge persistent HBsAg, we effectively prompted the therapeutic vaccine to provoke conventional plasma cell differentiation. This resulted in an enhanced anti-HBs antibody response and facilitated HBsAg clearance. Sustained high levels of HBsAg limit the ability of therapeutic hepatitis B vaccines to induce the canonical plasma cell differentiation necessary for anti-HBs antibody production. Employing a strategy combining antibodies with vaccines can surmount this altered humoral response associated with atypical pre-plasma cells, leading to improved therapeutic efficacy in HBV carrier mice. Therapeutic vaccines aimed at combatting HBV encounter suboptimal humoral responses in clinical settings, and the mechanisms impeding their effectiveness have remained obscure. Our research, utilizing the innovative E6F6-B mouse transfer model, reveals that the persistence of HBsAg can lead to the emergence of an atypical pre-plasma cell population, which proves to be relevant to the potency of therapeutic HBV vaccines. Targeting the aberrant differentiation process of these atypical pre-plasma cells stands out as a critical strategy to amplify the humoral response elicited by HBV therapeutic vaccines in carrier mouse models. This discovery suggests a compelling avenue for further study in the context of human chronic hepatitis B. Encouragingly, our findings indicate that synergistic therapy combining HBV-specific antibodies with vaccines offers a promising approach that could significantly advance the pursuit of a functional cure for HBV. [Display omitted] • The HBsAg-specific BCR knock-in mouse was constructed to study the characteristics of B cells in chronic HBV infection. • An atypical pre-plasma cell population was identified post therapeutic vaccination in chronic HBV carrier mice. • Atypical pre-plasma cells display enhanced BCR signaling, ER stress and apoptosis-related gene expression. • Combination therapy (antibody + vaccine) partially overcame abnormal B-cell differentiation and led to superior HBsAg suppression. [ABSTRACT FROM AUTHOR]

• This paper determines the RWRD of railway vehicles through computer vision technology. • A VPT method for predicting RWRD is presented. • The VPT method and the original UNet model are experimentally compared. • The feasibility, advantages, drawbacks and future directions for improvement of the VPT method are discussed. Relative wheel-rail displacement (RWRD) is an important physical quantity that responds to the hunting stability and running safety of railway vehicles but detecting this physical quantity is challenging during train operation due to the complex service environment and the nonlinearity of vehicle-rail system. To address this problem, this paper proposes a virtual point tracking (VPT) method to detect RWRD. First, a series of regions of interest (ROIs) in the preprocessed wheel-rail contact images are extracted using a simplified YOLO (SYOLO) model. Then, some key positions of the wheel and rail on the extracted ROIs are identified using an improved UNet (IUNet) model and characterized by virtual points. Finally, the global coordinates of the virtual points in the whole wheel-rail contact image are calculated to obtain the final RWRD. To demonstrate the feasibility of the VPT method, it is used to detect the RWRD of a vehicle operating on a full-scale roller rig. For comparison, the original UNet model is directly used to detect the RWRD. Two quantities, Mean Absolute Error (MAE) and Root Mean Square Error (RMSE), are applied for quantitative analysis and the results show that the VPT method can identify the RWRD more reliably and accurately. [ABSTRACT FROM AUTHOR]

The impact of COVID-19 on pregnant women and newborns continues to be a critical societal concern. However, the majority of research focuses on the disease resulting from the early pandemic variants, without sufficient study on the more recent BA.5.2/BF.7. We retrospectively recruited pregnant women giving birth during the surge of the BA.5.2/BF.7 and analysed the risk impact of COVID-19 on maternal and neonatal outcomes. Furthermore, subjects matched through propensity scores were used for the analysis of clinical laboratory tests. A total of 818 pregnant women were enrolled, among 276 (33.7%) were diagnosed with SARS-CoV-2 during childbirth. COVID-19 significantly increased the risk of a hospital length of stay equal to or greater than seven days and neonatal admission to the neonatal intensive care unit, with an aHR of 2.03 (95% CI, 1.22-3.38) and 1.51 (95% CI, 1.12-2.03), respectively. In the analysis of 462 matched subjects, it was found that subjects infected with SARS-CoV-2 tended slight leucopenia and coagulation abnormalities. We found that during the surge of the BA.5.2/BF.7, COVID-19 increased the risk of maternal and neonatal outcomes among Chinese pregnant women. This finding offers significant insights to guide clinical practices involving pregnant women infected with the recently emerged Omicron subvariants. [ABSTRACT FROM AUTHOR]

