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Abstract Objectives In adult hypertensive patients, blood pressure variability is considered a risk factor for heart failure. The relationship between pulse pressure variability and the risk of heart failure remains unclear. This study aims to explore the impact of pulse pressure variability (PPV) on heart failure through a secondary analysis of the SPRINT randomized controlled trial. Methods The data were derived from the SPRINT (Systolic Blood Pressure Intervention Trial) study. The trial recruited participants 50 years or older, with SBP ≥ 130 mm Hg and at least one additional CVD risk factor. We calculated pulse pressure based on the systolic and diastolic blood pressure obtained during follow-up, and used the coefficient of variation to represent pulse pressure variability (PPV) for statistical analysis. We considered the incidence of acute decompensated heart failure as the outcome measure. We employed multivariable Cox regression analysis to examine the relationship between PPV and the risk of heart failure occurrence. Additionally, we used a restricted cubic spline model to analyze the dose–response relationship between PPV and the risk of heart failure occurrence. Results In this study, a total of 9429 participants were included. During a median follow-up time of 3.87 years, 188 new cases of heart failure were observed. The mean age of the study population was 67.9 ± 9.4 years and 3382 participants (35.5%) were females. The average PPCV was 13.85 ± 5.37%. The results from the multivariable Cox regression analysis indicated that the risk of heart failure increased by 3% for every 1% increase in PPCV (HR = 1.030 [95% CI 1.016–1.044]; P

The reliability theory has been an important element of the classical geodetic adjustment theory and methods in the linear Gauss-Markov model. Although errors-in-variables (EIV) models have been intensively investigated, little has been done about reliability theory for EIV models. This paper first investigates the effect of a random coefficient matrix A on the conventional geodetic reliability measures as if the coefficient matrix were deterministic. The effects of such geodetic internal and external reliability measures due to the randomness of the coefficient matrix are worked out, which are shown to depend not only on the noise level of the random elements of A but also on the values of parameters. An alternative, linear approximate reliability theory is accordingly developed for use in EIV models. Both the EIV-affected reliability measures and the corresponding linear approximate measures fully account for the random errors of both the coefficient matrix and the observations, though formulated in a slightly different way. Numerical experiments have been carried to demonstrate the effects of errors-in-variables on reliability measures and compared with the conventional Baarda's reliability measures. The simulations have confirmed our theoretical results that the EIV-reliability measures depend on both the noise level of A and the parameter values. The larger the noise level of A, the larger the EIV-affected internal and external reliability measures; the larger the parameters, the larger the EIV-affected internal and external reliability measures.

The reliability theory has been an important element of the classical geodetic adjustment theory and methods in a linear Gauss-Markov model since Baarda invented reliability in 1968. Although geodetic reliability has been widely investigated and applied to a variety of geodetic, photogrammetric, and remote sensing problems, there is no report of theoretical progress to improve further Baarda’s reliability measures among linear models. We propose the power of the effect of the minimum detectable outlier on parameters as an alternative external reliability measure, present a regularized external reliability, and demonstrate for the first time that the external reliability measure of Baarda’s type is not the best and can be significantly improved through regularization for inverse ill-posed problems. An ill-posed regression example is used to illustrate the regularized external reliability measure, which is shown to perform much better than the external reliability measure of Baarda’s type.

Dielectric chiral metasurface is a new type of planar and efficient chiral optical device that shows strong circular dichroism or optical activity, which has important application potential in optical sensing and display. However, the two types of chiral optical responses in conventional chiral metasurfaces are often interdependent, as their modulation of the amplitudes and phases of orthogonal circularly polarized components is correlated, which limits the further progress of chiral meta-devices. Here we propose a new scheme for independently designing the circular dichroism and optical activity of chiral metasurfaces to further control the polarization and wavefront of transmitted waves. Inspired by mixtures of chiral molecular isomers, we use the dielectric isomer resonators to form “super-units” instead of single meta-atoms for chiral responses in terahertz band, which is called racemic metasurface. By introducing two levels of Pancharatnam-Berry phases between meta-atoms and “super-units”, the polarization rotation angle and wavefront of the beam can be designed without the far-field circular dichroism. We demonstrate the strong control ability on terahertz waves of this scheme through simulation and experiments. In addition, this new type of device with near-field chirality but no far-field circular dichroism may also have important value in optical sensing and other technologies.

Abstract A human cochlea is capable of continuously separating and amplifying sound of different frequencies to specific positions from 20 to 20,000 Hz, which makes it a high-resolution living sensor. The realization of cochlea-like structure for elastic waves in solids offers a highly desirable functionality on high throughput mechanical energy harvesting and sensing, but remains a challenging topic owing to narrow band and intricate configuration. Here we propose and demonstrate a generic framework of elastic cochlea on a thin plate, enabled by a pair of compact metafence layers. It is experimentally realized to harvest and separate flexural waves in quite a wide frequency range from 5.8 to 21.8 kHz, together with a continuous energy amplification exceeding one magnitude order. An enhanced mode, characterized by a near zero group velocity at a tailored cutoff width, is uncovered to illustrate the filtering and amplification physics. Moreover, complex information demultiplexing and undistorted decoding are further realized by harnessing the high-Q signal sensing and purification. The proposed prototype may stimulate substantial applications on information processing, non-destructive evaluation and other wave regulation scenarios.

Abstract Bipolar disorder (BD) is linked to an increased risk of neurodegenerative diseases such as dementia and Parkinson disease (PD), yet several uncertainties still remain and the extent to which the associations could be explained by BD-related medications (antipsychotics, lithium, and antiepileptics) was unknown. This study included 501,233 UK Biobank participants (mean [standard deviation] age, 56.5 [8.10] years; 54.4% women), free of dementia and PD at baseline. After a median 13.8 year follow-up, 9422 cases of dementia and 3457 PD cases were identified. Participants with BD had a significantly higher risk of dementia (adjusted hazard ratio [HR] 2.52, 95% CI 2.00–3.19) and PD (adjusted HR 2.88, 95% CI 2.03-4.08). Findings suggest that up to two-thirds of the association of neurodegenerative diseases with BD may be mediated by BD-related medications. Further research is needed to confirm these findings and explore the underlying mechanisms.

