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Yongbin Wang,1,* Chunjie Xu,2,* Jingchao Ren,1 Weidong Wu,1 Xiangmei Zhao,1 Ling Chao,1 Wenjuan Liang,1 Sanqiao Yao1 1Department of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 2Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongbin WangDepartment of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, Xinxiang, Henan 453000, People’s Republic of ChinaTel +86 373 383 1646Email wybwho@163.comObjective: Tuberculosis (TB) is a major public health problem in China, and contriving a long-term forecast is a useful aid for better launching prevention initiatives. Regrettably, such a forecasting method with robust and accurate performance is still lacking. Here, we aim to investigate its potential of the error-trend-seasonal (ETS) framework through a series of comparative experiments to analyze and forecast its secular epidemic seasonality and trends of TB incidence in China.Methods: We collected the TB incidence data from January 1997 to August 2019, and then partitioning the data into eight different training and testing subsamples. Thereafter, we constructed the ETS and seasonal autoregressive integrated moving average (SARIMA) models based on the training subsamples, and multiple performance indices including the mean absolute deviation, mean absolute percentage error, root-mean-squared error, and mean error rate were adopted to assess their simulation and projection effects.Results: In the light of the above performance measures, the ETS models provided a pronounced improvement for the long-term seasonality and trend forecasting in TB incidence rate over the SARIMA models, be it in various training or testing subsets apart from the 48-step ahead forecasting. The descriptive results to the data revealed that TB incidence showed notable seasonal characteristics with predominant peaks of spring and early summer and began to be plunging at on average 3.722% per year since 2008. However, this rate reduced to 2.613% per year since 2015 and furthermore such a trend would be predicted to continue in years ahead.Conclusion: The ETS framework has the ability to conduct long-term forecasting for TB incidence, which may be beneficial for the long-term planning of the TB prevention and control. Additionally, considering the predicted dropping rate of TB morbidity, more particular strategies should be formulated to dramatically accelerate progress towards the goals of the End TB Strategy.Keywords: tuberculosis, incidence, SARIMA, ETS, models, forecasting

Yongjian Yang, Dahai Qiu, Yajun Liu, Lei Chao Department of Anesthesiology, Jinan Central Hospital Affiliated to Shandong University, Ji’nan, Shandong Province 250013, People’s Republic of ChinaCorrespondence: Lei ChaoDepartment of Anesthesiology, Jinan Central Hospital Affiliated to Shandong University, No. 105 Jiefang Road, Ji’nan, Shandong Province 250013, People’s Republic of ChinaTel +86 05 318 569 5114Email leichaojncp@outlook.comPurpose: Hyaluronic acid-poly(ethylene glycol)-distearoyl phosphoethanolamine (HA-PEG-DSPE) modified and tocopheryl polyethylene glycol 1000 succinate (TPGS) contained nanostructured lipid carriers (NLCs) were prepared loading ropivacaine and dexmedetomidine to improve the topical anesthetic analgesic anesthesia efficiency.Methods: NLCs were prepared by the solvent diffusion method. The average particle size, zeta potential, release behavior, and cytotoxicity of the NLCs were tested. Ex vivo skin permeation was studied using a Franz diffusion cell mounted with depilated rat skin. Local anesthesia antinociceptive efficiency was evaluated by rat tail flick latency study in vivo.Results: NLCs have sizes of about 100 nm, with negative zeta potentials. All the NLCs formulations were found to be significantly less cytotoxic than free drugs at equivalent concentrations. The cumulative amount of drugs penetrated through rat skin from NLCs was 2.0–4.7 folds higher than that of the drugs solution. The in vivo anesthesia antinociception study displayed that NLCs showed stronger and longer anesthesia antinociceptive effect when compared with single drugs loaded NLCs and drugs solution even at a lower dosage of drugs.Conclusion: The results demonstrated that the HA modified, TPGS contained, dual drugs loaded NLCs could perform a synergistic effect and may reduce the amount of drugs, which can lower the toxicity of the system and at the meanwhile, increase the anesthesia antinociceptive efficiency.Keywords: topical anesthetic analgesic, skin penetration, hyaluronic acid, long-acting nanostructured lipid carriers, tocopheryl polyethylene glycol 1000 succinate

Abstract Background The association between MicroRNAs (miRNAs) and diseases is crucial in treating and exploring many diseases or cancers. Although wet-lab methods for predicting miRNA-disease associations (MDAs) are effective, they are often expensive and time-consuming. Significant advancements have been made using Graph Neural Network-based methods (GNN-MDAs) to address these challenges. However, these methods still face limitations, such as not considering nodes’ deep-level similarity associations and hierarchical learning patterns. Additionally, current models do not retain the memory of previously learned heterogeneous historical information about miRNAs or diseases, only focusing on parameter learning without the capability to remember heterogeneous associations. Results This study introduces the K-means disentangled high-level biological similarity to utilize potential hierarchical relationships fully and proposes a Graph Attention Heterogeneous Biological Memory Network architecture (DiGAMN) with memory capabilities. Extensive experiments were conducted across four datasets, comparing the DiGAMN model and its disentangling method against ten state-of-the-art non-disentangled methods and six traditional GNNs. DiGAMN excelled, achieving AUC scores of 96.35%, 96.10%, 96.01%, and 95.89% on the Data1 to Data4 datasets, respectively, surpassing all other models. These results confirm the superior performance of DiGAMN and its disentangling method. Additionally, various ablation studies were conducted to validate the contributions of different modules within the framework, and’s encoding statuses and memory units of DiGAMN were visualized to explore the utility and functionality of its modules. Case studies confirmed the effectiveness of DiGAMN’s predictions, identifying several new disease-associated miRNAs. Conclusions DiGAMN introduces the use of a disentangled biological similarity approach for the first time and successfully constructs a Disentangled Graph Attention Heterogeneous Biological Memory Network model. This network can learn disentangled representations of similarity information and effectively store the potential biological entanglement information of miRNAs and diseases. By integrating disentangled similarity information with a heterogeneous attention memory network, DiGAMN enhances the model’s ability to capture and utilize complex underlying biological data, significantly outperforming many existing models. The concepts used in this method also provide new perspectives for predicting miRNAs associated with diseases.

