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Abstract The identification and evaluation of barriers to artificial intelligence (AI) adoption in food supply chain finance (FSCF) can be addressed as a multiattribute decision-making problem. However, only a few studies have reported the application of decision models for evaluating barriers to the implementation of AI in FSCF, especially within an uncertain context. Hence, this work explores the evaluation issue of implementation barriers via an integrated decision model. In this model, the conventional additive ratio assessment (ARAS) model integrated with the Choquet integral and criteria importance through intercriteria correlation (CRITIC) is extended into the interval-valued Fermatean fuzzy (IVFF) setting for ranking the barriers. The IVFF weighted average operator based on the Choquet integral is introduced to form a group decision matrix. Then, the developed ARAS model with the IVFF-CRITIC method is proposed to evaluate the implementation barriers for AI in FSCF, which can depict the interactions between the barriers. Finally, a case of an FSCF, including four participants, is presented to illustrate the application of the reported model and demonstrate its reliability. The result shows that “Data privacy” ( $${c_{10}}$$ ) is the main barrier impeding AI adoption in FSCF, and the participant “small and medium-sized processing enterprises” ( $${a_3}$$ ) has the highest barrier level to AI adoption.

Abstract Protein-energy wasting (PEW) is a major contributor to the high mortality among maintenance hemodialysis (MHD) patients. Cardiovascular disease (CVD) is the leading cause of death in dialysis patients, and PEW can significantly increase cardiovascular mortality in MHD patients. Previous studies have confirmed that PA may be a good objective indicator for determining the nutritional status and prognosis of MHD patients. Our study aimed to determine the predictive value of phase angle (PA) as detected by bioelectrical impedance analysis (BIA) on PEW and cardiovascular (CV) risk among MHD patients. Our retrospective observational study involved 161 adult patients with HD. The Cardiovascular risk score is a risk model based on the Japan Dialysis Outcome and Practice Patterns Study (J-DOPPS). We established LASSO logistic regression analysis model to identify key parameters related to body composition that can predict PEW in MHD patients. The area under the curve (AUC) values for PA, appendicular skeletal muscle mass index (ASMI), body cell mass (BCM), and mid-arm circumference (MAC) in predicting PEW in male MHD patients were relatively large, with 0.708, 0.674, 0.663, and 0.735, respectively. The predicted PEW values of these parameters were slightly lower in female patients than in men. We incorporated PA, ASMI, BCM, and MAC into a model that predicted the incidence of PEW in maintenance hemodialysis patients using LASSO technology. We discovered that the model predicted a greater AUC of PEW occurrence than any single factor, 0.877 for men and 0.76 for women. The results of the univariate logistic regression analysis showed that the low PA tertile array group had a greater incidence of PEW than the high PA group (P

Abstract Objective The selection of appropriate materials and techniques for reconstructing skull base defects is crucial for restoring function, minimizing complications, and enhancing aesthetics. Dermal fat grafts (DFGs) have been established in many surgeries for contour correction. However, there is little literature describing the application of free dermal fat grafts for reconstruction of lateral skull base surgery defects. Therefore, the aim of this study was to evaluate the clinical effect of using free dermal fat grafts in the reconstruction of lateral skull base defects. Methods In this study, 32 patients who underwent primary autologous free dermal fat graft reconstruction for lateral skull base defects were enrolled. Postoperative complications both in the donor and recipient area were evaluated. Three-dimensional (3D) reconstruction techniques were applied to visualize the fat graft shape and volume variations for the assessment of postoperative restoring function. A telephone questionnaire was used for the assessment of postoperative facial aesthetics and patient satisfaction. Results A total of 32 patients who met the inclusion criteria were included in the study, showing satisfying results in safety and aesthetics. Participants’ ages averaged at 42.03 years, with the youngest being 18 and the oldest at 75 years old. No patient had postoperative complications of abdominal wounds in the donor area, only two patients had postoperative infections and one patient had a postoperative effusion in the recipient area. The volume of the grafts ranged from a minimum of 24.4 cm³ to a maximum of 131 cm³, with the highest recorded resorption volume being 33.63 cm³. The average resorption rate of the dermal fat graft was 24.36%, ranging from a minimum of 11% to a maximum of 43%. 3D reconstruction based on MRI imaging data indicated that DFGs have a lower resorption rate than traditional free fat grafts. The telephone questionnaire revealed high patient satisfaction with facial aesthetics, with the majority rating their outcomes positively. Conclusions Dermal fat grafts have fewer complication and can provide better resistance to infection and radiation aspect. Based on 3D reconstruction techniques via MRI imaging data, we found that dermal fat grafts have lower resorption rate than traditional free fat grafts, which can be a suitable material for reconstruction of lateral skull base defects.

Abstract Meningeal metastasis (LM) is commonly seen in the advanced stages of cancer patients, often leading to a rapid decline in survival time and quality of life. Currently, there is still a lack of standardized treatments. Oncolytic viruses (OVs) are a class of emerging cancer therapeutics with the advantages of selectively replicating in cancer cells, delivering various eukaryotic transgenes, inducing immunogenic cell death, and promoting anti-tumor immunity. Some studies applying OVs intrathoracically or intraperitoneally for the treatment of malignant pleural and peritoneal effusions have shown promising therapeutic effects. If OVs could be applied to treat LM, it would bring significant survival benefits to patients with LM. In this review, we analyzed past research on the use of viruses to treat meningeal metastasis, summarized the efficacy and safety demonstrated by the research results, and analyzed the feasibility of oncolytic virus therapy for meningeal metastasis. We also summarized the existing data to provide guidance for the development of OVs that can be injected into the cerebrospinal fluid (CSF).

