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Abstract Necroptosis is intimately associated with the initiation and progression of colon adenocarcinoma (COAD). However, studies on necroptosis-related genes (NRGs) and the regulating long non-coding RNAs (NRGlncRNAs) in the context of COAD are limited. We retrieved the cancer genome atlas (TCGA) to collect datasets of NRGs and NRGlncRNAs on COAD patients. The risk model constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression was then employed to identify NRGs and NRGlncRNAs with prognostic significance. Subsequently, we validated the results using gene expression omnibus (GEO) datasets from different populations, conducted Mendelian randomization (MR) analysis to explore the potential causal relationships between prognostic NRGs and COAD, and conducted cell experiments to verify the expression of prognostic NRGlncRNAs in COAD. Furthermore, we explored potential pathways and regulatory mechanisms of these prognostic NRGlncRNAs and NRGs in COAD through enrichment analysis, immune cell correlation analysis, tumor microenvironment analysis, immune checkpoint analysis, tumor sample clustering, and so on. We identified eight NRGlncRNAs (AC245100.5, AP001619.1, LINC01614, AC010463.3, AL162595.1, ITGB1-DT, LINC01857, and LINC00513) used for constructing the prognostic model and nine prognostic NRGs (AXL, BACH2, CFLAR, CYLD, IPMK, MAP3K7, ATRX, BRAF, and OTULIN) with regulatory relationships with them, and their validation was performed using GEO and GWAS datasets, as well as cell experiments, which showed largely consistent results. These prognostic NRGlncRNAs and NRGs modulate various biological functions, including immune inflammatory response, oxidative stress, immune escape, telomere regulation, and cytokine response, influencing the development of COAD. Additionally, stratified analysis of the high-risk and low-risk groups based on the prognostic model revealed elevated expression of immune cells, increased expression of tumor microenvironment cells, and upregulation of immune checkpoint gene expression in the high-risk group. Finally, through cluster analysis, we identified tumor subtypes, and the results of cluster analysis were essentially consistent with the analysis between risk groups. The prognostic NGRlncRNAs and NRGs identified in our study serve as prognostic indicators and potential therapeutic targets for COAD, providing a theoretical basis for the clinical diagnosis and treatment of COAD and offering guidance for further research.

Abstract Background Grafting with dwarf rootstock is an efficient method to control plant height in fruit production. However, the molecular mechanism remains unclear. Our previous study showed that plants with Prunus mume (mume) rootstock exhibited a considerable reduction in plant height, internode length, and number of nodes compared with Prunus persica (peach) rootstock. The present study aimed to investigate the mechanism behind the regulation of plant height by mume rootstocks through transcriptomic and metabolomic analyses with two grafting combinations, ‘Longyan/Mume’ and ‘Longyan/Peach’. Results There was a significant decrease in brassinolide levels in plants that were grafted onto mume rootstocks. Plant hormone signal transduction and brassinolide production metabolism gene expression also changed significantly. Flavonoid levels, amino acid and fatty acid metabolites, and energy metabolism in dwarf plants decreased. There was a notable upregulation of PmLBD3 gene expression in plant specimens that were subjected to grafting onto mume rootstocks. Auxin signalling cues promoted PmARF3 transcription, which directly controlled this upregulation. Through its binding to PmBAS1 and PmSAUR36a gene promoters, PmLBD3 promoted endogenous brassinolide inactivation and inhibited cell proliferation. Conclusions Auxin signalling and brassinolide levels are linked by PmLBD3. Our findings showed that PmLBD3 is a key transcription factor that regulates the balance of hormones through the auxin and brassinolide signalling pathways and causes dwarf plants in stone fruits.

Abstract Cancer stem cells (CSCs), a small subset of cells in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, and maintain tumor heterogeneity. Cancer continues to be a significant global disease burden. In the past, surgery, radiotherapy, and chemotherapy were the main cancer treatments. The technology of cancer treatments continues to develop and advance, and the emergence of targeted therapy, and immunotherapy provides more options for patients to a certain extent. However, the limitations of efficacy and treatment resistance are still inevitable. Our review begins with a brief introduction of the historical discoveries, original hypotheses, and pathways that regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, and their crosstalk. We focus on the role of CSCs in various therapeutic outcomes and resistance, including how the treatments affect the content of CSCs and the alteration of related molecules, CSCs-mediated therapeutic resistance, and the clinical value of targeting CSCs in patients with refractory, progressed or advanced tumors. In summary, CSCs affect therapeutic efficacy, and the treatment method of targeting CSCs is still difficult to determine. Clarifying regulatory mechanisms and targeting biomarkers of CSCs is currently the mainstream idea.

Abstract Background Multiple species of the genera Cytauxzoon and Hepatozoon can infect wild felines, but the diversity of these and other apicomplexan parasites in Eurasian lynx is scarcely known. The aim of this study was to detect Cytauxzoon and Hepatozoon species with molecular methods in Eurasian lynxes and their ticks in northwestern China. Methods DNA was extracted from the heart, liver, spleen, lung, and kidney samples of three Eurasian lynxes as well as from their five ixodid ticks. These DNA samples were screened with polymerase chain reactions (PCRs) for Cytauxzoon with the partial cytochrome b gene (CytB), cytochrome c oxidase subunit I gene (COI), and small subunit ribosomal RNA gene (18S rRNA), and Hepatozoon with three different fragments of small subunit ribosomal RNA gene (18S rRNA). PCR products were sequenced, aligned, and phylogenetically analyzed. Results One adult female of Eurasian lynx (#1, adult female) was co-infected with Cytauxzoon manul and Hepatozoon felis genotype I, while an adult male lynx (#2) was infected with C. manul. Interestingly, H. felis genotype I was both detected in a male cub (#3) and two out of five infesting Hyalomma asiaticum ticks. Conclusions For the first time, Cytauxzoon manul is reported here from Eurasian lynx. In addition, H. felis has not been known to occur in this host species in China and Central Asia. Thus, the findings of this study extend our knowledge on the geographical distribution and host range of these haemoprotozoan parasites. Moreover, this is also the first evidence of C. manul and H. felis co-infection in Eurasian lynx. Graphical Abstract

