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Abstract As a traditional Chinese medicine formula used in clinical practice for an extended period, Suxin-Hugan-Fang (SXHGF) exhibits excellent anti-inflammatory properties. However, the efficacy of SXHGF in treating ulcerative colitis (UC) and its mechanism of action are still unclear. In this study, the therapeutic effects of SXHGF on UC were evaluated using network pharmacology and experimental validation, while also investigating its mechanism of action. By administering DSS to C57BL/6 mice to construct a mouse model of ulcerative colitis, the therapeutic effect of SXHGF on ulcerative colitis was evaluated based on weight loss percentage, disease activity index, colon length changes, and pathological conditions as indicators. The main chemical components of SXHGF were determined by LC-MS-QTOF method. The potential targets and mechanisms of action of SXHGF in the treatment of UC were inferred using bioinformatics methods, and further validated through ELISA, IHC, and Western blotting assays. The experimental results demonstrate that SXHGF can suppress oxidative stress and oxidative damage in the colon tissue of UC mice, and alleviate DSS-induced ulcerative colitis by inhibiting the JAK2/STAT3 and NFκB pathways.

It has been widely acknowledged that probability-based methodologies play a crucial role in guiding decision-making processes when faced with uncertain or vague circumstances. To ensure that decisions made under such conditions are both meaningful and productive, a variety of methodologies centered around probability have been developed, endorsed, and put into practice. This study also aims to contribute to the existing body of knowledge by introducing a new probability model known as the weighted sine generalized Rayleigh distribution. For the proposed model, certain properties are derived. Furthermore, the parameter estimation technique and simulation studies based on the proposed model are also presented. Finally, the proposed model is successfully implemented on three distinct data sets sourced from sports and different engineering disciplines. By evaluating the statistical significance through the p-value and other various tests, it is evident that the proposed model consistently outperforms its competitor distributions. The practical illustration, emphasizes the efficacy and potential of the proposed model for widespread applications in sports and engineering research and practice.

Abstract This study aims to evaluate the biomechanical performance of the Gamma 3 nail with an anti-rotation screw (GNS) and compare it to two established gold-standard methods for treating unstable femoral neck fractures (UFNFs). Synthetic bone models were prepared with Pauwels’ type III osteotomy and an additional posterior wedge. Three different implant configurations were tested: three cannulated crews (3CS) in an inverted triangle configuration, a dynamic hip screw with an anti-rotation screw (DHSS), and GNS. Non-destructive cyclic axial loading was applied at 7° adduction, with 1000 cycles ranging from 100 to 1000 N. Subsequently, a construct failure test was conducted using progressive axial compression, and fracture reduction loss was recorded. The average axial stiffness was 321 ± 52 N/mm for 3CS, 430 ± 71 N/mm for DHSS, and 519 ± 104 N/mm for GNS. The average ultimate failure loads were 2699.3 N for 3CS, 3427.1 N for DHSS, and 3758.9 N for GNS. GNS demonstrated significantly greater axial stiffness compared to the other two groups (P

Abstract Synthetic membrane nanopores made of DNA are promising systems to sense and control molecular transport in biosensing, sequencing, and synthetic cells. Lumen-tunable nanopore like the natural ion channels and systematically increasing the lumen size have become long-standing desires in developing nanopores. Here, we design a triangular DNA nanopore with a large tunable lumen. It allows in-situ transition from expanded state to contracted state without changing its stable triangular shape, and vice versa, in which specific DNA bindings as stimuli mechanically pinch and release the three corners of the triangular frame. Transmission electron microscopy images and molecular dynamics simulations illustrate the stable architectures and the high shape retention. Single-channel current recordings and fluorescence influx studies demonstrate the low-noise repeatable readouts and the controllable cross-membrane macromolecular transport. We envision that the proposed DNA nanopores could offer powerful tools in molecular sensing, drug delivery, and the creation of synthetic cells.

Abstract Rockburst present substantial hazards in both deep underground construction and shallow depths, underscoring the critical need for accurate prediction methods. This study addressed this need by collecting and analyzing 69 real datasets of rockburst occurring within a 500 m burial depth, which posed challenges due to the dataset's multi-categorized, unbalanced, and small nature. Through a rigorous comparison and screening process involving 11 machine learning algorithms and optimization with KMeansSMOKE oversampling, the Random Forest algorithm emerged as the most optimal choice. Efficient adjustment of hyper parameter was achieved using the Optuna framework. The resulting KMSORF model, which integrates KMeansSMOKE, Optuna, and Random Forest, demonstrated superior performance compared to mainstream models such as Gradient Boosting (GB), Extreme Gradient Boosting (XBG), and Extra Trees (ET). Application of the model in a tungsten mine and tunnel project showcased its ability to accurately forecast rockburst levels, thereby providing valuable insights for risk management in underground construction. Overall, this study contributes to the advancement of safety measures in underground construction by offering an effective predictive model for rockburst occurrences.

Abstract The dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics.

Abstract Background Broilers stand out as one of the fastest-growing livestock globally, making a substantial contribution to animal meat production. However, the molecular and epigenetic mechanisms underlying the rapid growth and development of broiler chickens are still unclear. This study aims to explore muscle development patterns and regulatory networks during the postnatal rapid growth phase of fast-growing broilers. We measured the growth performance of Cornish (CC) and White Plymouth Rock (RR) over a 42-d period. Pectoral muscle samples from both CC and RR were randomly collected at day 21 after hatching (D21) and D42 for RNA-seq and ATAC-seq library construction. Results The consistent increase in body weight and pectoral muscle weight across both breeds was observed as they matured, with CC outpacing RR in terms of weight at each stage of development. Differential expression analysis identified 398 and 1,129 genes in the two dimensions of breeds and ages, respectively. A total of 75,149 ATAC-seq peaks were annotated in promoter, exon, intron and intergenic regions, with a higher number of peaks in the promoter and intronic regions. The age-biased genes and breed-biased genes of RNA-seq were combined with the ATAC-seq data for subsequent analysis. The results spotlighted the upregulation of ACTC1 and FDPS at D21, which were primarily associated with muscle structure development by gene cluster enrichment. Additionally, a noteworthy upregulation of MUSTN1, FOS and TGFB3 was spotted in broiler chickens at D42, which were involved in cell differentiation and muscle regeneration after injury, suggesting a regulatory role of muscle growth and repair. Conclusions This work provided a regulatory network of postnatal broiler chickens and revealed ACTC1 and MUSTN1 as the key responsible for muscle development and regeneration. Our findings highlight that rapid growth in broiler chickens triggers ongoing muscle damage and subsequent regeneration. These findings provide a foundation for future research to investigate the functional aspects of muscle development.

Abstract Nicotine, a crucial constituent of tobacco smoke, can bind to and activate nicotinic acetylcholine receptors (nAChRs), thereby regulating various biological functions. However, the specific mechanisms through which nicotine mediates nAChRs to regulate the metastasis of laryngeal squamous cell carcinoma (LSCC) remain elusive. In this study, smoking status was found to be closely associated with metastasis in patients with LSCC. In addition, nicotine exposure potentiated the hematogenous and lymphatic metastatic capacity of LSCC cells. Nicotine activates membrane-bound CHRNA5, promoting cell migration and invasion, EMT and cell–ECM adhesion in LSCC. Furthermore, this study demonstrated that the Ras superfamily protein RABL6 directly interacted with CHRNA5, which preferentially binds to the RABL6-39-279aa region, and this interaction was enhanced by nicotine. Nicotine-mediated activation of CHRNA5 enhanced its interaction with RABL6, triggering the JAK2/STAT3 signalling pathway and eventually augmenting the metastatic potential of LSCC cells. This study reveals a novel mechanism through which nicotine-mediated CHRNA5–RABL6 interaction promotes the metastasis of LSCC. The findings of this study may help to develop effective strategies for improving the outcome of patients with LSCC in clinical settings.