Abstract Septic lung injury is strongly associated with polarization of M1 macrophages and excessive cytokine release. Fibroblast growth factor (FGF) signaling plays a role in both processes. However, the impact of FGF2 deficiency on macrophage polarization and septic acute lung injury remains unclear. To investigate this, we obtained macrophages from FGF2 knockout mice and examined their polarization and inflammatory cytokine expression. We also eliminated endogenous macrophages using clodronate liposomes and administered FGF2 knockout or WT macrophages intravenously in conjunction with cecal ligation and puncture (CLP) surgery to induce sepsis. In vitro analysis by flow cytometry and real-time PCR analysis demonstrated that FGF2 deficiency resulted in increased expression of M1 markers (iNOS and CD86) and inflammatory cytokines (CXCL1, IL1β, and IL6), especially after LPS stimulation. Additionally, immunofluorescence demonstrated increased nuclear translocation of p65 NF-κB in FGF2 knockout macrophages and RNA-seq analysis showed enrichment of differentially expressed genes in the IL17 and TNFα inflammatory signaling pathways. Furthermore, in vivo experiments revealed that depletion of FGF2 in macrophages worsened sepsis-induced lung inflammation, lung vascular leak, and lung histological injury, accompanied by an increase in CD86-positive cells and apoptosis. Our study suggests that FGF2 deficiency in macrophages plays a critical role in the pathogenesis of septic ALI, possibly because of the enhanced M1 macrophage polarization and production of proinflammatory cytokines. These findings provide empirical evidence for potential therapeutic interventions targeting FGF2 signaling to modulate the polarization of M1 and M2 macrophages in the management of sepsis-induced acute lung injury.

Abstract The aim of this study was to examine the effects of free swimming (FS), aquatic resistance training (ART), and their combination (FS&ART) on the body composition, blood pressure, and physical fitness of older adults. The study employed a randomized controlled design, comparing three experimental groups with a control group. Eighty volunteers aged between sixty and seventy years (age: 66.2 ± 2.3 years; body mass index: 25.8 ± 4.3 kg/m²) participated in the 16-week intervention, consisting of two weekly sessions. Assessments were conducted at baseline and post-intervention, including anthropometric measurements, blood pressure readings, and the Senior Fitness Test. Significant differences were found between groups in post-intervention considering the chair stand test (p = 0.017; ES = 0.125), arm curl test (p = 0.029; ES = 0.111), 8-foot up and go test (p = 0.042; ES = 0.102), and walk test − 6 min (p = 0.005; ES = 0.156). Specifically, both ART (+ 20.1%; p

Abstract As the role of RNA modification in gene expression regulation and human diseases, the “epitranscriptome” has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A modification is the most common post-transcriptional modification of eukaryotic mRNA, accounting for 80% of RNA methylation modifications. At the same time, several other modifications of RNA, such as N1-methyladenosine (m1A), 5-methylcytosine (m5C), 3-methylcytosine (m3C), pseudouridine (Ψ) and N7-methylguanosine (m7G) have also been demonstrated to be involved in cancer and drug resistance. This review mainly discusses the research progress of RNA modifications in the field of cancer and drug resistance and targeting of m6A regulators by small molecule modulators, providing reference for future study and development of combination therapy to reverse cancer drug resistance.

Abstract Percutaneous coronary intervention (PCI) combined with stent implantation is currently one of the most effective treatments for coronary artery disease (CAD). However, in-stent restenosis (ISR) significantly compromises its long-term efficacy. Mitophagy plays a crucial role in vascular homeostasis, yet its role in ISR remains unclear. This study aims to identify mitophagy-related biomarkers for ISR and explore their underlying molecular mechanisms. Through differential gene expression analysis between ISR and Control samples in the combined dataset, 169 differentially expressed genes (DEGs) were identified. Twenty-three differentially expressed mitophagy-related genes (DEMRGs) were identified by intersecting with mitophagy-related genes (MRGs) from the GeneCards, and functional enrichment analysis indicated their significant involvement in mitophagy-related biological processes. Using Weighted Gene Co-expression Network Analysis (WGCNA) and three machine learning algorithms (Logistic-LASSO, RF, and SVM-RFE), LRRK2, and ANKRD13A were identified as mitophagy-related biomarkers for ISR. The nomogram based on these two genes also exhibited promising diagnostic performance for ISR. Gene Set Enrichment Analysis (GSEA) as well as immune infiltration analyses showed that these two genes were closely associated with immune and inflammatory responses in ISR. Furthermore, potential small molecule compounds with therapeutic implications for ISR were predicted using the connectivity Map (cMAP) database. This study systematically investigated mitophagy-related biomarkers for ISR and their potential biological functions, providing new insights into early diagnosis and precision treatment strategies for ISR.

Abstract This study aimed to explore the selection of induction chemotherapy (IC) cycles for stage N3 nasopharyngeal carcinoma (NPC). We employed propensity score matching (PSM) to categorize patients into 3-cycle and 4-cycle IC groups (IC = 3 and IC = 4). The log-rank and chi-squared tests were used respectively to evaluate the differences in survival and acute toxicities. Survival outcomes including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were evaluated among the two groups. After PSM, each group comprised 99 patients. The IC = 4 group exhibited markedly improved survival outcomes compared with the IC = 3 group. Multivariate analysis revealed that pre-EBV DNA was an independent risk factor affecting PFS and DMFS. For high-risk patients with pre-EBV DNA ≥ 7800 copies/ml, the IC = 4 group demonstrated greater survival compared to the IC = 3 group. Among low-risk patients with pre-EBV DNA

Abstract The prevalence of human Demodex mites has surged in recent years, prompting significant concern among both patients and the medical community. This study aimed to investigate the survival duration and morphological alterations of Demodex folliculorum under diverse temperature conditions and in various culture media. We employed the eyelash sampling technique to procure the mites. The collected specimens were then subjected to culture at two distinct temperature ranges (16–22 °C and 4 °C) across a spectrum of media, including 30% tea tree oil (TTO), phosphate-buffered saline (PBS), pure water, 0.9% physiological saline, 5 µg/ml propidium iodide (PI), liquid paraffin, glycerol, and a blank culture medium. Post-administration, the mites’ activity and morphological changes were meticulously documented. Our findings indicate that the survival span of Demodex mites within the same medium was notably extended at 4 °C compared to room temperature. Specifically, under 4 °C, the use of liquid paraffin as a culture medium yielded the longest survival time of 12 days, surpassing all other conditions. Remarkably, the morphological integrity of the mites in this group remained largely unaltered. These results suggest that 4 °C is the optimal temperature for the in vitro cultivation of Demodex mites, offering insights into the environmental preferences of these organisms and potentially informing future therapeutic strategies.

