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Abstract The existing methods for determining the module arrangement in photovoltaic (PV) farms are considered insufficient as they are generally limited to the environment of flat ground without considering both physical and electrical factors. The orientations of PV modules may be very diverse when installed in places with complex topography, e.g. mountains and abandoned mine sites. Thus, the received irradiance by the modules is inconsistent directly results in current differences and hence leads to significant mismatch loss in the PV arrays. This paper proposes a solution to determine the most appropriate combination of tilts and orientations of PV modules as well as the arrangement of PV arrays. The complex topographies are fully considered to minimize the mismatch loss phenomenon, and hence the power generation degradation. The solution adopts a set of models, i.e. the irradiation model for the calculation of optimal module tilts and orientations, the shadow model for shadow effect analysis, and the mismatch model for mismatch condition analysis. A two‐layer multi‐objective optimization is implemented for the optimal arrangement. The proposed solution is assessed through the case study of a 30 MW PV farm. The result confirms the effectiveness of the proposed solution for the optimal spatial module placement.

Imperialist competitive algorithm (ICA) is an efficient meta-heuristic algorithm by simulating the competitive behaviour among imperialist countries. However, it still suffers from slow convergence and deficiency in exploration. To address these issues, an improved ICA is proposed by combining ICA with a quasi-opposition-based learning (QOBL) strategy, which is named QOBL-ICA. The improvements include two aspects. First, the QOBL strategy is adopted to generate a population of fitter individuals. Second, a QOBL-assisted assimilation strategy is proposed to enhance the exploration ability of ICA. As a result, the proposed QOBL-ICA has more powerful exploration ability than ICA as well as faster convergence speed. The effectiveness of the proposed QOBL-ICA is verified by testing on 20 benchmark functions and 3 engineering design problems. Experimental results show that the performance of QOBL-ICA is superior to most state-of-the-art meta-heuristic algorithms in terms of global optimum reached and convergence speed.

Abstract Turbo codes play a crucial role in wireless communication systems, and their compiled code structures are key factors affecting the performance of the entire communication system. As a result, the study of turbo compiled code structures has been a focal point for researchers. The iterative decoding of turbo code structures has multiple limitations and large storage resource consumption, leading to poor system anti‐interference ability and a rapid increase in BER. To address these issues, this paper proposes the mimic turbo compiled code structure (MTCCS) for wireless communication systems. MTCCS is based on the DHR idea, incorporating dynamic, heterogeneous, and redundancy characteristics. Dynamicity is achieved through a dynamic scheduling algorithm based on abnormal feedback information. Heterogeneity is achieved through a codec component collection design method based on intrinsic and extrinsic heterogeneity. Redundancy is achieved through a majority voting algorithm. At the beginning of information transmission, MTCCS randomly selects heterogeneous codecs from the heterogeneous codec collection to enter the runtime pool. After the information transmission is complete, the majority voting algorithm is used to adjudicate the multi‐mode output of the codecs, resulting in a relatively accurate decoding outcome. Meanwhile, the dynamic scheduling module calculates the abnormal feedback information of each codec and accordingly dynamically schedules the mimic turbo codecs to replace the abnormal ones. Through the above process, MTCCS realizes the adaptive compilation code and improves the anti‐interference ability of turbo code. Simulation experiments are conducted on MTCCS in both non‐interference and interference scenarios. Simulation experiments show that MTCCS introducing the DHR idea achieves a balance between anti‐interference and decoding performance. It effectively addresses the issue of poor anti‐interference ability in turbo codes, and the decoding performance of MTCCS is superior to that of the previous single conventional turbo codes.

Abstract Background We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy. Methods We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials ( https://clinicaltrials.gov/ ). The data was analyzed by using Rstudio. Results Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1–5 cough, 0.176 (95%CI: 0.113–0.274, I2 = 92.36%); grades 1–5 pneumonitis, 0.118 (95%CI: 0.067–0.198, I2 = 88.64%); grades 1–5 upper respiratory tract infection, 0.064 (95%CI: 0.049–0.080, I2 = 0.98%); grades 3–5 cough, 0.050 (95%CI: 0.012–0.204, I2 = 8.90%); grades 3–5 pneumonitis, 0.052 (95%CI: 0.031–0.078, I2 = 83.86%); grades 3–5 upper respiratory tract infection, 0.040 (95%CI: 0.007–0.249, I2 = 45.31%). Conclusions Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients.

Abstract Recent studies have established that cellular electrostatic interactions are more influential than assumed previously. Here, we use cryo-EM and perform steady-state kinetic studies to investigate electrostatic interactions between cytochrome (cyt.) c and the complex (C) III2-IV supercomplex from Saccharomyces cerevisiae at low salinity. The kinetic studies show a sharp transition with a Hill coefficient ≥2, which together with the cryo-EM data at 2.4 Å resolution indicate multiple cyt. c molecules bound along the supercomplex surface. Negatively charged loops of CIII2 subunits Qcr6 and Qcr9 become structured to interact with cyt. c. In addition, the higher resolution allows us to identify water molecules in proton pathways of CIV and, to the best of our knowledge, previously unresolved cardiolipin molecules. In conclusion, the lowered electrostatic screening renders engagement of multiple cyt. c molecules that are directed by electrostatically structured CIII2 loops to conduct electron transfer between CIII2 and CIV.