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. Methods and design The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. Conclusions As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. Registration Number in ClinicalTrials.gov NCT05311072.

Abstract As a structural protein of SARS‐CoV‐2, the envelope (E) protein not only plays a key role in the formation of viral particles, but also forms ion channels and has pathogenic functions, including triggering cell death and inflammatory responses. The stability of E proteins is controlled by the host ubiquitin‐proteasome system. By screening human deubiquitinases, it is found that ubiquitin‐specific protease 33 (USP33) can enhance the stability of E proteins depending on its deubiquitinase activity, thereby promoting viral replication. In the absence of USP33, E proteins are rapidly degraded, leading to a reduced viral load and inflammation. Using lipid nanoparticle (LNP) encapsulation of siUSP33 by adjusting the lipid components (ionizable cationic lipids), siUSP33 is successfully delivered to mouse lung tissues, rapidly reducing USP33 expression in the lungs and maintaining knockdown for at least 14 days, effectively suppressing viral replication and virulence. This method of delivery allows efficient targeting of the lungs and a response to acute infections without long‐term USP33 deficiency. This research, based on the deubiquitination mechanism of USP33 on the E protein, demonstrates that LNP‐mediated siRNA delivery targeting USP33 plays a role in antiviral and anti‐inflammatory responses, offering a novel strategy for the prevention and treatment of SARS‐CoV‐2.

IntroductionThe incidence of hemangioblastoma is low, constituting only 1-5% of all spinal cord tumors. Specifically, intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome represents an exceedingly rare condition.MethodsWe report the first documented case of cervical intradural extramedullary hemangioblastoma in China. A 53-year-old male patient presented with a 3-year history of mild right hemiplegia, segmental muscle strength and sensation impairment, and a positive pyramidal tract sign. MRI showed an abnormal oval signal focus in the intradural and extramedullary region at the C6-C7 vertebral level. Before surgery, angiography was performed to identify the supplying arteries and draining veins. Subsequent interventional therapy achieved over 90% occlusion of blood vessels, creating optimal conditions for complete resection of the spinal tumor.ResultsThe patient demonstrated satisfactory postoperative recovery with significant restoration of sensory and motor functions. Pathological examination showed a significant upregulation of CD31 in tumor cells and a substantial presence of the neuro-specific marker S100 in the tumor stroma, consistent with the diagnostic criteria for spinal hemangioblastoma.ConclusionThe rarity of cervical intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome was reaffirmed by a comprehensive review of the existing literature. Complete tumor resection remains the optimal approach for managing this uncommon condition, generally resulting in a favorable prognosis. Traditional open fenestration surgery is linked to elevated risks of bleeding and trauma. Meanwhile, endovascular injection of embolic agents may lead to residual lesions and an increased risk of recurrence. Therefore, we recommend a one-time combined treatment conducted in a hybrid operating room to achieve complete resection and effectively reduce intraoperative bleeding risk. Despite presenting challenges and requiring high proficiency, we still recommend this type of combined surgery as a suitable therapeutic option for such diseases.

Many studies have confirmed that PM2.5 exposure can cause a variety of diseases. Because people spend most of their time indoors, exposure to PM2.5 in indoor environments is critical to population health. Large-population, long-term, continuous, and accurate indoor PM2.5 data are important but scarce because of the difficulties in monitoring the indoor air quality on a large scale. Model simulation provides a new research direction. In this study, an advanced machine learning model was constructed using environmental health big data to predict the daily indoor PM2.5 concentration data in 22 typical air pollution cities in China from 2013 to 2017. The test R2 value of this model reached as high as 0.89, and the RMSE of the model was 9.13. The predicted annual indoor PM2.5 concentrations of the cities ranged from 54.6 μg/m3 to 82.7 μg/m3, and showed a decreasing trend year by year. The pollution level exceeds the recommended AQG level of PM2.5 and has potential impact on human health. The results could take a breakthrough in obtaining accurate big data of indoor PM2.5 and contribute to research on the indoor air quality and human health in China. Synopsis: This study established a machine learning model and predicted indoor PM2.5 big data, which could support the research of indoor PM2.5 and health.

Abstract The waste of resources associated with fruit decay is rapidly spreading globally, threatening the interests of relevant practitioners and the health of consumer groups, and demanding precise solutions. Controlling fruit ripening through ethylene regulation is one of the most important strategies for providing high‐quality fruits. However, current materials for ethylene regulation still have difficulty realizing their application potential due to high manufacturing costs and performance deficiencies. In this review, the ethylene‐controlled release materials for ripening based on molecular encapsulation and the ethylene scavengers for preservation based on mechanisms such as oxidation, photodegradation, and adsorption are presented. We discuss and analyze a wide range of materials in terms of mechanism, performance, potential of applicability, and sustainability. The ethylene release behavior of encapsulating materials depends on the form in which the ethylene binds to the material as well as on environmental factors (humidity and temperature). For ethylene scavengers, there are a variety of scavenging mechanisms, but they generally require porous materials as adsorption carriers. We highlight the great opportunity of designing soft crystalline porous materials as efficient ethylene adsorbent due to their unique structural properties. We present this review, including a summary of practical characteristics and deficiencies of various materials, to establish a systematic understanding of fruit quality assurance materials applied to ethylene regulation, anticipating a promising prospect for these new materials.

Alzheimer's disease (AD) is a gradual neurodegenerative ailment that lacks any disease-modifying intervention. Our objective was to pinpoint pharmacological targets with a focus on amyloid beta (Aβ) and tau to treat and prevent AD in the European population. A proteome-wide Mendelian randomization (MR) analysis was carried out to estimate the associations between proteins and cerebrospinal fluid (CSF) Aβ-42 and phosphorylated Tau (p-Tau). We utilized colocalization and MR analysis to investigate whether the identified proteins were associated with the risk of AD. Additionally, we expanded our investigation to include non-AD phenotypes by conducting a phenome-wide MR analysis of 1646 disease traits based on the FinnGen and UK Biobank databases to explore potential side effects. We identified 11 proteins that were genetically associated with both CSF Aβ-42 and p-Tau levels. The genetically predicted levels of three proteins, GAL3ST2, POLR1C, and BIN1, were found to be associated with an increased risk of AD with high colocalization. In the phenome-wide MR analysis, two out of the three biomarkers were associated with at least one disease, except for GAL3ST2, which was not associated with any disease under the threshold of FDR

Summary: Uniformly distributed fluid shear stress can promote axonal growth, aiding in the efficient construction of functional neural interfaces. However, challenges remain in the construction of the micro-scale environment with a uniform fluidic stress distribution. In this study, we designed and fabricated a microfluidic chip with arched-section microfluidic channels (AMCs) to increase primary cortical neuron growth rate and terminal number by constructing a uniform-stress-distributed environment. Inspired by the three-dimensional (3D) microenvironment where cerebrospinal-fluid-contacting neurons are located, the surface curvature of the traditional rectangular-section microfluidic channel (RMC) was adjusted to construct structures with 3D curved surfaces. Compared with those on the RMC chips, the average growth rate of the axons on the AMC chips increased by 8.9% within 19 days, and the average number of terminals increased by 14.9%. This platform provides a structure that can effectively promote neuron growth and has potential in constructing more complex functional neural interfaces.

