Search

The ability to predict tunnel deformation holds great significance for ensuring the reliability, safety, and sustainability of tunnel structures. However, existing deformation prediction models often simplify or overlook the impact of spatial characteristics on deformation by treating it as a time series prediction issue. This study utilizes monitoring data from the Grand Canyon Tunnel and introduces an effective data-driven method for predicting tunnel deformation based on the spatio-temporal characteristics of the historical deformation of adjacent sections. The proposed model, a combination of graph attention network (GAT) and bidirectional long and short-term memory network (Bi-LSTM), is equipped with robust spatio-temporal predictive capabilities. Additionally, the study explores other possible spatial connections and the scalability of the model. The results indicate that the proposed model outperforms other deep learning models, achieving favorable root mean square error (RMSE), mean absolute error (MAE), and coefficient of determination (R2) values of 0.34 mm, 0.23 mm, and 0.94, respectively. The graph structure based on intuitive spatial connections proves more suitable for meeting the challenges of predicting deformation. Integrating GAT-LSTM with transfer learning technology, remains stable performance when extended to other tunnels with limited data.

Abstract Background Altered metabolism has become an important characteristic of cancer, and acyl-CoA dehydrogenase short-chain (ACADS), a regulator of lipid synthesis, is involved in carcinogenesis-associated metabolic pathways. DNA methylation is an important mechanism for silencing ACADS in various malignancies. However, the specific role of ACADS in hepatocellular carcinoma (HCC) pathogenesis remains poorly understood. Methods and results Using RNA sequencing data from different tumours in The Cancer Genome Atlas database, we observed that ACADS was downregulated and hypermethylated in HCC. Three potential CpG island sites (cg01535453, cg08618068, and cg10174836) were identified in the ACADS promoter. Through in vivo and in vitro experiments, we confirmed that cg08618068 was methylated in HCC. We defined this site as ACADS methylation site-2 (ACADS MS-2). Methylation of ACADS MS-2 was associated with worse survival, and mutation of MS-2 increased ACADS mRNA levels in five HCC cell lines. Sustained overexpression of ACADS not only suppressed the proliferation, migration, and invasion of HCC cells but also promoted immunogenic cell death (ICD) via the upregulation of calreticulin. Subsequently, we established a specific nomogram based on ACADS methylation levels to evaluate the 3- and 5-year overall survival rates of patients with HCC who underwent surgical resection. Conclusions Our work clarified that ACADS acts as a putative tumour suppressor in HCC and confirmed that a nomogram including ACADS methylation had good predictive performance in HCC. We also discovered a correlation between ACADS and ICD, suggesting that ACADS is an essential target for immunotherapy in HCC. Graphical Abstract

Abstract Deep learning (DL) methods have demonstrated remarkable effectiveness in assisting with lung cancer risk prediction tasks using computed tomography (CT) scans. However, the lack of comprehensive comparison and validation of state-of-the-art (SOTA) models in practical settings limits their clinical application. This study aims to review and analyze current SOTA deep learning models for lung cancer risk prediction (malignant-benign classification). To evaluate our model’s general performance, we selected 253 out of 467 patients from a subset of the National Lung Screening Trial (NLST) who had CT scans without contrast, which are the most commonly used, and divided them into training and test cohorts. The CT scans were preprocessed into 2D-image and 3D-volume formats according to their nodule annotations. We evaluated ten 3D and eleven 2D SOTA deep learning models, which were pretrained on large-scale general-purpose datasets (Kinetics and ImageNet) and radiological datasets (3DSeg-8, nnUnet and RadImageNet), for their lung cancer risk prediction performance. Our results showed that 3D-based deep learning models generally perform better than 2D models. On the test cohort, the best-performing 3D model achieved an AUROC of 0.86, while the best 2D model reached 0.79. The lowest AUROCs for the 3D and 2D models were 0.70 and 0.62, respectively. Furthermore, pretraining on large-scale radiological image datasets did not show the expected performance advantage over pretraining on general-purpose datasets. Both 2D and 3D deep learning models can handle lung cancer risk prediction tasks effectively, although 3D models generally have superior performance than their 2D competitors. Our findings highlight the importance of carefully selecting pretrained datasets and model architectures for lung cancer risk prediction. Overall, these results have important implications for the development and clinical integration of DL-based tools in lung cancer screening.

Abstract Purpose This study aims to investigate the suitable surgical strategies for applying TaBw01 porous tantalum rod across different stages of osteonecrosis of the femoral head (ONFH). Methods TaBw01 tantalum rods were fabricated using type FTaY-1 tantalum powder via the foam impregnation-sintering method. Mechanical testing with the Instron 8801 universal testing machine and finite element analysis (FEA) assessed single tantalum rod implantation and impaction bone grafting combined with rod implantation. A total of 86 osteonecrosis of the femoral head (ONFH) patients (94 hips) were treated: the experimental group (45 patients, 50 hips) underwent surgical hip dislocation (SHD) with impaction bone grafting and tantalum rod implantation, while the control group (41 patients, 44 hips) received single rod implantation. Primary failure criteria included femoral head collapse (≥ 2 mm) or total hip arthroplasty. Patient-reported outcomes (PROs), including Harris Hip Score (HHS), Visual Analog Score (VAS), Hip Outcome Score Activities of Daily Living Subscale (HOS-ADL), and Hip Outcome Score Sport-Specific Subscale (HOS-SSS), were analyzed based on Minimum Clinically Important Difference (MCID). Results FEA confirmed stresses below the material’s yield and compressive strength. At 3 years, survival rates for ARCO (Association Research Circulation Osseous) stage IIb and IIc were higher in the experimental group (100%, 80.38%) than the control group, while stage IIa survival was 100% in the control group. The experimental group also had higher MCID attainment for HHS, HOS-ADL, and HOS-SSS. Conclusions Compared with single TaBw01 implantation, impaction bone grafting combined with TaBw01 implantation via SHD demonstrated superior outcomes for ARCO stage IIb and IIc, with a minimum 2-year follow-up. while single TaBw01 implantation may be more suitable for stage IIa. This study emphasizes the importance of combining biological and biomechanical reconstruction in ONFH treatment.

Abstract Background With the rapid ageing of the global population, the number of older adults with physical frailty has been gradually increasing, making ageing at home a key strategy for coping with this demographic change. The opinions of older adults regarding their willingness to age at home deserve to be considered respectfully. As a result, this study aimed to investigate willingness to age at home and any associated underlying mechanisms involving physical frailty among older Chinese adults. Methods This study was a national cross-sectional survey. Stratified random and quota sampling were used before and after the individual level respectively. Willingness to age at home was compared between older adults with different characteristics using the Mann–Whitney U test and Kruskal–Wallis H test. A Spearman rank test was conducted to explore the correlations among physical frailty, loneliness, family health, and willingness to age at home. The path hypothesis that loneliness and family health influence the relationship between physical frailty and willingness to age at home among older adults was further tested through sequential multiple mediation analysis. Results A total of 3,837 older adults were included in this study. They returned a median score of 78 in terms of willingness to age at home. Physical frailty (β = − 0.044, P