Abstract Optimizing the geometric configuration of the tool cutting surface, reducing the resistance in the cutting process and energy consumption, are always a concern. Through the method of bionic design, the directrix function of the longitudinal section of the beaver tooth rake face is extracted, and its variable curvature characteristics are analyzed. Based on this, a turning tool with variable curvature directrix configuration rake face is designed. The cutting force experiment and machining surface quality analysis experiment were carried out with the designed tool and the linear directrix configuration rake face tool respectively. The measured data of the variable curvature directrix configuration rake face tool is better than the linear directrix configuration rake face tool and its drag reduction performance of the tool is verified by experiments. Through the analysis of the working rake angle and shear angle of the tool with variable curvature directrix configuration rake face, the relationship between the parameters of the variable curvature directrix function and the working rake angle, and shear angle has been obtained. By the method of finite element simulation analysis, the stress field in the cutting zone of two different configuration tools has been analyzed. It has been found that the tool with variable curvature directrix rake face has a ‘bending moment’ effect on the tool-chip interface due to its curved surface configuration, and a ‘prying’ effect at the tool tip. These two effects promote the separation of chips from the workpiece and make the cutting process more force-saving. The research of this paper will have reference significance for the design and application of the curved surface configuration rake face tool.

Abstract Reliability technology plays a significant role in ensuring the safe operation of the subsea control system. To perform a comprehensive analysis of the reliability of complex systems, a combination of Failure Mode and Effects Analysis (FMEA) and Fuzzy Fault Tree Approach (FFTA) is introduced. Firstly, the FMEA method is used to analyze the potential failure modes and causes of system failure by completing the qualitative analysis of system reliability from the perspective of multi-factor failure modes. And the risk matrix diagram is applied to determine the degree of harm of different failure modes to the system. Then, the system reliability is quantitatively analyzed using FFTA, and a fault tree model is established by dividing the system into "system-subsystem-component" and solving for the minimum cut set. In addition, the failure probability of the top-level event is quantitatively calculated by introducing fuzzy set theory, and the probabilistic importance of the bottom-level event is analyzed to find out the weak points of each subsystem. Finally, a qualitative and quantitative reliability analysis is conducted by using FMEA-FFTA method for subsea control system. Effective measures should be taken to focus on preventive protection and regular testing for the high risk, medium–high risk and medium risk modes for subsea control system.

Abstract Background Unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) is a minimally invasive procedure for treating lumbar degenerative diseases. However, the use of endoscopic lumbar interbody fusion does not completely eliminate the risk of dural and nerve root injuries. This study has refined UBE-TLIF to incorporate en bloc resection of the ligamentum flavum for bilateral decompression and aim to detail the surgical procedure and evaluate the clinical outcomes of this modification. Methods This study analyzes the outcomes of 109 consecutive patients treated by a single surgeon for lumbar degenerative disease using UBE-TLIF. Patients were divided into two groups: Group A (51 patients) underwent en bloc resection of the ligamentum flavum, while Group B (58 patients) underwent routine piecemeal resection. Assessed outcomes included surgery-related complications, operation time, estimated blood loss, postoperative stay, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). The surgical technique is detailed within the study. Results In Group A, no nerve root or dura injuries were observed, whereas Group B reported one case of nerve root injury and three dura tears. The average operation time for Group A was shorter than that for Group B; however, the difference was not statistically significant (P > 0.05). No significant differences were found in the VAS score, ODI, estimated blood loss, or postoperative stay between the groups during follow-up. Conclusions En bloc resection of the ligamentum flavum for bilateral decompression in UBE-TLIF demonstrates satisfactory clinical outcomes and low perioperative complications rates, offering a safe and innovative alternative for the treatment of lumbar degenerative disease.

Abstract Neutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells, thereby initiating downstream signal transduction pathways. Dysfunctions in neutrophils and disruptions in neutrophil homeostasis have been implicated in the pathogenesis of numerous diseases, including cancer and inflammatory disorders, often due to aberrant intracellular signaling. This review provides a comprehensive synthesis of neutrophil biological functions, integrating recent advancements in this field. Moreover, it examines the biological roles of receptors on neutrophils and downstream signaling pathways involved in the regulation of neutrophil activity. The pathophysiology of neutrophils in numerous human diseases and emerging therapeutic approaches targeting them are also elaborated. This review also addresses the current limitations within the field of neutrophil research, highlighting critical gaps in knowledge that warrant further investigation. In summary, this review seeks to establish a comprehensive and multidimensional model of neutrophil regulation, providing new perspectives for potential clinical applications and further research.

Background: Second-generation antipsychotics (SGAs) frequently cause metabolic syndrome (MetS), which raises the risk of heart disease, type 2 diabetes, morbid obesity, atherosclerosis, and hypertension. MetS also impairs cognitive function in patients with schizophrenia. However, the fundamental reasons of MetS caused by SGAs are not yet fully understood. Thus, we aimed to identify potential therapeutic targets for MetS induced by SGAs. Methods: The serum biochemical parameters and the RNA-sequencing of peripheral blood mononuclear cells were measured in three groups (healthy controls and patients with schizophrenia with and without MetS taking SGAs). The study of the weighted gene co-expression network was utilized to pinpoint modules that were significantly connected to clinical markers. Results: Statistical analysis showed significant differences in triglyceride and high-density lipoprotein among the three groups. The TNF signaling pathway, TGF-β signaling pathway, fatty acid metabolism, NF-kappa B signaling pathway, MAPK signaling pathway, and Toll-like receptor signaling pathway were the pathways that were primarily enriched in the two unique co-expression network modules that were found. Finally, five specific genes (TNF, CXCL8, IL1B, TIMP1, and ESR1) associated with metabolism and immunity pathways were identified. Conclusions: This study indicated that SGAs differentially induced MetS of patients with schizophrenia through metabolic and inflammation-related pathways. Therefore, the potential side effects of drugs on inflammatory processes need to be considered when using SGAs for the treatment of schizophrenia.

Objective The pore system of low-permeability sandstone reservoirs is intricate, and the distribution of pore-throat sizes is highly variable. The microscopic pore structure significantly influences the reservoir′s petrophysical properties and plays a critical role in controlling fluid flow within sandstone reservoirs. Traditional approaches for evaluating pore structures primarily rely on morphological analyses of pore throat size distributions or regression analyses of pore structure parameters. These methods are significantly affected by human bias and often lack precise evaluation frameworks. Methods Poroperm analysis, mercury injection capillary pressure, nuclear magnetic resonance (NMR) measurements, and X-ray computed tomography (X-ray CT) scanning experiments were performed to characterize the pore structures of the Es4s low-permeability sandstones in the G oilfield, Bohai Bay Basin. On this basis, 15 parameters that reflect the microscopic features of low-permeability sandstones were selected, and four types of pore structures were classified by applying an unsupervised self-organizing-map neural network algorithm. Results The findings reveal that the Type Ⅰ pore structure predominantly features large pore throats, with a median throat radius (r50) ranging from 0.38 to 2.35 μm. This type exhibits excellent pore connectivity, contributing significantly to permeability. The petrophysical properties and pore connectivity of Type Ⅱ pore structures are second only to those of Type Ⅰ pore structures. The movable fluid porosity ranges from 2.76% to 5.61%, and the median throat radius (r50) is primarily distributed in the range of 0.01 to 0.23 μm. Type Ⅲ pore structures display good pore connectivity along with considerable microscopic heterogeneity. The petrophysical properties and seepage properties of Type Ⅲ pore structures are comparable to those of Type Ⅰ and Type Ⅱ pore structures. The Type Ⅳ pore structures are characterized by small pore throats and poor microscopic connectivity, which hinders fluid movement within the sandstones. Conclusion The self-organizing map neural network algorithm effectively classifies pore structure types in cases involving multiple parameters. The classification results are not affected by inaccurate user-defined information, and there is no limitation on the number of parameters involved in the training process, making the application effect in pore structure classification remarkable. The established pore structure evaluation scheme, which is based on a self-organizing feature map neural network algorithm, is vital for investigating the microscopic seepage behavior and reservoir quality of low-permeability sandstones.