IntroductionSubjective cognitive decline (SCD) and mild cognitive impairment (MCI) are stages 2 and 3, respectively, of the Alzheimer’s continuum. The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog’s) ten-words recall test is a validated method for the early detection of cognitive impairment in Alzheimer’s disease. However, limited studies have investigated its ability to differentiate between SCD and MCI.Methods203 participants with SCD and 62 participants with MCI underwent multiple neuropsychological assessments. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MOCA-B) served as brief global cognition tests. A binary logistic regression model was used to analyze the potential factors affecting MCI. The accuracy of the ten-words recall test was assessed using the area under the receiver operating characteristic (ROC) and the area under the curve (AUC).ResultsThe neuropsychological assessment revealed significant differences in the ten-words recall test scores between the SCD (median age 61 years; 70.44% female) and MCI (median age 64 years; 61.29% female) groups (p < 0.001), with the MCI group scoring the highest. Using a cut-off value of 3.15 for the ten-words recall test, sensitivity for distinguishing MCI from SCD reached 87%, while specificity stood at 61% (AUC 0.777, p < 0.001). DeLong’s test indicated no statistically significant difference in the ten-words recall test’s ability to distinguish between SCD and MCI compared to the total score of ADAS-Cog (AUC 0.833, p) and MMSE (AUC 0.784, p > 0.05). However, a significant difference was observed when compared to MoCA-B (AUC 0.973, p < 0.001). In the population with an education level of ≤ 9 years, the optimal cut-off value for the ten-words recall test was 3.15, yielding a sensitivity of 91% and a specificity of 45% (AUC = 0.674, p = 0.030). In the population with an education level > 9 years, the optimal cut-off value was 3.63, resulting in a sensitivity of 79% and a specificity of 71% (AUC = 0.785, p < 0.001).DiscussionThe ten-words recall test from the ADAS-cog may detect MCI early owing to its simplicity and quick administration. It is an effective and convenient tool for rapidly identifying mild cognitive impairment.

Summary: The stop signal is produced in response to negative experiences at the food source and inhibits honey bee (Apis mellifera) waggle dancing. Here, we present a protocol for measuring the effects of an inhibitory signal associated with danger on honey bee dopamine levels. We describe steps for observing honey bee colonies, training them with artificial nectar, and simulating hornet attacks. We then detail procedures for recording waggle dancing and stop signals and measuring brain dopamine levels during different treatments.For complete details on the use and execution of this protocol, please refer to Dong et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

This paper reviews the potential of gamified cultural heritage in immersive virtual exhibitions. A systematic literature review following PRISMA guidelines identified 78 relevant papers from ACM and IEEE databases. Gamification and immersive technologies can provide interactive experiences to engage visitors and enhance their understanding of exhibits’ historical and cultural significance. Theoretical frameworks, including gamification theory, heritage interpretation theory, participatory heritage, immersive experience theory, and pedagogy, guide designing compelling experiences. Case studies like “Rome Reborn”, “Sutton House Stories”, and “Assassin’s Creed: Origins” demonstrate the efficacy of gamification in disseminating heritage. Key strategies include integrating augmented/virtual reality, multimodal data and 3D reconstruction, interactive narratives and gameplay, personalized experiences, advanced interfaces, balancing education and entertainment, and ensuring cultural sensitivity. Future work can explore AI-adaptive experiences, AR/VR integration, remote collaboration, educational game elements, and digital creativity models. Gamification and immersion provide innovative preservation and inheritance of cultural heritage. This review promotes digitalization and identifies literature gaps, supporting reflection on engagement’s past, present, and future. It aims to enable a broader appreciation of cultural heritage through technology.

Abstract Despite its effectiveness in treating diabetic cardiomyopathy (DCM), Qigui Qiangxin Mixture (QGQXM) remains unclear in terms of its active ingredients and specific mechanism of action. The purpose of this study was to explore the active ingredients and mechanism of action of QGQXM in the treatment of DCM through the comprehensive strategy of serum pharmacology, network pharmacology and combined with experimental validation. The active ingredients of QGQXM were analyzed using Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS). Network pharmacology was utilized to elucidate the mechanism of action of QGQXM for the treatment of DCM. Finally, in vivo validation was performed by intraperitoneal injection of STZ combined with high-fat feeding-induced DCM rat model. A total of 25 active compounds were identified in the drug-containing serum of rats, corresponding to 121 DCM-associated targets. GAPDH, TNF, AKT1, PPARG, EGFR, CASP3, and HIF1 were considered as the core therapeutic targets. Enrichment analysis showed that QGQXM mainly treats DCM by regulating PI3K-AKT, MAPK, mTOR, Insulin, Insulin resistance, and Apoptosis signaling pathways. Animal experiments showed that QGQXM improved cardiac function, attenuated the degree of cardiomyocyte injury and fibrosis, and inhibited apoptosis in DCM rats. Meanwhile, QGQXM also activated the PI3K/AKT signaling pathway, up-regulated Bcl-2, and down-regulated Caspase9, which may be an intrinsic mechanism for its anti-apoptotic effect. This study preliminarily elucidated the mechanism of QGQXM in the treatment of DCM and provided candidate compounds for the development of new drugs for DCM.

The Yaogou landslide, located in Zhushan County, Hubei Province, exhibits distinctive aquifer characteristics and varying permeability, leading to the retention of groundwater within the landslide after rainfall, forming confined water. This kind of landslide aquifer underlying weakly permeable rock and soil mass is called a “stagnant water structure”. By monitoring a two-year dataset of rainfall, groundwater level, water content and displacement of the Yaogou landslide, it was found that the confined water head of the landslide fell slowly with the sharp rise of rainfall, which showed an obvious "stagnant water" pattern. Geostudio software was used to simulate the rainfall infiltration process, and it was verified that the sliding body was subjected to the action of confined water, and the lifting amplitude and acting position of confined water were basically consistent with the observed situation. The landslide stability coefficient and pressure head exhibited a reverse curve with a consistent curvature. It showed that the "water stagnation structure" of the landslide had a significant controlling effect on the formation of confined water head and the stability of landslide. This emphasizes the significant control exerted by the "water stagnation structure" on confined water head formation and landslide stability.

Abstract Background Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes. Methods We generated Morn2 –/– mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc. Results The Morn2 –/– mice were infertile, and their sperm showed severe motility defects. Morn2 –/– sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity. Conclusions Our study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.

Porcine epidemic diarrhea virus (PEDV) causes diarrhea and vomiting in piglets, leading to a mortality rate of 100%. Due to the high frequency of mutation, it is important to monitor the evolution of PEDV and develop potential vaccine candidates. In this study, two PEDV strains (ZJ2022 and ZQ2022) were identified by PCR. These strains were subsequently isolated, and their genome sequences, growth characteristics, and pathogenicity were compared. Phylogenetic and recombination analyses revealed that both strains belonged to GIIa-subgroup, and ZQ2022 was identified as a recombinant strain derived from ZJ2022. Further sequence analysis showed that the ZJ2022 strain had a modified top region of the S1 protein due to a three amino acid insertion (T380_Y380insGGE) in the S1 gene. According to the virus growth curve, ZJ2022 exhibited better cellular adaptation than ZQ2022, with higher viral titers from 8 hpi to 24 hpi. Additionally, ZQ2022 exhibited a high level of pathogenicity, causing severe diarrhea in piglets at 36 hpi and a 100% mortality rate by 96 hpi. In contrast, ZJ2022 showed lower pathogenicity, inducing severe diarrhea in piglets at 60 hpi, with a mortality rate of 60% at 96 hpi and 100% at 120 hpi. In summary, our findings provided evidence of the undergoing mutations in Chinese PEDV strains. Furthermore, the S gene insertion strain ZJ2022 exhibited strong cellular adaptability and low pathogenicity, making it a potential candidate strain for vaccine development.

