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Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Tanshinone IIA, a compound derived from traditional Chinese medicine, has demonstrated anti-inflammatory properties and may enhance treatment outcomes when combined with mesalazine. This study aims to determine the overall response rate of Tanshinone IIA in combination with mesalazine for the treatment of UC. Methods We reviewed articles from the establishment of the databases until April 2023 in the PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases. They included a randomized controlled trial in which the intervention group was given tanshinone IIA plus mesalazine (T + M), while the comparative group was given only mesalazine (M). We removed duplicates or similar papers; papers with no available full text or incomplete data; animal research; and review and systematic review articles. STATA 15.1 was used to analyze the data. Results The perceived total effectiveness rate of T + M was found to be higher than M and the difference was found to be significant (P = 0.000). Additionally, pooled results show that TNF-α (P = 0.000) and CRP (P = 0.000) levels in the T + M group were all significantly lower than that in the M group. Furthermore, MHC-II expression in the T + M group was minors compared to that of the M group (P = 0.001). However, there was no significant difference in the incidence of adverse events between the T + M and M groups (P = 0.700). Conclusion This meta-analysis demonstrates that combining tanshinone IIA with mesalazine significantly enhances the overall treatment efficacy for ulcerative colitis compared to mesalazine alone. Tanshinone IIA also exhibits anti-inflammatory effects by reducing TNF-α, CRP levels, and MHC-II expression without notably increasing adverse events. Despite some limitations, these findings suggest that tanshinone IIA can be a promising adjunctive therapy for ulcerative colitis. Further large-scale, multi-center studies are needed to confirm these results and establish the long-term safety and effectiveness of this combination therapy.

Abstract Background Measurements, nowcasts, or forecasts ideally should correctly reflect changes in the values of interest. In this article, we focus on how to assess the ability of measurements, nowcasts, or forecasts to correctly predict the direction of changes in values - which we refer to as the ability to track changes (ATC). Methods We review and develop visual techniques and quantitative measures to assess ATC. Extensions for noisy data and estimation uncertainty are implemented using bootstrap confidence intervals and exclusion areas. Results We exemplarily illustrate the proposed methods to assess the ability to track changes for nowcasting during the COVID-19 pandemic, patient admissions to an emergency department, and non-invasive blood pressure measurements. The proposed methods effectively evaluate ATC across different applications. Conclusions The developed ATC assessment methods offer a comprehensive toolkit for evaluating the ATC of measurements, nowcasts, and forecasts. These techniques provide valuable insights into model performance, complementing traditional accuracy measures and enabling more informed decision-making in various fields, including public health, healthcare management, and medical diagnostics.

Abstract In the financial field, constructing efficient investment portfolios is a focal point of research, encompassing asset selection and optimization of asset allocation. With the advancements in Large Language Models (LLMs), generative Artificial Intelligence (AI) tools have showcased capabilities never seen before. However, the black-box nature of these tools renders their outputs difficult to interpret directly, often necessitating iterative fine-tuning to align with users’ expected outcomes. This study presents a structured prompt framework specifically designed for stock selection, aiming to provide direct and interpretable stock-selecting tools for investors of various levels. By creating representative scenarios and combining them into different cases for experimentation, we can explore how the construction of prompts influences the responses generated by generative AI tools. Additionally, this paper proposes a novel algorithm that combines the Nonlinear-Activated Beetle Antennae Search strategy with the Egret Swarm Optimization Algorithm (NBESOA) to address the Mean-Variance Portfolio Selection problem with Transaction Costs and Cardinality Constraints (MVPS-TCCC), utilizing real stock market data to construct portfolios based on generative AI tools recommendations. Simulation results indicate that, compared to other algorithms, NBESOA prefers optimizing portfolio configurations to achieve the highest Sharpe Ratio with the strictest constraints, bringing the outcomes closer to the portfolio’s efficient frontier.

Abstract The quality of broiler meat affects consumers’ purchasing decisions. Numerous studies have shown that phosphorylation of proteins in muscle can affect muscle quality. Here, metabolomics and transcriptomics were used to systematically identify the genetic regulation of differences in meat flavor among different broiler. By constructing the meat flavor-related metabolite-gene networks, we identified that protein phosphatase magnesium/manganese-dependent 1J (PPM1J), which is known to regulate a range of biological processes by modulating reversible protein phosphorylation, was a differentially expressed gene with the highest connectivity to meat flavor-related metabolites. Gain- and loss-of-function analysis revealed that PPM1J induced muscular atrophy, improved meat quality and regulated the composition of glycerophospholipids. More importantly, phosphoproteome and metabolome results found that PPM1J participates in the regulation of meat quality feature and glycerophospholipids composition by catalyzing protein dephosphorylation. Our study provides a basis for further understanding the molecular mechanism of meat quality feature and glycerophospholipids composition in broiler.

Abstract Circadian clock serves as a regulator of gastrointestinal health, and the disruption of circadian rhythm may trigger the dysregulation of the intestinal barrier functions. This study investigated the effectiveness of capsaicin (CAP) in mitigating intestinal barrier dysfunction induced by circadian disruption in male SPF C57BL/6J mice. Our findings indicated that CAP supplementation attenuated abnormal weight gain, alterations in serum lipid levels, and misalignment in hepatic and colonic circadian clock gene expressions in mice caused by constant darkness (CD) treatment. The restoration of the intestinal barrier integrity was also observed through the increase in mucosal thickness and goblet cell numbers. Both the diversity and the circadian rhythm of gut microbiota were improved in CAP‐treated group. Correlation analysis indicated that CAP could modulate the gut microbiota by affecting intestinal barrier function and systemic metabolism in CD‐treated mice. These results highlight the potential of CAP as a functional food component in maintaining the intestinal barrier homeostasis through regulating gut microbiota.

Abstract Background Abnormal sphingolipid metabolism (SM) is closely linked to the incidence of cancers. However, the role of SM in pancreatic cancer (PC) remains unclear. This study aims to explore the significance of SM in the prognosis, immune microenvironment, and treatment of PC. Methods Single-cell and bulk transcriptome data of PC were acquired via TCGA and GEO databases. SM-related genes (SMRGs) were obtained via MSigDB database. Consensus clustering was utilized to construct SM-related molecular subtypes. LASSO and Cox regression were utilized to build SM-related prognostic signature. ESTIMATE and CIBERSORT algorithms were employed to assess the tumour immune microenvironment. OncoPredict package was used to predict drug sensitivity. CCK-8, scratch, and transwell experiments were performed to analyze the function of ANKRD22 in PC cell line PANC-1 and BxPC-3. Results A total of 153 SMRGs were acquired, of which 48 were linked to PC patients’ prognosis. Two SM-related subtypes (SMRGcluster A and B) were identified in PC. SMRGcluster A had a poorer outcome and more active SM process compared to SMRGcluster B. Immune analysis revealed that SMRGcluster B had higher immune and stromal scores and CD8 + T cell abundance, while SMRGcluster A had a higher tumour purity score and M0 macrophages and activated dendritic cell abundance. PC with SMRGcluster B was more susceptible to gemcitabine, paclitaxel, and oxaliplatin. Then SM-related prognostic model (including ANLN, ANKRD22, and DKK1) was built, which had a very good predictive performance. Single-cell analysis revealed that in PC microenvironment, macrophages, epithelial cells, and endothelial cells had relatively higher SM activity. ANKRD22, DKK1, and ANLN have relatively higher expression levels in epithelial cells. Cell subpopulations with high expression of ANKRD22, DKK1, and ANLN had more active SM activity. In vitro experiments showed that ANKRD22 knockdown can inhibit the proliferation, migration, and invasion of PC cells. Conclusion This study revealed the important significance of SM in PC and identified SM-associated molecular subtypes and prognostic model, which provided novel perspectives on the stratification, prognostic prediction, and precision treatment of PC patients.