Abstract Gallibacterium anatis (G. anatis) is an opportunistic pathogen previously associated with deaths in poultry and is also a pathogen that rarely causes human diseases. G. anatis has only been reported twice as the causative agent of a human disease (both in France). Here, we report a 62-year-old male patient with hypertension and type 2 diabetes who suffered from acute watery diarrhea caused by this bacterium which was identified by MALDI-TOF MS and 16 S rRNA sequencing. Despite human diarrhea caused by G.anatis is rare, with the continuous emergence of multidrug-resistant isolates of G. anatis in recent years, this case report will inform clinicians that G. anatis especially drug-resistant G. anatis may be a possible infectious source of human diarrhea in immune-suppressed populations.

Abstract Background Haem is essential but toxic for metazoan organisms. Auxotrophic nematodes can acquire sufficient haem from the environment or their hosts in the meanwhile eliminate or detoxify excessive haem through tightly controlled machinery. In previous work, we reported a role of the unique transporter protein HRG-1 in the haem acquisition and homeostasis of parasitic nematodes. However, little is known about the haem efflux and detoxification via ABC transporters, particularly the multiple drug resistance proteins (MRPs). Results Here, we further elucidate that a member of the mrp family (mrp-3) is involved in haem efflux and detoxification in a blood-feeding model gastrointestinal parasite, Haemonchus contortus. This gene is haem-responsive and dominantly expressed in the intestine and inner membrane of the hypodermis of this parasite. RNA interference of mrp-3 resulted in a disturbance of genes (e.g. hrg-1, hrg-2 and gst-1) that are known to be involved in haem homeostasis and an increased formation of haemozoin in the treated larvae and lethality in vitro, particularly when exposed to exogenous haem. Notably, the nuclear hormone receptor NHR-14 appears to be associated the regulation of mrp-3 expression for haem homeostasis and detoxification. Gene knockdown of nhr-14 and/or mrp-3 increases the sensitivity of treated larvae to exogenous haem and consequently a high death rate (> 80%). Conclusions These findings demonstrate that MRP-3 and the associated molecules are essential for haematophagous nematodes, suggesting novel intervention targets for these pathogens in humans and animals.

Abstract Vibrio vulnificus, a significant marine pathogen, undergoes opaque (Op)-translucent (Tr) colony switching based on whether capsular polysaccharide (CPS) is produced. CPS phase variation is sometime accompanied by genetic variation or down-regulation of particular genes, such as wzb. In addition, CPS prevents biofilm formation and is important to the virulence of V. vulnificus. However, the extent to which there is a difference in gene expression between Tr and Op colonies and the impact of CPS phase variation on other behaviors of V. vulnificus remain unknown. In this work, the data have shown that CPS phase variation of V. vulnificus is affected by incubation time. Tr and Op strains exhibited similar growth rates. However, Tr strains had enhanced biofilm formation capacities but reduced swimming motility compared to Op strains. The RNA-seq assay revealed 488 differentially expressed genes, with 214 downregulated and 274 upregulated genes, between Tr and Op colonies. Genes associated with Tad pili and CPS were downregulated, whereas those involved in flagellum were upregulated, in Tr colonies compared with Op colonies. In addition, 9 putative c-di-GMP metabolism-associated genes and 28 genes encoding putative regulators were significantly differentially expressed, suggesting that CPS phase variation is probably strictly regulated in V. vulnificus. Moreover, 8 genes encoding putative porins were also differentially expressed between the two phenotypic colonies, indicating that bacterial outer membrane was remodeled during CPS phase variation. In brief, this work highlighted the gene expression profiles associated with CPS phase variation, but more studies should be performed to disclose the intrinsic mechanisms in the future.

Abstract Recent studies indicate that Glypican 1 (GPC-1) is aberrantly expressed and plays a key role in certain cancers, but little is known in the hepatocellular carcinoma. Raw data from TCGA, GTEx and TIMER databases were utilized to comprehensively analyze GPC-1 expression landscape in pan-cancer, and the biological function of GPC-1 was investigated in liver cancer cells. The results revealed that GPC-1 is highly expressed in HCC, negatively correlated with survival, and also positively correlated with immune infiltration and clinical stage. Furthermore, GPC-1 promoted cell proliferation and inhibited apoptosis in the HCC cell lines. WGCNA analysis and HCCDB database revealed that Akt acted as a key molecule related to GPC-1, influencing biological functions and regulating cell malignant behaviors via the AKT signaling pathway. In conclusion, our findings provide a relatively comprehensive understanding of the oncogenic role of GPC-1 in HCC, implying that GPC-1 could serve as an innovative therapeutic target.