The emergence of the digital information age has sparked considerable interest in predictive analytics within the realm of finance. Predicting uncertainty lies at the heart of Financial Engineering, where crafting investment or trading strategies using suitable prediction methods can optimize profits. This paper provides a novel work that approves the application of computer deep learning neural network has ability to predict volatility of the Black-Scholes model and its derivatives. Employing a data-driven methodology, deep learning neural networks are utilized for volatility prediction, investigating their potential to enhance the accuracy of stock volatility forecasts and options pricing. Subsequently, the forecasted outcomes are leveraged for designing and executing hedging strategies, leading to the creation of three delta hedging approaches based on the anticipated stock volatility. The effectiveness of deep learning neural networks in volatility prediction is demonstrated, showcasing their ability to dynamically capture volatility shifts and outperform traditional models in forecasting accuracy.

The objective of the study is to analyze the implementation effect of the Live Attenuated Varicella Vaccine (VarV) Vaccination Program for eligible children in Bao’an District, Shenzhen, and evaluate the vaccine effectiveness. Children’s vaccination data was obtained from the Shenzhen Immunization Planning Information Management System, while varicella case data came from the China Disease Prevention and Control Information System. The Joinpoint regression method examined vaccination rate trends, and a retrospective cohort study assessed vaccine effectiveness. After program implementation, VarV vaccination rates significantly increased, surpassing provincial and national averages. Overall incidence declined 54.6% across age groups, with the largest reductions among 7- and 6-year-olds. One year post-vaccination, single-dose vaccine effectiveness was 91.1% (95% CI: 79.2% to 96.2%). However, two doses remained 91.4% effective(95% CI: 89.1% to 93.2%) after 7 years. Overall, Shenzhen’s VarV program achieved positive results. For children under six, routine immunization with two doses of VarV should be strengthened. Furthermore, we recommend that physicians conduct thorough inquiries to ascertain patients’ vaccination history and previous varicella infections. This will enable doctors to provide tailored vaccination recommendations based on comprehensive, practical evaluations.

ABSTRACTTo evaluate the performance of “Vaccination Rates Monitoring Report System” implemented by Shenzhen CDC, we conducted an analysis of the data quality and identify key areas for system improvement. Following evaluation guidelines provided by WHO and United States CDC, we established six evaluation attributes: representativeness, simplicity, acceptability, data reliability, stability and timeliness. In eastern, central and western regions of Shenzhen, we selected one district from each region, of which the local CDC and ten CHSCs under jurisdiction were chosen for evaluation. On-site inspections, questionnaires survey and interviews were utilized for data collection, while the Likert scale method was used for attributes rating evaluation. A total of 70 participants were surveyed, consisting of 60 CHSCs and 10 CDCs staff. The gender ratio was 1:2.5 (males to females), with the majority falling within the 25–34 age range (46%). Most participants held full-time positions (80%) and had more than 5 years of work experience (62%). The system achieved 100% coverage of all CHSCs and CDCs (100%). The cumulative percentage scores for the overall favorable options of simplicity, acceptability, data reliability, stability, and timeliness were 79%, 85%, 73%, 50%, and 71% respectively. The system operates normally with strong representativeness. Acceptability was rated as “good.” Simplicity, data reliability, and system timeliness were rated as “average,” while system stability was rated as “poor.” Based on these survey results, developers should urgently investigate reasons for poor stability, particularly addressing concerns from CHSCs users. Additionally, the issues and shortcomings identified in other attributes should also be gradually improved.

Abstract Introduction First‐line osimertinib plus chemotherapy significantly prolonged progression‐free survival of patients with EGFR‐mutated advanced non‐small cell lung cancer (NSCLC) compared to osimertinib, according to the FLAURA2 trial. Methods We established a Markov model to compare the cost‐effectiveness of osimertinib plus chemotherapy with that of osimertinib alone. Clinical data were obtained from the FLAURA and FLAURA2 trials, and additional data were extracted from online resources and publications. Sensitivity analyses were conducted to evaluate the robustness of the findings. We used A willingness‐to‐pay threshold of $150,000 per quality‐adjusted life‐years (QALYs) gained. The main outcomes were QALYs, overall costs, incremental cost‐effectiveness ratio (ICER), incremental net monetary benefit, and incremental net health benefit. Subgroup analyses were conducted according to patients' mutation type and central nervous system (CNS) metastatic status. Results In a 20‐year time horizon, the ICER of osimertinib plus chemotherapy versus osimertinib alone was $223,727.1 per QALY gained. The sensitivity analyses identified the cost of osimertinib and the hazard ratio for overall survival as the top 2 influential factors and a 1.9% probability of osimertinib plus chemotherapy to be cost‐effective. The subgroup analyses revealed ICERs of $132,614.1, $224,449.8, $201,464.1, and $130,159.7 per QALY gained for L858R mutations, exon 19 deletions, CNS metastases, and no CNS metastases subgroups, respectively. Conclusions From the perspective of the United States health care system, osimertinib plus chemotherapy is not cost‐effective compared to osimertinib alone for treatment‐naïve patients with EGFR‐mutated advanced NSCLC, but more favorable cost‐effectiveness occurs in patients with L858R mutations and patients without baseline CNS metastases.

Abstract The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre‐mRNA alternative splicing (AS) at the post‐transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA‐seq and LACE‐seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre‐mRNA splicing during the early steps of spermatogenesis.

This study investigates the impact of city healthcare resources on immigrants’ employment quality. It has implications for promoting equity in the distribution of healthcare resources, which is critical for immigrants’ survival and settlement. Moreover, the relationship between healthcare resources and employment quality is equally relevant to developing-country urbanization. Using data from the China Migrants Dynamic Survey (CMDS) from 2016 to 2018, we demonstrate the effect of healthcare resources on employment quality. Cities’ healthcare resources are significantly correlated with immigrants’ quality of employment. The more healthcare resources are available, the higher the income from work, the shorter the working hours, and the more stable the employment of immigrants. The quality-enhancing effect of healthcare resources on employment quality is substantial among immigrants with health training and medical files. Urban medical insurance has important differentiating implications for immigrants’ access to healthcare resources. Healthcare resources enhance the employment quality of immigrants by improving their health status and integration into local society. Promoting equalizing healthcare resources and adjusting the differences between urban and rural medical insurance systems increase immigrant employment quality.