ABSTRACTBackground: Nurses in emergency departments are at a high risk of experiencing secondary traumatic stress because of their frequent exposure to trauma patients and high-stress environments.Objective: This systematic review and meta-analysis aimed to determine the overall prevalence of secondary traumatic stress among emergency nurses and to identify the contributing factors.Method: We conducted a systematic search for cross-sectional studies in databases such as PubMed, Web of Science, Embase, CINAHL, Wanfang Database, and China National Knowledge Internet up to October 21, 2023. The Joanna Briggs Institute’s appraisal checklists for prevalence and analytical cross-sectional studies were used for quality assessment. Heterogeneity among studies was assessed using Cochrane’s Q test and the I2 statistic. A random effects model was applied to estimate the pooled prevalence of secondary traumatic stress, and subgroup analyses were performed to explore sources of heterogeneity. Descriptive analysis summarized the associated factors.Results: Out of 345 articles retrieved, 14 met the inclusion criteria, with 11 reporting secondary traumatic stress prevalence. The pooled prevalence of secondary traumatic stress among emergency nurses was 65% (95% CI: 58%–73%). Subgroup analyses indicated the highest prevalence in Asia (74%, 95% CI: 72%–77%), followed by North America (59%, 95% CI: 49%–72%) and Europe (53%, 95% CI: 29%–95%). Nine studies identified associated factors, including personal, work-related, and social factors. In the subgroup of divided by recruitment period, emergency department nurses in the COVID-19 outbreak period had a higher prevalence of secondary traumatic stress (70%, 95% CI: 62%–78%).Conclusions: Secondary traumatic stress prevalence is notably high among emergency department nurses, with significant regional variations and period differences. The factors affecting secondary traumatic stress also varied across studies. Future research should focus on improving research designs and sample sizes to pinpoint risk factors and develop prevention strategies.Registration: PROSPERO CRD42022301167.

Abstract Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.

Abstract Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.

BackgroundColorectal cancer is a prevalent malignancy of the digestive system, with an increasing incidence. Lower extremity deep vein thrombosis (DVT) is a frequent postoperative complication, occurring in up to 40% of cases.ObjectiveThis research aims to develop and validate a machine learning model (ML) to predict the risk of lower limb deep vein thrombosis in patients with colorectal cancer, facilitating preventive and therapeutic measures to enhance recovery and ensure safety.MethodsIn this retrospective cohort study, we collected data from 429 colorectal cancer patients from January 2021 to January 2024. The medical records included age, blood test results, body mass index, underlying diseases, clinical staging, histological typing, surgical methods, and postoperative complications. We employed the Synthetic Minority Oversampling Technique to address imbalanced data and split the dataset into training and validation sets in a 7:3 ratio. Feature selection was performed using Random Forest (RF), XGBoost, and Least Absolute Shrinkage and Selection Operator algorithms (LASSO). We then trained six machine learning models: Logistic Regression (LR), Naive Bayes (NB), Gaussian Process (GP), Random Forest, XGBoost, and Multilayer Perceptron (MLP). The model’s performance was evaluated using metrics such as area under the Receiver Operating Characteristic curve, accuracy, sensitivity, specificity, F1 score, and confusion matrix. Additionally, SHAP and LIME were used to enhance the interpretability of the results.ResultsThe study combined Random Forest, XGBoost algorithms, and LASSO regression with univariate regression analysis to identify significant predictive factors, including age, preoperative prealbumin, preoperative albumin, preoperative hemoglobin, operation time, PIKVA2, CEA, and preoperative neutrophil count. The XGBoost model outperformed other ML algorithms, achieving an AUC of 0.996, an accuracy of 0.9636, a specificity of 0.9778, and an F1 score of 0.9576. Moreover, the SHAP method identified age and preoperative prealbumin as the primary determinants influencing ML model predictions. Finally, the study employed LIME for more precise prediction and interpretation of individual predictions.ConclusionThe machine learning algorithms effectively predicted postoperative lower limb deep vein thrombosis in colorectal cancer patients. The XGBoost model demonstrated strong potential for improving early detection and treatment in clinical settings.

Major depressive disorder (MDD) is a debilitating mental health condition that poses significant risks and burdens. Resting-state functional magnetic resonance imaging (fMRI) has emerged as a promising tool in investigating the neural mechanisms underlying MDD. However, a comprehensive bibliometric analysis of resting-state fMRI in MDD is currently lacking. Here, we aimed to thoroughly explore the trends and frontiers of resting-state fMRI in MDD research. The relevant publications were retrieved from the Web of Science database for the period between 1998 and 2022, and the CiteSpace software was employed to identify the influence of authors, institutions, countries/regions, and the latest research trends. A total of 1501 publications met the search criteria, revealing a gradual increase in the number of annual publications over the years. China contributed the largest publication output, accounting for the highest percentage among all countries. Particularly, the University of Electronic Science and Technology of China, Capital Medical University, and Harvard Medical School were identified as key institutions that have made substantial contributions to this growth. Neuroimage, Biological Psychiatry, Journal of Affective Disorders, and Proceedings of the National Academy of Sciences of the United States of America are among the influential journals in the field of resting-state fMRI research in MDD. Burst keywords analysis suggest the emerging research frontiers in this field are characterized by prominent keywords such as dynamic functional connectivity, cognitive control network, transcranial brain stimulation, and childhood trauma. Overall, our study provides a systematic overview into the historical development, current status, and future trends of resting-state fMRI in MDD, thus offering a useful guide for researchers to plan their future research.

Abstract Background Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. Results To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. Conclusions This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy. Graphical Abstract

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson’s disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson’s disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson’s disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore, bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson’s disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson’s disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson’s disease, particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremor-dominant and non-tremor-dominant Parkinson’s disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity, and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson’s disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

The sanding process caused by karstification in dolomite creates a special sandy dolomite stratum, where the frequent catastrophic instability of the surrounding rock occurred during tunnel construction. In this study, the micro-origin and macro-performance of the sandy dolomite stratum are first discussed. Then, a numerical model based on the coupling method between the discontinuous deformation analysis and smoothed particle hydrodynamics is proposed to depict the heterogeneous dolomite formation with different sanding degrees. Following, the mechanical behaviors of the heterogeneous dolomite samples under uniaxial compression are studied after calibrating the numerical parameters with the two single materials sampled from the tunnel site respectively. Further, the instability disasters of the dolomite surrounding rock with different sanding degrees are reproduced, and the failure behaviors of tunnels are explained with respect to the stress distribution and plastic zone. The obtained results show that the rotation and dislocation of the remained dolomite block contribute to the unsmooth stress–strain curve and deterioration in uniaxial compressive strength. However, the block serves as the skeleton in the transmission of field stress in underground space, which improves the stability of the formation.

Abstract Context With the development of society, the number of patients with osteoporosis is increasing. The prevention and control of osteoporosis has become a serious and urgent issue. With the continuous progress of biomedical research, ferroptosis has attracted increased attention. However, the pathophysiology and mechanisms of ferroptosis and osteoporosis still need further study. Natural products are widely used in East Asian countries for osteoporosis prevention and treatment. Objective In this paper, we will discuss the basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, and in vitro and in vivo studies of natural products to prevent osteoporosis by interfering with ferroptosis. Methods This article takes ferroptosis, natural products, osteoporosis, osteoblasts and osteoclast as key words. Retrieve literature from 2012 to 2023 indexed in databases such as PubMed Central, PubMed, Web of Science, Scopus and ISI. Results Ferroptosis has many regulatory mechanisms, including the system XC -/GSH/GPX4, p62/Keap1/Nrf2, FSP1/NAD (P) H/CoQ10, P53/SAT1/ALOX15 axes etc. Interestingly, we found that natural products, such as Artemisinin, Biochanin A and Quercetin, can play a role in treating osteoporosis by promoting ferroptosis of osteoclast and inhibiting ferroptosis of osteoblasts. Conclusions Natural products have great potential to regulate OBs and OCs by mediating ferroptosis to prevent and treat osteoporosis, and it is worthwhile to explore and discover more natural products that can prevent and treat osteoporosis.