Fault slip rates are critical for understanding the evolution of active faults, earthquake recurrence, and crustal deformation. Yet variations in slip rate along the Haiyuan Fault Zone (HYFZ), a large-scale sinistral strike-slip fault in the northeastern margin of the Tibetan Plateau, remain disputed. Here, we investigate in detail late Quaternary and present-day fault slip rates for several segments across the HYFZ based on previously published geologic and geodetic (i.e. GNSS and InSAR) estimates. Our results reveal that the strike-slip rates increase from ~1.6±0.4–1.8±0.3 mm/a on the Halahu (HLH) fault to ~5.2±1.3–6.2±0.9 mm/a on the Lenglongling (LLL) and Jinqianghe (JQH) faults, then decrease to ~3.9±0.8–4.6±0.3 mm/a on the Maomaoshan (MMS) and Laohushan (LHS) faults, subsequently remain relatively constant (i.e. ~4.6±0.8–4.8±0.7 mm/a) on the Haiyuan (HY) fault (in narrow sense), and finally decrease to ~1.3±0.1–1.5±0.3 mm/a on the Liupanshan (LPS) fault, from west to east. These results indicate that the strike-slip rates on the LLL and JQH faults are highest and decrease toward fault tips along the HYFZ, approximating an asymmetrical bell-shaped distribution. Furthermore, geodetic (short-term) and geologic (long-term) slip rates are in general agreement, indicating that the slip rates were relatively constant in the recent geologic history. Despite the shallow creep on the LHS fault, the Tianzhu Seismic Gap, Tuolaishan (TLS), LLL, and LPS faults have a large locking depth, strain accumulation, and/or long seismic quiescence period, underscoring the substantial seismic hazard in these areas. Our study contributes to characterizing the total slip rate budget across the HYFZ and provides insight into further understanding of seismic hazard and regional crustal deformation.

Abstract Background Base editing is a powerful tool for artificial evolution to create allelic diversity and improve agronomic traits. However, the great evolutionary potential for every sgRNA target has been overlooked. And there is currently no high-throughput method for generating and characterizing as many changes in a single target as possible based on large mutant pools to permit rapid gene directed evolution in plants. Results In this study, we establish an efficient germline-specific evolution system to screen beneficial alleles in Arabidopsis which could be applied for crop improvement. This system is based on a strong egg cell-specific cytosine base editor and the large seed production of Arabidopsis, which enables each T1 plant with unedited wild type alleles to produce thousands of independent T2 mutant lines. It has the ability of creating a wide range of mutant lines, including those containing atypical base substitutions, and as well providing a space- and labor-saving way to store and screen the resulting mutant libraries. Using this system, we efficiently generate herbicide-resistant EPSPS, ALS, and HPPD variants that could be used in crop breeding. Conclusions Here, we demonstrate the significant potential of base editing-mediated artificial evolution for each sgRNA target and devised an efficient system for conducting deep evolution to harness this potential.

Abstract Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Abstract This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4+ T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4+ T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4+ T cells might play a pivotal role in SAB PB.

IntroductionProvision of agricultural productive services to farmers is crucial for integrating them into the modern agricultural system. However, small-scale farmers often face difficulties in accessing these services. One internationally recognized approach to addressing this issue is the government-led provision of productive services to small-scale farmers. In China, production services are provided through village collectives, which are economic organizations established in townships and villages to manage collective assets, develop resources and economy, and provide services to members. Farmer participation in these services can enhance inclusive service dynamics, improving access to services and promoting rural equity.MethodsFarmers’ subjective evaluations directly reflect their access to collective agricultural productive services. This study utilized a binary logit model to analyze the impact and mechanism of farmer participation in cooperatives on the collective supply of agricultural productive services. The study involved 3,900 farmers from 29 provinces (autonomous regions and municipalities) in China.Results and discussionThis study proposes for the first time a “cooperative+collective” model for the provision of productive services. In China, safeguarding social equity is one of the important objectives of the Government, and safeguarding and supporting the interests of small-scale farmers is crucial to safeguarding social equity. Participation in cooperatives increased farmers’ access to agricultural productive services. The analysis revealed that farmers have significantly increased their level of access to agricultural production services through participation in the “cooperative+collective” model of productive services. Farmers have participation in cooperatives helped integrate and expand farmers’ demand, leading to the continuous operation and expansion of business scale, thereby enhancing the collective supply of agricultural productive services. Furthermore, those income low-income, older farmers derived more benefits from participating in cooperatives in terms of accessing these services. This study offers empirical evidence supporting the effectiveness of collective agricultural services.

In automatic safety monitoring of hazardous chemical warehouses,point cloud acquisition with structured light cameras is one of the means to obtain scene data.The complex point cloud of the hazardous chemical warehouse scene has large sc-ale,uneven density and redundant information,which requires simplifying the point cloud.Inter-stack ranging is a key tech-nology for the safety monitoring of hazardous materials warehouses.Therefore,more attention should be paid to the conti-nuity of the edge of the stack point cloud and the integrity of the gap when the point cloud is simplified.The paper firstly a-dopts the optimal raster partition method for downsampling,which better retains the sparse point cloud information while sieving out the dense point cloud;then,aiming at the problem that the stack gap data is easy to be simplified,the local info-rmation entropy is calculated by the normal vector of the point cloud,and the point cloud is simplified based on it.The exp-erimental results show that the point cloud density after simplification is more uniform,and the stacking shape can be ret-ained more completely.At the same time, the method is also applicable to public datasets.