BackgroundAnxiety, depression, and sleep problems are prevalent comorbid mental disorders among university students. The World Health Organization (WHO) emphasized a mental health promotion objective, recommending the consideration of protective health-promoting factors in strategies aimed at preventing mental disorders. Integrating theoretically significant constructs (such as protective factors) enhances our comprehension of the intricate mechanisms that underpin mental disorders. This study employed network analysis to first identify core and bridge symptoms within comorbid mental disorders and then explore how health-promoting lifestyles (HPLs) were associated with these disorders. The ultimate goal is to offer health promotion recommendations to enhance students’ quality of life.MethodsA total of 3,896 qualified university students participated in this study. Anxiety, depression, sleep problems, and HPLs were assessed using the GAD-7, PHQ-9, PSQI, and HPLP-II scales. A Gaussian Graphical Model was used to construct the networks. The Network Comparison Test was applied to determine whether the associations between HPLs and comorbid symptoms vary by gender, educational level, family sibling, and mental health status.ResultsLow energy (PHQ4) had the highest strength centrality, followed by Daytime dysfunction (PSQI7) and Trouble relaxing (GAD4). Five bridge symptoms were identified: Daytime dysfunction (PSQI7), Self-harm even suicide (PHQ9), Sad mood (PHQ2), Low energy (PHQ4), and Feeling afraid (GAD7). Regarding protective HPLs, Physical activity, Spiritual growth, and Stress management generally emerged as the top three central mental health-promoting behaviors.ConclusionTargeting core and bridge symptoms with timely and appropriate interventions can alleviate anxiety, depression, and sleep problems in this population. Moreover, promoting physical activity, fostering spiritual growth, and managing stress are likely to significantly enhance the overall mental health of university students.

Novel semiconductor material with both high strength and ductility is urgently needed to meet the demands of increasing complex applications for electronic components. However, overcoming the inherent trade-off between strength and ductility has remained a longstanding challenge in materials science research. Herein, we proposed a three-dimensional carbon allotrope, oc-C24 with pure sp2 hybridization. This structure comprises arrays of carbon chains in an “8”-shape helix configuration, in between the C-chains which interlinked by the oriented ethylene with a planar π-conjugation. The distinctive structural unit imbues oc-C24 with remarkable tensile behavior, characterized by multi-stage chemical bond rearrangements and structural phase transitions along [010] crystallographic direction, displaying multi-level stress re-enhancement phenomena. A tensile strength of 104.2 GPa and a record strain of 1.05 are observed along [010] direction. Electronic band analysis reveals that oc-C24 is a semiconductor with an indirect band gap of 2.91 eV. The impressive tensile resistance and ductility of oc-C24 suggest its strong potential applications in electronic devices under extreme conditions. Our findings offer valuable insights and methodological strategies for designing novel carbon allotropes with unique mechanical responses.

Abstract Understanding how age and body size vary across elevations can provide insights into the evolution of life‐history traits in animals. In the present study, we compared the demographic (using skeletochronology) and morphological traits of the Tibetan toad (Bufo tibetanus) between two populations from different elevational habitats (2650 vs. 3930 m). We found that (1) the mean age and body size of females were significantly greater than those of males in both populations; (2) both sexes of toads from the higher elevation tended to be significantly older in age and larger in body size; (3) there was a significant positive relationship between age and body size within each sex of the toad at both elevations; and (4) growth rates varied between the two populations, with the higher rate observed in the lower‐elevation population. Our results suggested that factors other than age, such as elevation‐associated temperature, influence the observed differences in body size between the two populations. Future research at a broader range of elevations should focus on these factors and evaluate their influence on animal growth patterns.

Pyrrolizidine alkaloids (PAs) and their N-oxide (PANOs), as emerging environmental pollutants and chemical hazards in food, have become the focus of global attention. PAs/PANOs enter crops from soil and reach edible parts, but knowledge about their uptake and transport behavior in crops is currently limited. In this study, we chose tea (Camellia sinensis L.) as a representative crop and Sp/SpNO as typical PAs/PANOs to analyze their root uptake and transport mechanism. Tea roots efficiently absorbed Sp/SpNO, utilizing both passive and active transmembrane pathways. Sp predominantly concentrated in roots and SpNO efficiently translocated to above-ground parts. The prevalence of SpNO in cell-soluble fractions facilitated its translocation from roots to stems and leaves. In soil experiment, tea plants exhibited weaker capabilities for the uptake and transport of Sp/SpNO compared to hydroponic conditions, likely due to the swift degradation of these compounds in the soil. Moreover, a noteworthy interconversion between Sp and SpNO in tea plants indicated a preference for reducing SpNO to Sp. These findings represent a significant stride in understanding the accumulation and movement mechanisms of Sp/SpNO in tea plants. The insights garnered from this study are pivotal for evaluating the associated risks of PAs/PANOs and formulating effective control strategies.

Controlling intracranial pressure, nerve cell regeneration, and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury. There is currently a lack of effective treatment methods. Hibernation has the characteristics of low temperature, low metabolism, and hibernation rhythm, as well as protective effects on the nervous, cardiovascular, and motor systems. Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body's metabolism, lowering the body's core temperature, and allowing the body to enter a state similar to hibernation. This review introduces artificial hibernation technology, including mild hypothermia treatment technology, central nervous system regulation technology, and artificial hibernation-inducer technology. Upon summarizing the relevant research on artificial hibernation technology in acute brain injury, the research results show that artificial hibernation technology has neuroprotective, anti-inflammatory, and oxidative stress-resistance effects, indicating that it has therapeutic significance in acute brain injury. Furthermore, artificial hibernation technology can alleviate the damage of ischemic stroke, traumatic brain injury, cerebral hemorrhage, cerebral infarction, and other diseases, providing new strategies for treating acute brain injury. However, artificial hibernation technology is currently in its infancy and has some complications, such as electrolyte imbalance and coagulation disorders, which limit its use. Further research is needed for its clinical application.

Aggressive behavior is an important indicator of chicken welfare assessment. At present, the aggressive behavior of chickens typically requires human observation for welfare assessment, and the assessment results are influenced by the subjective judgment of humans. This paper proposes an aggressive chicken behavior identification method based on a hybrid strategy improved Sparrow Search Algorithm combined with Support Vector Machine (ISSA-SVM). Nine-axis inertial sensors were used to collect the behavioral data of chickens. A total of 231-dimensional feature data in the time and frequency domains of the behavioral data were extracted through a 1 s sliding window. To reduce feature redundancy, the initial population is initialized using circle chaotic mapping instead of random initialization of the original sparrow algorithm to increase the uniformity of the initial population distribution in the feature space; adaptive weights are introduced to increase the search range of the early iteration, and the global optimal solution of the previous generation is introduced to improve the global search capability of the algorithm; the optimal solution is perturbed using the dimension-by-dimension mutation strategy of adaptive t-distribution to increase the diversity of the feature distribution. ISSA-SVM reduced the feature dimensionality from 231 to 17, indicating a reduction of 92.6%. The recognition overall accuracy of ISSA-SVM for aggressive chicken behavior was 94.27%, which improved by 1.33% compared to SVM. The results of the experiment show that of all the aggressive chicken behaviors during the 5-day experiment, fighting behavior occurred most frequently from 11:00 to 13:00 and from 17:00 to 18:00. This study provides a method for the automatic identification of aggressive chicken behavior and can serve as an informational tool for poultry welfare assessment.