Abstract Air quality is closely linked to human health and social development, making accurate air quality prediction highly significant. The Air Quality Index (AQI) is inherently a time series. However, most previous studies have overlooked its temporal features and have not thoroughly explored the relationship between pollutant emissions and air quality. To address this issue, this study establishes a historical correlation model for air quality based on a time series model—the Gaussian Hidden Markov Model (GHMM)—using industrial exhaust emissions and historical air quality data. Firstly, a traversal method is used to select the optimal number of hidden states for the GHMM. To optimize the traditional GHMM and reduce error accumulation in the prediction process, the Multi-day Weighted Matching method and the Fixed Training Set Length method are utilized. Both direct and indirect prediction modes are then used to predict the AQI in the Zhangdian District. Experimental results indicate that the improved GHMM with the indirect mode provides higher accuracy and more stable state estimation results (MAE = 13.59, RMSE = 17.59, mean forecasted value = 117.94). Finally, the air quality historical correlation model is integrated with the air quality meteorological correlation model from a previous study, further improving prediction accuracy (MAE = 11.59, RMSE = 14.87, mean forecasted value = 120.88). This study demonstrates that the GHMM’s strong ability to analyze temporal features significantly enhances the accuracy and stability of air quality predictions. The integration of the air quality historical correlation model with the air quality meteorological correlation model from a previous study leverages the strengths of each sub-model in handling different feature groups, leading to even more accurate predictions.

Abstract To investigate the effects of different typical exogenous salt concentrations on total soil salinity and the growth of Lycium barbarum under brackish water irrigation, and to determine the salinity threshold of irrigated brackish water that is conducive to the normal growth of Lycium barbarum while mitigating soil salinity accumulation. Four typical exogenous salts (NaCl, CaCl2, NaHCO3, Na2SO4) were selected and set at four concentrations (0.1, 0.5, 2.0, 4.0 g L−1) to conduct a field crossover experiments in the downstream region of the Hetao Irrigation District. The results showed that in the same fertility period, the growth rates of new branches, ground diameter, and crown width first increased and then decreased with rising concentrations of NaCl, CaCl2, and Na2SO4, but showed an inverse relationship with NaHCO3 concentrations. Furthermore, increasing salt concentrations linearly reduced the yield of dry fruits from Lycium barbarum and led to a notable accumulation of total soil salts. Utilizing an experimental research approach, a comprehensive analysis of involving multiple growth indices, stable yield, and soil salinity control of Lycium barbarum revealed that optimal growth occurs at salt concentrations of 0.1–0.5 g L−1 for different water quality areas within the irrigation area; using the method of path analysis identified the total soil salt and crown width as the primary direct and indirect factors influencing the yield of Lycium barbarum. The results of this study provide scientific basis and significant theoretical support for the safe and rational utilization of brackish water and cultivation of Lycium barbarum in typical regions with varying saline water qualities of Hetao irrigation area.

Abstract Background We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. Methods This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. Results Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI − 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). Conclusions The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Abstract Breast cancer (BC) stands as a predominant global malignancy, significantly contributing to female mortality. Recently uncovered, histone lysine lactylation (kla) has assumed a crucial role in cancer progression. However, the correlation with lncRNAs remains ambiguous. Scrutinizing lncRNAs associated with Kla not only improves clinical breast cancer management but also establishes a groundwork for antitumor drug development. We procured breast tissue samples, encompassing both normal and cancerous specimens, from The Cancer Genome Atlas (TCGA) database. Utilizing Cox regression and XGBoost methods, we developed a prognostic model using identified kla-related lncRNAs. The model's predictive efficacy underwent validation across training, testing, and the overall cohort. Functional analysis concerning kla-related lncRNAs ensued. We identified and screened 8 kla-related lncRNAs to formulate the risk model. Pathway analysis disclosed the connection between immune-related pathways and the risk model of kla-related lncRNAs. Significantly, the risk scores exhibited a correlation with both immune cell infiltration and immune function, indicating a clear association. Noteworthy is the observation that patients with elevated risk scores demonstrated an increased tumor mutation burden (TMB) and decreased tumor immune dysfunction and exclusion (TIDE) scores, suggesting heightened responses to immune checkpoint blockade. Our study uncovers a potential link between Kla-related lncRNAs and BC, providing innovative therapeutic guidelines for BC management.

Abstract Background Medical school learning environment (MSLE) has a holistic impact on students’ psychosomatic health, academic achievements, and personal development. Students in different grades perceive MSLE in different ways. Thus, it is essential to investigate the specific role of student’s grade in the perception of MSLE. Methods Using the Johns Hopkins Learning Environment Scale (JHLES) as a quantification instrument for the perception level of MSLE, 10,901 medical students in 12 universities in China were categorized into low or high JHLES group according to their questionnaires. We investigated the relationship between student’s grade and JHLES category by univariate analysis employing Pearson Chi-square test and Welch’s ANOVA. Then multivariable logistic regression analysis confirmed the predictive efficacy of student’s grade. A nomogram concerning the prediction of low JHLES score probability in medical students was also constructed. Results A significant difference between two JHLES categories among students in different grades was observed (p

Abstract. Background:. Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. Methods:. In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. Results:. In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962–1.000 in the training cohort and 0.969–0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. Conclusion:. ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. Trial Registration:. Chictr.org.cn: ChiCTR2200059599.

Abstract With the development of science and technology and economy, UAV is used more and more widely. However, the existing UAV trajectory planning methods have the limitations of high cost and low intelligence. In view of this, grey Wolf algorithm is being used to achieve collaborative trajectory optimization of UAV groups. However, it is found that the Grey Wolf optimization algorithm (GWO) has the problem of weak cooperation. In this study, based on the traditional GWO pheromone factor is introduced to improve it.. Aiming at the problem of unstable performance of swarm intelligence optimization algorithm under dynamic threat, deep reinforcement learning is used to optimize the model. An unmanned aerial vehicle swarm trajectory planning model was constructed based on the improved grey wolf algorithm. Through experimental analysis, the optimal fitness value of the improved grey wolf algorithm was lower than 0.43 of the grey wolf algorithm. Compared with other algorithms, the fitness value of this algorithm is significantly reduced and the stability is higher. In complex scenarios, the improved grey wolf algorithm had a trajectory length of 70.51 km and a planning time of 5.92 s, which was clearly superior to other algorithms. The path length planned by the research and design model was 58.476 km, which was significantly smaller than the other three models. The planning time was 5.33 s and the number of path extension points was 46. The indicator values of the Unmanned Aerial Vehicle swarm trajectory planning model designed by this research were all smaller than the other three models. By analyzing the results, the model can achieve low-cost trajectory optimization, providing more reasonable technical support for unmanned aerial vehicle mission execution.