BackgroundType 2 diabetes (T2D) contributes to significant morbidity and mortality for Chinese immigrants in the United States, exacerbated by social determinants of health (SDOH) barriers such as language barriers, limited access to healthy foods, and low health literacy. ObjectiveThe goal of the Integrating Cultural Aspects into Diabetes Education (INCLUDE) study is to test a social media–based intervention adapting the Diabetes Prevention Program (DPP) for Chinese immigrants alongside a culturally adapted, community-supported agriculture program. Here, we report the protocol for the INCLUDE study. MethodsINCLUDE is a 3-year randomized controlled trial (n=150). Participants with prediabetes or at risk for T2D are enrolled and randomized into either the control or intervention group (n=75 each). Participants from the intervention group receive 2-3 culturally tailored, in-language DPP videos weekly for 12 weeks, as well as biweekly phone calls from bilingual study staff to review video content, support goal setting, and assess and address SDOH-related barriers such as food insecurity. Intervention participants will also be given produce for 10 weeks as part of the community-supported agriculture program. Weight (primary outcome), self-efficacy, diet, physical activity, and food insecurity (secondary outcomes) are measured at baseline, 3-month, and 6-month intervals. Splined linear mixed models will be used to examine group differences in longitudinal weight and other secondary outcomes. The INCLUDE study was approved by the Institutional Review Board at the NYU Grossman School of Medicine. ResultsRecruitment started in May 2023, with the first cohort of 75 participants enrolled and randomized into 2 groups in July 2023. The 3-month and 6-month assessment of the first-year cohort has been completed. We have recruited 75 participants for the second cohort as of July 2024. ConclusionsThe INCLUDE study will serve as an innovative model for culturally adapted, multilevel interventions for underserved communities previously unable to access evidence-based diabetes prevention initiatives. Aligning with several national calls for multilevel interventions, the INCLUDE intervention will provide critical data that will inform how researchers and public health professionals address SDOH barriers faced by underserved populations and prevent diabetes. Trial RegistrationClinicalTrials.gov NCT05492916; https://clinicaltrials.gov/study/NCT05492916 International Registered Report Identifier (IRRID)DERR1-10.2196/65455

Summary: T helper (Th)17 cells mediate both protective anti-bacterial immune responses and autoimmune pathogenesis, but the distinct pathways regulating these Th17 responses remain unclear. Retinoid-related orphan receptor γ t (RORγt) is a master transcription factor that governs Th17 cell generation and effector functions. We found that a K256R mutation in RORγt impairs Th17-mediated experimental autoimmune encephalomyelitis (EAE) without affecting the clearance of Citrobacter rodentium. This indicates distinct RORγt roles in central nervous system pathogenesis versus gut-associated protective Th17 responses. Mechanically, RORγt/Runx1-dependent upregulation of galectin-3 (Lgals3) and chemokine receptor Ccr6 in CD4+ T cells is essential for EAE development but not for bacterial clearance. Moreover, Lgals3 is selectively required for recruiting macrophages to produce interleukin (IL)-1β, which in turn promotes Ccr6 expression on CD4+ T cells during EAE pathogenesis. Our findings highlight different RORγt-regulated Th17 pathways in autoimmunity and anti-bacterial immunity, with implications for therapies targeting Th17-mediated autoimmunity while preserving effective anti-bacterial responses.

This study highlights the importance of sustainable social demographic growth. It uses a model that combines the Decision-making Trial and Evaluation Laboratory (DEMATEL) with the Analytic Network Process (ANP) to examine key factors affecting this growth and their interactions. The analysis focuses on six critical factors: economic development, education and gender equality, health services, environmental sustainability, immigration policies, and technological advancement. Experiments using government and international organization databases include comparative experiments with deep learning prediction models, ensemble learning models, Causal Inference Models, complex network analysis models, and agent-based models. Comparison metrics cover accuracy, precision, recall, and F1 score. The results indicate that, with a data volume of 4000, the optimized model achieves an accuracy of 0.973, precision of 0.981, recall of 0.969, and an F1 score of 0.89, demonstrating the model's superior performance. The DEMATEL method analyzes the direct relationships among the factors. The results show that economic development and technological advancement have impact scores of 3.91 and 3.43, respectively, indicating their strong influence on other factors and their role in promoting sustainable demographic growth. Education and gender equality, health services, and technological advancement each have impact scores of 3.39, meaning they are significantly affected by other factors and are sensitive in the growth process. Finally, the ANP method is used to calculate the weights of each factor, determining their relative importance in sustainable social demographic growth. The results highlight that economic development level and technological advancement and innovation are core factors influencing sustainable social demographic growth, with significant direct and indirect impacts on other factors and a crucial role in the overall system. These findings provide a scientific basis for formulating relevant policies and interventions, particularly in prioritizing and strengthening economic and technological development strategies. This study offers valuable insights for research in demography, sustainable development, and social policy formulation.

In this study, it is the first that the Viticis Fructus (VF) was used as the raw material for extracting total flavonoids using the ultrasound-assisted enzyme extraction (UAE) method. Response surface methodology was employed to determine the optimal extraction parameters. The optimal conditions were as follows: 60 % ethanol solution as the extract solvent, material–liquid ratio of 1:25, pH value of 4, enzyme addition amount of 1.5 %, enzymatic hydrolysis time of 30 min, enzymatic hydrolysis temperature of 40 ℃, and ultrasonic time of 50 min. Comparing the total flavonoid yield of VF and processed VF (PVF) extracted using different methods, it was observed that UAE resulted in a higher total flavonoid yield compared to traditional ultrasound extraction and enzyme extraction. Additionally, the total flavonoid yield of PVF extracted by all three methods was generally higher than that of VF. The PVF solution extracted by UAE also demonstrated better in vitro antioxidant activity compared to VF. These results suggest that UAE is an effective method to enhance the activity of natural total flavonoids. The study of the physicochemical properties and in vitro antioxidant activity of VF and PVF showed that the total flavonoid yield and antioxidant activity significantly increased after VF stir-frying, indicating that their efficacy can also be enhanced.

Abstract Multivariate time series forecasting is widely used in various fields in real life. Many time series prediction models have been proposed. The current forecasting model lacks the mining of correlation between sequences based on different periods and correlation of periodical features between different periods when dealing with data. In this paper, we propose a multivariate data prediction model FAFTransformer based on the reorganization of multi‐periodic features, which first extracts the multi‐periodic information of the time series using the method of frequency domain analysis. The temporal dependencies within sequences are then captured using convolution based on different periods, and the correlations between sequences are learned by combining the multivariate attention mechanism to obtain the intra‐sequence and inter‐sequence correlations under the same period. Finally, period fusion is proposed to capture the correlation of period characteristics between different periods. The experimental results show that the model achieves the best results on multiple datasets compared to the latest seven predictive models for time‐series data.