Abstract The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skin‐related diseases in humans. Here, single‐cell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods. The cross‐species comparison of skin cells illustrated that the pig epidermis is more representative of the human epidermis than mice epidermis. Moreover, Phenome‐wide association study analysis revealed that the conserved genes between pigs and humans are strongly associated with human skin‐related diseases. In the epidermis, two lineage differentiation trajectories describe hair follicle (HF) morphogenesis and epidermal development. By comparing normal and hairless fetal pigs, it is found that the hair placode (Pc), the most characteristic initial structure in HFs, arises from progenitor‐like OGN+/UCHL1+ cells. These progenitors appear earlier in development than the previously described early Pc cells and exhibit abnormal proliferation and migration during differentiation in hairless pigs. The study provides a valuable resource for in‐depth insights into HF development, which may serve as a key reference atlas for studying human skin disease etiology using porcine models.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic chemicals, encompassing compounds like perfluorooctane sulfonate (PFOS), which have widespread applications across various industries, including food packaging and firefighting. In recent years, China has increasingly employed 6:2 Cl-PFESA as an alternative to PFOS. Although the association between PFAS exposure and hepatocellular carcinoma (HCC) has been demonstrated, the underlying mechanisms that promote HCC proliferation are uncleared. Therefore, we aimed to investigate the effects and differences of PFOS and 6:2 Cl-PFESA on HCC proliferation through in vivo and in vitro tumor models. Our results reveal that both PFOS and 6:2 Cl-PFESA significantly contribute to HCC proliferation in vitro and in vivo. Exposure led to reduced population doubling times, enlarged cell colony sizes, enhanced DNA synthesis efficiency, and a higher proportion of cells undergoing mitosis. Furthermore, both PFOS and 6:2 Cl-PFES) have been shown to activate the PI3K/AKT/mTOR signaling pathway and inhibit necroptosis. This action consequently enhances the proliferation of HCC cells. Our phenotypic assay findings suggest that the tumorigenic potential of 6:2 Cl-PFESA surpasses that of PFOS; in a subcutaneous tumor model using nude mice, the mean tumor weight for the 6:2 Cl-PFESA-treated cohort was 2.33 times that observed in the PFOS cohort (p

In this work, the azoxytriazolone (AZTO) was synthesized by electrochemical reduction 5-nitro-1,2,4-triazol-3-one (NTO) under different types of electrolytes which were Na2SO4 and H2SO4. By comparing the yield of AZTO/azoTO synthesized under different electrolyte conditions, the work found that sulfuric acid as the electrolyte has a positive effect on the synthesis of AZTO. On this basis, the high-concentration AZTO was prepared by regulating the concentrations of sulfuric acid (0.05M, 0.1M, 0.5M, 1M). Finally, by introducing an appropriate amount of NaOH, we successfully achieved the separation and purification of AZTO from the mixture of AZTO and azoTO. In addition, single crystal AZTO was also prepared in this experiment to test its crystal structure, which illustrated that the crystal density of AZTO is 1.902 g/cm3 at 193 K, belonging to the monoclinic crystal system with space group P21/n. The thermal properties results of AZTO showed that the thermal stability properties of AZTO were affected by AZTO/azoTO ratio, and the thermal decomposition peak of pure AZTO is 352°C when the content of azoTO is zero. On the contrary, the BAM susceptibility tester test demonstrated the impact susceptibility is 30 J and the friction susceptibility is greater than 360 N of AZTO, which are unaffected on azoTO. According to the K-J empirical formula, the blasting velocity and detonation pressure of AZTO were 7713.5 m/s and 26.1 GPa, respectively. The influences of different types of electrolytes and sulfuric acid concentrations on the yield of AZTO were evaluated, and the relevant reaction mechanism of electrochemical synthesis of AZTO and azoTO was supplemented in this paper.

Abstract Hepatocellular carcinoma (HCC) is one of the most lethal tumor types worldwide. Glycosylation has shown promise in the study of tumor mechanisms and treatment. The glycosylation status of HCC and the underlying molecular mechanisms are still not fully elucidated. Using bioinformatic analysis we obtained a more comprehensive characterization of glycosylation of HCC. Our analysis presented that high glycosylation levels might correlate with tumor progression and poor prognosis. Subsequent Experiments identified key molecular mechanisms for ST6GALNAC4 promoting malignant progression by inducing abnormal glycosylation. We confirmed the contribution of ST6GALNAC4 to proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies revealed that ST6GALNAC4 may be induced abnormal TGFBR2 glycosylation, resulting in the higher protein levels of TGFBR2 and TGF $$\beta$$ β pathway increased activation. Our study also provided a further understand of immunosuppressive function of ST6GALNAC4 through T antigen-galectin3+ TAMs axis. This study has provided one such possibility that galectin3 inhibitors might be an acceptable treatment choice for HCC patients with high T antigen expression.

Temperature plays a critical role in the efficiency and stability of industrial wastewater treatment plants (WWTPs). This study focuses on the effects of temperature on activated sludge (AS) communities within the A2O process of 19 industrial WWTPs in the Yangtze River Delta, a key industrial region in China. The investigation aims to understand how temperature influences AS community composition, functional assembly, and carbon transformation processes, including CO2 emission potential. Our findings reveal that increased operating temperatures lead to a decrease in alpha diversity, simplifying community structure and increasing modularity. Dominant species become more prevalent, with significant decreases in the relative abundance of Chloroflexi and Actinobacteria, and increases in Bacteroidetes and Firmicutes. Moreover, higher temperatures enhance the overall carbon conversion potential of AS, particularly boosting CO2 absorption in anaerobic conditions as the potential for CO2 emission during glycolysis and TCA cycles grows and diminishes, respectively. The study highlights that temperature is a major factor affecting microbial community characteristics and CO2 fluxes, with more pronounced effects observed in anaerobic sludge. This study provides valuable insights for maintaining stable A2O system operations, understanding carbon footprints, and improving COD removal efficiency in industrial WWTPs.

Northwest China faces an imbalance between scarce water resources and increasing water use demands for agricultural production and economic growth. However, the shifts in virtual water flow (VWF) patterns in Northwest China and its the driving factors are still unclear. In this study, we employed the Multiregional Input–Output (MRIO) method to investigate the evolution of VWF patterns among Northwest China’s primary, secondary, and tertiary industries and analyze their driving factors through Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model. The results show that (1) Northwest China changed from 7.24 × 108 m3 net inflow to 175.70 × 108 m3 net outflow from 2002 to 2007. (2) More than 90 % of virtual water of the primary industry was used locally, but both secondary and tertiary industries depended more on virtual water inflow in Northwest China. (3) The virtual water outflow from Northwest China is mostly to the Jing-Jin Region, followed by the Northern Coast, and the main inflow is from the Central Region. (4) Population, economy, and technology affect virtual water from inflow to outflow, and technological development helps to decrease virtual water flow volumes. In conclusion, dramatic decrease of second and third industries inflow is the main reason for the changes from net inflow to net outflow of Northwest China. Meanwhile, it is feasible to increase technological support to further reducing virtual water consumption in primary industry, and strengthen virtual water trades of secondary and tertiary industrial virtual water inflows by promoting population and economic conditions.