Abstract Background This study aimed to explore the efficacy of hookwire for computed tomography (CT)-guided pulmonary nodule (PN) localization before video-assisted thoracoscopic surgery (VATS) resection and determine the risk factors for localization-related complications. Methods We enrolled 193 patients who underwent preoperative CT-guided PN hookwire localization. The patients were categorized into groups A (103 patients had no complications) and B (90 patients had complications) according to CT and VATS. Uni- and multivariate logistic regression analyses were used to identify risk factors for localization-related complications. A numerical rating scale was used to evaluate hookwire localization-induced pain. Results We successfully performed localization in 173 (89.6%) patients. Pneumothorax was the main complication in 82 patients (42.5%). Patient gender, age, body mass index, tumor diameter, consolidation tumor ratio, pathologic diagnosis, position adjustment during location, lesion location, waiting time for surgery, and pleural adhesions were not significantly different between the two groups. The number of nodules, number of punctures, scapular rest position, and depth of insertion within the lung parenchyma were significant factors for successful localization. Multivariate regression analysis further validated the number of nodules, scapular rest position, and depth of insertion within the lung parenchyma as risk factors for hookwire-localization-related complications. Hookwire localization-induced pain is mainly mild or moderate pre- and postoperatively, and some patients still experience pain 7 days postoperatively. Conclusions Hookwire preoperative PN localization has a high success rate, but some complications remain. Thus, clinicians should be vigilant and look forward to further improvement.

Abstract The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.

Abstract Passively harmonic mode-locking has been experimentally demonstrated in an erbium-doped fiber laser with large normal dispersion using single-multi-single mode structure as artificial saturable absorber. By increasing the pump power under the same polarization setting, the mode-locking operation can switch from fundamental mode-locked to 5th order harmonic mode-locked. Highest repetition rate of 4.26 MHz (5th order harmonic) is observed, with pulse width and pulse energy ascertained at 290 fs and 3.0 nJ, respectively. Excellent signal-to-noise ratio (SNR) of above 50 dB is observed for all harmonic orders. The findings validated that SMS structure can be used to generate stable and switchable high order of harmonic mode-locked. The low-cost SMS fiber for harmonic mode-locked generation technique could lay the groundwork for future sustainable industrial growth.

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting, coagulation, and thermal injury of ex vivo animal tissues, aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia. Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment, respectively. Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s. The effects of layers at powers of 60, 90, 120, 150, and 160 W on tissue injury were observed. Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury. Additionally, in coagulation mode, the effects of 30, 40, and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5, 10, and 15 seconds.Results When the optical fiber was placed 1 cm away from the tissue, the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue. However, at a distance of 0.5 cm, the 120 W, 150 W, or 160 W lasers caused slight damage to the bladder tissue. In addition, with the increase in output power, the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased, showing a good linear correlation between vaporization volume and total energy consumption (P0.05). Moreover, when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2, the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power (P0.05). Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation, cutting, and coagulation effect on ex vivo tissues, with a good linear correlation between the effect and the output energy.

Abstract In response to the current challenges fire detection algorithms encounter, including low detection accuracy and limited recognition rates for small fire targets in complex environments, we present a lightweight fire detection algorithm based on an improved YOLOv5s. The introduction of the CoT (Contextual Transformer) structure into the backbone neural network, along with the creation of the novel CSP1_CoT (Cross stage partial 1_contextual transformer) module, has effectively reduced the model’s parameter count while simultaneously enhancing the feature extraction and fusion capabilities of the backbone network; The network’s Neck architecture has been extended by introducing a dedicated detection layer tailored for small targets and incorporating the SE (Squeeze-and-Excitation) attention mechanism. This augmentation, while minimizing parameter proliferation, has significantly bolstered the interaction of multi-feature information, resulting in an enhanced small target detection capability; The substitution of the original loss function with the Focal-EIoU (Focal-Efficient IoU) loss function has yielded a further improvement in the model’s convergence speed and precision; The experimental results indicate that the modified model achieves an mAP@.5 of 96% and an accuracy of 94.8%, marking improvements of 8.8% and 8.9%, respectively, over the original model. Furthermore, the model’s parameter count has been reduced by 1.1%, resulting in a compact model size of only 14.6MB. Additionally, the detection speed has reached 85 FPS (Frames Per Second), thus satisfying real-time detection requirements. This enhancement in precision and accuracy, while simultaneously meeting real-time and lightweight constraints, effectively caters to the demands of fire detection.

Abstract Sarcopenia (low muscle mass, i.e., quantity) is associated with poor clinical outcomes in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to illustrate the clinical prognostic value of myosteatosis (muscle fat infiltration) for short-term mortality in patients with ACLF. We retrospectively enrolled consecutive patients with ACLF between January 2019 and January 2022. Computed tomography-based body composition analysis was performed at the third lumbar vertebral level to determine skeletal muscle radiation attenuation. Fine and Gray’s competing risk regression model, with liver transplantation as a competing risk, was used to assess the factors associated with 90-day mortality. A total of 431 patients with ACLF were included. Myosteatosis and sarcopenia were observed in 261 (60.6%) and 87 (20.2%) patients, respectively. Competitive risk regression showed that age (HR 1.021, 95% CI 1.000–1.043, P = 0.042), APASL ACLF Research Consortium (AARC) score (HR 1.498, 95% CI 1.312–1.710, P

Abstract Background Tumor necrosis factor receptor-associated factors family genes play a pivotal role in tumorigenesis and metastasis, functioning as adapters or E3 ubiquitin ligases across various signaling pathways. To date, limited research has explored the association between tumor necrosis factor receptor-associated factors family genes and the clinicopathological characteristics of tumors, immunity, and the tumor microenvironment (TME). This comprehensive study investigates the relationship between tumor necrosis factor receptor-associated factors family and prognosis, TME, immune response, and drug sensitivity in a pan-cancer context. Methods Utilizing current public databases, this study examines the expression levels and prognostic significance of tumor necrosis factor receptor-associated factors family genes in a pan-cancer context through bioinformatic analysis. In addition, it investigates the correlation between tumor necrosis factor receptor-associated factors expression and various factors, including the TME, immune subtypes, stemness scores, and drug sensitivity in pan-cancer. Results Elevated expression levels of tumor necrosis factor receptor-associated factor 2, 3, 4, and 7 were observed across various cancer types. Patients exhibiting high expression of these genes generally faced a worse prognosis. Furthermore, a significant correlation was noted between the expression of tumor necrosis factor receptor-associated factors family genes and multiple dimensions of the TME, immune subtypes, and drug sensitivity.