Tungsten carbide (WC) nanopowder is crucial for preparing high-performance WC-Co cemented carbides, but the synthesis of WC nanopowder still remains huge challenges. In this study, we report a novel method for synthesizing high-purity WC nanopowder by carbothermal reduction-carbonization. The effects of the reaction atmosphere, temperature, and time on the morphology and size of WC powder were studied. It was found that vacuum atmosphere was more conducive to prepare WC nanopowder, which could reduce the onset temperature of carbothermal reduction reaction and effectively improve the reaction efficiency. The final products in vacuum were more homogeneous and smaller compared with argon atmosphere. Furthermore, the mechanism of effect of atmosphere on prepared WC nanopowder was analyzed in detail. The particle size of WC showed an increasing trend with the increase of temperature and holding time. Following calcination at 1100 °C for 5 h, the as-prepared WC nanopowder attained an average particle size of 82 nm.

To confront the growing difficulty along with the increasing complexity and comprehensiveness of airborne system, an airborne system integrating architecture for multiple types of models are proposed. A platform based on virtual data bus and adapters is developed. The platform’s accuracy for single model simulation is tested compared to the model’s original platform using the wind speed model of a real airplane. The platform’s integration ability, a display and control joint model containing PFD, MFD, ND, engine status collecting device, wind speed model and visualization software is established. The result shows this platform is able to efficiently integrate multiple types of models and is capable of supporting the development of complex airborne systems.

The collapse of high-steep dangerous rock is a common geological disaster in the mountainous areas of China. However, due to the limitation of objective factors such as traffic difficulties, the efficiency of artificial geological exploration is low and the safety risk is high, and the investigation in some places is unreachable. Based on the Laoshucuo 3# high-steep dangerous rock mass in the Three Gorges Reservoir area, this study established an analysis method system of high-steep dangerous rock mass by integrating UAV nap-of-the-object photogrammetry and airborne LiDAR technology. The three-dimensional geological model of Laoshucuo 3# dangerous rock mass was constructed systematically, and the engineering geological characteristics of the dangerous rock mass were characterized. The results show that there are five structural planes in the dangerous rock mass of Laoshucuo 3#, with the widest weak layer of 27.30 m and the deepest cavity of 2.19 m. The collapse type is toppling collapse. The stability coefficient of the dangerous rock mass is 1.375 under the natural condition, which is in a stable state, and 1.01 under the rainstorm condition, which is in an unstable state and needs to be treated. The technical method in this study has good complementarity to the investigation of high-steep dangerous rock mass, providing a new investigation method for non-contact measurement, geological information acquisition, and stability analysis of high-steep dangerous rock mass, and technical support for disaster prevention and mitigation in the reservoir area.

Secondary aluminum (Al) dross (SAD) is a hazardous waste discharged from Al production, processing and recycling. Over 6.7 million tons of SAD was discharged on the planet in 2023. SAD is consisted of 40–60 wt% of alumina (Al2O3), 10–30 wt% of AlN, 5–15 wt% of salts and 3–10 wt% of heavy metal oxides. Currently, recycling of SAD to make Al2O3 by hydrometallurgy is a promising method for disposal of SAD. Hydrometallurgy method is mainly divided into acid leaching and alkali leaching. In acid leaching, Al, AlN and Al2O3 react with acid to form aluminum sulfate and aluminum chloride. In alkali leaching, Al, AlN and Al2O3 react with alkali to form sodium aluminate. High-purity Al2O3 is obtained after precipitation, washing, drying and calcination from the leachate. Resource consumption and emission was calculated to evaluate the economic and environmental benefits. About 147.9 and 172.6 dollars was earned after making Al2O3 from a ton of SAD by alkali and acid leaching process, respectively. And carbon emissions of a ton of Al2O3 was risen about 596.5 and 2216.0 kg CO2, respectively, compared with the Bayer process with bauxite. We proposed a calcination pre-treatment with quicklime on SAD to reduce the carbon emission. The Al and AlN are oxidized into Al2O3 after calcination, and the Al2O3 reacts with CaO to form CaO·Al2O3. The Al in CaO·Al2O3 can be leached out easily with a low concentration of alkali. This review provides a guidance for the recycling of SAD by hydrometallurgy, and proposes a novel idea for the energy and consumption reduction in alumina (Al₂O₃) production.

Abstract Background Identifying critical genes is important for understanding the pathogenesis of complex diseases. Traditional studies typically comparing the change of biomecules between normal and disease samples or detecting important vertices from a single static biomolecular network, which often overlook the dynamic changes that occur between different disease stages. However, investigating temporal changes in biomolecular networks and identifying critical genes is critical for understanding the occurrence and development of diseases. Methods A novel method called Quantifying Importance of Genes with Tensor Decomposition (QIGTD) was proposed in this study. It first constructs a time series network by integrating both the intra and inter temporal network information, which preserving connections between networks at adjacent stages according to the local similarities. A tensor is employed to describe the connections of this time series network, and a 3-order tensor decomposition method was proposed to capture both the topological information of each network snapshot and the time series characteristics of the whole network. QIGTD is also a learning-free and efficient method that can be applied to datasets with a small number of samples. Results The effectiveness of QIGTD was evaluated using lung adenocarcinoma (LUAD) datasets and three state-of-the-art methods: T-degree, T-closeness, and T-betweenness were employed as benchmark methods. Numerical experimental results demonstrate that QIGTD outperforms these methods in terms of the indices of both precision and mAP. Notably, out of the top 50 genes, 29 have been verified to be highly related to LUAD according to the DisGeNET Database, and 36 are significantly enriched in LUAD related Gene Ontology (GO) terms, including nuclear division, mitotic nuclear division, chromosome segregation, organelle fission, and mitotic sister chromatid segregation. Conclusion In conclusion, QIGTD effectively captures the temporal changes in gene networks and identifies critical genes. It provides a valuable tool for studying temporal dynamics in biological networks and can aid in understanding the underlying mechanisms of diseases such as LUAD.

Abstract Non-healing skin wounds pose significant clinical challenges, with biologic products like exosomes showing promise for wound healing. Saliva and saliva-derived exosomes, known to accelerate wound repair, yet their extraction is difficult due to the complex environment of oral cavity. In this study, as a viable alternative, we established human minor salivary gland organoids (hMSG-ORG) to produce exosomes (MsOrg-Exo). In vitro, MsOrg-Exo significantly enhanced cell proliferation, migration, and angiogenesis. When incorporated into a GelMA-based controlled-release system, MsOrg-Exo demonstrated controlled release, effectively improving wound closure, collagen synthesis, angiogenesis, and cellular proliferation in a murine skin wound model. Further molecular analyses revealed that MsOrg-Exo promotes proliferation, angiogenesis and the secretion of growth factors in wound sites. Proteomic profiling showed that MsOrg-Exo’s protein composition is similar to human saliva and enriched in proteins essential for wound repair, immune modulation, and coagulation. Additionally, MsOrg-Exo was found to modulate macrophage polarization, inducing a shift towards M1 and M2 phenotypes in vitro within 48 h and predominantly towards the M2 phenotype in vivo after 15 days. In conclusion, our study successfully extracted MsOrg-Exo from hMSG-ORGs, confirmed the effectiveness of the controlled-release system combining MsOrg-Exo with GelMA in promoting skin wound healing, and explored the potential role of macrophages in this action.