In object detection algorithms, the bounding box regression (BBR) loss directly influences the model’s accuracy in predicting object positions. Initially, we conducted simulation experiments on the proposed intersection over union-based loss. Through in-depth analysis, we discovered that the width and height components of the distance term could hinder BBR. To address this, we proposed the AIoU-v1 loss, which decouples the width and height components of the distance term, thereby preventing the suppression of BBR loss by the distance term. Additionally, issues such as the imbalance between sample quantity and sample quality in the dataset, as well as labeling errors, can adversely affect BBR. To tackle these dataset problems, we designed an adaptive dynamic non-monotonic focusing mechanism with strong robustness and wide applicability. Finally, we proposed a post-processing algorithm that combines fusion and non-maximum suppression, resulting in more accurate bounding boxes during the post-processing stage. Our source code and data are available at https://github.com/Wenhua-Zheng/AIOU.

ObjectivesThis research aimed to assess the value of radiomics combined with multiple machine learning algorithms in the diagnosis of pancreatic ductal adenocarcinoma (PDAC) lymph node (LN) metastasis, which is expected to provide clinical treatment strategies.MethodsA total of 128 patients with pathologically confirmed PDAC and who underwent surgical resection were randomized into training (n=93) and validation (n=35) groups. This study incorporated a total of 13 distinct machine learning algorithms and explored 85 unique combinations of these algorithms. The area under the curve (AUC) of each model was computed. The model with the highest mean AUC was selected as the best model which was selected to determine the radiomics score (Radscore). The clinical factors were examined by the univariate and multivariate analysis, which allowed for the identification of factors suitable for clinical modeling. The multivariate logistic regression was used to create a combined model using Radscore and clinical variables. The diagnostic performance was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA).ResultsAmong the 233 models constructed using arterial phase (AP), venous phase (VP), and AP+VP radiomics features, the model built by applying AP+VP radiomics features and a combination of Lasso+Logistic algorithm had the highest mean AUC. A clinical model was eventually constructed using CA199 and tumor size. The combined model consisted of AP+VP-Radscore and two clinical factors that showed the best diagnostic efficiency in the training (AUC = 0.920) and validation (AUC = 0.866) cohorts. Regarding preoperative diagnosis of LN metastasis, the calibration curve and DCA demonstrated that the combined model had a good consistency and greatest net benefit.ConclusionsCombining radiomics and machine learning algorithms demonstrated the potential for identifying the LN metastasis of PDAC. As a non-invasive and efficient preoperative prediction tool, it can be beneficial for decision-making in clinical practice.

ABSTRACT: Improving feed utilization is a vital strategy to meet the growing global demand for meat and promote sustainable food production. Over the past few decades, significant improvements in the feed intake (FI) and feed utilization efficiency of broilers have been achieved through advanced breeding procedures, although dynamic changes in FI and their effects on the feed conversion ratio (FCR) have remained unclear. In this study, we measured individual weekly FI and body weight of 274 male broilers to characterize the dynamic FI patterns and investigate their relationship with growth performance. The broilers were from 2 purebred lines and their crossbreed and measurements were collected from 4 to 6 wk of age. Overall, a continuous increase in the weekly FI occurred from 4 to 6 wk of age, whereas the body weight gain (BWG) reached an inflection point in wk 5. The dynamic change in weekly FI was observed to follow 3 distinct FI patterns: pattern 1, a continuous weekly increase in FI; pattern 2, an increase followed by a plateau; pattern 3, an increase followed by a decrease. The prevalence of these patterns was similar in the purebred and crossbred populations: pattern 2 was most frequent, followed by a moderate proportion of pattern 1, and the lowest proportion of pattern 3. Broilers following pattern 1 displayed significantly better growth performance and feed utilization efficiency than those following pattern 3, emphasizing the importance of maintaining good appetite in the last stage of broiler production. In summary, this study has characterized the dynamic patterns of FI and their association with growth performance. Our results offer a new foundation for improving feed utilization efficiency and investigating feeding regulation in broilers.

Abstract CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a β-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4–β-catenin transcription complex through competitive to β-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/β-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing β-catenin signaling may serve as a potential therapeutic candidate.

Abstract In current five-axis computer numerical control (CNC) machining, the use of minute linear path segments as an approximation for the ideal cutter contacting (CC) point trajectory is still prevalent. However, introducing rotation axes leads to a deviation of the actual CC point trajectory from the ideal, resulting in nonlinear errors. An integrated method is proposed in this paper for compensating and correcting both the contour error, associated with the approximation of the part surface by the ideal CC point trajectory and the nonlinear error of the CC point trajectory based on the information in the CC point data. By analyzing the spatial relationship between the tool posture and the CC point path during the five-axis linear interpolation process, two adjacent machining tool positions containing CC point data information are selected as the starting and ending points of the five-axis linear interpolation machining. The ideal tool center point and the actual CC point are calculated during the interpolation process, as well as the distance and the unit vector in the perpendicular direction between the actual CC point and the ideal CC point trajectory segment. In the comprehensive error compensation and correction phase, the obtained unit vectors are used as direction vectors for error compensation, and the tool center point during interpolation is first compensated and corrected. This ensures the actual CC point and the contour curve are on the same plane. The compensation direction for contour error is calculated using the start/end tool axis vectors and the ideal CC point trajectory vectors. The size of the contour error approximating the contour curve is calculated through the chord error. A second compensation and correction are applied to the tool center point for interpolation, ultimately achieving comprehensive compensation and correction of nonlinear errors. The data calculations were conducted in the MATLAB environment using actual machining data. After compensation and correction, the contour error was reduced by 76%, the nonlinear error of the CC point trajectory decreased to below 0.88 μm, and the comprehensive nonlinear error of the CC point trajectory was reduced from 19 to 1.5 μm, a reduction of 93%. This demonstrates significant practical value in enhancing the accuracy of five-axis CNC machining. Through actual machining verification, after using the method described in this paper, the average surface roughness decreased from 1.133 to 0.220 μm, and the maximum surface roughness decreased from 6.667 to 1.240 μm. This significantly demonstrates that the compensation and correction method proposed in this paper can significantly improve the surface quality of machined parts.

Abstract Osteoporosis is usually caused by excessive bone resorption and energy metabolism plays a critical role in the development of osteoporosis. However, little is known about the role of energy metabolism-related genes in osteoporosis. This study aimed to explore the important energy metabolism-related genes involved in the development of osteoporosis and develop a diagnosis signature for osteoporosis. The GSE56814, GSE62402, and GSE7158 datasets were downloaded from the NCBI Gene Expression Omnibus. The intersection of differentially expressed genes between high and low levels of body mineral density (BMD) and genes related to energy metabolism were screened as differentially expressed energy metabolism genes (DE-EMGs). Subsequently, a DE-EMG-based diagnostic model was constructed and differential expression of genes in the model was validated by RT-qPCR. Furthermore, a receiver operating characteristic curve and nomogram model were constructed to evaluate the predictive ability of the diagnostic model. Finally, the immune cell types in the merged samples and networks associated with the selected optimal DE-EMGs were constructed. A total of 72 overlapped genes were selected as DE-EMGs, and a five DE-EMG based diagnostic model consisting B4GALT4, ADH4, ACAD11, B4GALT2, and PPP1R3C was established. The areas under the curve of the five genes in the merged training dataset and B4GALT2 in the validation dataset were 0.784 and 0.790, respectively. Moreover, good prognostic prediction ability was observed using the nomogram model (C index = 0.9201; P = 5.507e−14). Significant differences were observed in five immune cell types between the high- and low-BMD groups. These included central memory, effector memory, and activated CD8 T cells, as well as regulatory T cells and activated B cells. A network related to DE-EMGs was constructed, including hsa-miR-23b-3p, DANCR, 17 small-molecule drugs, and two Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways and pyruvate metabolism. Our findings highlighted the important roles of DE-EMGs in the development of osteoporosis. Furthermore, the DANCR/hsa-miR-23b-3p/B4GALT4 axis might provide novel molecular insights into the process of osteoporosis development.