This paper presents the design and experiment results for a W-band sheet beam electron gun of the extended interaction oscillator (EIO). A 3D simulation has been performed, and then, the structure parameters of the electron gun have been optimized. The simulation results show that the beam waist (BW) and transmission ratio are extremely sensitive to the distance between the cathode and the focus electrode. By observing the beam waist and the beam range, the maximum beam range is up to 46 mm, which is measured at the beginning of the beam-wave interaction cavity. In addition, the thickness of the beam waist decreases rapidly when the cathode is moved along the positive axial direction by 0.03 mm. Moreover, the voltage on the focus electrode has a significant impact on the beam trajectory. At last, by considering the deviation, experiment results show that the transmission is improved to 98%. [ABSTRACT FROM AUTHOR]

Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC–MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using n-butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC–MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin. [ABSTRACT FROM AUTHOR]

The comorbidity between bipolar disorder (BD) and inflammatory bowel disease (IBD) has been widely reported in observational studies. However, unclear whether this comorbidity reflects a shared genetic architecture. Leveraging large-scale genome-wide association study (GWAS) summary statistics of BD, IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD), we performed a genome-wide pleiotropic analysis to estimate heritability and genetic correlation, identify pleiotropy loci/genes, and explore the shared biological pathway. Mendelian randomization (MR) studies were subsequently employed to infer whether the potential causal relationship is present. We found a positive significant genetic correlation between BD and IBD (r g = 0.10, P = 7.00 × 10−4), UC (r g = 0.09, P = 2.90 × 10−3), CD (r g = 0.08, P = 6.10 × 10−3). In cross-trait meta-analysis, a total of 29, 24, and 23 independent SNPs passed the threshold for significant association between BD and IBD, UC, and CD, respectively. We identified five novel pleiotropy genes including ZDHHC2 , SCRN1 , INPP4B , C1orf123 , and BRD3 in both BD and IBD, as well as in its subtypes UC and CD. Pathway enrichment analyses revealed that those pleiotropy genes were mainly enriched in several immune-related signal transduction pathways and cerebral disease-related pathways. MR analyses provided no evidence for a causal relationship between BD and IBD. Our findings corroborated that shared genetic basis and common biological pathways may explain the comorbidity of BD and IBD. These findings further our understanding of shared genetic mechanisms underlying BD and IBD, and potentially provide points of intervention that may allow the development of new therapies for these co-occurrent disorders. Schematic overview of the study design. IBD: inflammatory bowel disease; SNP: single nucleotide polymorphism; BD: bipolar disorder; LDSC: linkage disequilibrium score regression. [Display omitted] • A positive significant genetic correlation was identified between BD and IBD. • Shared loci and common biological pathways may explain the comorbidity of BD and IBD. • No evidence of causality was found between BD and IBD. [ABSTRACT FROM AUTHOR]

Geometric complexities of a fault system have a significant impact on the rupture behavior of the fault. The 2021 Mw7.4 Maduo earthquake occurred on a multi-segmented complex sinistral fault in the interior of the Bayan-Har block in the northern Tibetan Plateau. Here, we integrate centimeter-resolution surface rupture zones and Sentinel-2 optical displacement fields to accurately determine the geometric parameters of the causative fault in detail. An adaptive quadtree down-sampling method for interferograms was employed to enhance the reliability of the coseismic slip model inversion for interferograms. The optimal coseismic slip model indicated a complex non-planar structure with varying strike and dip angles. The largest slip of ~6 m, at a depth of ~7 km, occurred near a 6 km-wide stepover (a geometric complexity area) to the east of the epicenter, which occurred at the transition zone from sub-shear to super-shear rupture suggested by seismological studies. Optical and SAR displacement fields consistently indicated the local minimization of effective normal stress on releasing stepovers, which facilitated rupture through them. Moreover, connecting intermediate structures contributes to maintaining the rupture propagation through wide stepovers and may even facilitate the transition from subshear to supershear. Our study provides more evidence of the reactivation of a branched fault at the western end during the mainshock, which was previously under-appreciated. Furthermore, we found that a strong asymmetry in slip depth, stress drop, and rupture velocity east and west of the epicenter was coupled with variations in geometric and structural characteristics of fault segments along the strike. Our findings highlight the sensitivity of rupture behaviors to small-scale details of fault geometry. [ABSTRACT FROM AUTHOR]