AIM:To test and compare the perceptual eye position and fixation stability of adolescents with emmetropia and adolescents with low myopia, investigating the characteristics of the perceptual eye position and fixation stability of adolescents with low myopia.METHODS: Cross-sectional study. A total of 132 adolescents(264 eyes)who visited in the ophthalmology clinic of our hospital from April to December 2023 were randomly selected as the research subjects. Participants were categorized into normal control group(n=45, 90 eyes), simple low myopia group(n=45, 90 eyes)and low myopia with anisometropia group(n=42, 84 eyes)according to their refractive status and were underwent assessments for perceptual eye position and fixation stability.RESULTS: Compared with the normal control group, the static and dynamic horizontal perceptual eye position deviation of the simple low myopia group and the low myopia with anisometropia group were significantly increased(P0.05); compared with the normal control group, the horizontal and vertical fixation stability of the simple low myopia group and the low myopia with anisometropia group were significantly worse(all P0.05).CONCLUSION: Abnormalities are observed in perceptual eye position and fixation stability function in adolescents with low myopia compared with those adolescents with emmetropia, even at best corrected visual acuity. The occurrence of anisometropia could lead to an increased degree of horizontal perceptual eye position displacement.

Achieving stable and reliable autonomous driving in complex traffic environments while ensuring safety under unpredictable conditions is a critical challenge in autonomous driving technology. To address this issue, this study proposes the Safedrive Dreamer navigation framework, which aims to reduce the reliance on trial-and-error learning in real-world scenarios, thereby mitigating the risks associated with dynamic driving conditions and enhancing vehicle foresight. This framework integrates the predictive capabilities of world models with the constrained Markov decision process (CMDP) and safety reinforcement learning to accurately anticipate future environmental changes. This ensures the reliability of autonomous driving routes, thereby improving both safety and efficiency. Furthermore, to reduce trial-and-error costs in real-world applications, this study employs PAC-Bayesian methods to derive generalization error bounds between simulations and reality, enabling a more effective transfer of knowledge and experience from simulations to real-world scenarios. Validation experiments in simulated and real environments showed that Safedrive Dreamer significantly outperformed existing autonomous driving solutions by 3.8% in key safety metrics, excelling in collision avoidance and risk reduction. This study provides new insights into the integration of world models into decision-making processes to enhance decision-making capabilities in safety–critical applications, thereby contributing significantly to the improvement of autonomous driving safety and reliability.

The launch of the carbon-allowance trading market has changed the cost structure of the power industry. There is an asynchronous coupling mechanism between the carbon-allowance-trading market and the day-ahead power-system dispatch. In this study, a data-driven model of the uncertainty in the annual carbon price was created. Subsequently, a collaborative, robust dispatch model was constructed considering the annual uncertainty of the carbon price and the daily uncertainty of renewable-energy generation. The model is solved using the column-and-constraint generation algorithm. An operation and cost model of a carbon-capture power plant (CCPP) that couples the carbon market and the economic operation of the power system is also established. The critical, profitable conditions for the economic operation of the CCPP were derived. Case studies demonstrated that the proposed low-carbon, robust dispatch model reduced carbon emissions by 2.67% compared with the traditional, economic, dispatch method. The total fuel cost of generation decreases with decreasing, conservative, carbon-price-uncertainty levels, while total carbon emissions continue to increase. When the carbon-quota coefficient decreases, the system dispatch tends to increase low-carbon unit output. This study can provide important guidance for carbon-market design and the low-carbon-dispatch selection strategies.

Abstract We study a specific class of CFTs that involve coupled free fermions, arising from parafermion CFTs and lattice constructions. We analyse their representation spaces and the underlying exclusion statistics of coupled free fermions using specific bases. In one particular case, we reveal an unexpected connection between the coset construction of parafermions, the lattice construction, and the orbifold thereof. This connection is supported by proving a range of character identities within the context of coupled free fermions. Simultaneously, we obtain explicit expressions of certain string functions in terms of Dedekind eta functions.

Abstract The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy. Graphical Abstract

Abstract Background Cyp19a1a is a key enzyme in the pathway that converts androgens into estrogen and is regulated by TGF-β signaling. Smad4 and FoxH1 are downstream effectors of TGF-β signaling and may play important roles in ovarian development in M. albus. Methods We investigated the expression pattern of the Smad4 and FoxH1 using qRT‒PCR and immunofluorescence, then tested the changes of smad4 and foxh1 by qRT‒PCR after ovary incubation with FSH in vitro, and analysed the regulation of cyp19a1a transcription by Smad4 and FoxH1 by dual-luciferase reporter assays. Results We found that Smad4 encoded a putative protein of 449 amino acids and harbored the three conserved domains typical of this protein family. Smad4 and foxh1 exhibited similar expression patterns during ovarian development and after FSH incubation, with Pearson’s coefficients of 0.873 and 0.63–0.81, respectively. Furthermore, Smad4, FoxH1 and Cyp19a1a colocalized in the granulosa cells and theca cells of ovaries during the mid-to-late vitellogenic stage. Smad4 repressed cyp19a1a activity via SBE1 (− 1372/−1364) and SBE2 (− 415/−407) in the cyp19a1a promoter, whereas mutating SBE1 or SBE2 restored cyp19a1a promoter activity. Co-overexpression of Smad4 and FoxH1 significantly reduced cyp19a1a promoter activity. Conclusions This study provides new insights into the potential functions of transcription factors Smad4 and FoxH1 in ovarian development and the transcriptional regulation mechanism of cyp19a1a in M. albus, which will reveal Smad4/FoxH1-mediated TGF-β signaling in reproduction and the regulation of the cyp19a1a. Plain English summary Aromatase, encoded by cyp19a1a, is involved in ovarian development and plays an important role in the quality of eggs, as well the sex ratio, of the teleost fish, M. albus. The research on the transcriptional regulation of cyp19a1a has contributed to the understanding of its role in ovarian development. In previous study, it was shown that FoxH1 inhibits cyp19a1a transcription. In the present study, Smad4 was confirmed as a cyp19a1a transcriptional repressor and Smad4 may also coordinate with FoxH1 to repress cyp19a1a transcription. At present, we provide a new perspective for the transcriptional regulation of cyp19a1a by transcription factors Smad4 and FoxH1 in teleost fish ovary. In the future, the regulatory networks of Smad4 and FoxH1 will be further studied and the gene editing technology will be applied to screen specific regulatory factors of cyp191a1a gene, so as to alter the female cycle and modulate the sex ratio of the eggs production.

Abstract Background Multiplexed positron emission tomography (mPET) imaging can measure physiological and pathological information from different tracers simultaneously in a single scan. Separation of the multiplexed PET signals within a single PET scan is challenging due to the fact that each tracer gives rise to indistinguishable 511 keV photon pairs, and thus no unique energy information for differentiating the source of each photon pair. Methods Recently, many applications of deep learning for mPET image separation have been concentrated on pure data-driven methods, e.g., training a neural network to separate mPET images into single-tracer dynamic/static images. These methods use over-parameterized networks with only a very weak inductive prior. In this work, we improve the inductive prior of the deep network by incorporating a general kinetic model based on spectral analysis. The model is incorporated, along with deep networks, into an unrolled image-space version of an iterative fully 4D PET reconstruction algorithm. Results The performance of the proposed method was evaluated on a simulated brain image dataset for dual-tracer [ $$^{18}$$ 18 F]FDG+[ $$^{11}$$ 11 C]MET PET image separation. The results demonstrate that the proposed method can achieve separation performance comparable to that obtained with single-tracer imaging. In addition, the proposed method outperformed the model-based separation methods (the conventional voxel-wise multi-tracer compartment modeling method (v-MTCM) and the image-space dual-tracer version of the fully 4D PET image reconstruction algorithm (IS-F4D)), as well as a pure data-driven separation [using a convolutional encoder-decoder (CED)], with fewer training examples. Conclusions This work proposes a kinetic model-informed unrolled deep learning method for mPET image separation. In simulation studies, the method proved able to outperform both the conventional v-MTCM method and a pure data-driven CED with less training data.