Abstract Objective To exploit the improved prediction performance based on dynamic contrast-enhanced (DCE) MRI by using dynamic radiomics for microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods We retrospectively included 175 and 75 HCC patients who underwent preoperative DCE-MRI from September 2019 to August 2022 in institution 1 (development cohort) and institution 2 (validation cohort), respectively. Static radiomics features were extracted from the mask, arterial, portal venous, and equilibrium phase images and used to construct dynamic features. The static, dynamic, and dynamic–static radiomics (SR, DR, and DSR) signatures were separately constructed based on the feature selection method of LASSO and classification algorithm of logistic regression. The receiver operating characteristic (ROC) curves and the area under the curve (AUC) were plotted to evaluate and compare the predictive performance of each signature. Results In the three radiomics signatures, the DSR signature performed the best. The AUCs of the SR, DR, and DSR signatures in the training set were 0.750, 0.751 and 0.805, respectively, while in the external validation set, the corresponding AUCs were 0.706, 0756 and 0.777. The DSR signature showed significant improvement over the SR signature in predicting MVI status (training cohort: P = 0.019; validation cohort: P = 0.044). After external validation, the AUC value of the SR signature decreased from 0.750 to 0.706, while the AUC value of the DR signature did not show a decline (AUCs: 0.756 vs. 0.751). Conclusions The dynamic radiomics had an improved effect on the MVI prediction in HCC, compared with the static DCE MRI-based radiomics models.

Abstract How to deal with large tibial bone defects is still controversial. The purpose of this research was to compare the semi-focal bone transport (SFBT) technique with traditional bone transport (TBT) technique for treating such patients. Sixty-two patients were included and retrospectively analyzed. In all cases, after radical debridement large tibial bone defects remained. Patients were treated by the SFBT or TBT technique. The distraction, consolidation duration and complications were recorded by the patients’ medical files. Based on the Association for the Study and Application of Methods of Ilizarov (ASAMI) standard, the bone and functional results were evaluated. The mean bone defect size was 7.7 ± 1.6 cm and 7.5 ± 2.1 cm for SFBT and TBT patients. The mean external fixation index (EFI) was 1.51 ± 0.14 months/cm and 1.89 ± 0.25 months/cm for SFBT and TBT patients (p 0.05). The mean number of complications per patient was 1.1 ± 0.6 and 1.6 ± 0.7 for SFBT and TBT patients (p

The Dongwuyang Bay of Fujian Province is the core production area for sea cucumber culture in South China; however, research on the environmental status and bacterial community structure in this area is still limited. In this study, we investigated and evaluated the seawater quality in January, which is the peak culture period for sea cucumber in this area, and analyzed the diversity and differential characteristics of seawater and sediment bacterial community structure using the high-throughput sequencing method and analyzed the correlation between environmental factors and bacterial community structure. The following results were obtained: The Makeng eutrophication index reached 21.60, which indicated that this area was experiencing serious eutrophication. Dong´an and Leijiang were experiencing severe eutrophication, and only the Shawan sea area was experiencing moderate eutrophication. The organic pollution assessment showed that Dong´an and Shawan had light organic pollution, while Makeng and Leijiang had moderate organic pollution. A total of 1 520 OTUs were obtained via high-throughput sequencing, belonging to 28 phyla, 57 orders, 163 families, 322 families, and 581 genera. The diversity analysis revealed that the level of bacterial community diversity in the sediment of each region was significantly higher than that of the corresponding seawater diversity and presented stronger spatial heterogeneity. The diversity and abundance in Shawan were the highest. The results of the principal coordinate analysis and similarity analysis showed that there were significant differences in the bacterial community composition between sediment and seawater. The cluster analysis revealed that the cluster was influenced by water exchange and site location. Vibrionaceae, a family with potential pathogenicity, was one of the dominant species in all seawater and sediment samples. LEFSe (line discriminant analysis effect size) analysis of seawater column samples and sediment samples screened 74 specific OTUs (operational taxonomic units) of bacteria at different taxonomic levels. Prediction of gene function and COG (clusters of orthologous groups of proteins) classification statistics showed significant differences in 12 metabolic pathways between seawater and sediment samples (P < 0.05). LEFSe analysis of bacterial community structure from four sites screened 30 specific OTUs at different taxonomic levels. The RDA (redundancy analysis) of the seawater bacterial community structure with environmental factors revealed that temperature, dissolved oxygen, and chlorophyll-a concentration were the major environmental factors affecting the structure in the four sites. Related studies should provide basic data and scientific reference for the management of sea cucumber culture in Fujian Province.

Abstract Background He long noncoding RNA small nucleolar host RNA 5 (SNHG5) is highly expressed in many cancers, and there is a notable correlation between the elevated expression of SNHG5 and survival outcome in cancer patients. The objective of this study was to conduct a meta-analysis to evaluate the correlation between SNHG5 expression and the clinical outcome of cancer patients. Methods Six relevant electronic databases were exhaustively searched, and, depending on the inclusion and exclusion criteria, appropriate literature was obtained. The Newcastle-Ottawa Scale (NOS) score was utilized to evaluate the quality of the research for every article included, and pertinent data from each study were carefully extracted. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were combined to explore the association of SNHG5 expression levels with cancer prognosis, and sensitivity analyses and assessments of publication bias were also conducted to investigate any possibility in the publication of the studies. Results Eleven studies encompassing 721 patients were ultimately collected. When combined, the hazard ratios (HRs) revealed a substantial direct correlation between elevated SNHG5 expression and an unfavourable prognosis for cancer patients (HR = 1.90, 95% CI 0.87–4.15); however, the correlation did not reach statistical significance. Furthermore, high SNHG5 expression was predictive of advanced TNM stage (OR: 1.988, 95% CI 1.205–3.278) and larger tumour size (OR: 1.571, 95% CI 1.090–2.264); moreover, there were nonsignificant relationships between SNHG5 expression and DM (OR: 0.449, 95% CI 0.077–2.630), lymph node metastasis (OR: 1.443, 95% CI 0.709–2.939), histological grade (OR: 2.098, 95% CI 0.910–4.838), depth of invasion (OR: 1.106, 95% CI 0.376–3.248), age (OR: 0.946, 95% CI 0.718–1.247) and sex (OR: 0.762, 95% CI 0.521–1.115). Conclusion SNHG5 expression is typically increased in the majority of tumour tissues. Elevated SNHG5 expression may indicate poor prognosis in cancer patients. Therefore, SNHG5 is a promising potential therapeutic target for tumours and a reliable prognostic biomarker.

Abstract Aims Primary mucoepidermoid carcinomas (MECs) of the sinonasal tract and nasopharynx are rare entities that represent a diagnostic challenge, especially in biopsy samples. Herein, we present a case series of MECs of the sinonasal and skull base and its mimics to evaluate the clinicopathological and molecular characteristics in order to avoid misdiagnosis. Methods We reviewed the pathology records of patients diagnosed from 2014 to 2022. Thirty MECs were consecutively diagnosed during that period. Results Based on morphological and fluorescence in situ hybridization (FISH) analyses, 30 tumors originally diagnosed as MECs were separated into MAML2 fusion-positive (7 cases) and MAML2 fusion-negative groups (23 cases), in which 14 tumors were positive for the EWSR1::ATF1 fusion; these tumors were reclassified to have hyalinizing clear cell carcinoma (HCCC). The remaining nine MAML2 FISH negative cases were reconfirmed as squamous cell carcinoma (SCC, 3 cases) which showed keratinization and high Ki-67 expression; DEK::AFF2 carcinomas (2 cases), in which DEK gene rearrangement was detected by FISH; and MECs as previously described (4 cases) with typical morphological features. Including 7 MAML2 rearrangements tumors, 11 MEC cases had a male-to-female ratio of 4.5:1, and 6 tumors arose from the nasopharyngeal region, while 5 tumors arose from the sinonasal region. The prognosis of this series of salivary gland-type MECs was favorable. Conclusions Our study confirmed that HCCC runs the risk of being misdiagnosed as MEC in the sinonasal tract and nasopharynx, particularly with biopsy specimens. Careful histological evaluation with supporting molecular testing can facilitate pathological diagnoses.