Background: Circular RNA (circRNA) plays a critical role in tumour progression. Circ-CCT3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, the role of circ-CCT3 in hepatocellular carcinoma remains elusive.Methods: Here, circ-CCT3 (a circRNA derived from exons 3, 4 and 5 of the CCT3 gene, hsa_circ_0004680) was identified by circRNA microarray and validated by qRT-PCR. RNA immunoprecipitation (RIP) was performed to confirm the binding between ALKBH5 along with METTL3 and circ-CCT3. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m 2A) levels of circ-CCT3. CircRNAs in vivo precipitation, luciferase reporter assay, biotin-coupled microRNA capture, and fluorescence in situ hybridization were conducted to assess the interaction between circ-CCT3 and miR-378a-3p. The functions of circ-CCT3 in HCC were evaluated both in vitro and in vivo.Results: We demonstrated that circ-CCT3 was highly expressed in HCC which indicated the poor prognosis. Circ-CCT3 expression served as an independent risk factor for overall survival in patients with HCC. Knocking-down of circ-CCT3 inhibited the proliferation, invasion and migration of HCC cells, and angiogenesis of HUVEC. Mechanistically, ALKBH5 and METTL3 could bind and regulate m A-modification of circ-CCT3. Further, circ-CCT3 upregulated the expression of FLT-1 by sponging miR-378a-3p.Conclusions: Circ-CCT3 was significantly up-regulated in HCC and promoted liver cancer development via miR-378a-3p-FLT1 axis. It was also found that circ-CCT3 was under m A-modification mediated by ALKBH5 and METTL3. Our study highlights circ-CCT3 as a potential therapeutic target of HCC treatment, which provides a novel understanding on mechanisms of circRNAs in HCC progression.

Abstract Background Biomechanical and finite element analyses were performed to investigate the efficacy of second-generation bone cement-injectable cannulated pedicle screws (CICPS) in osteoporosis. Methods This study used the biomechanical test module of polyurethane to simulate osteoporotic cancellous bone. Polymethylmethacrylate (PMMA) bone cement was used to anchor the pedicle screws in the module. The specimens were divided into two groups for the mechanical tests: the experimental group (second-generation CICPS) and control group (first-generation CICPS). Safety was evaluated using maximum shear force, static bending, and dynamic bending tests. Biomechanical stability evaluations included the maximum axial pullout force and rotary torque tests. X-ray imaging and computed tomography were used to evaluate the distribution of bone cement 24 h after PMMA injection, and stress distribution at the screw fracture and screw–cement–bone interface was assessed using finite element analysis. Results Mechanical testing revealed that the experimental group (349.8 ± 28.6 N) had a higher maximum axial pullout force than the control group (277.3 ± 8.6 N; P 0.05). The screw-in and spin-out torques of the experimental group were higher than those of the control group (spin-in, 0.793 ± 0.015 vs. 0.577 ± 0.062 N, P

Abstract Radiation pneumonitis (RP) affects both patients and physicians during radiation therapy for lung cancer. To date, there are no effective drugs for improving the clinical outcomes of RP. The activation of angiotensin-converting enzyme 2 (ACE2) improves experimental acute lung injury caused by severe acute respiratory syndrome coronavirus, acid inhalation, and sepsis. However, the effects and underlying mechanisms of ACE2 in RP remain unclear. Therefore, this study aimed to investigate the effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on RP and ACE2/angiotensin-(1–7)/Mas receptor pathway activation. We found that radiotherapy decreased the expression of ACE2 and that overexpression of ACE2 alleviated lung injury in an RP mouse model. Moreover, captopril and valsartan restored ACE2 activation; attenuated P38, ERK, and p65 phosphorylation; and effectively mitigated RP in the mouse model. Further systematic retrospective analysis illustrated that the incidence of RP in patients using renin-angiotensin system inhibitors (RASis) was lower than that in patients not using RASis (18.2% vs. 35.8% at 3 months, p = 0.0497). In conclusion, the current findings demonstrate that ACE2 plays a critical role in RP and suggest that RASis may be useful potential therapeutic drugs for RP.

The impact of the piston wind caused by vehicle traffic on the temperature field distribution of the tunnel cannot be ignored, especially in spiral tunnels, where the temperature field distribution is more complicated than that in straight tunnels. Based on the world's longest highway spiral tunnel, this study explores the influence of traffic on the temperature fields of spiral and straight tunnels, and proposes a new design method for laying length of insulation layer. The results show that traffic has a significant effect on the temperature field distribution in the tunnel. The influence degree of different traffic elements decreases in the following order: average vehicle speed > daily traffic > morning rush hour > evening rush hour. The temperature field distribution of spiral tunnels is asymmetry on the left and right compared with straight tunnels, while the influence degree of traffic on the outside of spiral tunnels is similar to that of straight tunnels. Due to the difference of wind direction and traffic direction at different tunnel openings, an asymmetric insulation layer laying method is proposed. It is suggested that the lengths of the insulation layers of the Jinjiazhuang Tunnel should be 1200 m for the right tunnel inlet, 700 m for the right tunnel outlet, 700 m for the left tunnel inlet, and 1400 m for the left tunnel outlet.

The spherulite morphology is common among crystalline materials and melt-crystallized products, however, the structural determination of spherulites by X-ray diffraction remains difficult due to their polycrystalline nature. Here, the authors report the direct structure determination of the polymorphism of vemurafenib in compact spherulite form using 3D electron diffraction.

Aqueous zinc ions lower the corrosion rate of Alloy 600, which helps lower the radiation dose rate in pressurized water reactors (PWRs). The influence of zinc on the electrochemical behavior of Alloy 600 in PWR primary water (PW) at 320 °C was investigated using a combination of electron microscopy and electrochemical impedance spectroscopy (EIS). Secondary electron microscopy (SEM) and scanning transmission electron microscopy (STEM)/energy-dispersive X-ray spectroscopy (EDS) indicated duplex surface films were formed on the Alloy 600 in PWR PW with and without 100 ppb of zinc. There was no effect of zinc on the chromium-rich inner layer (IL) (of Cr2O3 and/or CrOOH). Zinc had a significant effect on the outer layer (OL). In the absence of zinc, a highly porous OL formed that was mostly composed of nickel oxide whiskers. In the presence of zinc, a zinc-containing, denser OL of oxide was formed. The EIS data were acquired in laboratory simulated PWR PW at 320 °C with and without 100 ppb zinc. The spectra were measured at nine different values of potential that spanned a 500 mV-wide range. The EIS indicated there was no effect of zinc on the oxidation rate of metals at the alloy/IL interface nor on the transport of ions through the IL. Zinc lowered the corrosion rate because the dense OL inhibited the release of nickel ions from the IL into the solution.

Floral scent is a crucial characteristic that greatly affects the reproductive process and also the market value of numerous ornamental crops. As the pivotal species in basal dicotyledonous, Clematis is widely favored as an ornamental vine plant due to its varied colors and shapes of flowers. However, the diversity and complexity of the floral fragrance in Clematis is largely unexplored. Thus, on the basis of the initial sensory survey, four fragrant wild Clematis species and five cultivars were selected to investigate the variation of the floral volatile profiling between the wild Clematis species and their cultivars. Our results demonstrated that a total of 162 volatile compositions, including terpenoids, benzenoids, fatty acid derivatives, and N-containing compounds, were successively detected by the combination of dynamic headspace collection and GC-MS analysis. The qualitative and quantitative comparison combined with clustering and PCA analysis indicated the interspecific discrepancy in floral volatiles between the wild Clematis species and cultivars. C. finetiana exhibited a higher emission with the characteristic releasing pattern being distinct from other species. In conclusion, the exploitation of the emission patterns, biosynthesis, and potential biological functions of floral scent, especially for terpenoids and methyl esters, provides a comprehensive understanding of volatile metabolism in fragrant Clematis species and their cultivars. These findings can be useful for aromatic resources screening and breeding strategies developing to create new aromatic cultivars of Clematis.