ABSTRACT: The bovine hemoplasmas include Mycoplasma wenyonii and Candidatus Mycoplasma haemobos, which are increasingly recognized as infecting cattle throughout the world. Infection with hemotropic mycoplasma has been reported to be widespread in mature dairy cows, but little is known about its prevalence in calves and heifers. The objective of this study was to investigate the prevalence and dynamics of infection with M. wenyonii and C. M. haemobos in calves and replacement heifers on Michigan dairy farms and assess the potential associations between infection status and hematological values. The study was designed as a prospective cross-sectional study with a longitudinal component. A convenience sample of 11 farms agreed to participate and were visited twice between March and September 2022. During the first farm visit, researchers collected blood samples from up to 94 animals per farm distributed among newborn and preweaning calves (n ≤ 31), weaned calves (n = 21), pre-breeding heifers (n = 21), and pregnant heifers (n = 21). During the first visit, blood samples (n = 174) were also collected from a convenience sample of mature cows to confirm the herd infection status. The same calves and heifers were sampled again ∼95 d (±3.0) later. During the first visit, blood samples were collected from 797 calves and replacement heifers, whereas 675 samples were collected during the second visit due to the inability to locate some animals. Detection of M. wenyonii and C. M. haemobos was based on results of real-time PCR. The hematocrit was determined using microcentrifugation, and the concentration of leukocytes using an automated cell counter. In all herds, most mature cows that were sampled tested positive for infection. The within-herd apparent prevalence of hemoplasma in calves and replacement heifers was 100% for both M. wenyonii and C. M. haemobos. The apparent prevalence of hemoplasma in youngstock was associated with age. In calves that were 1 to 6 mo old, the prevalence of infection was 6% to 8% but sharply increased to 31% by 8 mo of age. In older animals, the prevalence remained high, and was almost 100% in animals greater than 17 mo of age. Based on calves and heifers sampled twice, the cumulative incidence varied widely among herds, ranging from 3.7% to 96.0%, and increased with the age of the animals. We found no difference in hematocrit or number of lymphocytes, monocytes, neutrophils, or total leukocytes based on infection status. The number of eosinophils was greater in infected animals. This is the first study to report the prevalence of hemoplasmas in calves and replacement heifers in the United States. It indicates that young calves can be infected with hemoplasmas, but the rate of infection is low. The likelihood of infection increases as animals age, with a notable rise in the proportion of infected heifers occurring by 8 mo old, and the prevalence eventually reaching nearly 100% in older animals. Once infected, heifers appear to remain chronic carriers. Hemoplasma infection alone does not usually lead to the development of clinical signs, and most of the animals remain apparently healthy.

The significant demand of coal mine intelligence has put forward some higher requirements for the intelligent perception of underground mobile robots in coal mines, and the Visual Simultaneous Localization and Mapping (VSLAM) is a key technology for the intelligent perception of coal mine robots. However, due to unstructured environmental features, weak textures, uneven illumination, and small space in underground coal mines, the existing methods that rely on heuristic thresholds for keyframe selection cannot meet the localization and mapping requirements of visual SLAM in underground coal mines. Therefore, a visual SLAM keyframe selection method with multiple constraints in underground coal mines was proposed, which achieves a real-time and robust pose estimation of mobile robot in coal mines and provides data for digital twin in coal mines. Firstly, the proposed method was constrained according to geometric structure, adaptive thresholding was used instead of static heuristic thresholding for keyframe selection to achieve the effectiveness and robustness of keyframe selection. Secondly, the distribution of effective feature points was homogenized by the balance of gravity principle to further ensure the stability of keyframe selection and the denseness and accuracy of created map points. Finally, the steering place was further constrained by using the heading angle threshold to reduce the impact of viewpoint abrupt change on the visual SLAM accuracy. In order to verify the effectiveness of the proposed method, an experimental analysis was conducted in indoor scenes and underground coal mines respectively using an independently designed mobile robot data acquisition platform. Then, the qualitative and quantitative evaluations were made from Absolute Trajectory Error (ATE) and Root Mean Square Error (RMSE). The results show that compared with the heuristic keyframe selection method, the proposed method improves the trajectories RMSE by 29% and 44% in the indoor scenes and the fully enclosed promenade environment, respectively. The proposed method also has a higher robustness, localization accuracy and globally consistent map building effect in underground coal mines.

The numb taste profiles of green pepper samples collected from seven regions in Sichuan and Chongqing were characterized by time-intensity (TI) sensory evaluation, and the contents of the major numb-taste components of these samples were determined by high performance liquid chromatography (HPLC). Meanwhile, correlation analyses between the numb-taste components and the sensory characteristics of green pepper were carried out by partial least squares regression (PLSR). The results showed that the numbness of green pepper rapidly rose initially, followed by a slow decline, reaching its peak after around 100 s. Amide content varied greatly among different samples, from 5 505.77 to 8 639.30 mg/100 g. The results of PLSR indicated that the numb taste of green pepper was closely related to its amide composition, and the maximum intensity, total duration (Ttot) and area under the curve (AUC) were strongly positively correlated with hydroxy-α-sorcinin, and Ttot was strongly positively correlated with hydroxy-ε-sorcinin and hydroxy-β-sorcinin. The numb taste and amide composition of green pepper varied among the geographical areas. Hydroxy-α-sorcinol and pepper oleoresin were the key substances responsible for the differences in the numb taste of different green pepper samples. We hope that this study will provide basic data reference and a scientific basis for follow-up evaluation of the numb taste quality of green pepper from Sichuan and Chongqing.

Roadside cameras play a crucial role in road traffic, serving as an indispensable part of integrated vehicle-road-cloud systems due to their extensive visibility and monitoring capabilities. Nevertheless, these cameras face challenges in continuously tracking targets across perception domains. To address the issue of tracking vehicles across nonoverlapping perception domains between cameras, we propose a cross-camera vehicle tracking method within a Vehicle–Road–Cloud system that integrates visual and spatiotemporal information. A Gaussian model with microlevel traffic features is trained using vehicle information obtained through online tracking. Finally, the association of vehicle targets is achieved through the Gaussian model combining time and visual feature information. The experimental results indicate that the proposed system demonstrates excellent performance.

Abstract Brain metastases (BM) are common in patients with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) and confer poor prognoses. Zorifertinib (AZD3759), an EGFR‐tyrosine kinase inhibitor (TKI) with high blood‐brain barrier penetration, has previously demonstrated promising systemic and intracranial antitumor activity in phase 1–3 studies. This is the first report of a patient with EGFR‐mutant (exon 21 L858R) NSCLC and symptomatic untreated multiple BM who achieved a long overall survival (OS) of more than 65 months after sequential treatment with zorifertinib and a third‐generation EGFR‐TKI. This new treatment paradigm offers a new treatment option and deserves further clinical exploration to prolong OS of patients with EGFR‐mutant NSCLC and untreated multiple BM.

Abstract Acute anterior uveitis (AAU) is a common extra‐articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)‐B27 genetic marker. To explore the underlying mechanisms of HLA‐B27+ AS‐associated AAU, we employed single‐cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA‐B27+ AS‐associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune‐associated proteins, Th17‐related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X‐inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA‐B27+ AS‐associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.