The Poisson ridge estimator (PRE) is a commonly used parameter estimation method to address multicollinearity in Poisson regression (PR). However, PRE shrinks the parameters toward zero, contradicting the real association. In such cases, PRE tends to become an insufficient solution for multicollinearity. In this work, we proposed a new estimator called the Poisson average maximum likelihood‐centered penalized estimator (PAMLPE), which shrinks the parameters toward the weighted average of the maximum likelihood estimators. We conducted a simulation study and case study to compare PAMLPE with existing estimators in terms of mean squared error (MSE) and predictive mean squared error (PMSE). These results suggest that PAMLPE can obtain smaller MSE and PMSE (i.e., more accurate estimates) than the Poisson ridge estimator, Poisson Liu estimator, and Poisson K‐L estimator when the true β$$ \beta $$s have the same sign and small variation. Therefore, we recommend using PAMLPE to address multicollinearity in PR when the signs of the true β$$ \beta $$s are known to be identical in advance. [ABSTRACT FROM AUTHOR]

Diabetic chronic foot ulcers pose a significant therapeutic challenge as a result of the oxidative stress caused by hyperglycemia. Which impairs angiogenesis and delays wound healing, potentially leading to amputation. Gynura divaricata (L.) DC. (GD), a traditional Chinese herbal medicine with hypoglycemic effects, has been proposed as a potential therapeutic agent for diabetic wound healing. However, the underlying mechanisms of its effects remain unclear. In this study, we aimed to reveal the effect and potential mechanisms of GD on accelerating diabetic wound healing in vitro and in vivo. The effects of GD on cell proliferation, apoptosis, reactive oxygen species (ROS) production, migration, mitochondrial membrane potential (MMP), and potential molecular mechanisms were investigated in high glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) using CCK-8, flow cytometry assay, wound healing assay, immunofluorescence, DCFH-DA staining, JC-1 staining, and Western blot. Full-thickness skin defects were created in STZ-induced diabetic rats, and wound healing rate was tracked by photographing them every day. HE staining, immunohistochemistry, and Western blot were employed to investigate the effect and molecular mechanism of GD on wound healing in diabetic rats. GD significantly improved HUVEC survival, decreased apoptosis, lowered ROS production, restored MMP, improved migration ability, and raised VEGF expression. The use of Nrf2-siRNA completely abrogated these effects. Topical application of GD promoted angiogenesis and granulation tissue growth, resulting in faster healing of diabetic wounds. The expression of VEGF, CD31, and VEGFR was elevated in the skin tissue of diabetic rats after GD treatment, which upregulated HO-1, NQO-1, and Bcl-2 expression while downregulating Bax expression via activation of the Nrf2 signaling pathway. The findings of this study indicate that GD has the potential to serve as a viable alternative treatment for diabetic wounds. This potential arises from its ability to mitigate the negative effects of oxidative stress on angiogenesis, which is regulated by the Nrf2 signaling pathway. The results of our study offer valuable insights into the therapeutic efficacy of GD in the treatment of diabetic wounds, emphasizing the significance of directing interventions towards the Nrf2 signaling pathway to mitigate oxidative stress and facilitate the process of angiogenesis. [Display omitted] • GD showed remarkable amelioration effects on diabetic wound healing. • GD elicited the accelerating diabetic wound healing effect by inhibiting oxidative stress and promoting angiogenesis. • GD exerted the wound healing effects by activating the Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

• A diagnostic method for freight wagons hunting performance is proposed. • An evaluation indicator H C is utilized to describe the hunting stability. • The detection principle and performance validation through simulations and experiments. • The proposed method has been applied on practical railway engineering. Vehicle hunting instability can cause a great threat to the operational safety of freight wagons, which urgently requires condition monitoring. To address this challenge, an innovative diagnostic method is proposed by employing an indicator called Hunting Coefficient (H C) applied on a wayside hunting detection system (WHDS). Firstly, a diagnostic index H C is defined according to the vehicle hunting characteristics, specifically related to the wheelset lateral amplitude A and frequency f. Subsequently, an in-depth analysis on hunting stability is conducted and a mapping relationship between H C and the vehicle hunting state is established, validated through a rig test. Furthermore, building on the detection principle, a case analysis is performed to verify the feasibility of the proposed method applied on WHDS. This approach provides a means to conduct condition monitoring for freight wagons hunting instability, offering a crucial foundation for condition-based maintenance. [ABSTRACT FROM AUTHOR]