Aiming at the difficulties of mobile robots in the underground tunnel of a coal mine, such as difficult position sensing and low positioning accuracy due to the influence of the environment, a precise positioning method for mobile robots using laser targets as the positioning reference is proposed. According to the characteristics of the roadway environment and the laser tracking detection principle, establish the distributed deployment strategy of the laser target network, construct the body positioning detection platform based on the laser target network and laser tracker; based on the known spatial information of the roadway and the laser target position information, construct the roadway coordinate system and the position information database and build it into the laser target, and utilize the positioning detection platform to decipher the actual position information of the laser target under the laser transmitter coordinate system, and establish the laser target positioning accuracy. The actual position information of the laser target in the coordinate system of the laser transmitter is solved using the positioning detection platform, and the correlation relationship between the coordinate system of the laser target in the roadway and the coordinate system of the fuselage is established; the coordinate information of the four characteristic points of the laser tracker stored in the database is used as the input of the positioning model of the laser transmitter, and the laser target, and the position information of the fuselage is solved by the EPnP (Efficient Perspective-n-Point) algorithm, and the roadway of the laser target is used to solve the position information of the fuselage. The body position information is solved by EPnP (Efficient Perspective-n-Point) algorithm, and the minimum residual sum of squares of the laser target lane coordinates and the measured coordinates is used to characterize the body position error, construct the body position error model, and minimize the body position error by Levenberg-Marquardt algorithm, and obtain the accurate position information of the mobile robot in the lane coordinate system through the spatial coordinate conversion. After experimental verification, the maximum error of mobile robot distance measurement along the direction of the roadway, the width direction, and the height direction is less than 11.33, 8.12, 8.57 mm; the maximum errors of the actual and theoretical positions of the dynamic trajectory measurement in the roadway direction, width direction and height direction are 2.74%, 3.14% and 2.36 %, and the stable measurement of body positioning is guaranteed in the complex roadway with turns. The stable measurement of body positioning meets the requirements of positioning accuracy of mobile robots in underground coal mines.

Spermiation is the process that releases mature spermatids from Sertoli cells into the lumen of the seminiferous tubule. Tubulobulbar complexes (TBCs) are elaborate cytoskeleton-related structures that are indispensable for spermiation. Despite well-defined ultrastructural events, the molecular regulation of TBCs during spermiation remains largely unknown. Here, we show that autophagy is active in TBC regions, and impaired autophagy in Sertoli cells affects spermiation. Further studies demonstrated that many TBC components bound to LC3 and could be selectively degraded through the autophagy-lysosome pathway. Perturbed autophagy impaired the degradation of some TBC components in Sertoli cells, such as VCL and CTTN, and led to the accumulation of TBC components surrounding the spermatid head, which may be associated with the sperm-releasing defect. Together, our results reveal that autophagy is essential for the TBC components degradation in mouse Sertoli cells and define a functional role of autophagy during spermiation.

Abstract Background There is no regulation in the current guidelines on the sequence of ligation of the inferior mesenteric artery and vein during rectal cancer surgery owing to a lack of sufficient evidence. Circulating tumor cells (CTCs) in peripheral blood can be used as potential indicators for predicting prognosis in colorectal cancer patients. This study aims to explore the feasibility of different ligation sequences for the inferior mesenteric vessels and their potential influence on CTCs. Methods This pilot study involved 29 stage I-III rectal adenocarcinoma patients undergoing laparoscopic surgery. Patients were allocated into two groups based on the sequence of vascular ligation: vein-first (V-first) and artery-first (A-first). The primary objective was to assess the impact of the ligation sequence on peripheral blood CTC levels pre- and post-operatively. Secondary outcomes included intraoperative complications, surgical duration, blood loss, and number of lymph nodes harvested, and postoperative complications. The study was approved by the ethics committee of our hospital (SCCHEC-02-2024-102), and all patients provided informed consent. Results No significant differences were found between the two groups regarding surgical duration, blood loss, lymph nodes harvested, or postoperative complications. A reduction in CTCs postoperatively was observed in 36% of patients in the V-first group, in comparison to 20% in the A-first group. Conclusion Both A-first and V-first ligation sequences are viable and safe options in laparoscopic rectal cancer surgery. The V-first approach may be more effective in reducing levels of CTCs in peripheral blood. Further randomized studies are warranted to explore these findings comprehensively.

Abstract Background Increasing studies focused on the efficacy of acupuncture on pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization-embryo transfer (IVF-ET). However, debatable conclusions have been drawn from different randomized controlled trials (RCTs), which might be related to different doses of acupuncture. Objective To evaluate whether acupuncture has a dose-dependent effect on pregnancy outcomes in patients with PCOS undergoing IVF-ET in systematically reviewing. Methods Seven electronic databases were searched from inception to October 10th, 2024. The Cochrane Collaboration’s tool ROB 2.0 (ROB 2.0) provided an assessment for the risk of bias. The acupuncture dose was extracted, then categorized into high, medium, and low dose according to the scoring system results, the evidence was assessed by Slavin’s qualitative best-evidence synthesis approach in a rigours methodological way. Clinical pregnancy rate (CPR) was regarded as the primary outcome. Results A total of 953 subjects met the eligibility criteria in 12 RCTs were included, among which two studies were low dose, four were medium dose, and six were high dose. The overall quality of included studies was low, 50.00% (6/12) studies were low risk, 16.67% (2/12) studies were some concerns, and 33.33% (4/12) studies were high risk. Comparing the results, the consistent high-dose result among high-quality trials provides strong evidence for a positive correlation between high-dose acupuncture and pregnancy outcomes. Conclusion A trend indicates that higher acupuncture doses yield better outcomes for PCOS patients undergoing IVF-ET. Further confirmation through direct comparisons of different doses was needed. Trial registration The systematic review has been registered on PROSPERO ( https://www.crd.york.ac.uk/prospero/ ), and the registration number is CRD42023400187.