Toxoplasma gondii is an obligate intracellular parasite that can infect humans and diverse animals. Fatty acids are critical for the growth and proliferation of T. gondii, which has at least two pathways to synthesize fatty acids, including the type II de novo synthesis pathway in the apicoplast and the elongation pathway in the endoplasmic reticulum (ER). Acetyl-CoA is the key substrate for both fatty acid synthesis pathways. In the apicoplast, acetyl-CoA is mainly provided by the pyruvate dehydrogenase complex. However, how the ER acquires acetyl-CoA is not fully understood. Here, we identified a putative acetyl-CoA transporter (TgAT1) that localized to the ER of T. gondii. Deletion of TgAT1 impaired parasite growth and invasion in vitro and attenuated tachyzoite virulence in vivo. Metabolic tracing using 13C-acetate found that loss of TgAT1 reduced the incorporation of 13C into certain fatty acids, suggesting reduced activities of elongation. Truncation of AT1 was previously reported to confer resistance to the antimalarial compound GNF179 in Plasmodium falciparum. Interestingly, GNF179 had much weaker inhibitory effect on Toxoplasma than on Plasmodium. In addition, deletion of AT1 did not affect the susceptibility of Toxoplasma to GNF179, suggesting that this compound might be taken up differently or has different inhibitory mechanisms in these parasites. Together, our data show that TgAT1 has important roles for parasite growth and fatty acid synthesis, but its disruption does not confer GNF179 resistance in T. gondii.

Mangroves are one of the most important marine ecosystems globally, their spatial distribution is crucial for promoting mangrove ecosystems conservation, restoration, and sustainable managements. This study proposed a novel Unet-Multi-Scale High-Resolution Vision Transformer (UHRViT) model for classifying mangrove species using unmanned aerial vehicle (UAV-RGB), UAV-LiDAR, and Gaofen-3 Synthetic Aperture Radar (GF-3 SAR) images. The UHRViT utilized a multi-scale high-resolution visual Transformer as its backbone network and was designed to a multi-branch U-shaped network structure to extract features of different scales layer by layer, and to facilitate the interaction of high and low-level semantic information. We further verified the classification performance superiority of UHRViT model by comparing to HRViT and HRNetV2 algorithms. We also systematically investigated the effects of active–passive image combination ratios on mangrove communities mapping. The results revealed that: UAV-RGB images exhibited the better classification accuracy (mean F1-score＞95 %) for mangrove species than UAV-LiDAR and GF-3 SAR images; The classification performances and stability of UHRViT algorithm in the fifteen datasets outperformed the HRViT and HRNetV2 algorithms; Combining UAV-RGB with GF-3 SAR or UAV-LiDAR images respectively, both achieved better classifications than the single data source. Based on the UHRViT algorithm, the combination of UAV-RGB and UAV-LiDAR achieved the highest classification accuracy (Iou = 0.944, MIou = 50.2 %) for Avicennia corniculatum (AC). When the combination ratio of UAV-RGB with GF-3 SAR or UAV-LiDAR was 3:1, Avicennia marina and AC both obtained the optimal classification accuracy with average F1-scores of 98.19 % and 97.3 %, respectively. Our works revealed that the changes in the classification accuracies of mangrove communities under multi-sensor image combination ratios, and demonstrated that our model could effectively improve the classification accuracy of mangrove communities.

Mangroves face decline and degradation due to human activities and natural forces, making their accurate mapping and dynamic monitoring essential. However, most of the existing mangrove indices that rely on multispectral image spectral characteristics suffer from limitations in terms of recognition accuracy and universality. Therefore, this study aimed to develop a robust and efficient Phenology and Water level Time-series Mangrove Index (PWTMI) for mangrove monitoring. PWTMI is constructed by combining spectral and temporal characteristics from dense time-series multispectral data, wherein phenology and water level time-series characteristics are extracted from NDVI and MNDWI time series. The results show that PWTMI outperforms existing multispectral-based mangrove indices and has an accuracy similar to a hyperspectral-based mangrove index, with overall accuracy ranging from 91.49% to 98.83% and F1 score ranging from 0.91 to 0.98 in four typical areas in China, indicating great potential for long time-series and large-scale mangrove monitoring.

Objective To investigate the correlation between the serum levels of ischaemia-modified albumin (IMA) and disease severity in rats with acute pancreatitis (AP). Methods A rat AP model was established and blood samples from each group were analysed at different time points. After the experiment, the pancreatic tissues of the rats were collected for pathological examination and the measurement of protein levels of NF-κB and NF-κB p65. Serum levels of amylase (α-AMY), tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8 were also compared between groups of rats. Results The serum IMA concentration in the severe acute pancreatitis (SAP) group was greater than that in the mild acute pancreatitis (MAP) group. The levels of the NF-κB and NF-κB p65 proteins were increased in the MAP and SAP groups in a time-dependent manner. α-AMY, TNF-α and IL-6 were increased at all time points in the MAP and SAP groups. The increases were greatest at 24 h in the SAP group. In terms of pathological changes in the pancreas, renal and lung tissues, the damage in the SAP group was more obvious than that in the MAP group. Conclusions Serum IMA level was associated with inflammatory markers and NF-κB p65 in rats with AP.

Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications.

The impact of environmental, social, and governance (ESG) performance gaps on firm green innovation is examined in this paper by a panel database of A-share Chinese listed companies from 2011 to 2021. Using multiple linear regression and conducting a series of endogeneity tests and robustness checks, our empirical analysis shows that firm ESG performance gaps have significantly positive effect on green innovation. Both ESG performance below historical aspiration and social aspiration levels enhance a firm’s green innovation. Confucian culture negatively moderates the positive relationship between ESG performance gaps and green innovation, suggesting that firms more influenced by Confucian culture exhibit reduced green innovation than those less influenced. Additionally, firm digitalization positively moderates the positive relationship between ESG performance gaps and green innovation, indicating that firms with higher levels of digitalization are better equipped to improve green innovation when facing ESG performance shortfalls. This study extends the existing knowledge of firm ESG performance and motivation of green innovation. The research findings offer practical insights for leveraging the motivation and capabilities of green innovation to attain firm ESG objectives.

Mangroves, primarily found along tropical and subtropical coastlines, are crucial ecosystems that offer significant ecological services, including coastal protection, carbon sequestration, and biodiversity support. However, these ecosystems are under severe threat from human activities such as aquaculture, agriculture, and urban development, leading to deforestation and degradation. This study aims to develop a comprehensive framework for assessing the health of mangrove ecosystems using the Pressure-State-Response (PSR) model with annual temporal resolution from 2019 to 2023. It consists of three dimensions: Pressure (human activities and natural factors affecting the ecosystem), State (current condition of the ecosystem), and Response (efforts to mitigate adverse effects and restore health). This study incorporates innovative physical and structural parameters alongside traditional indicators to improve the accuracy of the assessment. The method offers advantages such as ease of measurement, low cost, early warning capabilities for ecosystem damage, and high sensitivity to ecological changes. It provides valuable insights for decision-makers and enhances the ability to detect trends in mangrove health over time through a large-scale, multi-temporal analysis. Using remote sensing techniques and the Analytic Hierarchy Process (AHP), we identified 12 key indicators. The AHP method was used to determine the weight of each indicator, achieving a consistency ratio (CR) of less than 0.1, which ensures the reliability of the assessment. The evaluation included calculating and analysing the Comprehensive Health Index (CHI), Pressure (PHI), State (SHI), and Response (RHI) health indices. Results indicated that the mangrove ecosystems in the Beibu Gulf region were “healthy” state by 2019 through 2022. However, in 2023, the health status declined to “relatively healthy,” indicating a downward trend. In conclusion, this study presents a robust framework for assessing mangrove ecosystem health using the PSR model. The findings underscore the urgent need for conservation efforts to reverse the declining health trend and ensure the long-term sustainability of mangrove ecosystems in the Beibu Gulf.