Background and aims: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2−/− mice) and elucidate the underlying mechanisms. Methods: Mdr2−/−mice (12–14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical analyses were used to assess fibrotic liver injury severity. Total RNAseq and pathway analyses were used to identify the potential signaling pathways modulated by BBR in the liver. The expression levels of key genes involved in regulating hepatic fibrosis, bile duct proliferation, inflammation, and bile acid metabolism were validated by qRT-PCR or Western blot analysis. The bile acid composition and levels in the serum, liver, small intestine, and feces and tissue distribution of BBR were measured by LC–MS/MS. Intestinal inflammation and injury were assessed by gene expression profiling and histological analysis. The impact on the gut microbiome was assessed using 16S rRNA gene sequencing. Results: BBR treatment significantly ameliorated cholestatic liver injury, evidenced by decreased serum levels of AST, ALT, and ALP, and reduced bile duct proliferation and hepatic fibrosis, as shown by H&E, Picro-Sirius Red, and CK19 IHC staining. RNAseq and qRT-PCR analyses indicated a substantial inhibition of fibrotic and inflammatory gene expression. BBR also mitigated ER stress by downregulating Chop, Atf4 and Xbp-1 expression. In addition, BBR modulated bile acid metabolism by altering key gene expressions in the liver and small intestine, resulting in restored bile acid homeostasis characterized by reduced total bile acids in serum, liver, and small intestine and increased fecal excretion. Furthermore, BBR significantly improved intestinal barrier function and reduced bacterial translocation by modulating the gut microbiota. Conclusion: BBR effectively attenuates cholestatic liver injury, suggesting its potential as a therapeutic agent for PSC and other cholestatic liver diseases. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has limited effects in treating metastatic breast cancer. Immune checkpoints can deplete the function of immune cells; however, the expression of immune checkpoints after PDT is unclear. This study investigates whether the limited efficacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the efficacy. A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives (HpD-PDT). The anti-tumor effect of HpD-PDT was observed, as well as CD4 + T, CD8 + T and calreticulin (CRT) by immunohistochemistry and immunofluorescence. Immune checkpoints on T cells were analyzed by flow cytometry after HpD-PDT. When combining PDT with immune checkpoint inhibitors, the antitumor effect and immune effect were assessed. For HpD-PDT at 100 mW/cm2 and 40, 60 and 80 J/cm2, primary tumors were suppressed and CD4 + T, CD8 + T and CRT were elevated; however, distant tumors couldn't be inhibited and survival could not be prolonged. Immune checkpoints on T cells, especially PD1 and LAG-3 after HpD-PDT, were upregulated, which may explain the reason for the limited HpD-PDT effect. After PDT combined with anti-PD1 antibody, but not with anti-LAG-3 antibody, both the primary and distant tumors were significantly inhibited and the survival time was prolonged, additionally, CD4 + T, CD8 + T, IFN- γ + CD4 + T and TNF- α + CD4 + T cells were significantly increased compared with HpD-PDT. HpD-PDT could not combat metastatic breast cancer. PD1 and LAG-3 were upregulated after HpD-PDT. Anti-PD1 antibody, but not anti-LAG-3 antibody, could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer. [ABSTRACT FROM AUTHOR]

• The method for constructing an agent model for an equivalent built-in solenoid valve adjustable damper regulation mechanism was proposed. • A new control strategy was proposed for calculating the required damping force. • The proposed method can realize road condition-based adaptive control. As an important component of semi-active suspension (SAS) systems, the built-in solenoid valve adjustable damper (BSVAD) is now widely used in the field because of its advantages of fast response, continuously adjustable damping, and lightweight design. However, only a few studies have discussed the BSVAD-modeling method. Hence, this study proposes a method for constructing an agent model using a feedforward neural network (FNN) for an equivalent BSVAD regulation mechanism. Meanwhile, a new control strategy, i.e., a fuzzy sliding mode control method based on road conditions (RC-FSMC), is proposed for calculating the required damping force. The proposed method identifies and analyzes unsprung mass acceleration characteristics using a long short-term memory network to obtain the road condition of the moving vehicle and inputs the output results into the designed fuzzy rules to adjust the sliding mode switching gain and finally realize road condition-based adaptive control. Finally, through simulation test analysis, the results show that the designed RC-FSMC strategy can effectively reduce vehicle body acceleration and vehicle dynamic load under different road conditions to improve the adaptability of the vehicle to different roads. [ABSTRACT FROM AUTHOR]

Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP) and pancreatic stellate cells (PSCs) are the key cells of fibrosis. As an extracellular matrix (ECM) glycoprotein, cartilage oligomeric matrix protein (COMP) is critical for collagen assembly and ECM stability and recent studies showed that COMP exert promoting fibrosis effect in the skin, lungs and liver. However, the role of COMP in activation of PSCs and pancreatic fibrosis remain unclear. We aimed to investigate the role and specific mechanisms of COMP in regulating the profibrotic phenotype of PSCs and pancreatic fibrosis. ELISA method was used to determine serum COMP in patients with CP. Mice model of CP was established by repeated intraperitoneal injection of cerulein and pancreatic fibrosis was evaluated by Hematoxylin-Eosin staining (H&E) and Sirius red staining. Immunohistochemical staining was used to detect the expression changes of COMP and fibrosis marker such as α-SMA and Fibronectin in pancreatic tissue of mice. Cell Counting Kit-8, Wound Healing and Transwell assessed the proliferation and migration of human pancreatic stellate cells (HPSCs). Western blotting, qRT-PCR and immunofluorescence staining were performed to detect the expression of fibrosis marker, AKT and MAPK family proteins in HPSCs. RNA-seq omics analysis as well as small interfering RNA of COMP, recombinant human COMP (rCOMP), MEK inhibitors and PI3K inhibitors were used to study the effect and mechanism of COMP on activation of HPSCs. ELISA showed that the expression of COMP significantly increased in the serum of CP patients. H&E and Sirius red staining analysis showed that there was a large amount of collagen deposition in the mice in the CP model group and high expression of COMP, α-SMA, Fibronectin and Vimentin were observed in fibrotic tissues. TGF-β1 stimulates the activation of HPSCs and increases the expression of COMP. Knockdown of COMP inhibited proliferation and migration of HPSCs. Further, RNA-seq omics analysis and validation experiments in vitro showed that rCOMP could significantly promote the proliferation and activation of HPSCs, which may be due to promoting the phosphorylation of ERK and AKT through membrane protein receptor CD36. rCOMP simultaneously increased the expression of α-SMA, Fibronectin and Collagen I in HPSCs. In conclusion, this study showed that COMP was up-regulated in CP fibrotic tissues and COMP induced the activation, proliferation and migration of PSCs through the CD36-ERK/AKT signaling pathway. COMP may be a potential therapeutic candidate for the treatment of CP. Interfering with the expression of COMP or the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research. • COMP upregulation occurs in CP, and its high expression level correlates with fibrosis occurrence. • Knockdown of COMP dramatically suppressed cell proliferation, activation, and migration in PSCs. • COMP exerted fibrogenic function through its interaction with CD36 and activated MEK/ERK and PI3K/AKT signaling pathways. • COMP could be a potential therapeutic candidate in the treatment of CP, and interfering with the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research. [ABSTRACT FROM AUTHOR]

The main challenges faced by magnesium-sulfur (Mg–S) batteries are the polysulfide shuttle effect and slow kinetics of S cathode, causing the severe self-discharge behavior and rapid capacity decay. Herein, we elaborately design a MoO 2 -loaded activated carbon cloth (denoted as MoO 2 @ACC) functional interlayer to realize high-performance Mg–S batteries. The ACC possesses a remarkable adsorption effect, which can effectively mitigate the polysulfide shuttle effect and enable the Mg–S batteries with a high voltage plateau. Besides, the MoO 2 can observably reduce the polarization during charge/discharge process attributed by the fast reaction kinetics due to the catalytic effect. The Mg–S battery with this MoO 2 @ACC interlayer achieves a high energy density and good capacity retention (80.3 %) after 100 cycles (0.5 C) and effectively mitigates the Mg–S battery's self-discharge as well. This work illustrates the significant role of the interlayer with both adsorption and catalytic functions to boost the usability of the Mg–S batteries. [Display omitted] • The MoO 2 @ACC interlayer is prepared by a simple method. • The shuttle effect of the magnesium-sulfur battery is effectively blocked. • The kinetics of the magnesium-sulfur battery is significantly improved. • The magnesium-sulfur battery exhibits a high voltage plateau and high capacity retention of 80.3% at 0.5 C. [ABSTRACT FROM AUTHOR]