Key Clinical Message Adult‐onset immunodeficiency (AOID) is an emerging acquired immunodeficiency, characterized by multiple opportunistic infections including non‐tuberculous mycobacterium (NTM) due to the presence of anti‐IFN‐γ autoantibody (AIGA). This case highlights the challenges of accurate diagnosis of monoclonal gammaglobulinemia with NTM infection and favorable outcomes of anti‐plasma cell therapy in AOID. Abstract Adult‐onset immunodeficiency (AOID) is an emerging acquired immunodeficiency due to anti‐IFN‐γ autoantibody (AIGA) with low morbidity, frequent disseminated infections, a prolonged course, difficult diagnosis and treatment, and a poor prognosis. Here, we report a patient with positive AIGA and monoclonal gammaglobulinemia who was mimicking symptomatic multiple myeloma and resulting in a non‐tuberculous mycobacterial (NTM) infection. While he achieved an excellent therapeutic effect with anti‐plasma cell therapy, it also serves as a warning that monoclonal gammaglobulinemia with NTM infection is easily misdiagnosed as symptomatic multiple myeloma, and the screening for AIGA should not be ignored in patients with NTM infection.

Abstract Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune evasion. However, the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses, including flaviviruses, vaccinia viruses, coronaviruses, and extends even to mammals. Here, we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV, despite the presence of a consistently active catalytic center. We further identified critical residues (Leu-36, Asn-138 and Ile-153) which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and SARS-CoV. These residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA substrates. Of interest, a triple substitution (Leu36 → Ile36, Asn138 → His138, Ile153 → Leu153, from SARS-CoV-2 to SARS-CoV) within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral replication. Furthermore, it led to a significant upregulation of type I interferon (IFN-I) and proinflammatory cytokines both in vitro and vivo, relying on the cooperative sensing of melanoma differentiation-associated protein 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2). In conclusion, our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence pathogenesis. Monitoring changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.

Abstract Background Inflammation and oxidative stress play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aimed to explore the effects of copper chaperone Antioxidant-1 (Atox1) on macrophages in a mouse model of intestinal inflammation. Methods A mouse model of TNBS-induced colitis was established and verified using the disease activity index. Atox1 conditional knockout mice were applied. The proportion of macrophages in colonic lamina propria mononuclear cells and ROS production were analyzed using flow cytometry. Inflammatory cytokines were measured using ELISA. Expression of macrophage M1/M2 polarization markers, p47phox, NLRP3, and Caspase-1 p20 was measured using quantitative RT-PCR and Western blotting. Results Atox1 expression was up-regulated in colon tissues of TNBS-induced colitis mice. Macrophages isolated from TNBS-induced colitis mice showed M1 polarization and nuclear translocation of Atox1. Inhibiting copper chaperone activity decreased p47phox, ROS production, and M1 polarization induced by CuCl2 in macrophages. TNBS induced up-regulation of inflammatory cytokines, M1 polarization markers, and p47phox expression in mice, an effect which was preempted by Atox1 knockout. Inflammatory cytokines and expression of M1 polarization markers, p47phox, NLRP3, Caspase-1 p20 were also increased in macrophages isolated from TNBS-induced colitis mice. These changes were alleviated in mice with Atox1 knockout. The effects of Atox1 on macrophage polarization were mediated via the ROS-NLRP3 inflammasome pathway. Conclusion Atox1 plays a pro-inflammatory role, promotes M1 polarization of macrophages, and increases the concentrations of pro-inflammatory cytokines in intestinal tissue by regulating the ROS-NLRP3 inflammasome pathway. Atox1 is a potential therapeutic target in IBD.

Abstract Objective To explore the effect of dynamic changes in free triiodothyronine (FT3) level for predicting the 90 day prognosis of patients with hepatitis B virus–related acute-on-chronic liver failure (HBV-ACLF). Methods The clinical data of 122 hospitalised patients with HBV-ACLF between September 2018 and January 2020 were collected and divided into a survival group (77 cases) and a death group (45 cases) according to the 90 day prognosis. We statistically analysed the characteristics of FT3 changes in the two groups of patients. Binary logistic regression one-way analysis was used to assess the degree of influence of each factor. The Kaplan–Meier survival curve and receiver operating characteristic curve were used to evaluate the effect of a single change in FT3 level difference (single △FT3) and the FT3 level change range (△FT3 range) in predicting the 90-day prognosis of patients. Results There were only three types of changes in FT3 levels, which included 19 (15.6%) cases of continuous normal type, 35 (28.7%) cases of continuous decrease type and 68 (55.7%) cases of U-shaped change type. The difference in survival curves between the three types of patients was statistically significant (P

Abstract Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.

Abstract Background Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. Methods This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). Results A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173–2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082–1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307–2.439, p

Abstract Rainfall serves as a significant factor contributing to slope stability challenges in mountainous areas, and simulating the process of slope rainwater movement is a crucial approach for analyzing the stability of slopes triggered by rainfall. By combining computer numerical simulation technology with traditional hydraulic and hydrological calculation theories, it is possible to create an efficient and precise rainwater movement model that can simulate and analyze the process of rainwater movement on slopes. Utilizing natural slopes as the focal point of our research, the cellular automaton method was applied to simulate rainfall runoff on slopes, and a Cellular Automata (CA) based model for rainwater movement process was developed. This model modified the Green-Ampt (G-A) infiltration model by adopting an elliptical water content curve and introducing a coefficient that quantifies the ratio of saturated to unsaturated depth. Additionally, we refined the rules governing runoff generation and convergence within the slope and on its surface, enabling a comprehensive simulation of the entire rainwater movement process on the slope. Furthermore, the effectiveness of the model was validated through analytical solutions derived from simplified assumptions, laboratory experiments on infiltration and runoff in the flume, and a case study of a natural slope. The results show that the infiltration calculation results of the rainwater movement model are closer to the experimental values, and their overall values are slightly higher than the measured values, which are basically consistent with the model test results; The runoff calculation results show a phenomenon of initially increasing and gradually approaching the measured values compared to the measured values. When applying the model to an actual slope, it was found that the model comprehensively accounts for the influence of slope seepage, infiltration and runoff process, has better performance compared to G-A modified model. The model can be used to describe the spatial distribution and temporal variation of infiltration and runoff processes.