Abstract In recent years, the emergence of the squeezed branch pile has presented a new avenue for civil engineering, offering a distinctive structure and favorable mechanical characteristics. Squeezed branch piles have strong compressive, uplift, and horizontal load resistance capabilities. Due to the existence of discs, the geometric parameters of squeezed branch piles are abundant but important. This article selects number of discs, disc diameter, disc squeeze angle, and disc spacing as the main influencing factors on the bearing capacity of squeezed branch piles and conducts a qualitative analysis of their mechanical properties. The aim of this article is to analyze the different bearing performances of squeezed branch piles through orthogonal experimental design, simulate test conditions using finite element software ABAQUS, obtain relevant data, and finally determine the weight ranking and optimal combination of influencing factors through range analysis to provide better guidance for engineering practices. Through multi-objective optimization design, six optimization objectives including compressive performance, compressive economic efficiency, uplift performance, uplift economic efficiency, maximum horizontal displacement and maximum bending moment of pile body were analyzed. The analysis methods used included comprehensive balance method, queue scoring method, principal component analysis method, entropy weight method, and analytic hierarchy process. The conclusions obtained are similar, and based on the judgment, the squeezed branch pile with 4 discs, disc diameter of 2.5D, disc squeeze angle of 35°, and disc spacing of 3D is considered as the optimal combination under consideration of all optimization objectives.

The demand for psychological counselling has grown significantly in recent years, particularly with the global outbreak of COVID-19, which heightened the need for timely and professional mental health support. Online psychological counselling emerged as the predominant mode of providing services in response to this demand. In this study, we propose the Psy-LLM framework, an AI-based assistive tool leveraging large language models (LLMs) for question answering in psychological consultation settings to ease the demand on mental health professions. Our framework combines pre-trained LLMs with real-world professional questions-and-answers (Q&A) from psychologists and extensively crawled psychological articles. The Psy-LLM framework serves as a front-end tool for healthcare professionals, allowing them to provide immediate responses and mindfulness activities to alleviate patient stress. Additionally, it functions as a screening tool to identify urgent cases requiring further assistance. We evaluated the framework using intrinsic metrics, such as perplexity, and extrinsic evaluation metrics, including human participant assessments of response helpfulness, fluency, relevance, and logic. The results demonstrate the effectiveness of the Psy-LLM framework in generating coherent and relevant answers to psychological questions. This article discusses the potential and limitations of using large language models to enhance mental health support through AI technologies.

Abstract Background Patients with Alzheimer’s disease (AD) often exhibit neuropsychiatric symptoms (NPS), particularly delusions. Previous studies have shown an association between white matter hyperintensities (WMH) and specific NPS. This study aims to explore the relationship between WMH volume and delusions in AD patients by comparing the WMH volumes of delusional and non-delusional subgroups. Methods 80 AD patients were divided into a delusion group (n = 36) and a non-delusion group (n = 44) based on the Neuropsychiatric Inventory (NPI). The brain cortical volume and WMH volume were quantitatively calculated for all 80 patients, including total WMH volume, periventricular WMH (PVWMH) volume, deep WMH volume, as well as bilateral frontal lobe, temporal lobe, parietal lobe, and occipital lobe WMH volumes. Firstly, we compared the differences in WMH volumes between the delusion group and non-delusion group. Then, within the delusion group, we further categorized patients based on severity scores of their delusional symptoms into mild (1 point), moderate (2 points), or severe groups (3 points). We compared the WMH volumes among these three groups to investigate the role of WMH volume in delusional symptoms. Results There was a significant difference in left occipital lobe WMH volume between the delusion group and non-delusion group(P

Abstract Autism spectrum disorder (ASD) is a complex disorder of neurodevelopment, the function of long noncoding RNA (lncRNA) in ASD remains essentially unknown. In the present study, gene networks were used to explore the ASD disease mechanisms integrating multiple data types (for example, RNA expression, whole-exome sequencing signals, weighted gene co-expression network analysis, and protein-protein interaction) and datasets (five human postmortem datasets). A total of 388 lncRNAs and five co-expression modules were found to be altered in ASD. The downregulated co-expression M4 module was significantly correlated with ASD, enriched with autism susceptibility genes and synaptic signaling. Integrating lncRNAs from the M4 module and microRNA (miRNA) dysregulation data from the literature identified competing endogenous RNA (ceRNA) network. We identified the downregulated mRNAs that interact with miRNAs by the miRTarBase, miRDB, and TargetScan databases. Our analysis reveals that MIR600HG was downregulated in multiple brain tissue datasets and was closely associated with 9 autism-susceptible miRNAs in the ceRNA network. MIR600HG and target mRNAs (EPHA4, MOAP1, MAP3K9, STXBP1, PRKCE, and SCAMP5) were downregulated in the peripheral blood by quantitative reverse transcription polymerase chain reaction analysis (false discovery rate

Summary: Spermiogenesis defines the final phase of male germ cell differentiation. While multiple deubiquitinating enzymes have been linked to spermiogenesis, the impacts of deubiquitination on spermiogenesis remain poorly characterized. Here, we investigated the function of UAF1 in mouse spermiogenesis. We selectively deleted Uaf1 in premeiotic germ cells using the Stra8-Cre knock-in mouse strain (Uaf1 sKO), and found that Uaf1 is essential for spermiogenesis and male fertility. Further, UAF1 interacts and colocalizes with USP1 in the testes. Conditional knockout of Uaf1 in testes results in disturbed protein levels and localization of USP1, suggesting that UAF1 regulates spermiogenesis through the function of the deubiquitinating enzyme USP1. Using tandem mass tag-based proteomics, we identified that conditional knockout of Uaf1 in the testes results in reduced levels of proteins that are essential for spermiogenesis. Thus, we conclude that the UAF1/USP1 deubiquitinase complex is essential for normal spermiogenesis by regulating the levels of spermiogenesis-related proteins.

Eurasian lynx (Lynx lynx) is widely distributed in various habitats in Asia and Europe, and it may harbor multiple pathogens. Currently, the information on protozoan infection in Eurasian lynx is scarce. In this study, we performed nested polymerase chain reaction (nPCR) analysis to detect intestinal protozoan infection in three dead Eurasian lynxes, in northwestern China. Three dead Eurasian lynxes, an adult female (#1), an adult male (#2), and a cub male (#3), were sampled in West Junggar Mountain, the northwestern region of Xinjiang Uyghur Autonomous Region. The intestine samples were analyzed using nPCR. We used primers targeting the cytochrome C oxidase subunit I gene (COI) for detection of Sarcocystis and Eimeria species and targeting the small subunit 18 S ribosomal RNA gene (18S rRNA) for detection of Cystoisospora species. The nPCR-positive products were sequenced, aligned, and phylogenetically analyzed. Three intestinal protozoa, Sarcocystis albifronsi, Eimeria alpacae, and Cystoisospora felis, were found in three Eurasian lynxes. The intestine sample of Eurasian lynx #2 was detected with S. albifronsi and E. alpacae. In addition, C. felis was only found in the intestine sample of Eurasian lynx #3. To the best of our knowledge, S. albifronsi and E. alpacae were detected in Eurasian lynx for the first time. In addition, C. felis was firstly found in Eurasian lynx in China. These findings extend our knowledge of the geographical distribution and host range of intestinal protozoa.