Abstract Background Insights into the genetic basis of complex traits and disease in both human and livestock species have been achieved over the past decade through detection of genetic variants in genome-wide association studies (GWAS). A majority of such variants were found located in noncoding genomic regions, and though the involvement of numerous regulatory elements (REs) has been predicted across multiple tissues in domesticated animals, their evolutionary conservation and effects on complex traits have not been fully elucidated, particularly in ruminants. Here, we systematically analyzed 137 epigenomic and transcriptomic datasets of six mammals, including cattle, sheep, goats, pigs, mice, and humans, and then integrated them with large-scale GWAS of complex traits. Results Using 40 ChIP-seq datasets of H3K4me3 and H3K27ac, we detected 68,479, 58,562, 63,273, 97,244, 111,881, and 87,049 REs in the liver of cattle, sheep, goats, pigs, humans and mice, respectively. We then systematically characterized the dynamic functional landscapes of these REs by integrating multi-omics datasets, including gene expression, chromatin accessibility, and DNA methylation. We identified a core set (n = 6359) of ruminant-specific REs that are involved in liver development, metabolism, and immune processes. Genes with more complex cis-REs exhibited higher gene expression levels and stronger conservation across species. Furthermore, we integrated expression quantitative trait loci (eQTLs) and GWAS from 44 and 52 complex traits/diseases in cattle and humans, respectively. These results demonstrated that REs with different degrees of evolutionary conservation across species exhibited distinct enrichments for GWAS signals of complex traits. Conclusions We systematically annotated genome-wide functional REs in liver across six mammals and demonstrated the evolution of REs and their associations with transcriptional output and conservation. Detecting lineage-specific REs allows us to decipher the evolutionary and genetic basis of complex phenotypes in livestock and humans, which may benefit the discovery of potential biomedical models for functional variants and genes of specific human diseases.

BackgroundAtopic dermatitis (AD) has increased rapidly with rapid urbanization; however, the treatment options for AD are lacking because the commonly used therapies can only alleviate symptoms. Limosilactobacillus reuteri (L. reuteri), FN041 is a specific strain isolated from human breast milk, and its protective potential against AD has been confirmed. This study aims to assess the efficacy of maternal consumption of L. reuteri FN041 during late pregnancy and lactation in preventing infantile AD.MethodsFirst, a randomized, double-blind, placebo-controlled intervention study will be conducted on 340 pregnant females with babies at high risk for AD. These subjects will be randomly divided into four groups of different doses of L. reuteri FN041 (1 × 109, 5 × 109, and 1 × 1010 CFU/d) along with a placebo. The safety and efficacy of maternal use of L. reuteri FN041 for preventing infantile AD will be analyzed, and the most efficient dosage of L. reuteri FN041 will be determined. Subsequently, a multicenter cohort study of 500 pregnant females with babies at high risk for AD will be conducted to promote the maternal application of L. reuteri FN041. These subjects will be administered L. reuteri FN041 at the optimal dose determined during the first stage of late pregnancy and lactation, and their babies will be analyzed for AD development. Recruitment was initiated in October 2022.DiscussionThe primary outcome is the cumulative incidence of AD at 24 months after maternal consumption of L. reuteri FN041 during late pregnancy and lactation, whereas the secondary outcome is the efficiency of L. reuteri FN041 transfer from the mother’s gut to breast milk and then the infant’s gut after oral supplementation. This study will demonstrate the efficacy of edible probiotics isolated from breast milk in preventing or treating AD in infants. Accordingly, we provide population-based advice for administering specific probiotics for the primary prevention of AD in pregnant females. Understanding the underlying mechanisms of probiotic strains derived from breast milk can promote their application in preventing infant diseases associated with intestinal microbiota imbalance and immune disorders.Clinical trial registrationhttps://www.chictr.org.cn/, identifier [ChiCTR2300075611].

Abstract Background Circular RNAs (circRNAs) play a significant role in the initiation and progression of various cancers, including hepatocellular carcinoma (HCC). Circular syntaxin 6 (circSTX6, also known as hsa_circ_0007905) has been identified as a microRNA (miRNA) sponge in pancreatic adenocarcinoma. However, its full range of functions in terms of protein scaffold and translation remain largely unexplored in the context of HCC. Methods The expression of circSTX6 and its encoded protein was examined in HCC tumour tissues. N6‐methyladenosine (m6A) on circSTX6 was verified and quantified by methylated RNA immunoprecipitation (Me‐RIP), RIP and dual luciferase reporter assays. The biological functions of circSTX6 and its encoded protein in HCC were clarified by in vitro and in vivo experiments. Mechanistically, the interaction between circSTX6 and heterogeneous nuclear ribonucleoprotein D (HNRNPD) was investigated by RNA pull‐down, RIP and fluorescence in situ hybridization (FISH)/IF. The regulatory effects of circSTX6 and HNRNPD on activating transcription factor 3 (ATF3) mRNA were determined by mRNA stability and RIP assays. Furthermore, the presence of circSTX6‐encoded protein was verified by mass spectrometry. Results CircSTX6 and its encoded 144 amino acid polypeptide, circSTX6‐144aa, were highly expressed in HCC tumour tissues and served as independent risk factors for overall survival in HCC patients. The expression of circSTX6 was regulated by METTL14 in an m6A‐dependent manner. Functionally, circSTX6 accelerated HCC proliferation and tumourigenicity and reinforced tumour metastasis in vitro and in vivo. Mechanistically, circSTX6 acted as a sponge for HNRNPD protein, facilitating its binding to ATF3 mRNA, consequently promoting ATF3 mRNA decay. Meanwhile, circSTX6‐144aa promoted HCC proliferation, migration and invasion independent of circSTX6 itself. Conclusion Collectively, our study reveals that m6A‐modified circSTX6 drives malignancy in HCC through the HNRNPD/ATF3 axis, while its encoded circSTX6‐144aa contributes to HCC progression independent of circSTX6. CirSTX6 and its encoded protein hold promise as potential biomarkers and therapeutic targets in HCC.

Developments in connected and autonomous vehicle technologies provide drivers with many convenience and safety benefits. Unfortunately, as connectivity and complexity within vehicles increase, more entry points or interfaces that may directly or indirectly access in-vehicle networks (IVNs) have been introduced, causing a massive rise in security risks. An intrusion detection system (IDS) is a practical method for controlling malicious attacks while guaranteeing real-time communication. Regarding the ever-evolving security attacks on IVNs, researchers have paid more attention to employing deep learning-based techniques to deal with privacy concerns and security threats in the IDS domain. Therefore, this article comprehensively reviews all existing deep IDS approaches on in-vehicle networks and conducts fine-grained classification based on applied deep network architecture. It investigates how deep-learning techniques are utilized to implement different IDS models for better performance and describe their possible contributions and limitations. Further compares and discusses the studied schemes concerning different facets, including input data strategy, benchmark datasets, classification technique, and evaluation criteria. Furthermore, the usage preferences of deep learning in IDS, the influence of the dataset, and the selection of feature segments are discussed to illuminate the main potential properties for designing. Finally, possible research directions for follow-up studies are provided.