Abstract Objectives To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model. Methods The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model. The diagnosis performance was further validated in the validation and test sets. Prognostic aspects of the radiomics model were investigated using the Kaplan–Meier method and log-rank test. Differential gene expression analysis and gene ontology (GO) analysis were conducted to explore biological processes underlying the radiomics model based on RNA sequencing data. Results One hundred forty-three patients (mean age, 56.4 ± 10.5; 114 men) were enrolled, in which 73 (51.0%) were confirmed as MVI-positive. The radiomics model exhibited good performance in predicting MVI status, with the area under the curve of 0.935, 0.873, and 0.779 in training, validation, and test sets, respectively. Overall survival (OS) was significantly different between the predicted MVI-negative and MVI-positive groups (median OS: 25 vs 18 months, p = 0.008). Radiogenomic analysis revealed associations between the radiomics model and biological processes involved in regulating the immune response. Conclusion A robust MRI-based radiomics model was established for predicting MVI status in cHCC-CCA, in which potential prognostic value and underlying biological processes that regulate immune response were demonstrated. Critical relevance statement MVI is a significant manifestation of tumor invasiveness, and the MR-based radiomics model established in our study will facilitate risk stratification. Furthermore, underlying biological processes demonstrated in the radiomics model will offer valuable insights for guiding immunotherapy strategies. Key Points MVI is of prognostic significance in cHCC-CCA, but lacks reliable preoperative assessment. The MRI-based radiomics model predicts MVI status effectively in cHCC-CCA. The MRI-based radiomics model demonstrated prognostic value and underlying biological processes. The radiomics model could guide immunotherapy and risk stratification in cHCC-CCA. Graphical Abstract

Abstract. Objectives. This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors. Materials and methods. A total of 245 elderly patients diagnosed with prostate cancer and undergoing radical prostatectomy at a tertiary care general hospital in Jinan were included in this study. To assess the patients, several questionnaires were used. These included the General Situation Questionnaire, General Alienation Scale, Social Impact Scale, Modified Memorial Anxiety Scale for Prostate Cancer, and Perceived Social Support Scale. Pearson correlation analysis was conducted to examine the relationships between variables, whereas multiple linear regression was used to identify the factors influencing social alienation among patients who underwent radical prostatectomy. Results. Patients who underwent radical prostatectomy had a mean total score of 44.13 ± 7.24 on the Social Alienation Scale. The results of the Pearson correlation analysis indicated that social alienation showed an inverse association with social support (r = −0.627, p < 0.05) and positive associations with age, disease stigma, and anxiety (r = 0.325, 0.575, 0.421, all p’s < 0.01) among patients who underwent radical prostatectomy. The findings from multiple linear regression analysis demonstrated that educational level, age, urinary incontinence, disease stigma, anxiety, and social support significantly influenced social alienation among elderly patients who underwent radical prostatectomy (p < 0.05). Conclusions. Elderly patients who undergo radical prostatectomy often experience social alienation. This study found that social alienation was associated with factors such as educational level, age, urinary incontinence, social support, anxiety, and disease stigma. Consequently, healthcare providers should actively monitor the degree of social alienation in elderly patients after radical prostatectomy and provide suitable psychological care to facilitate positive social reintegration and alleviate their feelings of social alienation.

Abstract Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station. Overall, microgravity alters specific pathways for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, innate inflammation (e.g., Coronavirus pathogenesis pathway and IL-6 signaling), nuclear receptors, and sirtuin signaling. Microgravity directs monocyte inflammatory parameters, and impairs T cell and NK cell functionality. Using machine learning, we identify numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results define immune cell alterations in microgravity, and provide opportunities for countermeasures to maintain normal immunity in space.

Abstract Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a “spaceflight signature” of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

Abstract Telomeres are repetitive nucleoprotein complexes at chromosomal termini essential for maintaining genome stability. Telomeric RNA, or TERRA, is a previously presumed long noncoding RNA of heterogeneous lengths that contributes to end-capping structure and function, and facilitates telomeric recombination in tumors that maintain telomere length via the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. Here, we investigated TERRA in the radiation-induced DNA damage response (DDR) across astronauts, high-altitude climbers, healthy donors, and cellular models. Similar to astronauts in the space radiation environment and climbers of Mt. Everest, in vitro radiation exposure prompted increased transcription of TERRA, while simulated microgravity did not. Data suggest a specific TERRA DDR to telomeric double-strand breaks (DSBs), and provide direct demonstration of hybridized TERRA at telomere-specific DSB sites, indicative of protective TERRA:telomeric DNA hybrid formation. Targeted telomeric DSBs also resulted in accumulation of TERRA foci in G2-phase, supportive of TERRA’s role in facilitating recombination-mediated telomere elongation. Results have important implications for scenarios involving persistent telomeric DNA damage, such as those associated with chronic oxidative stress (e.g., aging, systemic inflammation, environmental and occupational radiation exposures), which can trigger transient ALT in normal human cells, as well as for targeting TERRA as a therapeutic strategy against ALT-positive tumors.