Abstract Purpose This study aimed to evaluate the potential of astragalus polysaccharide (APS) pretreatment in enhancing the homing and anti-peritoneal fibrosis capabilities of bone marrow mesenchymal stromal cells (BMSCs) and to elucidate the underlying mechanisms. Methods Forty male Sprague-Dawley rats were allocated into four groups: control, peritoneal dialysis fluid (PDF), PDF + BMSCs, and PDF + APSBMSCs (APS-pre-treated BMSCs). A peritoneal fibrosis model was induced using PDF. Dil-labeled BMSCs were administered intravenously. Post-transplantation, BMSC homing to the peritoneum and pathological alterations were assessed. Stromal cell-derived factor-1 (SDF-1) levels were quantified via enzyme-linked immunosorbent assay (ELISA), while CXCR4 expression in BMSCs was determined using PCR and immunofluorescence. Additionally, a co-culture system involving BMSCs and peritoneal mesothelial cells (PMCs) was established using a Transwell setup to examine the in vitro effects of APS on BMSC migration and therapeutic efficacy, with the CXCR4 inhibitor AMD3100 deployed to dissect the role of the SDF-1/CXCR4 axis and its downstream impacts. Results In vivo and in vitro experiments confirmed that APS pre-treatment notably facilitated the targeted homing of BMSCs to the peritoneal tissue of PDF-treated rats, thereby amplifying their therapeutic impact. PDF exposure markedly increased SDF-1 levels in peritoneal and serum samples, which encouraged the migration of CXCR4-positive BMSCs. Inhibition of the SDF-1/CXCR4 axis through AMD3100 application diminished BMSC migration, consequently attenuating their therapeutic response to peritoneal mesenchyme-to-mesothelial transition (MMT). Furthermore, APS upregulated CXCR4 expression in BMSCs, intensified the activation of the SDF-1/CXCR4 axis’s downstream pathways, and partially reversed the AMD3100-induced effects. Conclusion APS augments the SDF-1/CXCR4 axis’s downstream pathway activation by increasing CXCR4 expression in BMSCs. This action bolsters the targeted homing of BMSCs to the peritoneal tissue and amplifies their suppressive influence on MMT, thereby improving peritoneal fibrosis.

Abstract Background Cuscutae Semen (CS) has been prescribed in traditional Chinese medicine (TCM) for millennia as an aging inhibitor, an anti-inflammatory agent, a pain reliever, and an aphrodisiac. Its three main forms include crude Cuscutae Semen (CCS), wine-processed CS (WCS), and stir-frying-processed CS (SFCS). Premature ovarian insufficiency (POI) is a globally occurring medical condition. The present work sought a highly efficacious multi-target therapeutic approach against POI with minimal side effects. Finally, it analyzed the relative differences among CCS, WCS and SFCS in terms of their therapeutic efficacy and modes of action against H2O2-challenged KGN human granulosa cell line. Methods In this study, ultrahigh-performance liquid chromatography (UPLC)-Q-ExactiveTM Orbitrap-mass spectrometry (MS), oxidative stress indices, reactive oxygen species (ROS), Mitochondrial membrane potential (MMP), real-time PCR, Western blotting, and molecular docking were used to investigate the protective effect of CCS, WCS and SFCS on KGN cells oxidative stress and apoptosis mechanisms. Results The results confirmed that pretreatment with CCS, WCS and SFCS reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the KGN cells. CCS, WCS and SFCS upregulated the expression of antioxidative levels (GSH, GSH/GSSG ratio, SOD, T-AOC),mitochondrial membrane potential (MMP) and the relative mRNA(Nrf2, Keap1, NQO-1, HO-1, SOD-1, CAT). They inhibited apoptosis by upregulating Bcl-2, downregulating Bax, cleaved caspase-9, and cleaved caspase-3, and lowering the Bax/Bcl-2 ratio. They also exerted antioxidant efficacy by partially activating the PI3K/Akt and Keap1-Nrf2/HO-1 signaling pathways. Conclusions The results of the present work demonstrated the inhibitory efficacy of CCS, WCS and SFCS against H2O2-induced oxidative stress and apoptosis in KGN cells and showed that the associated mechanisms included Keap1-Nrf2/HO-1 activation, P-PI3K upregulation, and P-Akt-mediated PI3K-Akt pathway induction.

Abstract Aquifer confinement represents a pivotal property that significantly influences the vulnerability and contamination risk of groundwater resources. Several methods have been proposed for determining aquifer confinement by analyzing the response of well water level to Earth tides and atmospheric tides. In this study, we evaluated the performance of the existing single methods and put forward an optimized comprehensive approach. We compared the determination results of the three single methods with those of a comprehensive method using water-level data from 39 earthquake precursor monitoring wells in North China. The results demonstrate that the comprehensive method effectively determined aquifer confinement, significantly reducing the uncertainty associated with the three single methods. The application of the comprehensive method in North China reveals that aquifer confinement may undergo temporal variations during long-term continuous observation, especially in areas where the confining properties of aquifers may vary due to human activities and earthquakes. In such areas, the comprehensive method facilitates accurate assessment of groundwater vulnerability, as well as the potential dispersion of underground pollutants.

The tensile-shear interactive damage (TSID) model is a novel and powerful constitutive model for rock-like materials. This study proposes a methodology to calibrate the TSID model parameters to simulate sandstone. The basic parameters of sandstone are determined through a series of static and dynamic tests, including uniaxial compression, Brazilian disc, triaxial compression under varying confining pressures, hydrostatic compression, and dynamic compression and tensile tests with a split Hopkinson pressure bar. Based on the sandstone test results from this study and previous research, a step-by-step procedure for parameter calibration is outlined, which accounts for the categories of the strength surface, equation of state (EOS), strain rate effect, and damage. The calibrated parameters are verified through numerical tests that correspond to the experimental loading conditions. Consistency between numerical results and experimental data indicates the precision and reliability of the calibrated parameters. The methodology presented in this study is scientifically sound, straightforward, and essential for improving the TSID model. Furthermore, it has the potential to contribute to other rock constitutive models, particularly new user-defined models.