Identified as the pathogenic genes of Alzheimer's disease (AD), APP, PSEN1, and PSEN2 mainly lead to early-onset AD, whose course is more aggressive, and atypical symptoms are more common than sporadic AD. Here, a novel missense mutation, APP E674Q (also named “Shanghai APP”), was detected in a Chinese index patient with typical late-onset AD (LOAD) who developed memory decline in his mid-70s. The results from neuroimaging were consistent with AD, where widespread amyloid β deposition was demonstrated in 18F-florbetapir Positron Emission Tomography (PET). APP E674Q is close to the β-secretase cleavage site and the well-studied Swedish APP mutation (KM670/671NL), which was predicted to be pathogenic in silico. Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1. The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ. Furthermore, we applied an adeno-associated virus (AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice. AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain, implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation. Collectively, we report a strong amyloidogenic effect of the E674Q substitution in AD. To our knowledge, E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.

Glioma is the most prevalent primary malignant tumor of the central nervous system. While traditional treatment modalities such as surgical resection, radiotherapy, and chemotherapy have made significant advancements in glioma treatment, the prognosis for glioma patients remains often unsatisfactory. Ferroptosis, a novel form of programmed cell death, plays a crucial role in glioma and is considered to be the most functionally rich programmed cell death process. Histone deacetylases have emerged as a key focus in regulating ferroptosis in glioma. By inhibiting the activity of histone deacetylases, histone deacetylase inhibitors elevate acetylation levels of both histones and non-histone proteins, thereby influencing various cellular processes. Numerous studies have demonstrated that histone deacetylases are implicated in the development of glioma and hold promise for its treatment. This article provides an overview of research progress on the mechanism by which histone deacetylases contribute to ferroptosis in glioma.

Abstract Immunosuppression is a major hallmark of tumor progression in non‐small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro‐tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di‐methylation in the immunosuppressive tumor microenvironment (TME) remains unclear. Here, di‐methylation of CD147 at Lys148 (CD147‐K148me2) is identified as a common post‐translational modification (PTM) in NSCLC that is significantly associated with unsatisfying survival outcomes among NSCLC sufferers, especially those in the advanced stages of the disease. The methyltransferase NSD2 catalyzes CD147 to generate CD147‐K148me2. Further analysis demonstrates that CD147‐K148me2 reestablishes the immunosuppressive TME and promotes NSCLC progression. Mechanistically, this modification promotes the interaction between cyclophilin A (CyPA) and CD147, and in turn, increases CCL5 gene transcription by activating p38‐ZBTB32 signaling, leading to increased NSCLC cell‐derived CCL5 secretion. Subsequently, CD147‐K148me2‐mediated CCL5 upregulation facilitates M2‐like tumor‐associated macrophage (TAM) infiltration in NSCLC tissues via CCL5/CCR5 axis‐dependent intercellular crosstalk between tumor cells and macrophages, which is inhibited by blocking CD147‐K148me2 with the targeted antibody 12C8. Overall, this study reveals the role of CD147‐K148me2‐driven intercellular crosstalk in the development of NSCLC immunosuppression, and provides a potential interventional strategy for PTM‐targeted NSCLC therapy.

ABSTRACT: Long-term intensive genetic selection has led to significant differences between broiler and layer chickens, which are evident during the embryonic period. Despite this, there is a paucity of research on the genetic regulation of the initial formation of muscle fiber morphology in chick embryos. Embryonic d 17 (E17) is the key time point for myoblast fusion completion and muscle fiber morphology formation in chickens. This study aimed to explore the genetic regulatory mechanisms underlying the early muscle fiber morphology establishment in broiler chickens of Cornish (CC) and White Plymouth Rock (RR) and layer chickens of White Leghorn (WW) at E17 using the transcriptomic and chromatin accessibility sequencing of pectoral major muscles. The results showed that broiler chickens exhibited significant higher embryo weight and pectoral major muscle weight at E17 compared to layer chickens (P = 0.000). A total of 1,278, 1,248, and 892 differentially expressed genes (DEGs) of RNA-seq data were identified between CC vs. WW, RR vs. WW, and CC vs. RR, separately. All DEGs were combined for cluster analysis and they were divided into 6 clusters, including cluster 1 with higher expression in broilers and cluster 6 with higher expression in layers. DEGs in cluster 1 were enriched in terms related to macrophage activation (P = 0.002) and defense response to bacteria (P = 0.002), while DEGs in cluster 6 showed enrichment in protein-DNA complex (P = 0.003) and monooxygenase activity (P = 0.000). ATAC-seq data analysis identified a total of 38,603 peaks, with 13,051 peaks for CC, 18,780 peaks for RR, and 6,772 peaks for WW. Integrative analysis of transcriptomic and chromatin accessibility data revealed GOLM1, ISLR2, and TOPAZ1 were commonly upregulated genes in CC and RR. Furthermore, screening of all upregulated DEGs in cluster 1 from CC and RR identified GOLM1, ISLR2, and HNMT genes associated with neuroimmune functions and MYOM3 linked to muscle morphology development, showing significantly elevated expression in broiler chickens compared to layer chickens. These findings suggest active neural system connectivity during the initial formation of muscle fiber morphology in embryonic period, highlighting the early interaction between muscle fiber formation morphology and the nervous system. This study provides novel insights into late chick embryo development and lays a deeper foundation for further research.

Abstract Background In addition to lowering cholesterol levels, the proprotein convertase subtilis kexin 9 (PCSK9) inhibitor has a variety of effects, including anti‐neuroapoptosis. However, the effects of PCSK9 inhibitors on neurodegenerative diseases are controversial. Therefore, we used drug‐targeted Mendelian randomization (MR) analysis to investigate the effects of PCSK9 inhibitors on different neurodegenerative diseases. Methods We collected single nucleotide polymorphisms (SNPs) of PCSK9 from published statistics of genome‐wide association studies and performed drug target MR analyses to detect a causal relationship between PCSK9 inhibitors and the risk of neurodegenerative diseases. We utilized the effects of 3‐Hydroxy ‐3‐ methylglutaryl‐assisted enzyme A reductase (HMGCR) inhibitors (statin targets) for comparison with PCSK9 inhibitors. Coronary heart disease risk was used as a positive control, and primary outcomes included amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Results PCSK9 inhibitors marginally reduced the risk of ALS (OR [95%] = 0.89 [0.77 to 1.00], p = 0.048), while they increased the risk of PD (OR [95%] = 1.417 [1.178 to 1.657], p = 0.004). However, HMGCR inhibitors increased the risk of PD (OR [95%] = 1.907 [1.502 to 2.312], p = 0.001). Conclusion PCSK9 inhibitors significantly reduce the risk of ALS but increase the risk of PD. HMGCR inhibitors may be the risk factor for PD.