Abstract Comprehensive characterizations of genetic diversity and demographic models of ethnolinguistically diverse Chinese populations are essential for elucidating their forensic characteristics and evolutionary past. We developed a 114-plex NGS InDel panel to genotype 114 genome-wide markers and investigated the genetic structures of Zhuang, Hui, Miao, Li, Tibetan, Yi, and Mongolian populations, encompassing five language families. This panel demonstrated robust performance, with exceptional potential for forensic individual identification and paternity testing, evidenced by the combined power of discrimination for 77 autosomal InDels (ranged from 1-3.6400 × 10–30 to 1-3.5713 × 10–32) and the combined power of exclusion (ranged from 1-2.1863 × 10–6 to 1-2.1261 × 10–7). The cumulative mean exclusion chance for 32 X-chromosomal InDels varied between 0.99996 and 0.99999 for trios and 0.99760 to 0.99898 for duos. We also analyzed genetic similarities and differences between these populations and 27 global populations, revealing distinct clusters among African, South Asian, East Asian, and European groups, with a close genetic affinity to East Asians. Notably, we identified geography-related genetic substructures: Inner Mongolia Mongolians and Gansu Huis formed a northern branch, Tibetans and Yis from Sichuan constituted a highland branch, and Guangxi Zhuangs exhibited close ties with Hainan Lis and Guangxi Miaos in the southern branch. Additionally, many InDels proved to be ancestry-informative markers for biogeographic ancestry inference. Collectively, these findings underscore the utility of the 114-plex NGS InDel panel as a complementary tool for forensic investigations and as a source of insights into the genetic architecture of ethnolinguistically distinct Chinese populations.

Abstract Recent studies have identified SLC2A3 as being abnormally upregulated in multiple tumor types, correlating with poor survival and disrupted microenvironments. However, its prognostic significance in head and neck squamous cell carcinoma (HNSC) remains underexplored. In this study, SLC2A3 was screened as a potential risk gene influencing both immune and tumor components within the tumor microenvironment (TME) of 504 HNSC patients from the TCGA database. Immune infiltration analyses and clinical significance on SLC2A3 were conducted using ESTIMATE, CIBERSORT, ssGSEA, TIMER and clinical prognosis parameters. Additionally, the single-cell dataset is used to analyze the expression of SLC2A3 in various subpopulations. The magnetic activated cell sorting (MACS) is used to isolate CD8+ T cells from PBMCs or tumor tissues. Flow cytometry is used to identify purified and activated CD8+ T cells. GSEA and WB were used to investigate the molecular mechanism of SLC2A3 in CD8+ T cells. The co-culture system of CD8+ T cells and TU686 was used to investigate the effects of SLC2A3 on immune cells and tumor development. In this study, SLC2A3 was identified as a potential risk gene affecting both immune cells and tumor components within the TME of 504 HNSC patients derived from the TCGA database. We conducted immune infiltration analyses and assessed the clinical significance of SLC2A3 using various bioinformatics tools, including ESTIMATE, CIBERSORT, ssGSEA, and TIMER, along with clinical prognosis parameters. The single-cell RNA sequencing dataset was utilized to examine SLC2A3 expression across different cellular subpopulations. Magnetic activated cell sorting (MACS) was employed to isolate CD8+ T cells from peripheral blood mononuclear cells (PBMCs) or tumor tissues. Flow cytometry was implemented to confirm the purity and activation state of the isolated CD8+ T cells. GSEA and Western blot were applied to explore the molecular mechanisms underlying SLC2A3’s role in CD8+ T cells. Lastly, a co-culture system involving CD8+ T cells and TU686 tumor cells was established to study the impact of SLC2A3 on immune cell function and tumor progression. SLC2A3 emerges as an actively variable gene within the immune and stromal components of the TME, linked to aggravated immune infiltration and poor clinical outcomes. The upregulated expression of SLC2A3 is predominantly enriched in immune-related biological processes and linked to the suppression of CD8+ T cells, which are crucial for the survival of HNSC patients. Furthermore, SLC2A3 exhibits specific overexpression in CD8+ T cells and may potentially trigger ferroptosis. Knockdown of SLC2A3 led to a significant increase in the proliferation of CD8+ T cells compared to those without knockdown. In co-culture systems, CD8+ T cells with SLC2A3 knockdown demonstrated an enhanced ability to eliminate tumor cells compared to those without the knockdown. SLC2A3 is associated with changes in the TME and prognostic indicators. Moreover, high SLC2A3 expression in CD8+ T cells may drive cell death through ferroptosis, fostering tumor progression.

Abstract Recently, impressive progress has been made in cross-domain image translation using image generation models pre-trained on massive amounts of data since these pre-trained generative models have strong generative capabilities.However, due to the fact that these pre-trained generative models are usually generated based on the principle of diffusion, there are often the following issues, such as color pattern distortion and the inability to maintain content structure during the translation process. Existing methods fail to meet the requirements of cross-domain image translation, where the shape (content structure) of the image should remain unchanged or undergo minimal change. To address these challenges, we propose an unsupervised content and style learning method for cross-domain image translation. Our approach utilizes self-structure attention loss to preserve content structure and color constraint loss to map the color space of the reference image to the translated image. This effectively separates the image’s content structure from its color style, enabling high-quality multi-modal cross-domain image translation. Experiments on multiple datasets demonstrate that our method outperforms state-of-the-art approaches in metrics such as LPIPS, NDB, JS, IS, and excels in maintaining content structure and color patterns.

Abstract Background Machine learning (ML) has been widely applied to predict the outcomes of numerous diseases. The current study aimed to develop a prognostic prediction model using machine learning algorithms and identify risk factors associated with residual back pain in patients with osteoporotic vertebrae compression fracture (OVCF) following percutaneous vertebroplasty (PVP). Methods A total of 863 OVCF patients who underwent PVP surgery were enrolled and analyzed. One month following surgery, a Visual Analog Scale (VAS) score of ≥ 4 was deemed to signify residual low back pain following the operation and patients were grouped into a residual pain group and pain-free group. The optimal feature set for both machine learning and statistical models was adjusted based on a 2000-resample bootstrap-based internal validation via an exhaustive search. The area under the curve (AUC), classification accuracy, sensitivity, and specificity of each model were then calculated to evaluate the predictive performance of each model. Results In our current study, two main findings were observed: (1) Compared with statistical models, ML models exhibited superior predictive performance, with SVM demonstrating the highest prediction accuracy; (2) several variables were identified as the most predictive factors by both the machine learning and statistical models, including bone cement volume, number of fractured vertebrae, facet joint violation, paraspinal muscle degeneration, and intravertebral vacuum cleft. Conclusion Overall, the study demonstrated that machine learning classifiers such as SVM can effectively predict residual back pain for patients with OVCF following PVP while identifying associated predictors in a multivariate manner.