Abstract Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a “spatially competing distribution” (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.

Abstract It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.

Abstract Metabolic dysfunction‐associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet‐induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut‐liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut‐pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic‐guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease‐associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development.

BackgroundCervical cancer is the fourth most common cancer among women, HPV vaccine can reduce the incidence of cervical cancer by approximately 70%. Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. This study aimed to investigate the awareness of HPV and its vaccine among college students in Zhengzhou, and to explore the factors influencing their awareness of HPV vaccine, to understand college students’ willingness to receive the vaccine. The findings of this study will lay a foundation for cervical cancer prevention.MethodsUsing a multistage random sampling method, 650 college students from four universities in Zhengzhou were selected. A self-administered questionnaire on the awareness of HPV and its vaccine, and willingness to receive HPV vaccination was carried out. Logistic regression was used to analyze the factors influencing students’ awareness of the HPV vaccine.Results58.0% of college students had heard of HPV, and 72.8% of college students had heard of HPV vaccine. Logistic regression showed that gender, major, grade, mean monthly consumption level, sexual history, and mother cervical cancer screening participation significantly influenced the awareness of HPV vaccine (p

Objective: This study aims to evaluate the effectiveness of the Quality Risk Management (QRM) system in hospital pharmacy intravenous admixture services (PIVAS). Methods: Failure Modes and Effects Analysis (FMEA) and risk matrix methods were used to systematically assess the critical risk points in PIVAS. By collecting and comparing relevant data from 2019 to 2023, key performance indicators (KPIs) before and after the implementation of the QRM system were quantitatively evaluated. Results: The results showed that the safety and efficiency of pharmacy services significantly improved after the implementation of the QRM system. The medication error rate significantly decreased from 3.2% to 1.1%, the average medication preparation time reduced from 15.5 min to 8.2 min, and staff satisfaction increased from 6.0 to 8.5 points. Other indicators, such as cross-contamination rates and handling errors, also showed significant improvement (all outcomes p

Summary: Background: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. Methods: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. Findings: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186–20,893 vs 7447 IU/mL; 4646–11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. Interpretation: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. Funding: Singapore NMRC, USFDA, MRC.

Objectives: The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may improve antibody responses against new variants. Methods: A total of 107 participants, who had three COVID-19 WT mRNA vaccine doses, were recruited, and given either a monovalent (WT) or a bivalent mRNA vaccination (Pfizer/BioNTech Bivalent (WT and BA.4/BA.5) or Moderna Bivalent (WT and BA.1). Blood samples were taken before booster and at 28 days post-booster. Results: We found significantly lower fold change in serum binding IgA responses against BA.1, BA.5 and EG.5.1 spike in the bivalent booster group, compared with the monovalent (WT) booster group, following vaccination. However, this was only observed in individuals with prior infection. The relative fold change in serum binding IgA response was more skewed towards WT over variant (BA.1, BA.5 or EG.5.1) spike in previously infected bivalent-booster-vaccinees, as compared with previously infected monovalent-(WT)-booster-vaccinees. Conclusion: The findings suggest imprinting of antibody responses that is shaped by the first vaccination (WT spike). Previous infection also affects the boosting effect of follow-up vaccination. Studies are needed to understand how to induce a robust and long-lasting IgA immunity for protection against COVID-19 infection.

Background: To anticipate the potential molecular mechanism of Astragalus membranaceus (AM) and its monomer, Calycosin, against peritoneal fibrosis (PF) and related muscle atrophy using mRNA-seq, network pharmacology, and serum pharmacochemistry.Methods: Animal tissues were examined to evaluate a CKD-PF mice model construction. mRNA sequencing was performed to find differential targets. The core target genes of AM against PF were screened through network pharmacology analysis, and CKD-PF mice models were given high- and low-dose AM to verify common genes. Serum pharmacochemistry was conducted to clarify which components of AM can enter the blood circulation, and the selected monomer was further validated through cell experiments for the effect on PF and mesothelial mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs).Results: The CKD-PF mice models were successfully constructed. A total of 31,184 genes were detected in the blank and CKD-PF groups, and 228 transcription factors had significant differences between the groups. Combined with network pharmacology analysis, a total of 228 AM-PF-related targets were identified. Androgen receptor (AR) was the remarkable transcription factor involved in regulating transforming growth factor-β1 (TGF-β1). AM may be involved in regulating the AR/TGF-β1 signaling pathway and may alleviate peritoneal dialysis-related fibrosis and muscle atrophy in CKD-PF mice. In 3% peritoneal dialysis solution-stimulated HMrSV5 cells, AR expression levels were dramatically reduced, whereas TGF-β1/p-smads expression levels were considerably increased.Conclusion: AM could ameliorate PF and related muscle atrophy via the co-target AR and modulated AR/TGF-β1 pathway. Calycosin, a monomer of AM, could partially reverse PMC MMT via the AR/TGF-β1/smads pathway. This study explored the traditional Chinese medicine theory of “same treatment for different diseases,” and supplied the pharmacological evidence of “AM can treat flaccidity syndrome.”

Enterprise innovation remains a cornerstone of economic development, with the direct influence of financialization on enterprise innovation standing as a critical factor. In contrast with the existing research, this study constructs an evolutionary game model by utilizing the Cournot model to analyze the innovation behavior of enterprises, and analyzes the influence of financialization on enterprise innovation by incorporating investment returns, market competition, and demand scale into the research framework. In addition, this study selects the sample of the Chinese non-financial listed enterprises and using panel data for the period 2009 to 2021. Based on the findings from the empirical analysis, this study reveals that excessive financialization hinders innovation in Chinese enterprises. Additionally, an intermediary pathway involving 'financialization - investment returns - enterprise innovation' is identified as a transmission mechanism. The demand scale generated by innovation inversely correlates with the inhibitory effects of financialization on enterprise innovation behavior. Meanwhile, heightened market competition amplifies the inhibitory influence of financialization on innovation. This study provided valuable empirical evidence, facilitating the enhancement of enterprise innovation efficiency.