Infection by multidrug-resistant avian pathogenic Escherichia coli (APEC) in chickens always leads to the uselessness of antibiotics, highlighting the need for alternative antibacterial agents. Sophora flavescens and Coptis chinensis have been a classical combination used together in Traditional Chinese Medicine (TCM) formulas to treat diseases with similar symptoms to colibacillosis for an extended period, but the effect of their active ingredients' combination on APEC infection remains unstudied. The objective of this study was to explore the synergistic effect of matrine and berberine hydrochloride on colibacillosis caused by an isolated multidrug-resistant APEC. In this study, a highly pathogenic E. coli was isolated from the liver of a diseased chicken in a farm suspected of colibacillosis, and it was resistant to multiple antibiotics. The LD50 of the strain was approximately 3.759×108 CFU/mL. The strain harbored several antibiotic resistance genes and virulence genes. Matrine and berberine hydrochloride have synergistic antibacterial effect against the isolated strain in vitro. The combined use of matrine and berberine hydrochloride exhibited synergistic effects in the treatment of APEC infection by regulating the organ indices, improving the pathological situation, decreasing the bacterial load, and regulating the inflammatory factors to enhance the survival rate of chickens in vivo. These results provided a foundation for revealing the effective effects and possible mechanisms of matrine and berberine hydrochloride as potential antimicrobial agents on diseases caused by multidrug-resistant APEC in chickens.

Abstract Highly sensitive vertically aligned carbon nanotube arrays (VANTAs) interdigitated electrode (IDE) arrays are developed for electrochemical biosensing of two cytokines (i.e., interleukin‐10 (IL‐10) and interferon‐gamma (IFN‐γ)) that are useful for early detection Johne's disease (Bovine Paratuberculosis) in cattle. The high aspect ratio VANTA‐IDEs (50–60 µm in height) are grown through a chemical vapor deposition process from an iron (Fe) catalyst that is lithographically patterned on a silicon wafer with equal finger width and inter‐finger spacing of 25 µm. After functionalization with distinct antibodies the VANTA‐IDEs are capable of selective detection of both IL‐10 and IFN‐γ within an actual biological matrix (i.e., diluted bovine implant supernatant) over concentration ranges of 0.1 to 30 pg mL−1 (limit of detection – LOD: 0.0911 pg mL−1) and 50–500 pg mL−1 (LOD: 24.17 pg mL−1), respectively with a response time of

Abstract Background B7‐H3 protein is an important regulator of the adaptive immune response in human tumorigenesis. 4‐1BB is a co‐stimulatory receptor expressed on activated CD8+ T cells, and regulates T cell immunity. Here, we investigated the role of B7‐H3 in the growth and invasion of nasopharyngeal carcinoma (NPC) and the effect of its interaction with 4‐1BB on tumor immunity. Methods Short hairpin (sh) RNA was designed to knock down B7‐H3 expression in NPC cells. NPC cells with stable knockdown of B7‐H3 were established and injected into nude mice. The effects of B7‐H3 on cell proliferation, apoptosis, and epithelial‐to‐mesenchymal transition (EMT) were detected by the CCK8 assay, flow cytometry, TUNEL assay, and western blot analysis. The migration and invasion abilities were determined using the Transwell assay and scratch assay. Co‐immunoprecipitation (Co‐IP) assays were performed to study the interaction between B7‐H3 and 4‐1BB. Anti‐4‐1BB antibody was used in a co‐culture system and xenograft mice to study the effect of 4‐1BB on NPC development. Results NPC cells transfected with sh‐B7‐H3 showed a higher rate of apoptosis, slower growth rate, impaired migration, and less EMT in vitro. Xenograft mice with stable knockout of B7‐H3 had lower tumor burdens, and the stripped tumors had lower rates of cell proliferation, higher rates of apoptosis, and less EMT in vivo. Additionally, decreased B7‐H3 expression was positively correlated with interferon‐γ, tumor necrosis factor‐α, and 4‐1BB+CD8+ tumor‐infiltrating lymphocytes. Co‐IP studies showed that B7‐H3 interacts with 4‐1BB. Also, the inhibitory effects of sh‐B7‐H3 on NPC tumor growth, invasion, and tumor immunity could be alleviated by the anti‐4‐1BB antibody both in vivo and in vitro. Conclusion Our findings suggest that B7‐H3 may accelerate tumor growth, tumor cell invasion, and EMT, and interact with 4‐1BB to produce CD8+ T cell exhaustion that inhibits tumor immunity. B7‐H3 might serve as a novel target for treating NPC.

BackgroundTeduglutide, the first glucagon-like peptide 2 analogue, has been demonstrated to facilitate the absorption of gut nutrient and lessen the need for parenteral assistance in patients with Short Bowel Syndrome (SBS). However, its adverse drug events (AEs) are primarily documented in clinical trials, with a deficit in real-world data. This study evaluates the AEs profile of teduglutide based on Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data.MethodA disproportionality analysis of FAERS data from Quarter 1 (Q1) 2013 to Quarter 3 (Q3) 2023 was conducted to examine the association between teduglutide and adverse events, employing Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) methods.ResultsOut of 13,809,302 reports in the FAERS database, 10,114 reports identified teduglutide as the “primary suspect” in AEs identification. During the dosing observation period, the median occurrence of adverse events was 393 days (interquartile range [IQR] 97–996 days). Teduglutide-associated AEs occurred in 27 System Organ Classes (SOC), of which renal and urinary disorders is not mentioned in the specification. Based on the four algorithms, a total of 260 major disproportionality preferred terms (PTs) were filtered out, including previously unreported AEs including weight decreased (n = 805), vascular device infection (n = 683), dehydration (n = 596) and nephrolithiasis (n = 146).ConclusionOur findings corroborate the AEs listed in the teduglutide prescribing information and additionally unveil new adverse reaction signals such as nephrolithiasis. These discoveries could aid in clinical monitoring and risk identification for teduglutide.

BackgroundMale factory workers in China are vulnerable to HIV transmission. Commercial and nonmarital noncommercial contacts are the driving forces of heterosexual HIV transmission among male factory workers in China. There is a lack of effective HIV interventions for male factory workers in China. ObjectiveThe primary objective of this randomized controlled trial was to compare the efficacy of an enhanced versus the standard version of a WeChat mini program in reducing sexual intercourse with nonregular female sex partners and female sex workers among male factory workers in Shenzhen, China. MethodsA nonblinded 2-arm parallel randomized controlled trial was conducted between December 2021 and April 2023. Participants were adult male factory workers in Shenzhen who had access to a smartphone and WeChat. Those who had oral or anal sex with a man or self-reported as HIV positive were excluded. A total of 247 participants were randomly assigned to the intervention group (n=125, 50.6%) or the control group (n=122, 49.4%); 221 (89.5%) and 220 (89.1%) completed follow-up surveys at T1 (6 months after completion of the interventions) and T2 (6 months after T1). Participants in the control group had access to the standard WeChat mini program that provided basic HIV-related knowledge and information about local free HIV testing services. Participants in the intervention group had access to the enhanced WeChat mini program. The enhanced mini program covered all the information in the standard mini program. In addition, the enhanced mini program assessed users’ behaviors and invited users to watch different web-based videos on reducing nonmarital sexual contacts and promoting HIV testing based on their behavioral characteristics at months 0 and 1. The videos were developed based on in-depth interviews with male factory workers. Intention-to-treat analysis was used for outcome analyses. Multiple imputation was used to replace missing outcome values at T1 and T2. ResultsAt T1, fewer participants in the intervention group reported sexual intercourse with a nonregular female sex partner in the past 6 months compared with the control group (1/125, 0.8% vs 8/122, 6.6%; relative risk=0.12, 95% CI 0.02-0.96; P=.02). However, there were no between-group differences in sexual intercourse with a nonregular female sex partner at T2 (10/125, 8% vs 14/122, 11.5%; P=.36) or sexual intercourse with a female sex worker at T1 (2/125, 1.6% vs 2/122, 1.6%; P=.98) or T2 (8/125, 6.4% vs 8/122, 6.6%; P=.96). ConclusionsThe enhanced WeChat mini program was more effective than the standard WeChat mini program in reducing sexual intercourse with nonregular female sex partners among male factory workers in the short term but not in the longer term. Improvements should be made to the WeChat mini program before implementation. Trial RegistrationClinicalTrials.gov NCT05811611; https://clinicaltrials.gov/study/NCT05811611