Abstract Lithium metal, with ultrahigh theoretical specific capacity, is considered as an ideal anode material for the lithium‐ion batteries. However, its practical application is severely plagued by the uncontrolled formation of dendritic Li. Here, a cation‐loaded porous Mg2+‐Zeolite layer is proposed to enable the dendrite‐free deposition on the surface of Li metal anode. The skeleton channels of zeolite provide the low coordinated Li+‐solvation groups, leading to the faster desolvation process at the interface. Meanwhile, anions‐involved solvation sheath induces a stable, inorganic‐rich SEI, contributing to the uniform Li+ flux through the interface. Furthermore, the co‐deposition of sustained release Mg2+ realizes a new faster migration pathway, which proactively facilitates the uniform diffusion of Li on the lithium substrate. The synergistic modulation of these kinetic processes facilitates the homogeneous Li plating/stripping behavior. Based on this synergistic mechanism, the high‐efficiency deposition with cyclic longevity exceeding 2100 h is observed in the symmetric Li/Li cell with Mg2+‐Zeolite modified anode at 1 mA cm−2. The pouch cell matched with LiFePO4 cathode fulfills a capacity retention of 88.4% after 100 cycles at a severe current density of 1 C charge/discharge. This synergistic protective mechanism can give new guidance for realizing the safe and high‐performance Li metal batteries.

Summary: Deciphering how different behaviors and ultrasonic vocalizations (USVs) of rats interact can yield insights into the neural basis of social interaction. However, the behavior-vocalization interplay of rats remains elusive because of the challenges of relating the two communication media in complex social contexts. Here, we propose a machine learning-based analysis system (ARBUR) that can cluster without bias both non-step (continuous) and step USVs, hierarchically detect eight types of behavior of two freely behaving rats with high accuracy, and locate the vocal rat in 3-D space. ARBUR reveals that rats communicate via distinct USVs during different behaviors. Moreover, we show that ARBUR can indicate findings that are long neglected by former manual analysis, especially regarding the non-continuous USVs during easy-to-confuse social behaviors. This work could help mechanistically understand the behavior-vocalization interplay of rats and highlights the potential of machine learning algorithms in automatic animal behavioral and acoustic analysis.

Summary: Camellia oleifera is an economically and medicinally valuable oilseed crop. Honeybee, the most abundant pollinator, rarely visits C. oleifera because of the toxic sugars in the nectar and pollen. These toxic sugars cannot be fully digested by honeybees and inhibit the process of synthesizing trehalose in honeybees. C. oleifera exhibits self-incompatibility, and its pollination heavily depends on Andrena camellia. However, the mechanism by which A. camellia digests toxic sugars in C. oleifera nectar and pollen remains unknown. Consequently, we identified and validated four single-copy genes (α-N-acetyl galactosamine-like, galactokinase, galactose-1-phosphate uridyltransferase, and UDP-galactose-4′-epimerase, abbreviated as NAGA-like, GALK, GALT, and GALE) essential for detoxifying toxic sugars in vitro. Then, we cloned the four genes into Escherichia coli, and expressed enzyme successfully degraded the toxic sugars. The phylogeny suggests that the genes were conserved and functionally diverged among the evolution. These results provide novel insights into pollinator detoxification during co-evolution.

Employing electric double-layer (EDL) capacitors to harvest low-grade heat (LGH) is a novel technique in the high-efficiency energy absorption field. This work reports the fabrication of a vertical thermoelectric cell, based on a nanoporous graphene electrode immersed in low-concentration saline solution, for use as thermo-charging supercapacitors to convert LGH to electricity via thermally induced voltage. Because of a large specific area and a large number of micropores of nanoporous graphene films, the effective thermoelectric coefficient of the thermoelectric cell containing 0.01 M KCl solution can reach as high as 4.73 mV/°C. However, many factors, such as electrode materials, electrolyte solutions, and energy conversion device components, determine the efficiency of a thermoelectric conversion device. In summary, the device has a lower internal resistance and higher output voltage when the concentration of KCl solution is 0.05 M, and demonstrates higher thermoelectric conversion efficiency. Moreover, improving the conductivity of the electrolyte solution without affecting the device output voltage is also a way to reduce the internal power consumption of the device. The specific power and thermoelectric conversion efficiency of the device are increased by several orders of magnitude when uniformly dispersed silver nanoparticles are added to the potassium chloride solution to enhance the conductivity of the solution. The specific power underwent an increase from 0.50 mW g−1 to 42.37 mW g−1, and the thermoelectric conversion efficiency also increased from 0.0022% to 0.1358%.

Abstract Multivalent drugs targeting homo-oligomeric viral surface proteins, such as the SARS-CoV-2 trimeric spike (S) protein, have the potential to elicit more potent and broad-spectrum therapeutic responses than monovalent drugs by synergistically engaging multiple binding sites on viral targets. However, rational design and engineering of nanoscale multivalent protein drugs are still lacking. Here, we developed a computational approach to engineer self-assembling trivalent microproteins that simultaneously bind to the three receptor binding domains (RBDs) of the S protein. This approach involves four steps: structure-guided linker design, molecular simulation evaluation of self-assembly, experimental validation of self-assembly state, and functional testing. Using this approach, we first designed trivalent constructs of the microprotein miniACE2 (MP) with different trimerization scaffolds and linkers, and found that one of the constructs (MP-5ff) showed high trimerization efficiency, good conformational homogeneity, and strong antiviral neutralizing activity. With its trimerization unit (5ff), we then engineered a trivalent nanobody (Tr67) that exhibited potent and broad neutralizing activity against the dominant Omicron variants, including XBB.1 and XBB.1.5. Cryo-EM complex structure confirmed that Tr67 stably binds to all three RBDs of the Omicron S protein in a synergistic form, locking them in the “3-RBD-up” conformation that could block human receptor (ACE2) binding and potentially facilitate immune clearance. Therefore, our approach provides an effective strategy for engineering potent protein drugs against SARS-CoV-2 and other deadly coronaviruses. Graphical Abstract

To investigate the effects of particle size and phenolics bounded-insoluble dietary fiber (IB) of white kidney bean skin (WS) on in vitro fermentation profiles, the IB was extracted enzymatically, modified by ordinary and superfine grinding, followed by the preparation of different particle sizes. Their microscopic morphology was observed by scanning electron microscopy and laser confocal scanning microscopy. In vitro fermentation experiments and 16S rRNA sequencing were used to investigate the fermentation properties of the two sets of samples and their effects on the abundance of gut microbiota composition. The results showed that the bound phenolics were distributed more equally on the surface of the smaller particles. The slowed fermentation rate and short-chain fatty acid production of WS and IB increased with decreasing particle size. The smaller particle size promoted the Bacteroides and demoted the Lachnospira more significantly. The results suggested that IB could promote the beneficial bacteria such as Bacteroides, Bifidobacterium and Ruminococcaceae ruminococcus, and regulate the structure composition of the gut microbiota. The probiotic effect of IB was more significant than that of WS with the same particle size. This study provides the school of thought on the prebiotic effect of dietary fiber, guides on the modification of dietary fiber by superfine grinding, and suggests the comprehensive utilization of white kidney bean skin.

Abstract In the field of data analysis, it is often faced with a large number of missing values, especially in metabolomics data, this problem is more prominent. Data imputation is a common method to deal with missing metabolomics data, while traditional data imputation methods usually ignore the differences in missing types, and thus the results of data imputation are not satisfactory. In order to discriminate the missing types of metabolomics data, a missing data classification model (PX-MDC) based on particle swarm algorithm and XGBoost is proposed in this paper. First, the missing values in a given missing data set are obtained by panning the missing values to obtain the largest subset of complete data, and then the particle swarm algorithm is used to search for the concentration threshold of missing data and the proportion of low concentration deletions as a percentage of overall deletions. Next, the missing data are simulated based on the search results. Finally, the training data are trained using the XGBoost model using the feature set proposed in this paper in order to build a classifier for the missing data. The experimental results show that the particle swarm algorithm is able to match the traditional enumeration method in terms of accuracy and significantly reduce the search time in concentration threshold search. Compared with the current mainstream methods, the PX-MDC model designed in this paper exhibits higher accuracy and is able to distinguish different deletion types for the same metabolite. This study is expected to make an important breakthrough in metabolomics data imputation and provide strong support for research in related fields.