The paper investigates language transfers in third language acquisition of Chinese by native German and English speakers at intermediate level. Subjects are divided into two groups and complete a Grammaticality Judgment and Correction Task through a behavioral experiment online. The results from multiple sources show that: (1) both L1 and L2 are sources of language transfers and the perceived crosslinguistic similarity of abstract structural properties serves as the main reason; (2) language transfers can be non-facilitative on L3 learning; (3) as L3 proficiency level improves, the less likely learners are to be affected by non-facilitative language transfers in L3 learning, but it may not disappear completely; (4) the background language with higher proficiency level is more likely to impose language transfers in L3 learning. The research suggests that language transfers in TLA are simultaneously regulated by a number of factors, such as similarities of abstract structural properties between background languages and L3, as well as language proficiency levels. At the end, we discuss the application of the results to Chinese language teaching.

Abstract Background Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. Methods Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. Results Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. Conclusions Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract

Flood disasters occur frequently in semi-arid and sub-humid mountain watersheds, and their formation mechanism is affected by many factors, resulting in low simulation accuracy. The main purpose of this study is to evaluate the impact of adding actual river channel data on the accuracy of flood simulation. In order to obtain higher-resolution terrain data, an unmanned aerial vehicle (UAV) was used to survey the study area. Taking the Liulin Watershed in Xingtai City, Hebei Province as the research area, the HEC-HMS hydrological model and the HEC-HMS and HEC-RAS coupling model were constructed, respectively, to simulate 26 flood events during the period from 1982 to 2016. The results indicate that the coupled model can reflect the evolution process of river floods. When simulating certain major flood events, the percentage of flood peak error and Nash–Sutcliffe efficiency coefficient (NSE) have improved, such as the NSE of No. 160812 floods increasing from 0.9 to 0.95. However, the simulation accuracy of these two models for small floods in the watershed is relatively low. Future research should focus on how to accurately evaluate the parameter curve number (CN) of the watershed before rainfall and obtain more accurate runoff yield. HIGHLIGHTS This paper analyzes the difference in flood simulation accuracy between the hydrological model and the hydrological–hydrodynamic coupling model.; The high-precision DEM data in this study was obtained based on UAV.; This method can also be used for other similar hilly small watersheds.; The results are helpful in optimizing flood forecasting methods for small watersheds in mountainous areas.;

We investigated the effects of ultrasound-assisted ethylenediaminetetraacetic acid (EDTA) and citric acid (CA) washing on heavy metal (HM) removal, residual HM mobility, and sewage sludge quality. EDTA and CA washing of sewage sludge successfully reduced the total concentration of HMs after one round of washing, but the mobility of residual HMs increased significantly. The eluate had a high concentration of HMs and nutrients (nitrogen, phosphorus, potassium, and total organic carbon), although the nutritional content of the sludge remained high. The three-phase ratio of the sludge after six rounds of washing by CA was closest to the ideal three-phase ratio, and the degree of influence on the physical structure of the soil after a land application was reduced, according to the fluctuation of generalized soil structure index (GSSI) and soil three-phase structure distance (STPSD) values. The results indicate that CA as an environmental-friendly washing agent can be the superior choice for sludge HM washing; single washing of sewage sludge may increase the mobility of residual HMs, so multiple washings should be considered for land application of sludge. HIGHLIGHTS Ultrasound-assisted chemical washing is a useful and efficient solution to remove HMs from sewage sludge.; The higher concentration (≥0.4 M) of biodegradable CA eluent could effectively reduce HMs in the sewage sludge compared to the traditional non-biodegradable EDTA eluent.;

Abstract There is tremendous interest in employing collective excitations of the lattice, spin, charge, and orbitals to tune strongly correlated electronic phenomena. We report such an effect in a ruthenate, Ca3Ru2O7, where two phonons with strong electron-phonon coupling modulate the electronic pseudogap as well as mediate charge and spin density wave fluctuations. Combining temperature-dependent Raman spectroscopy with density functional theory reveals two phonons, B 2 P and B 2 M, that are strongly coupled to electrons and whose scattering intensities respectively dominate in the pseudogap versus the metallic phases. The B 2 P squeezes the octahedra along the out of plane c-axis, while the B 2 M elongates it, thus modulating the Ru 4d orbital splitting and the bandwidth of the in-plane electron hopping; Thus, B 2 P opens the pseudogap, while B 2 M closes it. Moreover, the B 2 phonons mediate incoherent charge and spin density wave fluctuations, as evidenced by changes in the background electronic Raman scattering that exhibit unique symmetry signatures. The polar order breaks inversion symmetry, enabling infrared activity of these phonons, paving the way for coherent light-driven control of electronic transport.

The effectiveness of road signs is hindered by obstructions, such as vegetation, mutual obstruction of signs, or the road alignment itself. The traditional evaluation of road sign recognition effectiveness is conducted through in-vehicle field surveys. However, this method has several drawbacks, including discontinuous identification, unclear positioning, incomplete coverage, and being time-consuming. Consequently, it is unable to effectively assess the recognition status of road signs at any arbitrary point within the road space. Therefore, this study employed laser scanning to construct a point-surface model, which was based on a point cloud algorithm and SLAM (Simultaneous Localization and Mapping), integrated LiDAR and inertial navigation system data, and optimized the point model after processing steps such as denoising, resampling, and three-dimensional model construction. Furthermore, a method for assessing the highway sign occlusion rate based on the picking algorithm was proposed. The algorithm was applied to an actual road environment, and the occlusion by other items was simulated. The results demonstrated the effectiveness of the method. This new method provides support for the fast and accurate calculation of road sign occlusion rates, which is of great importance for ensuring the safe traveling of vehicles.

Buses and subways are crucial modes of transportation for residents, yet frequent disturbances pose serious challenges to their daily commutes. To tackle these disruptions and boost the stability of the transportation network, it is vital to accurately measure the resilience of a bus–subway composite network under such events. Therefore, this study utilizes the generalized cost between stations as weights with which to construct a bus–subway weighted composite network. Subsequently, three indicators, namely reachability, path importance, and weighted coreness, are proposed to evaluate the significance of the nodes, thereby combining the improved CRITIC-TOPSIS method to identify the critical nodes. Then, deliberate attacks and preferential restorations are conducted on the nodes, considering their importance and the critical nodes sequences, respectively. Finally, network resilience changes are characterized by the network connectivity coefficient and global accessibility, and the network resilience is compared under different attack and recovery strategies. The research results indicate that resilience is lowest when using reachability sequences to attack and recover the network. The network’s recovery is most significant when using the critical nodes sequences. When 70% of the nodes are restored, the network’s performance is essentially fully recovered. Additionally, the resilience of a bus–subway network is higher than that of a single bus network. This study applies the generalized cost to weight the transportation network, and considers the impact of multiple factors on the ease of connectivity between the nodes, which facilitates the accurate measurement of the resilience of a bus–subway network and enhances the ability to cope with disruptions.