AIM: To understand the current status and differences in visual acuity of children of the same age from different regions of Xi'an, and to take an effective basis for the prevention of children's myopia.METHODS: Random stratified sampling was used to select the uncorrected distance visual acuity and computed dioptric data of 41 285 children aged 6-12 from 6 towns, 10 urban and rural areas and 112 country schools screened by Xi'an Central Hospital in December 2022.RESULTS: The myopia detection rate in different regions of Xi'an is 47.16% in towns, 38.59% in urban and rural areas, and 32.29% in the country, and the total myopia rate is 37.50%. The myopia rate of 6-12 years old in towns is higher than that in urban and rural areas, and that of urban and rural areas is higher than that of country; the myopia rate of girls is higher than that of boys; myopia rate increases with age; mild myopia: the myopia rate in towns is significantly higher than that of the urban and rural areas and the country; high myopia: the myopia rate in the country is significantly higher than that of the towns and the urban and rural areas. The total rate of deficient hyperopia reserves in different regions of Xi'an is 92.08% in towns, 93.67% in urban and rural areas, and 90.92% in the country, and the total rate of deficient hyperopia reserves is 92.09%. The rate of deficient hyperopia reserves at the age of 6-12 is higher in the urban and rural areas than in the towns, and higher in the towns than in the country; the total rate of deficient hyperopia reserve is higher in girls than in boys; it is the peak period of the development of hyperopia reserve rate before the age of 8.CONCLUSION: The total myopia rate and the total vision reserve deficiency rate of 6-12 years old in different regions of Xi'an are different, and 8-9 years old is the accelerated period of myopia development, and the peak of deficient hyperopia reserve is before the age of 8 years old. With the growth of age, the myopia rate shows a certain growth trend, and the rate of deficient hyperopia reserve shows a decreasing trend after reaching the peak. The total myopia rate and insufficient acuity reserve rate of girls are higher than those of boys.

Abstract Background Less than half of community pharmacies in the United States stock buprenorphine products indicated for the treatment of opioid use disorder. This lack of access to buprenorphine in community pharmacies is a significant barrier to care. To address this issue, this protocol outlines a comprehensive approach to develop a practice guideline aimed at improving access to safe and effective opioid use disorder treatment in community pharmacies. Methods The guideline development process will proceed in three phases, following a technique closely aligned with the Institute of Medicine’s guidance on guideline development. The first phase will involve conducting qualitative interviews with pharmacists in three states to identify their beliefs toward buprenorphine dispensing. As limitations on buprenorphine supply are related to constraints at all levels of the drug supply and regulatory system, the second phase, we will recruit representatives from regulatory agencies, pharmacy organizations, the Drug Enforcement Administration, pharmaceutical wholesalers as well as addiction medicine physicians and psychiatric pharmacists to develop consensus recommendations through a modified Delphi design. This will be followed by a public comment period and external expert review of the recommendations led by the National Association of Boards of Pharmacy. Finally, in the third phase, a national, mixed media dissemination campaign will be led by the National Community Pharmacists Association (NCPA) to convey recommendations to practicing pharmacists. Discussion The guideline development process aims to incorporate the perspectives of multiple stakeholders and emphasize the importance of addressing the regulatory and pharmacy-specific aspects of care in addition to clinical evidence and guidance. The development of this guideline will provide targeted, multidisciplinary guidance for pharmacists, improving access to safe and effective opioid use disorder treatment in the community setting. Preregistration This protocol was registered with the Open Science Framework in March of 2023. Registration may be found at: https://doi.org/10.17605/OSF.IO/6S9DY .

Abstract Non-SMC condensin II complex subunit D3 (NCAPD3) is a subunit of the non-structural maintenance of chromosomes condensin II complex, which involves chromosome condensation and segregation during mitosis. NCAPD3 has recently been demonstrated as a crucial oncogenic factor. However, the underlying mechanism of NCAPD3 in prostate cancer (PCa) remains not completely clear. In this study, we confirmed that lncRNA MALAT1 was induced by NCAPD3-STAT3, and the expression of miR-30a-5p was controlled by NCAPD3 in PCa cells by miRNA-seq. Through quantitative real-time PCR, fluorescence in situ hybridization, western blotting, and immunohistochemistry assay, we demonstrated that miR-30a-5p was lowly expressed in PCa cells and tissues compared to the controls, which was contrary to NCAPD3 expression and markedly downregulated by NCAPD3. Then, MALAT1 was analyzed for the complementary sequence in the potential interaction with miR-30a-5p by using the predicted target module of public databases. Dual-luciferase reporter assay and RNA immunoprecipitation were carried out to verify that MALAT1 functioned as a sponge for miR-30a-5p to reduce miR-30a-5p expression. Meanwhile, MYC acted as a transcriptional repressor to directly bind the promoter of the miR-30a-5p located gene and repress the miR-30a-5p expression. Furthermore, the upregulation of NCAPD3 on cell viability and migration was significantly attenuated in PC-3 cells when miR-30a-5p was overexpressed. NCAPD3 overexpression also accelerated tumor growth in the xenograft mouse model and repressed miR-30-5p. In summary, this work elucidates NCAPD3 inhibits miR-30a-5p through two pathways: increasing STAT3-MALAT1 to sponge miR-30a-5p and increasing MYC to directly inhibit miR-30a-5p transcription, which could serve as potential therapeutic targets for prostate cancer.

Abstract Background Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer’s disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The “Evaluating Rapamycin Treatment in Alzheimer’s Disease using Positron Emission Tomography” (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer’s disease. Methods ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer’s disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. Discussion The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer’s disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer’s disease. Trial registration ClinicalTrials.gov ID NCT06022068, date of registration 2023–08-30.

The volatile aroma compounds of wine fermented from goji berries were evaluated by liquid-liquid extraction-solvent-assisted evaporation-gas chromatography-mass spectrometry-olfactometry (LLE-SAFE-GC-MS-O) combined with GC-quadrupole-MS (GC-qMS) and GC-Orbitrap-MS. The key aroma compounds were identified by aroma reconstitution and quantitative descriptive sensory analysis. The results showed that ethyl esters (ethyl cinnamate, ethyl acetate, ethyl 2-methylpropanoate, ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, ethyl hexanoate, ethyl lactate, ethyl octanoate, and ethyl decanoate), other esters (isoamyl acetate and isoamyl lactate), C13-norisoprenoids (β-damascenone and β-ionone), volatile phenols (4-ethylguaiacol, eugenol, 2,4-di-t-butylphenol), alcohols (1-octen-3-ol, benzyl alcohol, phenylethyl alcohol and isopentyl alcohol) and other compounds (naphthalene, methionol, octanoic acid and 2-acetylpyrrole) contributed the major aroma attributes of goji berry wine. This finding will help to enrich and improve the theoretical basis of the aroma of goji berry wine and lay the foundation for aroma enhancement and quality improvement of goji berry wine.