Abstract Background This study aims to develop and validate an integrated predictive model combining CT radiomics and clinical parameters for early assessment of acute pancreatitis severity. Methods A retrospective cohort of 246 patients with acute pancreatitis was analyzed, with a 70%-30% split for training and validation groups. CT image segmentation was performed using ITK-SNAP, followed by the extraction of radiomics features. The stability of the radiomics features was assessed through inter-observer Intraclass Correlation Coefficient analysis. Feature selection was carried out using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation. A radiomics model was constructed through logistic regression to compute the radiomics score. Concurrently, univariate and multivariate logistic regression were employed to identify independent clinical risk factors for the clinical model. The radiomics score and clinical variables were integrated into a combined model, which was visualized with a nomogram. Model performance and net clinical benefit were evaluated through the area under the receiver operating characteristic curve (AUC), the DeLong test, and decision curve analysis. Results A total of 913 radiomics features demonstrated satisfactory consistency. Eight features were selected for the radiomics model. Serum calcium, C-reactive protein, and white blood cell count were identified as independent clinical predictors. The AUC of the radiomics model was 0.871 (95% CI, 0.793–0.949) in the training cohort and 0.859 (95% CI, 0.751–0.967) in the validation cohort. The clinical model achieved AUCs of 0.833 (95% CI, 0.756–0.910) and 0.810 (95% CI, 0.692–0.929) for the training and validation cohorts, respectively. The combined model outperformed both the radiomics and clinical models, with an AUC of 0.905 (95% CI, 0.837–0.973) in the training cohort and 0.908 (95% CI, 0.824–0.992) in the validation cohort. The DeLong test confirmed superior predictive performance of the combined model over both the radiomics and clinical models in the training cohort, and over the clinical model in the validation cohort. Decision curve analysis further demonstrated that the combined model provided greater net clinical benefit than the radiomics or clinical models alone. Conclusion The clinical-radiomics model offers a novel tool for the early prediction of acute pancreatitis severity, providing valuable support for clinical decision-making.

Abstract Background Circulating tumour DNA (ctDNA) has emerged as a valuable liquid biopsy biomarker in the field of oncology, including head and neck squamous cell carcinomas (HNSCCs), offering potential insights into cancer diagnosis, progression, and prognosis. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in HNSCC. Methods PubMed and Ovid were searched as part of our review. Studies that investigated the relationship between ctDNA and prognosis in HNSCC patients were included. Outcomes extracted included basic characteristics, ctDNA details and survival data. Meta-analysis was performed on eligible studies to determine pooled progression-free/recurrence-free survival (RFS/PFS) and overall survival (OS). Results Twenty-two studies were included, involving 5062 HNSCC patients from 11 countries. The meta-analysis demonstrated that the positive ctDNA/methylation detection was associated with worse OS (HR = 2.00, 95% CI 1.35–2.96) and worse PFS/RFS (HR = 3.54, 95% CI 1.05–11.85). Positive ctEBV DNA was associated with poorer OS (HR = 2.86, 95% CI 1.84–4.45) and poorer PFS/RFS (HR = 1.93, 95% CI 1.74–2.13). Positive ctHPV DNA was associated with poorer OS (HR = 1.38, 95% CI 1.07–1.38) but not PFS/PFS (HR = 1.33, 95% CI 0.96–1.85). Conclusion Meta-analysis indicates that the status of ctDNA is significantly associated with the prognosis of HNSCC patients, with ctDNA/methylation-negative patients demonstrating better PFS/RFS and OS.

Abstract The intricate tumor microenvironment presents formidable obstacles to the efficacy of adoptive T cell therapy in the management of solid tumors by limiting the infiltration and inducing exhaustion of the transferred T cells. Here, we developed a bacterial-based adjuvant approach that augments the efficacy of adoptive T-cell therapy for solid tumor treatment. Our study reveals that intratumor injection of E. coli MG1655 normalizes tumor vasculatures and reprograms tumor-associated macrophages into M1 phenotype that produce abundant CCL5, together facilitating tumor infiltration of adoptively transferred T cells. The depletion of tumor-associated macrophages or CCL5 neutralization in vivo leads to the significantly decreased solid tumor infiltration of adoptive T cells in the presence of bacteriotherapy. This combinatorial therapy, consisting of E. coli adjuvant and adoptive T-cell therapy, effectively eradicates early-stage melanoma and inhibits the progression of pancreatic tumors. Notably, this dual strategy also strengthened the distal tumor control capabilities of adoptive T-cell therapy through the induction of in situ tumor vaccination. This dual therapeutic approach involving bacterial therapy targeting the interior of solid tumors and adoptive T-cell therapy attacking the tumor periphery exhibits potent therapeutic efficacy in achieving the eradication of advanced-stage tumors, including melanoma and hepatocellular carcinoma, by converging attacks from both inside and outside the tumor tissues.

Al–Mg-Sc-Zr alloys with flat surface, low porosity and excellent mechanical properties were prepared by Laser Metal Deposition (LMD) and annealed (A) using secondary recycled Al–Mg-Sc-Zr powders in an open environment. The optimal LMD parameters are laser power 1800 W, scanning speed 5 mm/s and scanning spacing 3 mm The Al–Mg-Sc-Zr alloy deposited by multi-layer multi-track under optimal parameters and subsequent annealing treatment displays a flat surface, porosity of 2.08%, hardness of 134 HV, ultimate tensile strengthen (UTS) of 348 MPa, yield strength (YS) of 235 MPa and uniform elongation (εu) of 16.71%. The porosity mainly concentrates in the molten pool overlap due to the influence of Marangoni convection. Solute redistribution and compositional subcooling lead to periodic segregation of Sc elements, finally contributing to the appearance of bright and dark spiral stacking features centered in the molten pool. Due to the small G/R value of the molten pool, coarse and fine equiaxed grains are alternately developed during single-track deposition. The in-situ heat treatment induced by the subsequent multi-layer multi-track deposition transformed the alternately distributed coarse and fine equiaxed grain structure into a homogeneous grain structure. This results from the combination influence of the difference in the proportion of large-angle grain boundaries occupied by the coarse/fine grains and the pinning of the Al3(Sc,Zr) grains. The strength of the present alloy is mainly provided by solid solution strengthening, fine grain strengthening and second phase strengthening. The stress concentration is reduced for fine grain size and the intergranular strain transfer is favored because of small internal orientation difference. Meanwhile, the interlayer retention and annealing treatment timely release the thermal stresses during the LMD process, which results in the Al–Mg-Sc-Zr alloys keep good plasticity.