Abstract The COVID-19 pandemic has created significant challenges to the global economy, especially within the tourism industry. Economic downturns and psychological barriers make it even more challenging to attract tourists back. This paper explores the stimulating effect of digital travel vouchers on tourist mobility, as well as the heterogeneous effects of different vouchers modes. Using monthly data on tourist inflows in 306 cities from September 2020 to December 2021, collected by a web-crawling tool, and manually gathered information of digital travel vouchers issued during this period, our analyses show that digital travel vouchers can boost tourist inflows. Their effectiveness, however, depends on the method of issuance and the total number distributed. Furthermore, significant spillover effects among neighboring cities are found through a spatial econometric model.

Abstract LACTB is identified as a tumor suppressor in several tumors. However, preliminary study reveals that LACTB is overexpressed in osteosarcoma and indicates poor prognosis. Two missense mutations (rs34317102 and rs2729835) exist simultaneously in 92.31% of osteosarcoma patients and cause M5L and R469K double mutations in LACTB, suggesting the biologic function of LACTB protein may be altered in osteosarcoma. Moreover, LACTBM5L+R469K overexpression can promote malignant progression in different tumors, which suggests that the M5L and R469K mutations confer oncogene‐like functions to LACTB. Mechanistically, LACTBM5L+R469K not only reduces the wild type p53 via enhancing PSMB7 catalytic activity, but also protects p53R156P protein from lysosomal degradation, which suggesting LACTBM5L+R469K is a dual‐regulator for wt‐p53 and mutant p53, and derive oncogene‐like functions. More importantly, clavulanate potassium, a bacterial β‐lactamase inhibitor, can inhibit osteosarcoma proliferation and sensitize osteosarcoma to cisplatin by binding and blocking LACTBM5L+R469K. These findings revealed that the M5L and R469K double mutations can diminish the tumor suppressive ability of wild type LACTB and provide oncogene‐like functions to LACTB. Inhibiting LACTBM5L+R469K can suppress the progression of osteosarcoma harbouring wild‐type or mutant p53. Clavulanate potassium is a promising drug by targeting LACTBM5L+R469K‐p53 pathway for the treatment of osteosarcoma patients.

Extracting the precise parameters of photovoltaic (PV) cells has become very important for simulation, evaluation, control, and optimization of PV systems. However, it is still a challenging task to accurately and reliably extract the parameters of PV cells. To solve this difficult problem, in this paper, a new meta-heuristic algorithm called Gaussian bare-bone imperialist competitive algorithm with opposition-based learning (OBL-GBBICA) is proposed to extract the parameters of PV cells. To strengthen the exploring ability and speed up the convergence, opposition-based learning (OBL) is introduced into an imperialist competitive algorithm (ICA) for two considerations. First, OBL is adopted in the population initialization to produce a high-quality population. Second, the OBL is introduced into the assimilation step to guide ICA to explore more promising regions. The above improvements not only speed up the convergence of ICA but also enhance its searchability, which is beneficial to improving the accuracy and reliability of identification results. Experimental results show that OBL-GBBICA exhibits great superiority in extracting the PV cells parameters, compared with other methods in the literature.

To improve the efficiency of photovoltaic systems, it is essential to obtain the parameters of photovoltaic cells through an identification process. However, due to the nonlinear and multimodal characteristics, accurately and reliably identifying the parameters of photovoltaic cells still remains a challenging task. In this paper, a hybrid of the imperialist competitive algorithm (ICA) and particle swarm optimization (PSO), ICA-PSO, is proposed to effectively identify the parameters of photovoltaic cells. The position updating strategy of PSO is adopted to replace the colony’s position updating strategy in the ICA. The hybrid algorithm ICA-PSO integrates the multi-swarm search characteristic and the powerful exploration ability of PSO together, leading to an enhanced optimization performance. Experimental results of applying ICA-PSO to parameter identification of photovoltaic cells show that ICA-PSO can extract the parameters of photovoltaic cells with higher accuracy and reliability, thus outperforming many other methods presented in the literature.