Jiang-flavor Baijiu is popular among consumers because of its profound cultural deposits, traditional solid-state brewing process, unique flavor, and sensory experience. In this study, 537 sensory descriptors for Jiang-flavor Baijiu were obtained from 121 articles and 96 standards regarding ‘Jiang-flavor’ and ‘Jiang-flavor Baijiu’ retrieved from China National Knowledge Infrastructure (CNKI), the National Public Service Platform for Standards Information and the Foodmate Website. By sorting out and analyzing these literature data, this paper briefly describes the formation, development, trend and standardization of the sensory quality descriptions of Jiang-flavor Baijiu, summarizes the relationship between the flavor substances and the odor characteristics of Jiang-flavor Baijiu, analyzes the problems with the existing descriptors, and proposes ideas and suggestions for constructing a sensory quality description system for Jiang-flavor Baijiu and using modern sensory evaluation techniques to characterize the sensory quality of Jiang-flavor Baijiu.

Abstract Recently, machine learning methods, including reservoir computing (RC), have been tremendously successful in predicting complex dynamics in many fields. However, a present challenge lies in pushing for the limit of prediction accuracy while maintaining the low complexity of the model. Here, we design a data-driven, model-free framework named higher-order Granger reservoir computing (HoGRC), which owns two major missions: The first is to infer the higher-order structures incorporating the idea of Granger causality with the RC, and, simultaneously, the second is to realize multi-step prediction by feeding the time series and the inferred higher-order information into HoGRC. We demonstrate the efficacy and robustness of the HoGRC using several representative systems, including the classical chaotic systems, the network dynamical systems, and the UK power grid system. In the era of machine learning and complex systems, we anticipate a broad application of the HoGRC framework in structure inference and dynamics prediction.

Abstract Exercise is a potential treatment to improve sleep quality in middle-aged and elderly individuals. Understanding exercise-induced changes in functional plasticity of brain circuits that underlie improvements in sleep among middle-aged and older adults can inform treatment of sleep problems. The aim of the study is to identify the effects of a 12-week exercise program on sleep quality and brain functional connectivity in middle-aged and older adults with insomnia. The trial was registered with Chinese Clinical Trial Register (ChiCTR2000033652). We recruited 84 healthy sleepers and 85 individuals with insomnia. Participants with insomnia were assigned to receive either a 12-week exercise intervention or were placed in a 12-week waitlist control condition. Thirty-seven middle-aged and older adults in the exercise group and 30 in the waitlist group completed both baseline and week 12 assessments. We found that middle-aged and older adults with insomnia showed significantly worse sleep quality than healthy sleepers. At the brain circuit level, insomnia patients showed decreased connectivity in the widespread motor network. After exercise intervention, self-reported sleep was increased in the exercise group (P

This article offers a longitudinal perspective on communications during election campaigns from a political-party perspective, where strategic considerations about digital media are compared across time. Our analysis is grounded on the concepts of hybridisation and data-driven campaigning, where digital technology tends to play a central role without replacing all traditional campaign features. Empirically, the study is based on a longitudinal analysis of four election campaigns in Sweden during 2010–2022. The analysis shows that Swedish political parties have gradually integrated digital campaign features in their structure and strategy. The process is not linear, but rather back and forth, as party perceptions of the importance of communication channels vary across time. The results imply a development where all parties, regardless of size and ideology, are increasingly making rational judgments of which combinations of old and new campaign methods and communication channels are most effective.

Abstract Background In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR. Method Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting. Result Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability. Conclusions WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders. Graphical Abstract

Abstract Background This study aimed to explore the association of the second birth delivery mode and interval with maternal pelvic floor changes. Methods This prospective cohort study included women who had a first delivery and were in weeks 36–41 of a subsequent pregnancy at Panzhihua Central Hospital between July 2017 and June 2018. The primary outcomes of the study were the hiatus area at 6 months postpartum and bladder neck (mm) at rest and during a maximum Valsalva maneuver. Results There were 112 women with vaginal delivery and 182 with Cesarean section. The hiatus area and hiatus circumference decreased at all time points (all P

Abstract Glutamine metabolism plays a pivotal role in cancer progression, immune cell function, and the modulation of the tumor microenvironment. Dysregulated glutamine metabolism has been implicated in cancer development and immune responses, supported by mounting evidence. Cancer cells heavily rely on glutamine as a critical nutrient for survival and proliferation, while immune cells require glutamine for activation and proliferation during immune reactions. This metabolic competition creates a dynamic tug-of-war between cancer and immune cells. Targeting glutamine transporters and downstream enzymes involved in glutamine metabolism holds significant promise in enhancing anti-tumor immunity. A comprehensive understanding of the intricate molecular mechanisms underlying this interplay is crucial for developing innovative therapeutic approaches that improve anti-tumor immunity and patient outcomes. In this review, we provide a comprehensive overview of recent advances in unraveling the tug-of-war of glutamine metabolism between cancer and immune cells and explore potential applications of basic science discoveries in the clinical setting. Further investigations into the regulation of glutamine metabolism in cancer and immune cells are expected to yield valuable insights, paving the way for future therapeutic interventions.

Abstract Background Lagerstroemia indica is a widely cultivated ornamental woody shrub/tree of the family Lythraceae that is used as a traditional medicinal plant in East Asia and Egypt. However, unlike other ornamental woody plants, its genome is not well-investigated, which hindered the discovery of the key genes that regulate important traits and the synthesis of bioactive compounds. Results In this study, the genomic sequences of L. indica were determined using several next-generation sequencing technologies. Altogether, 324.01 Mb sequences were assembled and 98.21% (318.21 Mb) of them were placed in 24 pseudo-chromosomes. The heterozygosity, repeated sequences, and GC residues occupied 1.65%, 29.17%, and 38.64% of the genome, respectively. In addition, 28,811 protein-coding gene models, 327 miRNAs, 552 tRNAs, 214 rRNAs, and 607 snRNAs were identified. The intra- and interspecies synteny and Ks analysis revealed that L. indica exhibits a hexaploidy. The co-expression profiles of the genes involved in the phenylpropanoid (PA) and flavonoid/anthocyanin (ABGs) pathways with the R2R3 MYB genes (137 members) showed that ten R2R3 MYB genes positively regulate flavonoid/anthocyanin biosynthesis. The colors of flowers with white, purple (PB), and deep purplish pink (DPB) petals were found to be determined by the levels of delphinidin-based (Dp) derivatives. However, the substrate specificities of LiDFR and LiOMT probably resulted in the different compositions of flavonoid/anthocyanin. In L. indica, two LiTTG1s (LiTTG1-1 and LiTTG1-2) were found to be the homologs of AtTTG1 (WD40). LiTTG1-1 was found to repress anthocyanin biosynthesis using the tobacco transient transfection assay. Conclusions This study showed that the ancestor L. indica experienced genome triplication approximately 38.5 million years ago and that LiTTG1-1 represses anthocyanin biosynthesis. Furthermore, several genes such as LiDFR, LiOMTs, and R2R3 LiMYBs are related to anthocyanin biosynthesis. Further studies are required to clarify the mechanisms and alleles responsible for flower color development.