Abstract Welding process, as one of the crucial industrial technologies in ship construction, accounts for approximately 70% of the workload and costs account for approximately 40% of the total cost. The existing welding quality prediction methods have hypothetical premises and subjective factors, which cannot meet the dynamic control requirements of intelligent welding for processing quality. Aiming at the low efficiency of quality prediction problems poor timeliness and unpredictability of quality control in ship assembly-welding process, a data and model driven welding quality prediction method is proposed. Firstly, the influence factors of welding quality are analyzed and the correlation mechanism between process parameters and quality is determined. According to the analysis results, a stable and reliable data collection architecture is established. The elements of welding process monitoring are also determined based on the feature dimensionality reduction method. To improve the accuracy of welding quality prediction, the prediction model is constructed by fusing the adaptive simulated annealing, the particle swarm optimization, and the back propagation neural network algorithms. Finally, the effectiveness of the prediction method is verified through 74 sets of plate welding experiments, the prediction accuracy reaches over 90%.

Abstract Objective Myasthenia gravis (MG) is a complex autoimmune disease affecting the neuromuscular junction with limited drug options, but the field of MG treatment recently benefits from novel biological agents. We performed a drug-targeted Mendelian randomization (MR) study to identify novel therapeutic targets of MG. Methods Cis-expression quantitative loci (cis-eQTL), which proxy expression levels for 2176 druggable genes, were used for MR analysis. Causal relationships between genes and disease, identified by eQTL MR analysis, were verified by comprehensive sensitivity, colocalization, and protein quantitative loci (pQTL) MR analyses. The protein-protein interaction (PPI) analysis was also performed to extend targets, followed by enzyme-linked immunosorbent assay (ELISA) to explore the serum level of drug targets in MG patients. A phenome-wide MR analysis was then performed to assess side effects with a clinical trial review assessing druggability. Results The eQTL MR analysis has identified eight potential targets for MG, one for early-onset MG and seven for late-onset MG. Further colocalization analyses indicated that CD226, CDC42BPB, PRSS36, and TNFSF12 possess evidence for colocalization with MG or late-onset MG. pQTL MR analyses identified the causal relations of TNFSF12 and CD226 with MG and late-onset MG. Furthermore, PPI analysis has revealed the protein interaction between TNFSF12-TNFSF13(APRIL) and TNFSF12-TNFSF13B(BLyS). Elevated TNFSF13 serum level of MG patients was also identified by ELISA experiments. This study has ultimately proposed three promising therapeutic targets (TNFSF12, TNFSF13, TNFSF13B) of MG. Conclusions Three drug targets associated with the BLyS/APRIL pathway have been identified. Multiple biological agents, including telitacicept and belimumab, are promising for MG therapy.

Abstract Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

Abstract Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC‐derived extracellular vesicles (MSCs‐EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs‐EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs‐EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs‐EVs in cancer treatment, along with the challenges they face.

Background Chemotactic cytokines play a crucial role in the development of acute myeloid leukemia (AML). Thus, investigating the mechanisms of chemotactic cytokine-related genes (CCRGs) in AML is of paramount importance. Methods Using the TCGA-AML, GSE114868, and GSE12417 datasets, differential expression analysis identified differentially expressed CCRGs (DE-CCRGs). These genes were screened by overlapping differentially expressed genes (DEGs) between AML and control groups with CCRGs. Subsequently, functional enrichment analysis and the construction of a protein-protein interaction (PPI) network were conducted to explore the functions of the DE-CCRGs. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses identified relevant prognostic genes and developed a prognostic model. Survival analysis of the prognostic gene was performed, followed by functional similarity analysis, immune analysis, enrichment analysis, and drug prediction analysis. Results Differential expression analysis revealed 6,743 DEGs, of which 29 DE-CCRGs were selected for this study. Functional enrichment analysis indicated that DE-CCRGs were primarily involved in chemotactic cytokine-related functions and pathways. Six prognostic genes (CXCR3, CXCR2, CXCR6, CCL20, CCL4, and CCR2) were identified and incorporated into the risk model. The model’s performance was validated using the GSE12417 dataset. Survival analysis showed significant differences in AML overall survival (OS) between prognostic gene high and low expression groups, indicating that prognostic gene might be significantly associated with patient survival. Additionally, nine different immune cells were identified between the two risk groups. Correlation analysis revealed that CCR2 had the most significant positive correlation with monocytes and the most significant negative correlation with resting mast cells. The tumor immune dysfunction and exclusion score was lower in the high-risk group. Conclusion CXCR3, CXCR2, CXCR6, CCL20, CCL4, and CCR2 were identified as prognostic genes correlated to AML and the tumor immune microenvironment. These findings offerred novel insights into the prevention and treatment of AML.

Introduction Benign prostatic hyperplasia (BPH) is a condition commonly seen among men aged over 40, significantly affecting their quality of life and typically accompanied by lower urinary tract symptoms (LUTS). Acupuncture presents a potentially effective treatment option; however, the exact effects remain uncertain. Therefore, we design this multicentre randomised trial to evaluate the efficacy and safety of electroacupuncture (EA) for relieving LUTS in men with BPH.Methods and analysis A two-arm, sham-controlled, subject-blinded and assessor-blinded trial will be conducted in 11 hospitals in China to compare EA with sham electroacupuncture (SA) in treating moderate to severe LUTS of BPH among men aged 40–80. A total of 306 eligible male patients will be recruited and assigned at a 1:1 ratio to receive either EA or SA for 24 sessions over a succession of 8 weeks, with 24 weeks of follow-up. The primary outcome will be the proportions of participants with at least 30% reduction in the International Prostate Symptom Score total score from baseline at weeks 8 and 20. All statistical analyses will be conducted in accordance with the intention-to-treat principle, and a two-tailed p value less than 0.05 will be considered statistically significant.Ethics and dissemination The trial has been approved by the institutional review board of Guang’anmen Hospital (2022-203-KY), as well as other recruitment centres. Each participant will receive the detailed information of the trial, and sign the written informed consent. The results of the trial are expected to be published in a peer-reviewed journal.Trial registration number NCT05585450.