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

BackgroundEmerging evidence indicates that individuals with type 2 diabetes (T2D) are more prone to mental health issues than the general population; however, there is a significant lack of data concerning the mental health burden in Chinese Americans with T2D. ObjectiveThe aim of this study was to explore the comorbid mental health status, health-seeking behaviors, and mental service utilization among Chinese Americans with T2D. MethodsA cross-sectional telephone survey was performed among 74 Chinese Americans with T2D in New York City. We used standardized questionnaires to assess mental health status and to gather data on mental health–seeking behaviors and service utilization. Descriptive statistics were applied for data analysis. ResultsA total of 74 Chinese Americans with T2D completed the survey. Most participants (mean age 56, SD 10 years) identified as female (42/74, 57%), were born outside the United States (73/74, 99%), and had limited English proficiency (71/74, 96%). Despite nearly half of the participants (34/74, 46%) reporting at least one mental health concern (elevated stress, depressive symptoms, and/or anxiety), only 3% (2/74) were currently using mental health services. Common reasons for not seeking care included no perceived need, lack of information about Chinese-speaking providers, cost, and time constraints. The cultural and language competence of the provider was ranked as the top factor related to seeking mental health care. ConclusionsChinese Americans with T2D experience relatively high comorbid mental health concerns yet have low service utilization. Clinicians may consider team-based care to incorporate mental health screening and identify strategies to provide culturally and linguistically concordant mental health services to engage Chinese Americans with T2D.

Aiming to address the issue of mapping failure resulting from unsmooth motion during SLAM (Simultaneous Localization and Mapping) performed by a quadruped robot, a tightly coupled SLAM algorithm that integrates LIDAR and IMU sensors is proposed in this paper. Firstly, the IMU information, after undergoing deviation correction, is utilized to remove point cloud distortion and serve as the initial value for point cloud registration. Subsequently, a registration algorithm based on Normal Distribution Transform (NDT) and sliding window is presented to ensure real-time positioning and accuracy. Then, an error function combining IMU and LIDAR is formulated using a factor graph, which iteratively optimizes position, attitude, and IMU deviation. Finally, loop closure detection based on Scan Context is introduced, and loop closure factors are incorporated into the factor graph to achieve effective mapping. An experimental platform is established to conduct accuracy and robustness comparison experiments. Results showed that the proposed algorithm significantly outperforms the LOAM algorithm, the NDT-based SLAM algorithm and the LeGO-LOAM algorithm in terms of positioning accuracy, with a reduction of 65.08%, 22.81%, and 37.14% in root mean square error, respectively. Moreover, the proposed algorithm exhibits superior robustness compared to LOAM, NDT-based SLAM and LeGO-LOAM.

Abstract Background A subset of Graves’ disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. Methods A prospective cohort study (2018–2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. Results Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves’ ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium–low cumulative dosage group (average

Energetic Semiconductor bridge (ESCB) based on reactive multilayered films (RMFs) has a promising application in the miniature and intelligence of initiator and pyrotechnics device. Understanding the ignition enhancement mechanism of RMFs on semiconductor bridge (SCB) during the ignition process is crucial for the engineering and practical application of advanced initiator and pyrotechnics devices. In this study, a one-dimensional (1D) gas-solid two-phase flow ignition model was established to study the ignition process of ESCB to charge particles based on the reactivity of Al/MoO3 RMFs. In order to fully consider the coupled exothermic between the RMFs and the SCB plasma during the ignition process, the heat release of chemical reaction in RMFs was used as an internal heat source in this model. It is found that the exothermal reaction in RMFs improved the ignition performance of SCB. In the process of plasma rapid condensation with heat release, the product of RMFs enhanced the heat transfer process between the gas phase and the solid charge particle, which accelerated the expansion of hot plasma, and heated the solid charge particle as well as gas phase region with low temperature. In addition, it made up for pressure loss in the gas phase. During the plasma dissipation process, the exothermal chemical reaction in RMFs acted as the main heating source to heat the charge particle, making the surface temperature of the charge particle, gas pressure, and gas temperature rise continuously. This result may yield significant advantages in providing a universal ignition model for miniaturized ignition devices.

Abstract Although global navigation satellite systems (GNSS) have been routinely applied to determine attitudes, there exists no literature on determining angular velocity and/or angular acceleration from GNSS. Motivated by the invention of computerized accelerometers of the correspondence author and following the success of accurately recovering translational velocity and acceleration waveforms from very high-rate GNSS precise positioning by Xu and his collaborators in 2021, we propose the concept of GNSS gyroscopes and reconstruct angular velocity and acceleration from very high-rate GNSS attitudes by applying regularization under the criterion of minimum mean squared errors. The major results from the experiments can be summarized in the following: (i) angular velocity and acceleration waveforms computed by applying the difference methods to high-rate GNSS attitudes are too noisy and can be physically not meaningful and numerically incorrect. The same can be said about inertial measurement unit (IMU) attitudes, if IMU gyros are not of very high accuracy; (ii) regularization is successfully applied to reconstruct the high-rate angular velocity and acceleration waveforms from 50 Hz GNSS attitudes and significantly outperforms the difference methods, validating the proposed concept of GNSS gyroscopes. By comparing the angular velocity and acceleration results by using the difference methods and regularization, we find that the peak values of angular velocity and acceleration by regularization are much smaller by a maximum factor of 1.57 in the angular velocity to a maximum factor of 8662.53 times in the angular acceleration in the case of high-rate GNSS, and by a maximum factor of 1.26 in the angular velocity to a maximum factor of 2819.85 times in the angular acceleration in the case of IMU, respectively; and (iii) the IMU attitudes apparently lead to better regularized angular velocity and acceleration waveforms than the high-rate GNSS attitudes, which can well be explained by the fact that the former is of better accuracy than the latter. As a result, to suppress the significant amplification of noise in GNSS attitudes, larger regularization parameters have to be chosen for the high-rate GNSS attitudes, resulting in smaller peak angular accelerations by a maximum factor of 37.55 percent in the angular velocity to a maximum factor of 6.20 times in the angular acceleration in comparison of the corresponding IMU results. Nevertheless, the regularized angular acceleration waveforms for both GNSS and IMU look more or less similar in pattern or waveform shape.