Objective The ability of D‐dimer to diagnose periprosthetic joint infection (PJI) before revision hip or knee arthroplasty is still controversial, and the differences in diagnostic ability between serum‐ or plasma‐based assays of D‐dimer and fibrin (fibrinogen) degradation product (FDP) are uncertain. The prospective parallel study was performed to determine the ability of D‐dimer to diagnose PJI before revision hip or knee arthroplasty, and the differences in diagnostic ability between serum‐ or plasma‐based assays of D‐dimer and FDP. Methods Patients undergoing knee or hip arthroplasty at our institution were prospectively enrolled into the following groups: those without inflammatory diseases who were undergoing primary arthroplasty (“Prim” group), those with inflammatory arthritis who were undergoing primary arthroplasty (“Prim/Inflam”), those undergoing revision arthroplasty because of aseptic failure (“Rev/Asept”), or those undergoing revision arthroplasty because of PJI (“Rev/PJI”). The ability of preoperative levels of D‐dimer or FDP in serum or plasma to diagnose PJI in each group was assessed using areas under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators. The diagnostic performance of these assays was compared with that of C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results In the final analysis, Prim included 42 patients; Prim/Inflam, 40; Rev./Asept, 62; and Rev./PJI, 47. D‐dimer assays led to AUCs of 0.635 in serum and 0.573 in plasma, compared to 0.593 and 0.607 for FDP. Even in combination with CRP or ESR, these assays failed to perform as well as the combination of CRP and ESR for diagnosing PJI. Conclusion Levels of D‐dimer or FDP in serum or plasma, whether used alone or together with CRP or ESR, are unreliable for diagnosing PJI before revision arthroplasty.

Abstract Posterolateral (PL)-depression fractures of the tibial plateau are difficult to manage. The aim of this study was: (1) to present our experience with a novel technique of robot-assisted percutaneous reduction and fixation and (2) to compare it with the traditional percutaneous screw osteosynthesis (PSO) technique for the treatment of PL-depression tibial plateau fractures. The clinical data of patients with PL-depression tibial plateau fractures treated by robot-assisted percutaneous reduction and fixation technique and traditional PSO technique from January 2017 to January 2021 were retrospectively analyzed. Among them, there were 18 cases in the robot-assisted group (RA group) and 23 cases in the PSO group. All fractures were unilateral, closed and fresh PL-depression fractures of the tibial plateau. Patients in the RA group were treated by robot assisted reduction and minimally invasive absorbable screw fixation. The PSO group was treated by closed reduction and percutaneous absorbable screw osteosynthesis. The incision length, operation time, intraoperative blood loss, fluoroscopic times, inpatient time, weight training time and postoperative complications of the two groups were statistically analyzed. The Rasmussen radiological score was used to assess the reduction quality after operation while the Rasmussen functional score was used to evaluate knee joint functions at one year postoperatively. All patients were followed for at least one year. There was no significant difference in demographic information between the two groups (p > 0.05). Compared with the PSO group, the RA group showed less fluoroscopic times and better Rasmussen radiological and functional scores (p 0.05). The novel robot-assisted percutaneous reduction and fixation technique had the characteristics of less radiation, accurate reduction and fixation. It could accelerate the rehabilitation of patients with PL-depression fractures of the tibial plateau and enable patients to obtain good joint functions.

The investigation of metabolic pathways and regulatory mechanisms in newly discovered species can offer valuable insights into the nitrogen removal function of heterotrophic nitrification–aerobic denitrification (HN-AD) bacteria. To investigate the nitrogen removal mechanism of a new genus, Delftia, we analyzed the complete genome, metabolic pathways, and the related genes of Delftia sp. B7. We further examined the nitrogen removal capacity of Delftia sp. B7 under various nitrogen sources and real wastewater. Our results demonstrate the presence of several genes in Delftia sp. B7, including narGHI, nasAB, nirK, nirS, nirBD, norBC, nosZ, nxrAB, gdhA, glnA, gltBD, amt, and nrt. These genes encode enzymes that facilitate ammonia assimilation, assimilatory nitrate reduction to nitrite, HN-AD, and dissimilatory nitrate reduction (DNRA) in Delftia sp. B7. Specifically, we propose an HN-AD pathway in Delftia sp. B7, NH4+-N → NH2OH → NO2−-N → NO3−-N → NO2−-N → NO → N2O → N2, which accounts for the majority of nitrogen removal. Here, the transformation of NH4+-N to NO2−-N was achieved by unknown enzymes or by another pathway. When treating municipal wastewater, Delftia sp. B7 was able to remove 45.62 ± 1.29% of TN. These findings provide a theoretical basis for utilizing microbial resources to mitigate nitrogen contamination.

Background: Arterial thrombosis, a condition in which thrombi form in arteries, can lead to various acute cardiovascular diseases and impact the quality of life and survival of patients. Berberine (BBR), a quaternary ammonium alkaloid, has been shown to treat these diseases. However, further exploration is needed to understand underlying mechanisms of BBR. Methods and results: Rats were administered BBR via intramuscular injection. Then, an FeCl3-coated filter paper was applied to a carotid artery to induce thrombosis. The size of the thrombus and the blood flow velocity were evaluated by carotid ultrasound. The shape of the thrombus was observed using staining and microscopy. The expression levels of mRNA and proteins were verified. Additionally, mass spectrometry and single-cell RNA sequencing analysis were conducted. The administration of BBR resulted in a significant reduction in the thrombus area and an extension of the thrombus-clogging time. Furthermore, BBR administration effectively reversed the decreasing tissue–plasminogen activator (t-PA) expression and alterations in fibrinolysis system of model group. Additionally, the expression of PKM2 was suppressed following BBR administration, and the overexpression of PKM2 inhibited t-PA expression. Conclusions: BBR ameliorates thrombosis by modulating expression of PKM2, subsequently impacting the expression of t-PA within fibrinolytic system. These preliminary findings suggest that BBR could be a potential preventive and therapeutic strategy for arterial thromboembolic diseases.

This study investigates the impact of different diets on fish growth and bacterial community structure present in the intestine of goldfish (Carassius auratus) and their aquaculture water under recirculating water conditions. We assumed that different types of diet would form different intestinal microbiota that may affect host growth. Using Illumina MiSeq high-throughput sequencing, we analyzed bacterial communities in goldfish fed with formulated pellet feed, Tubifex worms (Limnodrilus hoffmeisteri), and an alternating diet of both. Over a 14-day feeding trial, no significant differences in juvenile goldfish growth were observed between groups. After 7 days, diet changes significantly influenced the abundance and diversity of intestinal bacteria, with the alternating diet notably enhancing bacterial diversity in both the intestines and water. However, these differences in bacterial diversity decreased by day 14. The results indicate that diet type affects microbial community diversity in the intestines and water of goldfish, and that goldfish intestines maintain a stable core bacterial community structure. This highlights the potential for optimizing diet types to enhance microbial health and stability in aquaculture systems and, in addition, provides an important scientific basis for alternative diets in goldfish aquaculture in the industry.

Invasive pests may disturb and destructively reformat the local ecosystem. The small hive beetle (SHB), Aethina tumida, originated in Africa and has expanded to America, Australia, Europe, and Asia. A key factor facilitating its fast global expansion is its ability to subsist on diverse food inside and outside honey bee colonies. SHBs feed on various plant fruits and exudates in the environment while searching for bee hives. After sneaking into a bee hive, they switch their diet to honey, pollen, and bee larvae. How SHBs survive on such a broad range of food remains unclear. In this study, we simulated the outside and within hive stages by providing banana and hive resources and quantified the SHB associated microbes adjusted by the diet. We found that SHBs fed on bananas were colonized by microbes coding more carbohydrate-active enzymes and a higher alpha diversity than communities from SHBs feeding on hive products or those collected directly from bee hives. SHBs fed on bananas and those collected from the hive showed high symbiont variance, indicated by the beta diversity. Surprisingly, we found the honey bee core symbiont Snodgrassella alvi in the guts of SHBs collected in bee hives. To determine the role of S. alvi in SHB biology, we inoculated SHBs with a genetically tagged culture of S. alvi, showing that this symbiont is a likely transient of SHBs. In contrast, the fungus Kodamaea ohmeri is the primary commensal of SHBs. Diet-based microbiome shifts are likely to play a key role in the spread and success of SHBs.