Abstract The flexibility of soft open point (SOP) in spatial power regulation enhances the distribution network's (DN) integration of large‐scale renewable energy sources. However, the high cost of SOP and its limited capability for temporal power regulation impede its widespread adoption. Given the rapid expansion of 5G base stations (BSs), utilizing their energy storage to participate in DN planning and operation optimization provides a promising solution. Therefore, this paper proposes an optimal planning method of SOP in DN, considering collaborations with 5G BSs. The objective is to enhance DN’s power regulation in both temporal and spatial dimensions, while minimizing the investment cost of SOP and fully utilizing the unused capacity in base station energy storage (BSES). Firstly, the flexible regulation models of SOP and 5G BS are established, with the real‐time dispatchability of BSES formulated. Then, a bi‐level optimization model is proposed, where the planning layer aims to minimize the total cost, while the operational layer aims to decrease the average voltage deviation. Additionally, an improved Shapley value method based on interactive power is developed for benefit allocation, which enhances the engagement of 5G BSs to participate in DN regulation. The effectiveness of proposed method is validated by simulation results.

Abstract Background The incidence of androgenetic alopecia in males is on the rise annually, with hair transplantation using follicular unit extraction (FUE) gaining increasing acceptance as an appropriate treatment for these individuals. Methods A retrospective study was undertaken, involving 158 male patients diagnosed with androgenetic alopecia, who underwent treatment between January 2016 and December 2020 at the Medical Cosmetology Department of the First Affiliated Hospital of Xi’an Medical University. Demographic data and treatment characteristics were documented and analyzed. Clinical efficacy, operation-related complications, patient satisfaction rates, and quality of life scores were assessed and analyzed. Results Following FUE hair transplantation, over 90% of the hair follicles survived in 158 patients, with more than 85% of patients achieving a hair follicle survival rate exceeding 95% at 12 months post-operation. Patient satisfaction rates exceeded 98%, while the complication rate was below 6%. Conclusion Our findings demonstrate that FUE is a minimally invasive hair transplant technique associated with a high hair follicle survival rate and optimal hair density. This approach proves effective in treating male androgenetic alopecia and merits further clinical application.

Abstract Accurate treatment response assessment using serial CT scans is essential in oncological clinical trials. However, oncologists’ assessment following the Response Evaluation Criteria in Solid Tumors (RECIST) guideline is subjective, time-consuming, and sometimes fallible. Advanced liver cancer often presents multifocal hepatic lesions on CT imaging, making accurate characterization more challenging than with other malignancies. In this work, we developed a tumor volume guided comprehensive objective response evaluation based on deep learning (RECORD) for liver cancer. RECORD performs liver tumor segmentation, followed by sum of the volume (SOV)-based treatment response classification and new lesion assessment. Then, it can provide treatment evaluations of response, stability, and progression, and calculates progression-free survival (PFS) and response time. The RECORD pipeline was developed with both CNN and ViT backbones. Its performance was evaluated in three longitudinal cohorts involving 60 multi-national centers, 206 patients, 891 CT scans, using internal five-fold cross-validation and external validations. RECORD with the most effective backbone achieved an average AUC-response of 0.981, AUC-stable of 0.929, and AUC-progression of 0.969 for SOV-based disease status classification, F1-score of 0.887 for new lesion identification, and accuracy of 0.889 for final treatment outcome assessments across all cohorts. RECORD’s PFS and response time predictions strongly correlated with clinician’s assessments (P

Abstract Background Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. Objective To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. Methods This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. Results A total of 1617 patients were enrolled. At week 12, patients in the adapalene–clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (− 66.85%), compared with adapalene alone (− 50.82%) or clindamycin gel alone (− 57.61%). The difference in the least square means of the adapalene–clindamycin gel group and adapalene group, or clindamycin gel group was − 16.08% (95% CI − 19.95% to − 12.21%) and − 9.38% (95% CI − 13.25% to − 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene–clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Conclusion Adapalene 0.1%–clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. Trial Registration ClinicalTrials.gov identifier NCT03615768.

Abstract Background Although mesenchymal stem cells (MSCs) have been proven to be appropriate candidates for the treatment of AKI-CKD, their efficacy is limited and variable. Astilbin (AST) had a protective effect on MSCs from oxidative stress via ROS-scavenging, however, whether it can improve MSCs’ renoprotection and the underlying mechanism need to be elucidated. Methods AST-pretreated MSCs were administered intravenously into the ischemia–reperfusion injury mice models and the renal function, pathological changes and inflammation. Were evaluated. In addition, DARTS, molecular docking, surface plasma resonance(SPR), dual-luciferase reporter gene assay and the ChIP-PCR were utilized to explore the potential signaling pathways through which AST exert renal protective effects on MSCs. Results AST-pretreated MSCs markedly improved kidney function, reduced kidney pathological injury and inflammation in AKI and AKI-CKD mice. RNA-seq results showed that PTGS2 related pathway was significantly up-regulated in MSCs after AST pretreatment. DARTS assay, molecular docking and SPR assay revealed that AST could bind with the transcriptional factor of Kruppel-Like Factor 4(KLF4) protein. The promoter of PTGS2 had the binding and transcriptional activation by KLF4. Furthermore, AST pretreatment promoted the secretion of PGE2 in MSCs. And then the westren blot results showed that the protein levels of CD163 and CD206 were upregulated after coculture in AST-pretreated MSCs, indicating that the polarization of RAW264.7 cells towards M2-like macrophages was induced. Knockdown of PTGS2 reversed the ability of AST-pretreated MSCs in converting macrophages to M2 phenotype and reducing their therapeutic effects on AKI-CKD mice. Conclusion AST pretreatment enhances the efficacy of MSCs on AKI and AKI-CKD mice by inducing of M2-like phenotype polarization in macrophages through the PTGS2-mediated pathway. This approach not only provides a novel strategy to strengthen the capability of MSCs but also helps elucidate the beneficial effects of the Chinese herbal medicine AST.

Abstract Background No specific triglyceride-lowering therapy is recommended in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP), primarily because of the lack of quality evidence. This study aimed to describe practice variations in triglyceride-lowering therapies for early HTG-AP patients and assess whether more rapid triglyceride decline is associated with improving organ failure. Methods This is a multicentre, prospective cohort study recruiting HTG-AP patients with elevated plasma triglyceride (> 11.3 mmol/L) admitted within 72 h from the onset of symptoms. Patients were dichotomised on study day 3 into either target reaching (plasma triglyceride ≤ 5.65 mmol/L) or not. The primary outcome was organ failure-free days (OFFD) to 14 days of enrolment. The association between target-reaching and OFFD was modelled. Additionally, the slope in plasma triglyceride over the first three days in response to treatment was calculated, and its association with OFFD was assessed as a sensitivity analysis. Results Among the 300 enrolled patients, 211 underwent exclusive medical treatment, and 89 underwent various blood purification therapies. Triglyceride levels were available in 230 patients on study day 3, among whom 122 (53.0%) had triglyceride levels of ≤ 5.65 mmol/l. The OFFD was not different between these patients and those in whom plasma triglyceride remained > 5.65 mmol/L [median (IQR): 13 (10–14) vs. 14 (10–14), p = 0.46], even after adjustment for potential confounders. For the decline slopes, there was no significant change in OFFD with a steeper decline slope [risk difference, − 0.088, 95% CI, − 0.334 to 0.158, p = 0.48]. Conclusions Triglyceride-lowering therapies vary greatly across centres. More rapid triglyceride decline was not associated with improving incidence and duration of organ failure.