Background: Externalizing problems, internalizing problems, and obesity are among the greatest challenges to adolescent health. However, the moderating and mediating mechanisms that underlie this association remain predominantly unexplored. Objectives: In this study, we examined the association between body mass index (BMI) and externalizing and internalizing scores in adolescents, tested whether traditional bullying and cyberbullying mediated the association, and explored the moderated role of sex. Methods: The data came from 1486 adolescents from grade 7, 8, and 10 living in Shantou, China. Information on BMI, traditional bullying, and cyberbullying victimization was obtained through a self-administered questionnaire. The students’ externalizing and internalizing scores were evaluated using the Strengths and Difficulties Questionnaire (SDQ). Furthermore, we built two parallel mediation models with sex as a moderating variable. Results: Compared to their peers with normal weight, adolescents with increased BMI reported higher externalizing and internalizing scores. Traditional bullying and cyberbullying were both significant mediators in the two relationships. Sex moderated the pathway from BMI to cyberbullying. But sex did not moderate the relationship between BMI and traditional bullying. Conclusions: The results highlight that it is imperative for educators to identify students who are subjected to weight-based bullying and provide them with recommendations for effective coping strategies. Meanwhile, both victims of traditional bullying and those affected by cyberbullying should be the focus of prevention and intervention efforts when developing a strategy to improve levels of internalizing and externalizing symptoms among adolescents with increased BMI.

ObjectivesDigestive system diseases have evolved into a growing global burden without sufficient therapeutic measures. Lactobacillus reuteri (L. reuteri) is considered as a new potential economical therapy for its probiotic effects in the gastrointestinal system. We have provided an overview of the researches supporting various L. reuteri strains’ application in treating common digestive system diseases, including infantile colic, diarrhea, constipation, functional abdominal pain, Helicobacter pylori infection, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases.MethodsThe summarized literature in this review was derived from databases including PubMed, Web of Science, and Google Scholar.ResultsThe therapeutic effects of L. reuteri in digestive system diseases may depend on various direct and indirect mechanisms, including metabolite production as well as modulation of the intestinal microbiome, preservation of the gut barrier function, and regulation of the host immune system. These actions are largely strain-specific and depend on the activation or inhibition of various certain signal pathways. It is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and it can also be recommended as an adjuvant strategy to diarrhea, constipation, Helicobacter pylori infection in therapeutic settings. While preclinical studies have shown the probiotic potential of L. reuteri in the management of functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases, its application in these disease settings still needs further study.ConclusionThis review focuses on the probiotic effects of L. reuteri on gut homeostasis via certain signaling pathways, and emphasizes the importance of these probiotics as a prospective treatment against several digestive system diseases.

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis, and novel treatment strategies are urgently needed. Mitochondria are key regulators of cellular homeostasis and potential targets for tumor therapy. Here, the role of mitochondrial translocator protein (TSPO) in the regulation of ferroptosis and antitumor immunity is investigated and the potential therapeutic implications for HCC are assessed. TSPO is highly expressed in HCC and associated with poor prognosis. Gain‐ and loss‐of‐function experiments present that TSPO promotes HCC cell growth, migration, and invasion in vitro and in vivo. In addition, TSPO inhibits ferroptosis in HCC cells via enhancing the Nrf2‐dependent antioxidant defense system. Mechanistically, TSPO directly interacts with P62 and interferes with autophagy, leading to the accumulation of P62. The P62 accumulation competes with KEAP1, preventing it from targeting Nrf2 for proteasomal degradation. Furthermore, TSPO promotes HCC immune escape by upregulating PD‐L1 expression through Nrf2‐mediated transcription. Notably, TSPO inhibitor PK11195 combines with anti‐PD‐1 antibody showing a synergistic anti‐tumor effect in a mouse model. Overall, the results demonstrated that mitochondrial TSPO promotes HCC progression by inhibiting ferroptosis and antitumor immunity. Targeting TSPO can be a promising new strategy for HCC treatment.

Abstract The aim of this study was to identify the applicability of an ultrasound-guided attenuation parameter (UGAP) for the noninvasive assessment of hepatic steatosis in clinical practice and to compare its correlation with B-mode ultrasound (US). From May to July 2021, 63 subjects with different body mass index (BMI) grades were included in the prospective study. All of them performed UGAP measurements, under different breathing manipulations, positions, diet statuses, and operators. After that, the UGAP values were compared with the visual grades of hepatic steatosis on B-mode US using a 4-point scale method. The intraclass correlation (ICC) of the UGAP values between the two radiologists was 0.862 (p 0.05), positions (p > 0.05), or diet statuses (p = 0.300). The UGAP values in the fasting (supine position, segment V, 1) condition among the lean (BMI

Graph convolutional networks (GCN), which can model the human body skeletons as spatial and temporal graphs, have shown remarkable potential in skeleton-based action recognition. However, in the existing GCN-based methods, graph-structured representation of the human skeleton makes it difficult to be fused with other modalities, especially in the early stages. This may limit their scalability and performance in action recognition tasks. In addition, the pose information, which naturally contains informative and discriminative clues for action recognition, is rarely explored together with skeleton data in existing methods. In this work, we proposed pose-guided GCN (PG-GCN), a multi-modal framework for high-performance human action recognition. In particular, a multi-stream network is constructed to simultaneously explore the robust features from both the pose and skeleton data, while a dynamic attention module is designed for early-stage feature fusion. The core idea of this module is to utilize a trainable graph to aggregate features from the skeleton stream with that of the pose stream, which leads to a network with more robust feature representation ability. Extensive experiments show that the proposed PG-GCN can achieve state-of-the-art performance on the NTU RGB+D 60 and NTU RGB+D 120 datasets.

Cattle have been essential for the development of human civilization since their first domestication few thousand years ago. Since then, they have spread across vast geographic areas following human activities. Throughout generations, the cattle genome has been shaped with detectable signals induced by various evolutionary processes, such as natural and human selection processes and demographic events. Identifying such signals, called selection signatures, is one of the primary goals of population genetics. Previous studies used various selection signature methods and normalized the outputs score using specific windows, in kbp or based on the number of SNPs, to identify the candidate regions. The recent method of iSAFE claimed for high accuracy in pinpointing the candidate SNPs. In this study, we analyzed whole-genome resequencing (WGS) data of ten individuals from Austrian Fleckvieh (Bos taurus) and fifty individuals from 14 Chinese indigenous breeds (Bos taurus, Bos taurus indicus, and admixed). Individual WGS reads were aligned to the cattle reference genome of ARS. UCD1.2 and subsequently undergone single nucleotide variants (SNVs) calling pipeline using GATK. Using these SNVs, we examined the population structure using principal component and admixture analysis. Then we refined selection signature candidates using the iSAFE program and compared it with the classical iHS approach. Additionally, we run Fst population differentiation from these two cattle groups. We found gradual changes of taurine in north China to admixed and indicine to the south. Based on the population structure and the number of individuals, we grouped samples to Fleckvieh, three Chinese taurines (Kazakh, Mongolian, Yanbian), admixed individuals (CHBI_Med), indicine individuals (CHBI_Low), and a combination of admixed and indicine (CHBI) for performing iSAFE and iHS tests. There were more significant SNVs identified using iSAFE than the iHS for the candidate of positive selection and more detectable signals in taurine than in indicine individuals. However, combining admixed and indicine individuals decreased the iSAFE signals. From both within-population tests, significant SNVs are linked to the olfactory receptors, production, reproduction, and temperament traits in taurine cattle, while heat and parasites tolerance in the admixed individuals. Fst test suggests similar patterns of population differentiation between Fleckvieh and three Chinese taurine breeds against CHBI. Nevertheless, there are genes shared only among the Chinese taurine, such as PAX5, affecting coat color, which might drive the differences between these yellowish coated breeds, and those in the greater Far East region.