Background: The Proximal Femoral Nail Antirotation (PFNA) device is the most commonly used implant to fix unstable femoral trochanteric fractures (UFTFs), but it has a relatively high incidence of complications. Due to this factor, the modified intramedullary nail (MIN) was created to treat patients with UFTFs. The aim was to exhibit the MIN and make a comparison with PFNA and InterTAN using biomechanical methods. Methods: An adult UFTF model was developed using Mimics software. The PFNA, InterTAN nail, and MIN models were drawn referring to the corresponding parameters and installed in the fracture models. Vertical, anteroposterior (AP) bending, and torsion loads of the femoral head were set in advance and loaded onto the fracture models. The value of maximal displacement and von Mises stress was evaluated via finite element analysis (FEA). Results: The MIN model had smaller values for maximal displacement than that of the PFNA model, and the increase in displacement was less pronounced for the MIN compared to PFNA under increasing vertical loads. For the indicator of von Mises stress, the MIN model showed lower stress compared with the PFNA model in vertical loads ranging from 300 N to 2100 N. Except for the maximal stress at implants under AP bending loads, the MIN demonstrated the most superior biomechanical properties under AP bending and torsional loads. Conclusion: The MIN offered obvious advantages in terms of mechanical stability and stress distribution among the three studied implants, providing a promising implant option for patients with UFTFs.

Abstract Patient‐Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient‐derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO‐derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX are identified. Among them, KLF14 and EGR2 footprints are enriched in PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient‐derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.

Uncertainty exists regarding the mechanisms by which hypoxia-inducible factors (HIFs) control CD8+T-cell migration into tumor microenvironments. Here, we found that HIF-1α knockdown or overexpression resulted in increased or decreased CXCL9, −10, and −11 expression in vitro, respectively. Gene Set Variation Analysis revealed that elevated HIF-1α levels correlated with a poor prognosis, severe pathological stage, and an absence of CD8+ T cells in the tumor microenvironment in colorectal cancer (CRC) patients. HIF-1α was inversely associated with pathways beneficial to anti-tumor immunotherapy and cytokine/chemokine function. In vivo, inhibiting HIF-1α or its upstream regulator BIRC2 significantly suppressed tumor growth and promoted CD8+ T-cell infiltration. CXCR3 neutralizing antibodies reversed these effects, implicating the involvement of CXCL9, −10, and −11/CXCR3 axis. The presence of HIF-1α weakened the upregulation of CXCL9, −10, and −11 by bleomycin and doxorubicin. Combining HIF-1α inhibition with bleomycin promoted CD8+ T-cell infiltration and tumor suppression in vivo. Moreover, doxorubicin could upregulate CXCL9, −10 and −11 by suppressing HIF-1α. Our findings highlight the potential of HIF-1α inhibition to improve CRC microenvironments and increase chemotherapy sensitivity.

Nicotine exposure from smoking constitutes a significant global public health concern. Furthermore, smoking represents a pivotal risk factor for head and neck squamous cell carcinoma (HNSCC). However, the influence of nicotine on HNSCC remains relatively underexplored. Our aim was to unravel the molecular mechanisms that underlie the effect of nicotine on the metastatic cascade of HNSCC. In this study, we discovered a significant association between smoking and HNSCC metastasis and prognosis. Nicotine significantly enhanced HNSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Analysis of TCGA-HNSCC and FDEENT-HNSCC cohorts revealed reduced miR-375–3p levels in HNSCC tumor tissues, particularly among current smokers. Additionally, miR-375–3p level was strongly correlated with both lymph node metastasis and tumor stage. By downregulating miR-375–3p, nicotine promotes HNSCC cell metastasis in vitro and hematogenous metastatic capacity in vivo. Utilizing transcriptomic sequencing, molecular docking, dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH), we demonstrated that miR-375–3p specifically binds to 3′ untranslated region (3’UTR) of NTRK2 mRNA. Thus, this study uncovers a novel nicotine-induced mechanism involving miR-375–3p-mediated NTRK2 targeting, which promotes HNSCC metastasis. These findings have implications for improving the prognosis of patients with HNSCC, especially in smokers.

Inflow and water demand prediction plays an important role in reservoir operation rulemaking. Uncertainties in meteorological and hydrological modeling increase the complexity of inflow and water demand prediction, which are not sufficiently considered in conventional inflow and water demand prediction. Thus, this study took cascade reservoirs as the research object. These cascade reservoirs were located in the mainstream of the Yellow River Basin (YRB). A three-step framework was proposed: (1) developing a distributed Soil & Water Assessment Tool (SWAT) model to determine historical and future water availability in the reservoirs; (2) constructing the AquaCrop agricultural irrigation water demand model to predict future water demand of water users at 264 nodes (reservoirs and hydrological stations) in the YRB; (3) developing an optimal regulation model of cascade reservoirs in the YRB mainstream to quantitively determine the influence of future environmental changes on hydropower generation and water supply benefits of cascade reservoirs. The results indicate that the inflow of cascade reservoirs increased in the flood season and decreased significantly during the non-flood season compared with that in the historical period (1970–2016). However, there was a slight increase in the agricultural irrigation water demand, and the contradiction became more prominent between water resource supply and demand. During the future period (2020–2050), the guaranteed rate of hydropower generation and water supply in the YRB’s lower reaches will increase significantly. Uncertainties in climate models greatly impact hydropower generation benefits and reservoir water supply, especially in the flood season. These findings can facilitate the understanding of the complexity of hydropower management and production of cascade reservoirs under future environmental changes (inflow and demand) and encourage the use of regulation models for impact assessment studies and adaptive reservoir management to mitigate climate change.

To investigate the distribution, contamination status, and antibiotic resistance of Listeria monocytogenes in four types of retail poultry meat, including chicken, duck, goose, and pigeon, sold in Jiading District, Shanghai, a total of 236 retail poultry meat samples were collected, and L. monocytogenes isolates were obtained for identification and antibiotic susceptibility testing against 14 common antibiotics. Forty-one L. monocytogenes isolates were detected from the 236 retail poultry meat samples, with detection rates of 24.47%, 19.44%, 14.75%, and 4.44% in chicken, goose, duck, and pigeon meat, respectively. Among refrigerated, frozen, and room temperature samples, refrigerated poultry had the highest detection rate at 25.40%, while frozen poultry had the lowest at 13.33%. The detection rate of L. monocytogenes in chicken meat differed significantly between the storage temperatures, while no significant differences were found for other poultry types. No significant differences in detection rates were observed between different retail locations or packaging methods. Isolates exhibited complete resistance to cefoxitin (FOX) and increasing resistance over time to tetracycline (TET) and clindamycin (CLI), while low levels of resistance were found for penicillin (PEN), oxacillin (OXA), and erythromycin (ERY). Resistance to ERY and TET suggests the potential for multidrug resistance. Significant differences in antibiotic resistance profiles were observed among L. monocytogenes from the various poultry types. In summary, contamination status and antibiotic resistance profiles differed among retail chicken, duck, goose, and pigeon meat sold and the resistance rate of strains continues to increase in Jiading District, Shanghai. Targeted control measures should be implemented to reduce the emergence of resistant strains, as retail conditions had minimal impact on L. monocytogenes prevalence in poultry meat.