Abstract Objective Myasthenia gravis (MG) is an autoimmune disease leading to fatigable muscle weakness. Extra‐ocular and bulbar muscles are most commonly affected. We aimed to investigate whether facial weakness can be quantified automatically and used for diagnosis and disease monitoring. Methods In this cross‐sectional study, we analyzed video recordings of 70 MG patients and 69 healthy controls (HC) with two different methods. Facial weakness was first quantified with facial expression recognition software. Subsequently, a deep learning (DL) computer model was trained for the classification of diagnosis and disease severity using multiple cross‐validations on videos of 50 patients and 50 controls. Results were validated using unseen videos of 20 MG patients and 19 HC. Results Expression of anger (p = 0.026), fear (p = 0.003), and happiness (p

Abstract Lots of real-world optimization problems are inherently constrained multi-objective optimization problems (CMOPs), but the existing constrained multi-objective optimization evolutionary algorithms (CMOEAs) often fail to balance convergence and diversity effectively. Therefore, a novel constrained multi-objective optimization evolutionary algorithm based on three-stage multi-population coevolution (CMOEA-TMC) for complex CMOPs is proposed. CMOEA-TMC contains two populations, called mainPop and helpPop, which evolve with and without consideration of constraints, respectively. The proposed algorithm divides the search process into three stages. In the first stage, fast convergence is achieved by transforming the original multi-objective problems into multiple single-objective problems. Coarse-grained parallel evolution of subpopulations in mainPop and guidance information provided by helpPop can facilitate mainPop to quickly approach the Pareto front. In the second stage, the objective function of mainPop changes to the original problem. Coevolution of mainPop and helpPop by sharing offsprings can produce solutions with better diversity. In the third stage, the mining of the global optimal solutions is performed, discarding helpPop to save computational resources. For CMOEA-TMC, the combination of parallel evolution, coevolution, and staging strategy makes it easier for mainPop to converge and maintain good diversity. Experimental results on 33 benchmark CMOPs and a real-world boiler combustion optimization case show that CMOEA-TMC is more competitive than the other five advanced CMOEAs.

Abstract Chouioia cunea Yang 1989 is a parasitic wasp of many lepidopteran insects during their pupal stage, and has been successfully used to control pests such as the fall webworm Hyphantria cunea. Here we reported the chromosome-level genome of C. cunea by using short (MGI-SEQ), long (Oxford Nanopore), chromatin-linked (Hi-C) sequencing reads and transcriptomic data, representing the first chromosome-level genome of parasitic wasps of the family Eulophidae. The total assembly length is 171.99 Mb, containing 6 pesudo-chromosomes with a GC content of 36.89% and the scaffold/contig N50 length of 31.70/26.52 Mb. The BUSCO completeness of the assembly was estimated to be 98.7%. A total of 12,258 protein-coding genes (PCGs), 10,547 3′-UTRs, and 10,671 5′-UTRs were annotated. This high-quality genome is an important step toward a better understanding of the genomes of the Eulophidae (Chalcidoidea), and will serve as a valuable resource for analyses of phylogenetic relationships and the evolution of Hymenoptera.

Abstract The soil microbiota is critical to plant performance. Improving the ability of plant-associated soil probiotics is thus essential for establishing dependable and sustainable crop yields. Although fertilizer applications may provide an effective way of steering soil microbes, it is still unknown how the positive effects of soil-borne probiotics can be maximized and how their effects are mediated. This work aims to seek the ecological mechanisms involved in cabbage growth using bio-organic fertilizers. We conducted a long-term field experiment in which we amended soil with non-sterilized organic or sterilized organic fertilizer either containing Trichoderma guizhouense NJAU4742 or lacking this inoculum and tracked cabbage plant growth and the soil fungal community. Trichoderma-amended bio-organic fertilizers significantly increased cabbage plant biomass and this effect was attributed to changes in the resident fungal community composition, including an increase in the relative abundance and number of indigenous soil growth-promoting fungal taxa. We specifically highlight the fundamental role of the biodiversity and population density of these plant-beneficial fungal taxa in improving plant growth. Together, our results suggest that the beneficial effects of bio-organic fertilizer seem to be a combination of the biological inoculum within the organic amendment as well as the indirect promotion through effects on the diversity and composition of the soil resident plant-beneficial fungal microbiome.

Abstract Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as a revolutionary cancer treatment modality, offering long-lasting responses and survival benefits for a substantial number of cancer patients. However, the response rates to ICIs vary significantly among individuals and cancer types, with a notable proportion of patients exhibiting resistance or showing no response. Therefore, dual ICI combination therapy has been proposed as a potential strategy to address these challenges. One of the targets is TIGIT, an inhibitory receptor associated with T-cell exhaustion. TIGIT has diverse immunosuppressive effects on the cancer immunity cycle, including the inhibition of natural killer cell effector function, suppression of dendritic cell maturation, promotion of macrophage polarization to the M2 phenotype, and differentiation of T cells to regulatory T cells. Furthermore, TIGIT is linked with PD-1 expression, and it can synergize with PD-1/PD-L1 blockade to enhance tumor rejection. Preclinical studies have demonstrated the potential benefits of co-inhibition of TIGIT and PD-1/PD-L1 in enhancing anti-tumor immunity and improving treatment outcomes in several cancer types. Several clinical trials are underway to evaluate the safety and efficacy of TIGIT and PD-1/PD-L1 co-inhibition in various cancer types, and the results are awaited. This review provides an overview of the mechanisms of TIGIT and PD-1/PD-L1 co-inhibition in anti-tumor treatment, summarizes the latest clinical trials investigating this combination therapy, and discusses its prospects. Overall, co-inhibition of TIGIT and PD-1/PD-L1 represents a promising therapeutic approach for cancer treatment that has the potential to improve the outcomes of cancer patients treated with ICIs.