Abstract G protein‐coupled receptors (GPCRs) are the most common and important drug targets. However, >70% of GPCRs are undruggable or difficult to target using conventional chemical agonists/antagonists. Small nucleic acid molecules, which can sequence‐specifically modulate any gene, offer a unique opportunity to effectively expand drug targets, especially those that are undruggable or difficult to address, such as GPCRs. Here, the authors report for the first time that small activating RNAs (saRNAs) effectively modulate a GPCR for cancer treatment. Specifically, saRNAs promoting the expression of Mas receptor (MAS1), a GPCR that counteracts the classical angiotensin II pathway in cancer cell proliferation and migration, are identified. These saRNAs, delivered by an amphiphilic dendrimer vector, enhance MAS1 expression, counteracting the angiotensin II/angiotensin II Receptor Type 1 axis, and leading to significant suppression of tumorigenesis and the inhibition of tumor progression of multiple cancers in tumor‐xenografted mouse models and patient‐derived tumor models. This study provides not only a new strategy for cancer therapy by targeting the renin‐angiotensin system, but also a new avenue to modulate GPCR signaling by RNA activation.

A suitable ionic liquid for methyl chloride drying experiment was screened out from 210 ionic liquids by COSMO-RS model. Moreover, the experimental mechanism of ionic liquids drying is further explained by the COSMO-RS model, and it is further confirmed by analyzing the binding energy. The solubility of methyl chloride in [EMIM][BF4] and TEG and [EMIM][BF4]+H2O was completed, and the experimental results well proved the reliability of the UNIFAC-Lei model. The unknown interaction parameters were obtained through the solubility data of this work and the experimental data in the literatures. The methyl chloride drying experiment was completed in the laboratory, and the water content of the methyl chloride can be reduced to below 200 ppm. The simulation of the methyl chloride drying process using [EMIM][BF4] or TEG as absorbents was carried out by ASPEN software on an industrial scale. The final simulation results show that the [EMIM][BF4] drying process has lower energy consumption and better drying effect.

In this study, a halotolerant yeast that is capable of efficiently decolorizing and detoxifying azo dyes was isolated, identified and characterized for coping with the treatment of azo-dye-containing wastewaters. A characterization of the yeast, including the optimization of its metabolism and growth conditions, its detoxification effectiveness and the degradation pathway of the target azo dye, as well as a determination of the key activities of the enzyme, was performed. Finally, the possible halotolerance mechanisms of the yeast were proposed through a comparative transcriptome analysis. The results show that a halotolerant yeast, A4, which could decolorize various azo dyes, was isolated from a marine environment and was identified as Meyerozyma guilliermondii. Its optimal conditions for dye decolorization were ≥1.0 g/L of sucrose, ≥0.2 g/L of (NH4)2SO4, 0.06 g/L of yeast extract, pH 6.0, a temperature of 35 °C and a rotation speed of ≥160 rpm. The yeast, A4, degraded and detoxified ARB through a series of steps, relying on the key enzymes that might be involved in the degradation of azo dye and aromatic compounds. The halotolerance of the yeast, A4, was mainly related to the regulation of the cell wall components and the excessive uptake of Na+/K+ and/or compatible organic solutes into the cells under different salinity conditions. The up-regulation of genes encoding Ca2+-ATPase and casein kinase II as well as the enrichment of KEGG pathways associated with proteasome and ribosome might also be responsible for its halotolerance.

Phosphorus utilization by crop plants is often limited, thereby resulting in large accumulations of residual phosphorus fertilizer in the soil. Trichoderma fungi function as natural decomposition agents that can contribute to increasing decomposition and promoting nutrient absorption in plants. In this study, we developed a novel fertilizer application strategy that reduces phosphate fertilizer and increases Trichoderma and examined its effects on the growth, nutrient absorption, and fruit quality of pepper (Capsicum annuum L.). We compared the efficacies of eight treatments: P100 = standard dose application of phosphorus fertilizer; P85 = 85% dose; P70 = 70% dose; P0 = no phosphorus fertilizer; and the TP100, TP85, TP70, and TP0 treatments, in which a Trichoderma mixture was added to the P100, P85, P70, and P0 treatments, respectively. The combined fertilizer application strategy stimulated plant growth, increased chlorophyll content, improved yield, and enhanced nutrient absorption. Additionally, the strategy improved pepper fruit quality by increasing the contents of soluble proteins, soluble sugars, vitamin C, capsaicin, and capsanthin. A comprehensive analysis indicated that the TP85 treatment was the optimal fertilization regime for pepper. This study provides a novel fertilizer application strategy for pepper that not only ensures good plant growth but also protects soil health.

The spherical, hollow and tubular Fe2O3 (s, h and t) and their graphene-based nanocomposites rGO-Fe2O3 (s, h and t) were fabricated using the facile solvothermal methods. The morphologies and compositions of the as-synthesized Fe2O3 (s, h and t) and rGO-Fe2O3 (s, h and t) nanocomposites were systematically characterized by SEM, TEM, XRD, FTIR and XPS methods. Then, the effect of the catalytic performance of Fe2O3 (s, h and t) and rGO-Fe2O3 (s, h and t) nanocomposites on the thermal decomposition of ammonium perchlorate (AP) were studied by DSC method. The DSC results showed that all of the Fe2O3 (s, h and t) and rGO-Fe2O3 (s, h and t) nanocomposites can effectively promote the thermal decomposition of AP. Besides, rGO-Fe2O3(s) nanocomposite has the best catalytic performance, and the high-temperature decomposition exothermic peak of AP was significantly reduced after its mixing with rGO-Fe2O3 (s) nanocomposite. It can be seen that the effects of Fe2O3 on AP decomposition is mainly reflected in the high temperature process, while the effects of rGO-Fe2O3 (s) on AP decomposition is reflected in both high and low temperature stages, and the effect on the high temperature stage is more significant. The excellent catalytic performance of rGO-Fe2O3 (s) nanocomposite can be attributed to the in-situ growth of Fe2O3 on the surface of rGO, which contributes to the low temperature decomposition process of AP.

Genotype imputation from BeadChip to whole-genome sequencing (WGS) data is a cost-effective method of obtaining genotypes of WGS variants. Beagle, one of the most popular imputation software programs, has been widely used for genotype inference in humans and non-human species. A few studies have systematically and comprehensively compared the performance of beagle versions and parameter settings of farm animals. Here, we investigated the imputation performance of three representative versions of Beagle (Beagle 4.1, Beagle 5.0, and Beagle 5.4), and the effective population size (Ne) parameter setting for three species (cattle, pig, and chicken). Six scenarios were investigated to explore the impact of certain key factors on imputation performance. The results showed that the default Ne (1,000,000) is not suitable for livestock and poultry in small reference or low-density arrays of target panels, with 2.47%–10.45% drops in accuracy. Beagle 5 significantly reduced the computation time (4.66-fold–13.24-fold) without an accuracy loss. In addition, using a large combined-reference panel or high-density chip provides greater imputation accuracy, especially for low minor allele frequency (MAF) variants. Finally, a highly significant correlation in the measures of imputation accuracy can be obtained with an MAF equal to or greater than 0.05.