Summary: Background: Response to antipsychotic drugs (APD) varies greatly among individuals and is affected by genetic factors. This study aims to demonstrate genome-wide associations between copy number variants (CNVs) and response to APD in patients with schizophrenia. Methods: A total of 3030 patients of Han Chinese ethnicity randomly received APD (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, haloperidol and perphenazine) treatment for six weeks. This study is a secondary data analysis. Percentage change on the Positive and Negative Syndrome Scale (PANSS) reduction was used to assess APD efficacy, and more than 50% change was considered as APD response. Associations between CNV burden, gene set, CNV loci and CNV break-point and APD efficacy were analysed. Findings: Higher CNV losses burden decreased the odds of 6-week APD response (OR = 0.66 [0.44, 0.98]). CNV losses in synaptic pathway involved in neurotransmitters were associated with 2-week PANSS reduction rate. CNV involved in sialylation (1p31.1 losses) and cellular metabolism (19q13.32 gains) associated with 6-week PANSS reduction rate at genome-wide significant level. Additional 36 CNVs associated with PANSS factors improvement. The OR of protective CNVs for 6-week APD response was 3.10 (95% CI: 1.33–7.19) and risk CNVs was 8.47 (95% CI: 1.92–37.43). CNV interacted with genetic risk score on APD efficacy (Beta = −1.53, SE = 0.66, P = 0.021). The area under curve to differ 6-week APD response attained 80.45% (95% CI: 78.07%–82.82%). Interpretation: Copy number variants contributed to poor APD efficacy and synaptic pathway involved in neurotransmitter was highlighted. Funding: National Natural Science Foundation of China, National Key R&D Program of China, China Postdoctoral Science Foundation.

Plasmodesmata are transmembrane channels embedded within the cell wall that can facilitate the intercellular communication in plants. Plasmodesmata callose-binding (PDCB) protein that associates with the plasmodesmata contributes to cell wall extension. Given that the elongation of cotton fiber cells correlates with the dynamics of the cell wall, this protein can be related to the cotton fiber elongation. This study sought to identify PDCB family members within the Gossypium. hirsutum genome and to elucidate their expression profiles. A total of 45 distinct family members were observed through the identification and screening processes. The analysis of their physicochemical properties revealed the similarity in the amino acid composition and molecular weight across most members. The phylogenetic analysis facilitated the construction of an evolutionary tree, categorizing these members into five groups mainly distributed on 20 chromosomes. The fine mapping results facilitated a tissue-specific examination of group V, revealing that the expression level of GhPDCB9 peaked five days after flowering. The VIGS experiments resulted in a marked decrease in the gene expression level and a significant reduction in the mature fiber length, averaging a shortening of 1.43–4.77 mm. The results indicated that GhPDCB9 played a pivotal role in the cotton fiber development and served as a candidate for enhancing cotton yield.

Abstract Background Men and women are known to show differences in the incidence and clinical manifestations of mood and anxiety disorders. Many imaging studies have investigated the neural correlates of sex differences in emotion processing. However, it remains unclear how anxiety might impact emotion processing differently in men and women. Method We recruited 119 healthy adults and assessed their levels of anxiety using State-Trait Anxiety Inventory (STAI) State score. With functional magnetic resonance imaging (fMRI), we examined regional responses to negative vs. neutral (Neg-Neu) picture matching in the Hariri task. Behavioral data were analyzed using regression and repeated-measures analysis of covariance with age as a covariate, and fMRI data were analyzed using a full-factorial model with sex as a factor and age as a covariate. Results Men and women did not differ in STAI score, or accuracy rate or reaction time (RT) (Neg-Neu). However, STAI scores correlated positively with RT (Neg-Neu) in women but not in men. Additionally, in women, STAI score correlated positively with lingual gyrus (LG) and negatively with medial prefrontal cortex (mPFC) and superior frontal gyrus (SFG) activity during Neg vs. Neu trials. The parameter estimates (βs) of mPFC also correlated with RT (Neg-Neu) in women but not in men. Generalized psychophysiological interaction (gPPI) analysis in women revealed mPFC connectivity with the right inferior frontal gyrus, right SFG, and left parahippocampal gyrus during Neg vs. Neu trials in positive correlation with both STAI score and RT (Neg-Neu). In a mediation analysis, mPFC gPPI but not mPFC activity fully mediated the association between STAI scores and RT (Neg-Neu). Conclusion With anxiety affecting the behavioral and neural responses to negative emotions in women but not in men and considering the known roles of the mPFC in emotion regulation, we discussed heightened sensitivity and regulatory demands during negative emotion processing as neurobehavioral markers of anxiety in women.

Abstract The shuffled frog leaping algorithm (SFLA) is a promising metaheuristic bionics algorithm, which has been designed by the shuffled complex evolution and the particle swarm optimization (PSO) framework. However, it is easily trapped into local optimum and has the low optimization accuracy when it is used to optimize complex engineering problems. To overcome the shortcomings, a novel modified shuffled frog leaping algorithm (MSFLA) with inertia weight is proposed in this paper. To extend the scope of the direction and length of the updated worst frog (vector) of the original SFLA, the inertia weight α was introduced and its meaning and range of the new parameters are fully explained. Then the convergence of the MSFLA is deeply analyzed and proved theoretically by a new dynamic equation formed by Z-transform. Finally, we have compared the solution of the 7 benchmark functions with the original SFLA, other improved SFLAs, genetic algorithm, PSO, artificial bee colony algorithm, and the grasshopper optimization algorithm with invasive weed optimization. The testing results showed that the modified algorithms can effectively improve the solution accuracy and convergence property, and exhibited an excellent ability of global optimization in high-dimensional space and complex function problems.

Abstract Background Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by complement dependent and proinflammatory activation of macrophages. However, effective treatment for complement activation in PAH is lacking. We aimed to explore the effect and mechanism of CP40-KK (a newly identified analog of selective complement C3 inhibitor CP40) in the PAH model. Methods We used western blotting, immunohistochemistry, and immunofluorescence staining of lung tissues from the monocrotaline (MCT)-induced rat PAH model to study macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1β and IL-18) release. Surface plasmon resonance (SPR), ELISA, and CH50 assays were used to test the affinity between CP40-KK and rat/human complement C3. CP40-KK group rats only received CP40-KK (2 mg/kg) by subcutaneous injection at day 15 to day 28 continuously. Results C3a was significantly upregulated in the plasma of MCT-treated rats. SPR, ELISA, and CH50 assays revealed that CP40-KK displayed similar affinity binding to human and rat complement C3. Pharmacological inhibition of complement C3 cleavage (CP40-KK) could ameliorate MCT-induced NLRP3 inflammasome activity, pulmonary vascular remodeling, and right ventricular hypertrophy. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cells is closely associated with macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1β and IL-18) release. Besides, C3a enhanced IL-1β activity in macrophages and promoted pulmonary arterial smooth muscle cell proliferation in vitro. Conclusion Our findings suggest that CP40-KK treatment was protective in the MCT-induced rat PAH model, which might serve as a therapeutic option for PAH.