Sedimentary provenance studies, which aim to identify the original source of sedimentary material, can offer valuable insights into transportation processes that occur within a given basin. Zircon and K-feldspar are complimentary and commonly used minerals in provenance tracing studies, given their representation of both stable and labile mineral components of different density. However, integration of detrital zircon and K-feldspar data has not been extensively explored for determining the source areas of the Yellow River Basin, which is one of the largest drainage basins in the world. In this study, published detrital zircon U Pb ages (n = 4773) and K-feldspar Pb isotopic compositions (n = 902) in the Yellow River Basin have been compiled and analyzed. Multidimensional scaling and inverse Monte Carlo modeling, allow holistic source-to-sink relationships for sediments in different sections of the Yellow River Basin to be established. Results show that: (1) There is no significant provenance relationship between the sediments from the upper Yellow River and those from the middle and lower reaches. (2) Sediments in the source area of the Yellow River primarily come from northeastern regions of the Tibetan Plateau. Additionally, the Western Loess Plateau and deserts contribute to the material composition of the upper Yellow River. The Yinchuan and Hetao plains are the main areas in the upper reaches of the Yellow River where substantial sediment deposition occurs. These sediments are from the recycling of older sediments transported from the upper reaches of the Yellow River to the Yinchuan and Hetao plains in the early Quaternary. (3) The detrital material in the middle reaches of the Yellow River directly from the Western North China Craton, which also supplied the Eastern Loess Plateau. Sanmen Gorge, located in the middle reaches of the Yellow River, serves as a depocentre for the detrital material from the Jinshan Gorge of the Yellow River and the Wei River, which is a major tributary of the Yellow River. (4) Sediment in the lower reaches of the Yellow River is mostly derived from the middle reaches of the river, with minor contributions from the Qinling Shan. The composition of detrital material in the Yellow River Basin exhibits spatial variations influenced by aeolian and fluvial transport processes resulting from tectonic and climatic activities in the upper and middle Yellow River. Human activities, such as the construction of reservoirs and the flushing of water and sediment along the Sanmen Gorge, have a notable impact on the material composition of the downstream section of the middle and lower Yellow River. The construction of reservoirs alters the natural flow of the Yellow River, leading to changes in sediment transport and deposition downstream. This can result in a decrease in sediment load, which affects the material composition of the riverbed and banks. Additionally, the flushing of water and sediment through the Sanmen Gorge can further modify the sediment distribution in the downstream section of the Yellow River. The U Pb ages of detrital zircon grains in the upper, middle, and lower reaches of the Yellow River exhibit broad agreement with the Pb isotope tracing results obtained from detrital K-feldspar grains, with proportional differences interpreted as relating to zircon recycling. This study provides an example of integrating multiple proxies to reconstruct the source of sediment in a large river system. The findings of this study can be used in the implementation of effective measures aimed at reducing the erosion of soil and protecting the ecology of the Yellow River Basin. [ABSTRACT FROM AUTHOR]

Today, building materials emit many hazardous gases in the event of a fire, causing great harm to human health and the environment. Therefore, it is of great significance to develop bio-based flame retardant materials and to realize preventive measures to reduce fires or their damage. In this work, we fabricated a novel multifunctional fire early-warning polylactic acid-based fabric (MFR-PBF) by coating MXene nanosheet, phytic acid @ furfurylamine (PA@FA) and ammonium polyphosphate (APP) via an eco-friendly layer-by-layer assembly method. MFR-PBF showed outstanding flame retardancy including a limiting oxygen index value of 35 % and better char formation capacity. More importantly, MFR-PBF exhibited sensitive fire early-warning capability (∼1 s) and excellent cyclic alarm stability (>15 cycles) due to the excellent semiconductor responsiveness (light and heat) and the significant catalytic char formation effect. Moreover, MFR-PBF is comfortable, flexible and strong enough to sew onto firefighter uniform to detect a variety of human motions, which can be monitored in the internet by using a LoRa emitter and a gateway. In addition, the controllable heating performance rendered MFR-PBF as a potential portable heater. This work provides new insights into the preparation and application of intelligent fire early-warning fabrics in the smart fire protection and Internet of Things. It is of great significance to develop bio-based flame retardant materials and to realize preventive measures to reduce fires or their damage. Integrating bio-based flame retardants into polylactic acid (PLA) fabric, our work proposes a new multifunctional green fabric that combines passive flame retardancy and active warning strategies. It achieves intelligent fire early-warning and is expected to be a footstone for constructing smart homes and smart firefighting in the future. [Display omitted] • A multifunctional polylactic acid-based fabric was constructed with MXene and N@P FR. • The intelligent fabric shows an ultrasensitive fire-warning capacity and high fire prevention. • Structure evolution of MFR-PBF is elucidated for fire early-warning mechanism. • A wireless smart fire warning system based on IoT • The Joule heating and photothermal conversion performance makes MFR-PBF a portable heater. [ABSTRACT FROM AUTHOR]