Abstract Background Tears in Schwartz-Matsuo syndrome are generally confirmed by preoperative ophthalmoscopic examination. A case of Schwartz-Matsuo syndrome with a tear detected by ultrasound biomicroscopy (UBM) and treated by UBM-guided scleral buckling was reported, and its mechanism was analysed. Case presentation A 40-year-old Chinese man presented with blurry vision and intermittent eye pain in his left eye for three days. The visual acuity of the left eye decreased from 20/20 to 20/40, and the intraocular pressure (IOP) fluctuated dramatically from 24.0 mmHg to 56.7 mmHg at the first visit. Gonioscopy revealed that the chamber angle remained open. A macula-involving inferior retinal detachment extending from 4:30 to 9:30 with no obvious causative break was observed through ophthalmoscopic examination. However, a single small tear was detected at the nonpigmented epithelium of pars plana of the ciliary body at approximately 7–8 o’clock by UBM. The loss of photoreceptor outer segments and ellipsoid zone and the existence of macular microcysts in the inner and outer nuclear layers were observed in the detached macula by optical coherence tomography. Then, he underwent successful scleral buckling guided by UBM. Three months later, the retina was flat with normal IOP, and the best corrected visual acuity of his left eye gradually improved to 20/25. UBM confirmed the closure of the tear. Conclusions Tear of the nonpigmented epithelium of the ciliary body is a rare condition associated with Schwartz-Matsuo syndrome. UBM plays a key role in detecting occult tears of the nonpigmented epithelium of the ciliary body, guiding scleral buckling surgery, and observing the closure of the tear postoperatively.

To address the spectrum shortage issue, the technology of sharing the unlicensed spectrum resource has been developed for terrestrial wireless networks, e.g., the New Radio Unlicensed technology. Recently, due to the limitation of terrestrial wireless networks, unmanned aerial vehicles (UAVs) have been proposed to improve the coverage for users. Hence, the combination of the unlicensed spectrum band technology and the UAV communication can fulfill the requirements of offering 3-D coverage while improving the spectrum efficiency. In this paper, we investigate the terrestrial and UAV heterogeneous network (HetNet), where both the terrestrial base stations and aerial base stations implement the random mode selection procedure to use either the licensed or unlicensed spectrum band. Based on stochastic geometry, we develop a tractable mathematical framework to characterize the medium access probability and the overall coverage probability. The accuracy of the analytical evaluations is validated by simulations. Our results show that the incorporation of the licensed and unlicensed spectrum band by using the mode selection scheme can improve the overall network performance, compared with the performance of the 3-D HetNet operating in the licensed spectrum band only. Furthermore, mode selection of the aerial network plays the dominant role in improving the overall coverage probability, and the mode selection probability (i.e., the probability of switching to use the unlicensed spectrum band) has to be selected carefully to maximize the overall coverage probability.

Cancer is a major cause of death worldwide and becomes particularly threatening once it begins to metastasize. During metastasis, the blood vessels serve as pathways for cancerous cell transportation and hence are crucial for understanding cancer growth. Existing medical imaging modalities can provide 3-D contrast images of the vascular tissues but with limited quality and detailedness. A much-needed tool for cancer research is thus one that can reconstruct vascular networks from low-quality clinical images. To this end, we developed a computational framework that takes 3-D medical images as input and reconstructs complete, patient-specific vascular network models using a mathematical optimization procedure. Our framework extracts major vessels from the images and uses the organ geometry to select vessel termination points. Then, it generates the remainder network based on physiological optimality principles. Using the framework, we obtained a set of network models with over 3000 terminal segments from a brain MRA scan. We analyzed the Strahler order, vessel radius, and branch length distributions of the models, which match with actual human data. We also performed fluid dynamics simulation inside the reconstructed vessels and showed that the pressure and shear stress distributions agree with existing in vivo measurements. The qualitative and quantitative agreements in vessel morphometry and hemodynamics demonstrate the effectiveness of the framework. Our method bridges the gap between image-based vessel models, accuracy of which is limited by the resolution of clinical images, and hypothetical models.

BackgroundThe optimal surgical approach, whether transabdominal (TA) or transthoracic (TT), for Siewert type II adenocarcinoma of the esophagogastric junction (AEG) remains controversial. This study compares the efficacy of TA and TT surgical approaches for Siewert type II AEG.MethodsStudies comparing the surgical and oncological outcomes of TA and TT surgical approaches for Siewert type II AEG up to June 2021 were systematically searched on the Web of Science, PubMed, Embase, and Cochrane Library. A pooled analysis was performed for the available data regarding the baseline features, surgical, and oncological outcomes. The RevMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted.ResultsTwelve studies with a total of 2,011 patients, including 985 patients in the TA group and 1,026 patients in the TT group, were included in this study. In the pooled analysis, the surgical outcomes, namely, operative time (MD = −54.61, 95% CI = −123.76 to 14.54, P = 0.12), intraoperative blood loss (MD = −28.85, 95% CI = −71.15 to 13.46, P = 0.18), the number of dissected lymph nodes (MD = 1.90, 95% CI = −1.32 to 5.12, P = 0.25), postoperative complications (OR = 0.84, 95% CI = 0.65 to 1.07, p = 0.16), anastomotic leakage rate (OR = 1.02, 95% CI = 0.63 to 1.65, p = 0.93), and postoperative death rate (OR = 0.89, 95% CI = 0.46 to 1.72, p = 0.73), and the oncological outcomes, namely, overall recurrence rate (OR = 0.75, 95% CI = 0.37 to 1.50, p = 0.41), 3-year overall survival (OS) rate (OR = 1.19, 95% CI = 0.54 to 2.65, p = 0.66), and 5-year OS rate (OR = 1.21, 95% CI = 0.84 to 1.74, p = 0.30) of the two groups were all comparable.ConclusionsBoth TA and TT surgical approaches are appropriate for Siewert type II AEG, and neither has a significant advantage in terms of short- and long-term outcomes. However, more high-quality randomized controlled trials are needed to confirm this conclusion.

The rapid development of intelligent connected vehicles has increased the attack surface of vehicles and made the complexity of vehicle systems unprecedented. Original equipment manufacturers (OEMs) need to accurately represent and identify threats and match corresponding security requirements. Meanwhile, the fast iteration cycle of modern vehicles requires development engineers to quickly obtain cybersecurity requirements for new features in their developed systems in order to develop system code that meets cybersecurity requirements. However, existing threat identification and cybersecurity requirement methods in the automotive domain cannot accurately describe and identify threats for a new feature while also quickly matching appropriate cybersecurity requirements. This article proposes a cybersecurity requirements management system (CRMS) framework to assist OEM security experts in conducting comprehensive automated threat analysis and risk assessment and to help development engineers identify security requirements prior to software development. The proposed CRMS framework enables development engineers to quickly model their systems using the UML-based (i.e., capable of describing systems using UML) Eclipse Modeling Framework and security experts to integrate their security experience into a threat library and security requirement library expressed in Alloy formal language. In order to ensure accurate matching between the two, a middleware communication framework called the component channel messaging and interface (CCMI) framework, specifically designed for the automotive domain, is proposed. The CCMI communication framework enables the fast model of development engineers to match with the formal model of security experts for threat and security requirement matching, achieving accurate and automated threat and risk identification and security requirement matching. To validate our work, we conducted experiments on the proposed framework and compared the results with the HEAVENS approach. The results showed that the proposed framework is superior in terms of threat detection rates and coverage rates of security requirements. Moreover, it also saves analysis time for large and complex systems, and the cost-saving effect becomes more pronounced with increasing system complexity.