Taiwan is currently experiencing high energy use, particularly in buildings. Traditional houses have the advantage of being able to adapt to their surroundings effectively. Several traditional houses are listed as local heritage in Taiwan’s Guanshan village. Considering these are historical buildings, reuse was intended. The temperature change, however, prevented this house from functioning as well as it once could. The application of modern thermal comforts, such as heaters and air conditioners, may alter the originality and character of a structure. This study aims to investigate the natural ventilation of Base 8, a historic Taiwanese residence in Guanshan, to reduce its energy consumption. An in-depth analysis of the case study, a comprehensive understanding of the passive system, site measurements (anemometers), and CFD simulation are used to maximize the potential of cross ventilation. According to the study, an opening perpendicular to the wind’s path would provide better wind passage than one parallel to it. In addition to reducing energy consumption, the study’s findings could help local governments develop guidelines for restoring historic homes in a way that preserves their original materials while preserving their historical heritage.

Abstract Chronic wounds are often infected with biofilm bacteria and characterized by high oxidative stress. Current dressings that promote chronic wound healing either require additional processes such as photothermal irradiation or leave behind gross amounts of undesirable residues. We report a dual-functionality hydrogel dressing with intrinsic antibiofilm and antioxidative properties that are synergistic and low-leaching. The hydrogel is a crosslinked network with tethered antibacterial cationic polyimidazolium and antioxidative N-acetylcysteine. In a murine diabetic wound model, the hydrogel accelerates the closure of wounds infected with methicillin-resistant Staphylococcus aureus or carbapenem-resistant Pseudomonas aeruginosa biofilm. Furthermore, a three-dimensional ex vivo human skin equivalent model shows that N-acetylcysteine promotes the keratinocyte differentiation and accelerates the re-epithelialization process. Our hydrogel dressing can be made into different formats for the healing of both flat and deep infected chronic wounds without contamination of the wound or needing other modalities such as photothermal irradiation.

Abstract Background The utilization of fructose as a carbon source and energy provider plays a crucial role in bacterial metabolism. Additionally, fructose metabolism directly impacts the pathogenicity and virulence of certain pathogenic microorganisms. Results In this study, we report the discovery of a fructose phosphotransferase system (PTS) in S. aureus. This system comprises three genes, namely fruR, fruK, and fruT, which are co-located in an operon that is indispensable for fructose utilization in S. aureus. Our findings confirm that these three genes are transcribed from a single promoter located upstream of the fruRKT operon. The fruR gene encodes a DeoR-type transcriptional regulator, designated as FruR, which represses the expression of the fruRKT operon by direct binding to its promoter region. Significantly, our experimental data demonstrate that the fruRKT operon can be induced by fructose, suggesting a potential regulatory mechanism involving intracellular fructose-1-phosphate as a direct inducer. Furthermore, we conducted RNA-seq analysis to investigate the specificity of FruR regulation in S. aureus, revealing that the fruRKT operon is predominantly regulated by FruR. Conclusions In summary, this study has uncovered a fructose phosphotransferase system (PTS) in S. aureus, highlighting the essential role of the fruR, fruK, and fruT genes in fructose utilization. We confirmed their co-location within an operon and established FruR as a key regulator by binding to the operon’s promoter. Importantly, we demonstrated that fructose can induce this operon, possibly through intracellular fructose-1-phosphate. Our identification of this PTS system represents the initial characterization of a fructose metabolism system in S. aureus.

Objective: Previous drug repositioning studies have suggested that parthenolide may be a differentiation-inducing agent for glioma cells. This study aimed to experimentally verify the neuronal differentiation-inducing effects and proliferative impact of parthenolide on human glioma cells and explore its potential mechanisms. Methods: HE staining was used to observe the morphological changes in human glioma cell lines U87 and A172 induced by parthenolide. Immunocytochemistry was conducted to detect the expression of differentiation markers. The Ki-67 detection and CCK-8 assay were used to assess the effects of parthenolide on cell proliferation. The sphere formation assay was conducted to evaluate the self-renewal. Glioma stem cells (GSCs) derived from U87 cells were utilized to assess the ability of parthenolide to induce differentiation in GSCs. Western blot was used to detect the expression of histone deacetylase 1 (HDAC1). Bioinformatics analysis based on the CGGA database was conducted to evaluate the role of HDAC1 in glioma. Results: Parthenolide (4 μM) altered the morphology of U87 and A172 cells, as elongated cell projections were observed. Parthenolide induced glioma cells to express neuronal markers NeuN, MAP2, SYP, and NEFL, but not astrocyte or oligodendrocyte markers. Parthenolide significantly inhibited proliferation and self-renewal in glioma cells. Similar effects were observed in U87 GSCs. Furthermore, parthenolide downregulated HDAC1 expression in glioma cells, and the bioinformatics analysis revealed a potential relationship between neuronal characteristics and low expression of HDAC1 in glioma. Conclusion: Parthenolide induced neuronal differentiation and inhibited the cell proliferation in human glioma cells, which might be associated with the inhibition of HDAC1.

The detection of tea bud targets is the foundation of automated picking of premium tea. This article proposes a high-performance tea bud detection model to address issues such as complex environments, small target tea buds, and blurry device focus in tea bud detection. During the spring tea-picking stage, we collect tea bud images from mountainous tea gardens and annotate them. YOLOv5 tea is an improvement based on YOLOv5, which uses the efficient Simplified Spatial Pyramid Pooling Fast (SimSPPF) in the backbone for easy deployment on tea bud-picking equipment. The neck network adopts the Bidirectional Feature Pyramid Network (BiFPN) structure. It fully integrates deep and shallow feature information, achieving the effect of fusing features at different scales and improving the detection accuracy of focused fuzzy tea buds. It replaces the independent CBS convolution module in traditional neck networks with Omni-Dimensional Dynamic Convolution (ODConv), processing different weights from spatial size, input channel, output channel, and convolution kernel to improve the detection of small targets and occluded tea buds. The experimental results show that the improved model has improved precision, recall, and mean average precision by 4.4%, 2.3%, and 3.2%, respectively, compared to the initial model, and the inference speed of the model has also been improved. This study has theoretical and practical significance for tea bud harvesting in complex environments.