Abstract Crystalline silica (CS) particle exposure leads to silicosis which is characterized as progressive fibrosis. Fibroblasts are vital effector cells in fibrogenesis. Emerging studies have identified immune sentinel roles for fibroblasts in chronic disease, while their immune-modulatory roles in silicosis remain unclear. Herein, we show that group 2 innate lymphoid cell (ILC2) conversion to ILC1s is closely involved in silicosis progression, which is mediated by activated fibroblasts via interleukin (IL)−18. Mechanistically, Notch3 signaling in mechanics-activated fibroblasts modulates IL-18 production via caspase 1 activity. The mouse-specific Notch3 knockout in fibroblasts retards pulmonary fibrosis progression that is linked to attenuated ILC conversion. Our results indicate that activated fibroblasts in silicotic lungs are regulators of ILC2–ILC1 conversion, associated with silicosis progression via the Notch3–IL-18 signaling axis. This finding broadens our understanding of immune-modulatory mechanisms in silicosis, and indicates potential therapeutic targets for lung fibrotic diseases.

Abstract Upconversion nanoparticles (UCNPs), capable of converting near-infrared (NIR) light into high-energy emission, hold significant promise for bioimaging applications. However, the presence of tissue barriers poses a challenge to the effective delivery of nanoparticles (NPs) to target organs. In this study, we demonstrate the core–shell UCNPs modified with cationic biopolymer, i.e., N, N-trimethyl chitosan (TMC), can overcome endothelial barriers. The core–shell UCNP is composed of NaGdF4: Yb3+,Tm3+ (16.7 ± 2.7 nm) as core materials and silica (SiO2) shell. The average particle size of UCNPs@SiO2 is estimated at 26.1 ± 3.7 nm. X-ray diffraction (XRD), transmission electron microscopy (TEM) and element mapping shows the formation of hexagonal crystal structure of β-NaGdF4 and elements doping. The surface of UCNPs@SiO2 has been modified with poly(ethylene glycol) (PEG) to enhance water dispersibility and colloidal stability, and further modified with TMC with the zeta potential increasing from -2.1 ± 0.96 mV to 26.9 ± 12.6 mV. No significant toxic effect is imposed to HUVECs when the cells are treated with core–shell UCNPs with surface modification up to 250 µg/mL. The transport ability of the core–shell UCNPs has been evaluated by using the in vitro endothelial barrier model. Transepithelial electrical resistance (TEER) and immunofluorescence staining of tight junction proteins have been employed to verify the integrity of the in vitro endothelial barrier model. The results indicate that the transport percentage of the UCNPs@SiO2 with PEG and TMC through the model is up to 4.56%, which is twice higher than that of the UCNPs@SiO2 with PEG but without TMC and six times that of the UCNPs@SiO2.

Abstract Background Ischemic stroke (IS) is a commonly seen cerebrovascular disease which seriously endangers the health of middle age and old people. However, its etiology and pathogenesis have not yet fully comprehended. miR-30 gene is a novel gene which may be involved in IS. However, no studies have investigated the relationship between IS and the single-nucleotide polymorphisms (SNPs) of miR-30. Therefore, this study examined the relationship between miR-30 polymorphisms (rs2222722, rs1192037, rs10095483 and rs16827546) and the risk of IS. Methods Totally 248 IS patients and 230 age-, sex- and race-matched controls were involved in this study. Based on SNPscan technique, four polymorphisms (rs2222722, rs1192037, rs10095483 and rs16827546) were genotyped. Results There exists a significant association between rs2222722 polymorphism and the risk of IS according to analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 1.616, 95% CI: 0.943–2.768, P = 0. 081); (AA vs. GG: adjusted OR = 2.447, 95% CI: 1.233–4.858, P = 0.011); dominant model: adjusted (OR = 1.806, 95% CI, 1.082–3.016, P = 0.024); (G vs. A: adjusted OR = 1.492, 95% CI: 1.148–1.939, P = 0.003). Besides, miR-30a expression was significantly higher in patients undergoing IS relative to that in controls (P

Abstract Background This study aims to evaluate the efficacy and clinical outcomes of Nice knot-assisted fixation in the management of comminuted and displaced clavicle fractures. Methods A systematic search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, China Biology Medicine (CBM) database, CNKI, Wanfang, and VIP database, to identify studies comparing Nice knot-assisted fixation with traditional surgical treatment for displaced midshaft clavicle fractures. The primary outcomes assessed included fracture healing times, hospitalization days, complications, and functional outcomes. Secondary outcomes such as intraoperative blood loss, operative time, incision length, and fluoroscopy time were also evaluated. Data were analyzed using random-effects models, and summary statistics including Mean Difference (MD), risk ratios (RRs) and theirs’ 95% confidence intervals (CIs) were calculated. Results Screening of the literature yielded a total of 11 studies meeting the inclusion criteria, involving 754 patients. Meta-analysis of the pooled data demonstrated a significant advantage of Nice knot-assisted fixation over traditional surgical treatment in terms of operative time (MD = -11.53, 95% CI: -18.16 to -4.91, p = 0.0006) and blood loss (MD = -14.19, 95% CI: -20.93 to -7.45, p = 0.00001). Additionally, Nice knot-assisted fixation was associated with reduced fracture healing time (MD = -0.63, 95% CI: -1.12 to -0.14, p = 0.01) rather than hospitalization days (MD = -0.47, 95% CI: -1.14 to 0.21, p = 0.18) and complications (RR = 0.48, 95% CI: 0.23 to 1.01, p = 0.05) compared to traditional surgical treatment. Moreover, nice knot-assisted fixation was associated with increased constant-murley score and Neer score, and reduced visual analogue scale (VAS) score compared to traditional surgical treatment. Conclusion This study highlights that Nice knot assistance offers advantages in reducing intraoperative blood loss, shortening operation time, and achieving favorable postoperative outcomes.