Abstract Purpose Stenotrophomonas maltophilia is a Gram-negative pathogen that most commonly causes hospital-acquired infections that can be extremely challenging to treat, contributing to underrecognized mortality throughout the world. The relative benefits of monotherapy as compared to combination therapy in patients diagnosed with S. maltophilia pneumonia, however, have yet to be established. Methods Data from 307 patients diagnosed with S. maltophilia hospital-acquired pneumonia (HAP) across four Chinese teaching hospitals from 2016 to 2022 were retrospectively analyzed. Results Of the analyzed patients, 55.7% (171/307) were administered combination definitive therapy, with a 30-day all-cause mortality rate of 41.0% (126/307). A propensity score weighting analysis revealed that compared with monotherapy, combination definitive therapy was associated with a comparable 30-day mortality risk in the overall patient cohort (OR 1.124, 95% CI 0.707–1.786, P = 0.622), immunocompetent patients (OR 1.349, 95% CI 0.712–2.554, P = 0.359), and patients with APACHE II scores

BackgroundIn medical imaging, the integration of deep-learning-based semantic segmentation algorithms with preprocessing techniques can reduce the need for human annotation and advance disease classification. Among established preprocessing techniques, Contrast Limited Adaptive Histogram Equalization (CLAHE) has demonstrated efficacy in improving segmentation algorithms across various modalities, such as X-rays and CT. However, there remains a demand for improved contrast enhancement methods considering the heterogeneity of datasets and the various contrasts across different anatomic structures.MethodThis study proposes a novel preprocessing technique, ps-KDE, to investigate its impact on deep learning algorithms to segment major organs in posterior-anterior chest X-rays. Ps-KDE augments image contrast by substituting pixel values based on their normalized frequency across all images. We evaluate our approach on a U-Net architecture with ResNet34 backbone pre-trained on ImageNet. Five separate models are trained to segment the heart, left lung, right lung, left clavicle, and right clavicle.ResultsThe model trained to segment the left lung using ps-KDE achieved a Dice score of 0.780 (SD = 0.13), while that of trained on CLAHE achieved a Dice score of 0.717 (SD = 0.19), pDiscussionOur results suggest that ps-KDE offers advantages over current preprocessing techniques when segmenting certain lung regions. This could be beneficial in subsequent analyses such as disease classification and risk stratification.

Background: Autism is a severe neurodevelopmental disorder characterized by social interaction deficits, impairments in communication, and restricted and repetitive stereotyped behavior and activities. Family and twin studies suggested an essential role of genetic factors in the etiology of autism spectrum disorder (ASD). Also, other studies found SORCS3 and GSDME (DFNA5) might be involved in brain development and susceptible to ASD. Methods: In this study, 17 genome-wide significant SNPs reported in previous ASD genome-wide association studies (GWAS) and 7 SNPs in strong linkage disequilibrium with known ASD GWAS hits were selected to investigate the association between these SNPs and autism in the Han Chinese population. Then, 10 tagSNPs in SORCS3 and 11 tagSNPs in GSDME were selected to analyze the association between these SNPs and autism. The selected 24 SNPs and tagSNPs were genotyped using the Agena MassARRAY SNP genotyping assay in 757 Han Chinese autism trios. Results: Rs1484144 in NAA11 was significantly associated with autism; significance remained after the Bonferroni correction (P

Abstract Background Hip resurfacing arthroplasty (HRA) is a less common but effective alternative method to total hip arthroplasty (THA) for hip reconstruction. In this study, we investigated the incidences of in-hospital complications between patients who had been subjected to THA and HRA. Methods The National Inpatient Sample data that had been recorded from 2005 to 2014 was used in this study. Based on the International Classification of Disease, Ninth Revision, Clinical Modification, patients who underwent THA or HRA were included. Data on demographics, preoperative comorbidities, length of hospital stay, total charges, and in-hospital mortality and complications were compared. Multiple logistic regression analysis was used to determine whether different surgical options are independent risk factors for postoperative complications. Results A total of 537,506 THAs and 9,744 HRAs were obtained from the NIS database. Patients who had been subjected to HRA exhibited less preoperative comorbidity rates, shorter length of stay and extra hospital charges. Moreover, HRA was associated with more in-hospital prosthesis loosening. Notably, patients who underwent HRA were younger and presented less preoperative comorbidities but did not show lower incidences in most complications. Conclusions The popularity of HRA gradually reduced from the year 2005 to 2014. Patients who underwent HRA were more likely to be younger, male, have less comorbidities and spend more money on medical costs. The risk of in-hospital prosthesis loosening after HRA was higher. The HRA-associated advantages with regards to most in-hospital complications were not markedly different from those of THA. In-hospital complications of HRA deserve more attention from surgeons.

Abstract The battery swapping mode is a promising way for electric vehicles (EVs) to participate in power grid frequency regulation. However, the operation mechanism and the uncertainty management in the process still lack research. Aiming at this issue, this paper proposes a day‐ahead bidding strategy for the battery swapping and charging system (BSCS) providing regulation reserve capacity in the ancillary service market. Firstly, a new BSCS‐based regulation model is established. Then, an ambiguity set based on Kullback–Leibler (KL) divergence is used to manage the uncertainty of regulation signals and battery swapping demands. Furthermore, a boundary expectation approach is proposed to turn the problem into robust optimization. Finally, after using the extreme scenario method (ESM) to generate extreme scenarios, a duality‐free column‐and‐constraint generation (C&CG) algorithm is employed to solve the problem. The case studies demonstrate that BSCS can provide economical and robust reserve capacity bidding plans in the day‐ahead market with the proposed strategy. At the same time, the BSCS‐based regulation service is simulated with the battery development trend in the future, and suggestions are given.

Intracellular delivery, the process of transporting substances into cells, is crucial for various applications, such as drug delivery, gene therapy, cell imaging, and regenerative medicine. Among the different approaches of intracellular delivery, mechanoporation stands out by utilizing mechanical forces to create temporary pores on cell membranes, enabling the entry of substances into cells. This method is promising due to its minimal contamination and is especially vital for stem cells intended for clinical therapy. In this review, we explore various mechanoporation technologies, including microinjection, micro–nano needle arrays, cell squeezing through physical confinement, and cell squeezing using hydrodynamic forces. Additionally, we highlight recent research efforts utilizing mechanoporation for stem cell studies. Furthermore, we discuss the integration of mechanoporation techniques into microfluidic platforms for high-throughput intracellular delivery with enhanced transfection efficiency. This advancement holds potential in addressing the challenge of low transfection efficiency, benefiting both basic research and clinical applications of stem cells. Ultimately, the combination of microfluidics and mechanoporation presents new opportunities for creating comprehensive systems for stem cell processing.

Six new 2α-hydroxy ursane triterpenoids, 3α-cis-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (1), 3α-trans-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (2), 3α-trans-p-coumaroyloxy-2α-hydroxy-12-ursen-28-oic acid (3), 3β-trans-p-coumaroyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (4), 3β-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (5), and 3α-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (6), along with eleven known triterpenoids (7–17), were isolated from the leaves of Diospyros digyna. Their chemical structures were elucidated by comprehensive analysis of UV, IR, HRESIMS, and NMR spectra. All the isolated compounds were evaluated for their PTP1B inhibitory activity. 3β-O-trans-feruloyl-2α-hydroxy-urs-12-en-28-oic acid (13) showed the best inhibition activity with an IC50 value of 10.32 ± 1.21 μM. The molecular docking study found that the binding affinity of compound 13 for PTP1B was comparable to that of oleanolic acid (positive control).