2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is a widely used brominated flame retardant belonging to persistent organic pollutants (POPs). After being released into the marine environment, BDE-47 can cause a range of toxic effects on marine organisms through bioaccumulation, biomagnification, and intergenerational transmission. These effects include lethality, impaired motility, photosynthetic toxicity, immune damage, liver toxicity, developmental impairments, and reproductive toxicity. This article reviews the latest research progress on the toxic effects and molecular mechanisms of BDE-47 mentioned above. The primary mechanisms underlying its toxicity include oxidative stress, DNA damage, cellular apoptosis, impaired metabolism, and activation of the MAPK signaling cascade.

The gradual integration of digital technology into traditional Chinese villages has triggered a shift in income distribution from labor to capital, posing challenges to the wage growth of employed peasants. Based on the theory of empowerment, this paper explores the mechanisms of credit availability and talent loss in the interplay between digital capabilities and wage augmentation among employed peasants. This study empirically examines or validates the mechanism of digital capabilities on wage growth for employed peasants through the entropy weight method, the OLS linear model, the mediation effect model, and propensity score matching while using survey data from 490 farmer entrepreneurs as samples. The findings are as follows. (1) The digital capabilities of farmer entrepreneurs have a significant positive impact on the wage growth of employed peasants, and this result remains robust after a series of robustness checks. In terms of hierarchical effects, digital foundational capabilities > digital application capabilities > digital innovation capabilities. (2) Credit availability and talent loss mediate the relationship between digital capabilities and wage growth for employed peasants. (3) The digital capabilities of farmer entrepreneurs who are young, highly educated, and have a low family-dependency ratio exert a more pronounced influence on the wage growth of employed peasants. Additionally, lower policy uncertainty enhances the effect of digital capabilities on wage growth for employed peasants. The study uncovers the empowerment mechanism of digital advancements embedded during the entrepreneurial journey, enriches research on digital capabilities and common prosperity, and provides a feasible path for governments to formulate reasonable entrepreneurship and digital promotion policies.

Free-living amoebae (FLA) are prevalent in nature and man-made environments, and they can survive in harsh conditions by forming cysts. Studies have discovered that some FLA species are able to show pathogenicity to human health, leading to severe infections of central nervous systems, eyes, etc. with an extremely low rate of recovery. Therefore, it is imperative to establish a surveillance framework for FLA in environmental habitats. While many studies investigated the risks of independent FLA, interactions between FLA and surrounding microorganisms determined microbial communities in ecosystems and further largely influenced public health. Here we systematically discussed the interactions between FLA and different types of microorganisms and corresponding influences on behaviors and health risks of FLA in the environment. Specifically, bacteria, viruses, and eukaryotes can interact with FLA and cause either enhanced or inhibited effects on FLA infectivity, along with microorganism community changes. Therefore, considering the co-existence of FLA and other microorganisms in the environment is of great importance for reducing environmental health risks.

ABSTRACT Drug efflux systems have recently been recognized as a significant mechanism responsible for multidrug resistance in bacteria. In this study, we described the identification and characterization of a new chromosomally encoded efflux pump (SA00565) in Staphylococcus aureus. SA00565, which belongs to the drug/metabolite transporter (DMT) superfamily, was predicted to be a 10-transmembrane segment transporter. To evaluate the role of sa00565 in resistance, we generated sa00565 gene deletion mutant (Δsa00565) and assessed its susceptibility to 35 different antibiotic treatments. Our results demonstrated that the Δsa00565 mutant exhibited reduced resistance to tetracycline and doxycycline, with 64-fold and 12-fold decreased MICs, respectively. The mechanism of SA00565-mediated tetracycline resistance was demonstrated that SA00565 possesses the capability to efficiently extrud intracellular tetracycline into the environment. The efflux activity of SA00565 was further validated using EtBr accumulation and efflux assays. In summary, our study uncovered a previously unknown function of a DMT family transporter, which serves as a tetracycline efflux pump, thereby contributing to tetracycline resistance in S. aureus.IMPORTANCEIn this study, we addressed the significance of drug efflux systems in multidrug resistance of Staphylococcus aureus, focusing on the unexplored efflux pump SA00565 in the drug/metabolite transporter (DMT) superfamily. Through phylogenetic analysis, gene knockout, and overexpression experiments, we identified the role of SA00565 in antibiotic resistance. The Δsa00565 mutant showed increased susceptibility to tetracycline and doxycycline in disk diffusion assays, with significantly lower MICs compared to the WT. Remarkably, intracellular tetracycline concentration in the mutant was two- to threefold higher, indicating SA00565 actively eliminates intracellular tetracycline. Our findings emphasize the pivotal contribution of SA00565 to tetracycline antibiotic resistance in S. aureus, shedding light on its functional attributes within the DMT superfamily and providing valuable insights for combating multidrug resistance.

Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS typically present with thymomas, reduced or absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity. We report the case of a 67-year-old woman diagnosed with GS following the development of a progressive, severe, refractory pulmonary infection and diffuse panbronchiolitis (DPB). She also had diabetes, characterized by anti-glutamic acid decarboxylase antibody positivity, leading to a diagnosis of latent autoimmune diabetes in adults (LADA). A thorough review of existing literature revealed that GS is often confirmed after multiple episodes of opportunistic infections or autoimmune diseases post-thymoma surgery. Due to their immunodeficiency, GS patients frequently suffer from recurrent infections over extended periods, and some succumb to severe infections. Regular immunoglobulin infusions may be effective in treating GS.