Abstract Age-related macular degeneration (AMD) is the leading cause of blindness in older people in developed countries. It has been suggested that heavy metal exposure may be associated with the development of AMD, but most studies have focused on the effects of a single metal with traditional methods. In this study, we analyzed the relationship between 13 urinary heavy metal concentrations and AMD using NHANES data between 2005 and 2008. We constructed and compared 11 machine learning models to identify the best model for predicting AMD risk. We further interpreted the models by Permutation Feature Importance (PFI), Partial Dependence Plot (PDP) analysis, and SHapley Additive exPlanations (SHAP) analysis. 216 AMD patients out of 2380 participants. The random forest (RF) model performed optimally in predicting the risk of AMD, with an AUC value of 0.970. PFI analyses revealed that age and urinary cadmium (Cd) were the main factors influencing the risk of AMD. SHAP analyses further confirmed the significance of Cd concentration in predicting the risk of AMD, and we revealed a significant interaction with significant interaction of race. Our study firstly explored the relationship between heavy metal exposure levels and AMD based on machine learning techniques, found that urinary Cd concentration had the greatest impact on AMD, and revealed the superior predictive performance of machine learning methods. Furthermore, our study provided a new perspective for early screening and intervention of AMD.

Abstract The current primary therapeutic approach for schizophrenia is antipsychotic medication, and antipsychotic-induced hyperprolactinemia occurs in 40–80% of patients with schizophrenia. Aripiprazole, an atypical antipsychotic belonging to the quinolinone derivative class, can reduce the likelihood of developing hyperprolactinemia, but the pharmacological mechanisms of this reduction are unknown. This study aimed to explore the molecular mechanism of action of aripiprazole in treating hyperprolactinemia based on network pharmacology and molecular docking techniques. This study identified a total of 151 potential targets for aripiprazole from the DrugBank, TCMSP, BATMAN-TCM, TargetNet, and SwissTargetPrediction databases. Additionally, 71 hyperprolactinemia targets were obtained from the PharmGKB, DrugBank, TTD, GeneCards, OMIM, and DisGENET databases. Utilizing Venny 2.1.0 software, an intersection of 27 genes was identified between aripiprazole and hyperprolactinemia. To construct a common target protein–protein interaction (PPI) network, the common targets obtained from both sources were input into the STRING database. The resulting PPI network was then imported into Cytoscape 3.7.2 software, which identified eight core targets associated with aripiprazole’s treatment of hyperprolactinemia. Subsequently, a PPI network was established for these targets. Enrichment analysis of the key targets was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes in the DAVID database. Additionally, molecular docking verification of the interaction between aripiprazole and the core targets was performed using AutoDock Vina software. Aripiprazole’s intervention in hyperprolactinemia primarily targets the following core proteins: Solute Carrier Family 6 Member 3 (SLC6A3), monoamine oxidase (MAO-B), Dopamine D2 receptor (DRD2), 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A), 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C), cytochrome P450 2D6 (CYP2D6), Dopamine D1 receptor (DRD1), Dopamine D4 receptor (DRD4). These targets are predominantly involved in biological processes such as the adenylate cyclase-activating adrenergic receptor signaling pathway, G-protein coupled receptor signaling pathway coupled to cyclic nucleotide second messenger, phospholipase C-activating G-protein coupled receptor signaling pathway, chemical synaptic transmission, and response to xenobiotic stimulus. Primary enrichment occurs in signaling pathways such as the neuroactive ligand-receptor interaction and serotonergic synapse pathways. Molecular docking results demonstrate a favorable affinity between aripiprazole and the core target proteins MAO-B, DRD2, SLC6A3, HTR2C, HTR2A, CYP2D6, DRD4, and DRD1. Network pharmacology predicted potential targets and signaling pathways for aripiprazole’s intervention in hyperprolactinemia, offering theoretical support and a reference basis for optimizing clinical strategies and drug development involving aripiprazole.

Abstract Background The zoonotic infectious diseases of poverty (zIDPs) are a group of diseases contributing to global poverty, with significant impacts on a substantial population. This study aims to describe the global, regional, and national burden of zIDPs—schistosomiasis, cystic echinococcosis, cysticercosis, and food-borne trematodiases (FBTs)—to support policy making and resource allocation for their control and elimination. Methods Data of zIDPs from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 were retrieved from 1990 to 2021. The age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rate were described and the estimated annual percentage changes (EAPCs) were calculated to quantify their burden and temporal trends. Spearman correlation analysis was conducted to examine the relationship between age-standardized rates and Socio-demographic Index (SDI). Results In 2021, these zIDPs exhibited a certain level of ASPRs and age-standardized DALY rates, while maintaining relatively low ASMRs. Noticeably, schistosomiasis presented the highest ASPR of 1914.299 (95% UI: 1378.920, 2510.853 per 100,000 population) and an age-standardized DALY rate of 21.895 (95% UI: 12.937, 37.278 per 100,000 population) among the zIDPs. The tapestry of burden—woven predominantly through low and lower-middle SDI regions—stretched across Africa, Latin America, and parts of Asia. From 1990 to 2021, a kaleidoscopic shift was observed globally as ASPRs, ASMRs, and age-standardized DALY rates declined significantly, as reflected by the EAPC values. Negative correlations were observed between the ASPRs, ASMRs, age-standardized DALY rates of schistosomiasis (r value = − 0.610, − 0.622 and − 0.610), cystic echinococcosis (− 0.676 of ASMR, − 0.550 of age-standardized DALYs), cysticercosis (− 0.420, − 0.797 and − 0.591) and the SDI. In contrast, a slight positive correlation was noted between the ASPR, age-standardized DALY rates of FBTs and SDI with r value of 0.221 and 0.213, respectively. Conclusion The burden of zIDPs declined across almost all endemic regions from 1990 to 2021, yet still predominated in low and low-middle SDI regions. Substantial challenges exist to achieve the goal of control and elimination of zIDPs, and integrated approaches based on One Health need to be strengthened to improve health outcomes. Graphical Abstract

Central Asia, a crucible of prehistoric and historical Trans-Eurasian interactions, has been pivotal in shaping cultural exchanges, population dynamics, and genetic admixture. Recent insights from ancient DNA studies have shed light on the extensive population turnover within this region, encompassing a spectrum of groups from Paleolithic hunter-gatherers to Holocene herders and the nomadic pastoralist empires of historical times. The genomic analysis of ancient pathogens across the Eurasian steppe has further deepened our understanding of pathogen origins, clonal expansions, and the intricate processes of host-pathogen coevolution in relation to varying pathogen exposures and their spread. We consolidate the latest findings pertaining to the ancient human and pathogen genomes of Central Asia, elucidating their profound influence on the genomic tapestry of contemporary Central Asians. A notable gap in the current genomic databases for Central Asia is underscored, particularly within the scope of genomics-driven precision medicine. We stress the urgent need for the development of extensive, region-specific genomic resources that hold promise for revealing the genetic blueprints underlying human traits and diseases, refining polygenic scoring models for predictive medicine, and bolstering genomic research endeavors across Central Asia.