Abstract High altitude exposure increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Machine learning techniques have been used to develop cardiovascular disease prediction models, but no reports exist for high altitude induced myocardial ischemia. Our objective was to establish a machine learning-based MI prediction model and identify key risk factors. Using a prospective cohort study, a predictive model was developed and validated for high-altitude MI. We consolidated the health examination and self-reported electronic questionnaire data (collected between January and June 2022 in 920th Joint Logistic Support Force Hospital of china) of soldiers undergoing high-altitude training, along with the health examination and second self-reported electronic questionnaire data (collected between December 2022 and January 2023) subsequent to their completion on the plateau, into a unified dataset. Participants were subsequently allocated to either the training or test dataset in a 3:1 ratio using random assignment. A predictive model based on clinical features, physical examination, and laboratory results was designed using the training dataset, and the model's performance was evaluated using the area under the receiver operating characteristic curve score (AUC) in the test dataset. Using the training dataset (n = 2141), we developed a myocardial ischemia prediction model with high accuracy (AUC = 0.86) when validated on the test dataset (n = 714). The model was based on five laboratory results: Eosinophils percentage (Eos.Per), Globulin (G), Ca, Glucose (GLU), and Aspartate aminotransferase (AST). Our concise and accurate high-altitude myocardial ischemia incidence prediction model, based on five laboratory results, may be used to identify risks in advance and help individuals and groups prepare before entering high-altitude areas. Further external validation, including female and different age groups, is necessary.

Abstract We experimentally demonstrated the generation of domain-wall dark pulse in an Erbium-doped fiber laser using the combination of a 10 cm graded index multimode fiber sandwiched by single mode fibers as artificial saturable absorber. The interaction of phase difference in grade index multimode fiber allowed the stable dual-wavelength oscillation in the cavity. The dual-wavelength centered at 1567.2 nm and 1569.4 nm produces the topological defect in temporal domain and achieved a dark pulse formation with repetition rate of 21.5 MHz. The highest average pulse energy is calculated as 769.6 pJ with pulse width of 5 ns. Throughout the operating pump power range, the average pulse energy and output power increase linearly, with R2 of 0.9999 and achieved the laser efficiency of 9.33%. From the measurement in frequency domain, the signal-to-noise ratio is measured as 49 dB. As compared to reported DW dark pulse works, the proposed structure only required a short length of multimode fiber, which allowed the domain-wall dark pulse to achieve higher pulse repetition rate. The venture of domain wall dark pulse is potentially to pave the foundation toward sustainable industrial growth.

Abstract Background/Aim Interpreting an electrocardiogram (ECG) is a vital skill for nurses in cardiology. This study aimed to evaluate the efficacy of the bridge-in, objective, preassessment, participatory learning, post-assessment, and summary (BOPPPS) model, when combined with case-based learning (CBL), in enhancing nursing students’ ECG interpretation capabilities. Materials & methods Nursing students were randomly divided into two groups: one utilizing the BOPPPS model combined with CBL (BOPPPS-CBL), and the other employing a traditional lecture-based learning (LBL) model. All participants underwent training and completed pre- and post-course quizzes. Results The BOPPPS-CBL model significantly improved nursing students’ abilities in ECG interpretation compared to the traditional LBL model group. The BOPPPS-CBL model proved to be a comprehensive and effective method for enhancing students’ attitudes towards teaching and learning. Discussion Our study demonstrated for the first time that the BOPPPS-CBL model is an innovative and effective method for promoting nurses’ accuracy in ECG interpretation. It highlights the potential of this approach as a superior alternative to traditional learning methods.

In recent years, an increasing number of studies have begun to use conversational data in spontaneous speech to estimate cognitive function in older people. The targets of spontaneous speech with older people used to be physicians and licensed psychologists, but it is now possible to have conversations with fully automatic AI agents. However, it has not yet been clarified what difference there is in conversational communication with older people when the examiner is a human or an AI agent. This study explored the psychological burden experienced by elderly participants during cognitive function assessments, comparing interactions with human and AI conversational partners. Thirty-four participants, averaging 78.71 years of age, were evaluated using the Mini-Mental State Examination (MMSE), the Visual Analogue Scale (VAS), and the State-Trait Anxiety Inventory (STAI). The objective was to assess the psychological impact of different conversational formats on the participants. The results indicated that the mental strain, as measured by VAS and STAI scores, was significantly higher during the MMSE sessions compared to other conversational interactions (p < 0.01). Notably, there was no significant difference in the mental burden between conversations with humans and AI agents, suggesting that AI-based systems could be as effective as human interaction in cognitive assessments.

In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis with cell growth and division. Although GpsB has been studied in several bacteria, the structure, function, and interactome of Staphylococcus aureus GpsB is largely uncharacterized. To address this knowledge gap, we solved the crystal structure of the N-terminal domain of S. aureus GpsB, which adopts an atypical, asymmetric dimer, and demonstrates major conformational flexibility that can be mapped to a hinge region formed by a three-residue insertion exclusive to Staphylococci. When this three-residue insertion is excised, its thermal stability increases, and the mutant no longer produces a previously reported lethal phenotype when overexpressed in Bacillus subtilis. In S. aureus, we show that these hinge mutants are less functional and speculate that the conformational flexibility imparted by the hinge region may serve as a dynamic switch to fine-tune the function of the GpsB complex and/or to promote interaction with its various partners. Furthermore, we provide the first biochemical, biophysical, and crystallographic evidence that the N-terminal domain of GpsB binds not only PBP4, but also FtsZ, through a conserved recognition motif located on their C-termini, thus coupling peptidoglycan synthesis to cell division. Taken together, the unique structure of S. aureus GpsB and its direct interaction with FtsZ/PBP4 provide deeper insight into the central role of GpsB in S. aureus cell division.