Objective The types and number of day surgeries have significantly increased, but the construction of the whole process nursing service system (WPNSS) for preoperative education, intraoperative cooperation, postoperative knowledge, and follow-up for day surgery patients is still in the exploratory stage. The aim of this study is to establish the WPNSS for day surgery patients using the Kano model and to preliminarily assess its efficacy. Methods WPNSS for day surgery was devised leveraging Internet hospital information systems and patient mobile terminals (WeChat), guided by the World Health Organization's conceptual framework for scaling-up strategies. The system was methodically developed, progressing from defining the overall framework to delineating modular functions and developing specific educational materials and tools. A pilot test was conducted in a hospital in China. Results WPNSS, a patient-centric remote education and monitoring system, seamlessly amalgamates health education, online consultations, and follow-up functionalities; offering semi-automated surgical consultations, inquiry services, and postoperative follow-ups, as well as autonomously disseminating perioperative health education content. Comprising both client and server components, patients utilizing the system are inclined to recommend day surgery at the hospital to others Conclusions WPNSS delivers personalized and precise health education, consultation, and postoperative follow-up services for day surgery patients. Current results suggest that the WPNSS may improve patients’ experience. Trial Registration Chinese Clinical Trial Register (ChiCTR2200066782).

Background Chimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability.Methods A 4-1BB-costimulated B-cell maturation antigen (BCMA) CAR-T integrating an independently-expressed OX40 (BCMA-BBZ-OX40) was designed and generated by a traditional manufacturing process (TraditionCART) or instant manufacturing platform (named InstanCART). The tumor-killing efficiency, differentiation, exhaustion, and expansion level were investigated in vitro and in tumor-bearing mice. An investigator-initiated clinical trial was performed in patients with R/R MM to evaluate the outcomes of both TraditionCART and InstanCART. The primary objective was safety within 1 month after CAR-T cell infusion. The secondary objective was the best overall response rate.Results Preclinical studies revealed that integrated OX40 conferred BCMA CAR-T cells with superior cytotoxicity and reduced exhaustion levels. InstanCART process further enhanced the proliferation and T-cell stemness of BCMA-BBZ-OX40 CAR-T cells. BCMA-BBZ-OX40 CAR-T cells were successfully administered in 22 patients with R/R MM, including 15 patients with TraditionCART and 7 patients with InstanCART. Up to 50% (11/22) patients had a high-risk cytogenetic profile and 36% (8/22) had extramedullary disease. CAR-T therapy caused grade 1–2 cytokine release syndrome in 19/22 (80%) patients, grade 1 neurotoxicity in 2/22 (9%) patients and led to ≥grade 3 adverse events including neutropenia (20/22, 91%), thrombocytopenia (15/22, 68%), anemia (12/22, 55%), creatinine increased (1/22, 5%), hepatic enzymes increased (5/22, 23%), and sepsis (1/22, 5%). The best overall response rate was 100%, and 64% (14/22) of the patients had a complete response or better. The median manufacturing time was shorter for InstanCART therapy (3 days) than for TraditionCART therapy (10 days). Expansion and duration were dramatically higher for InstanCART cells than for TraditionCART cells.Conclusions BCMA-BBZ-OX40 CAR-T cells were well tolerated and exhibited potent responses in patients with R/R MM. InstanCART shortened the manufacturing period compared to TraditionCART, and improved the cellular kinetics. Our results demonstrated the potency and feasibility of OX40-modified BCMA CAR-T cells using InstanCART technology for R/R MM therapy.Trial registration number This trial was registered at www.clinicaltrials.gov as #NCT04537442.

ABSTRACT Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = −0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = −0.4451) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = −0.3868) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

To study the failure of red sandstone under extremely high stress during the service life of tunnels, an in-depth study was conducted on the mechanical properties of red sandstone under uniaxial loading and cyclic loading and unloading processes at different pH values using the AG-250kNIS electronic precision material testing machine and MTS815 mechanical testing machine. The results show that as the acidity and alkalinity increase, the peak stress under uniaxial loading decreases and the axial strain increases,The peak stress at failure is 9.40, 12.37, 7.18, and 5.36 MPa, respectively, accounting for 74.19%, 68.91%, 40.38%, and 36.21% of the uniaxial compressive strength; The number of cycles significantly decreases during cyclic loading and unloading fatigue failure, and the stress required for sandstone failure gradually decreases. The peak strength and elastic modulus of sandstone show a decreasing trend, indicating that the hydrochemical environment plays an accelerating role in rock degradation. During the cyclic loading and unloading process of sandstone, there is a continuous increase in dissipated energy and finally a sudden increase, the Ud/U and Ue/U ratios at the peak point of sandstone in the natural state are 0.399 and 0.601, respectively, while the overall elastic energy shows an increasing trend; and a damage evolution model was established based on dissipative energy, which can better describe the degradation process of red sandstone.

Elucidating the underlying factors driving the rich biodiversity in mountainous regions remains a central yet unresolved question in ecology, especially for tropical regions. The classical community assembly theory posits that environmental filtering and interspecific competition result in spatial variation in local communities. In this study, we characterized the taxonomic, phylogenetic, and functional diversity of birds, and examined the potential role of deterministic processes in shaping community assembly along elevational gradients in Mt. Kenya, a typical Afromontane ecosystem. Furthermore, we employed a novel partial least squares regression (PLSR) methodology to investigate the potential ecological mechanisms that may account for bird distribution patterns. The gradual unimodal or monotonic decline in richness metrics (species richness, phylogenetic diversity, and functional diversity) and/or phylogenetic and functional mean pairwise distances with increasing elevation suggested a progressive loss of bird species across clades at higher elevations. Conversely, in the productivity-scarce highlands, heightened competition led to reduced functional affinity among community members, resulting in increased functional mean nearest taxon distance. Moreover, the shift from overdispersion to clustering in terms of phylogenetic community structure with elevation indicated a potential transformation from limiting similarity to abiotic filtering, while the lack of clear patterns or weak increased tendencies of the functional assemblage structures suggested complex interactions between ecological and evolutionary processes. Our investigation highlighted several potential explanations for the observed diversity gradients, including factors related to primary productivity (plant species richness and enhanced vegetation index), water-energy availability (annual mean temperature and potential evapotranspiration), and climatic stability (temperature annual range). Our findings highlight the need for a comparative approach incorporating multidimensional measures to study biodiversity spatial distribution patterns, community assembly processes, and sustainable conservation of tropical Afromontane biodiversity.

Abstract Background Previously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel clinical phenotypes in ARDS using trajectories of fluid balance, to test whether phenotypes respond differently to different treatment, and to develop a simplified model for phenotype identification. Methods FACTT (conservative vs liberal fluid management) trial was classified as a development cohort, joint latent class mixed models (JLCMMs) were employed to identify trajectories of fluid balance. Heterogeneity of treatment effect (HTE) for fluid management strategy across phenotypes was investigated. We also constructed a parsimonious probabilistic model using baseline data to predict the fluid trajectories in the development cohort. The trajectory groups and the probabilistic model were externally validated in EDEN (initial trophic vs full enteral feeding) trial. Results Using JLCMM, we identified two trajectory groups in the development cohort: Class 1 (n = 758, 76.4% of the cohort) had an early positive fluid balance, but achieved negative fluid balance rapidly, and Class 2 (n = 234, 24.6% of the cohort) was characterized by persistent positive fluid balance. Compared to Class 1 patients, patients in Class 2 had significantly higher 60-day mortality (53.5% vs. 17.8%, p

Abstract Gaussian bare-bone imperialist competitive algorithm (GBB-ICA) is an effective variant of imperialist competitive algorithm (ICA), which updates the position of colonies by sampling a Gaussian distribution. However, the mean and standard deviation adopted by GBB-ICA is calculated only using the positions of imperialist and the colony itself, making the searching tends to trap into local optimum. To overcome this drawback, a new double Gaussian sampling strategy is proposed in this paper. An extra Gaussian sampling point, whose mean and standard is calculated using the positions of the second best colony and the current colony itself, is introduced into GBB-ICA. To further speed up the convergence and explore informative region, the quasi-oppositional learning technique is incorporated into GBB-ICA to produce more potential candidates in the assimilation step as well as generating a higher quality initial population. The proposed algorithm is called quasi-oppositional learning-based double Gaussian sampling bare-bone imperialist competitive algorithm (QOLBDGSBB-ICA) and is tested on 20 benchmark functions and four engineering design problems. Experimental results show that the proposed algorithm outperforms over other referenced ICA variants on 19 benchmark functions, which well validates the effectiveness of the proposed algorithm.

Fractal theory offers a powerful tool for the precise description and quantification of the complex pore structures in reservoir rocks, crucial for understanding the storage and migration characteristics of media within these rocks. Faced with the challenge of calculating the three-dimensional fractal dimensions of rock porosity, this study proposes an innovative computational process that directly calculates the three-dimensional fractal dimensions from a geometric perspective. By employing a composite denoising approach that integrates Fourier transform (FT) and wavelet transform (WT), coupled with multimodal pore extraction techniques such as threshold segmentation, top-hat transformation, and membrane enhancement, we successfully crafted accurate digital rock models. The improved box-counting method was then applied to analyze the voxel data of these digital rocks, accurately calculating the fractal dimensions of the rock pore distribution. Further numerical simulations of permeability experiments were conducted to explore the physical correlations between the rock pore fractal dimensions, porosity, and absolute permeability. The results reveal that rocks with higher fractal dimensions exhibit more complex pore connectivity pathways and a wider, more uneven pore distribution, suggesting that the ideal rock samples should possess lower fractal dimensions and higher effective porosity rates to achieve optimal fluid transmission properties. The methodology and conclusions of this study provide new tools and insights for the quantitative analysis of complex pores in rocks and contribute to the exploration of the fractal transport properties of media within rocks.

Abstract Background Osteosarcoma is a diverse and aggressive bone tumor. Driver genes regulating osteosarcoma initiation and progression remains incompletely defined. Zinc finger protein 692 (ZNF692), a kind of Krüppel C2H2 zinc finger transcription factor, exhibited abnormal expression in different types of malignancies and showed a correlation with the clinical prognosis of patients as well as the aggressive characteristics of cancer cells. Nevertheless, its specific role in osteosarcoma is still not well understood. Methods We investigated the dysregulation and clinical significance of ZNF692 in osteosarcoma through bioinformatic method and experimental validation. A range of in vitro assays, including CCK-8, colony formation, EdU incorporation, wound healing, and transwell invasion tests, were conducted to assess the impact of ZNF692 on cell proliferation, migration, and invasion in osteosarcoma. A xenograft mouse model was established to evaluate the effect of ZNF692 on tumor growth in vivo. Western blot assay was used to measure the protein levels of MEK1/2, P-MEK1/2, ERK1/2, and P-ERK1/2 in cells that had been genetically modified to either reduce or increase the expression of ZNF692. The relationship between ZNF692 and tyrosine kinase non-receptor 2 (TNK2) were validated by qRT-PCR, chromatin immunoprecipitation and luciferase reporter assays. Results Expression of ZNF692 was increased in both human osteosarcoma tissues and cell lines. Furthermore, the expression of ZNF692 served as an independent predictive biomarker in osteosarcoma. The results of the survival analysis indicated that increased expression of ZNF692 was associated with worse outcome. Downregulation of ZNF692 inhibits the proliferation, migration, and invasion of osteosarcoma cells, whereas upregulation of ZNF692 has the opposite impact. Western blot assay indicates that reducing ZNF692 decreases phosphorylation of MEK1/2 and ERK1/2, whereas increasing ZNF692 expression enhances their phosphorylation. U0126, a potent inhibitor specifically targeting the MEK/ERK signaling pathway, partially counteracts the impact of ZNF692 overexpression on the proliferation, migration, and invasion of osteosarcoma cells. In addition, ZNF692 specifically interacts with the promoter region of TNK2 and stimulates the transcription of TNK2 in osteosarcoma cells. Forcing the expression of TNK2 weakens the inhibitory impact of ZNF692 knockdown on P-MEK1/2 and P-ERK1/2. Similarly, partly inhibiting TNK2 counteracts the enhancing impact of ZNF692 overexpression on the phosphorylation of MEK1/2 and ERK1/2. Functional tests demonstrate that the suppressive effects of ZNF692 knockdown on cell proliferation, migration, and invasion are greatly reduced when TNK2 is overexpressed. In contrast, the reduction of TNK2 hinders the ability of ZNF692 overexpression to enhance cell proliferation, migration, and invasion. Conclusion ZNF692 promotes the proliferation, migration, and invasion of osteosarcoma cells via the TNK2-dependent stimulation of the MEK/ERK signaling pathway. The ZNF692-TNK2 axis might potentially function as a possible predictive biomarker and a promising target for novel therapeutics in osteosarcoma.

Acute kidney injury (AKI) induced by cisplatin (DDP), which is accompanied with the generation of reactive oxygen species (ROS), is a severe side effect during treatment and restricts the application of DDP. In this study, we develop ultrasmall Mn3O4 nanozyme (UMON) with tumor microenvironment (TME) responsive ROS scavenging and generating as adjuvant to alleviate DDP induced AKI with improved efficacy. In kidney, UMON with superoxide dismutase and catalase activity acts as ROS scavenger to eliminate ROS generated by DDP, successfully protecting the renal cells/tissue and alleviating AKI during DDP treatment. Alternatively, UMON rapidly responses to the high GSH level in TME and release Mn2+ in tumor. This unique feature endows it to generate hydroxyl radicals (∙OH) through a Fenton-like reaction and deplete GSH in tumor cell and tissue, achieving high efficient chemodynamic therapy (CDT). More importantly, the Mn2+ successfully activates the cGAS-STING pathway, initiating the immune response and effectively inhibiting the tumor metastases. The synergistic CDT and immune therapy effectively improve the anti-tumor efficacy of DDP in vitro and in vivo. This study demonstrates that TME responsive ROS scavenger/generator shows the potential to reduce side effects of DDP while improve its therapeutic efficacy, providing a new avenue to achieve efficient chemotherapy and promoting the progress of clinical chemotherapy.

ABSTRACTNatural Language Processing (NLP) is a technology that permits computers to recognize human languages. Words are the fundamental unit of analysis in deep-level grammatical and semantic analysis. The main goal of NLP is typically word segmentation. Since the machine learning techniques cannot be directly applied to the practical issue of significant structural disparities between various data modalities in a multi-modal context. In this paper, English Vocabulary Learning Aid System Using Digital Twin Wasserstein Generative Adversarial Network Optimized using Jelly Fish Optimization Algorithm is proposed. The problematic of multiple modal data heterogeneity is handled by the feature extraction of Parameterized Local Maximum Synchro squeezing Transform and extract the features such as Phonetic features, sentence length, word embedding’s, part of speech tags, word frequencies, N-grams. Then, the Digital twin Wasserstein generative adversarial network classifies the English vocabulary to easy words, intermediate words, and difficult words. The performance of the proposed EVLS-DtwinWGAN-NLP approach attains 3.101%, 7.12%, 7.73% higher accuracy, 24.13%, 13.04%, 29.51% lower computation Time and 2.292%, 5.365%, 1.551% higher AUC compared with existing methods like Feature extraction and analysis of natural language processing for deep learning English language (EVLS-BiLSTM-NLP), State of art for semantic analysis of natural language processing (EVLS-SA-NLP) respectively.

Background: The limitations of prostate-specific antigen (PSA) in diagnosing prostate cancer (PCa) necessitate the exploration of novel biomarkers. Recent studies suggest a potential link between coagulation markers, particularly fibrinogen and D-dimer, and PCa. Methods: A retrospective single-center analysis on 466 biopsy-undergone patients was conducted, categorized into PCa and benign prostatic hyperplasia (BPH) groups. Baseline and coagulation parameter levels were analyzed. Utilizing a Mendelian randomization (MR) approach, we investigated the causative relationship between D-dimer and PCa risk. Results: Individuals with PCa, compared with those with BPH, exhibited significantly higher D-dimer levels ( P

Summary: Alzheimer’s disease (AD) is a complex pathophysiological disease. Allowing for heterogeneity, not only in disease manifestations but also in different progression patterns, is critical for developing effective disease models that can be used in clinical and research settings. We introduce a machine learning model for identifying underlying patterns in Alzheimer’s disease (AD) trajectory using longitudinal multi-modal data from the ADNI cohort and the AIBL cohort. Ten biologically and clinically meaningful disease-related states were identified from data, which constitute three non-overlapping stages (i.e., neocortical atrophy [NCA], medial temporal atrophy [MTA], and whole brain atrophy [WBA]) and two distinct disease progression patterns (i.e., NCA → WBA and MTA → WBA). The index of disease-related states provided a remarkable performance in predicting the time to conversion to AD dementia (C-Index: 0.923 ± 0.007). Our model shows potential for promoting the understanding of heterogeneous disease progression and early predicting the conversion time to AD dementia.

Bladder cancer is one of the most common malignancies of the urinary tract and a prevalent cancer worldwide, still requiring efficient therapeutic agents and approaches. 20-Hydroxyecdysone (20-HE), a steroid hormone, can be found in insects and few plants and mediate numerous biological events to control the progression of varying diseases; however, its impacts on bladder cancer remain unclear. In the study, we found that 20-HE treatments effectively inhibited the viability and proliferation of bladder cancer cells and induced apoptosis by activating Caspase-3. The migratory and invasive potential of bladder cancer cells was markedly repressed by 20-HE in a dose-dependent manner. The inhibitory effects of 20-HE on bladder cancer were confirmed in an established xenograft mouse model, as indicated by the markedly reduced tumor growth rates and limited lung and lymph node metastasis. High-throughput RNA sequencing was performed to explore dysregulated genes in bladder cancer cells after 20-HE treatment. We identified ubiquitin-specific protease 21 (USP21) as a key deubiquitinating enzyme for bladder cancer progression and a positive correlation between USP21 and nuclear factor-κB (NF-κB)/p65 in patients. Furthermore, 20-HE treatments markedly reduced USP21 expression, NF-κB/p65 mRNA, stability and phosphorylated NF-κB/p65 expression levels in bladder cancer cells, which were validated in animal tumor tissues. Mechanistic studies showed that USP21 directly interacted with and stabilized p65 by deubiquitinating its K48-linked polyubiquitination in bladder cancer cells, which could be abolished by 20-HE treatment, contributing to p65 degradation. Finally, we found that USP21 overexpression could not only facilitate the proliferation, migration, and invasion of bladder cancer cells, but also significantly eliminated the suppressive effects of 20-HE on bladder cancer. Notably, 20-HE could still perform its anti-tumor role in bladder cancer when USP21 was knocked down with decreased NF-κB/p65 expression and activation, revealing that USP21 suppression might not be the only way for 20-HE during bladder cancer treatment. Collectively, all our results clearly demonstrated that 20-HE may function as a promising therapeutic strategy for bladder cancer treatment mainly through reducing USP21/p65 signaling expression.

BackgroundThis systematic review and meta-analysis aims to investigate the effects of virtual reality (VR) exercise compared to traditional rehabilitation on pain, function, and muscle strength in patients with knee osteoarthritis (KOA). Additionally, the study explores the mechanisms by which VR exercise contributes to the rehabilitation of KOA patients.MethodsWe systematically searched PubMed, the Cochrane Library, Embase, Web of Science, Scopus, and PEDro according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search spanned from the library construction to 24 May 2024, focusing on randomized controlled trials Primary outcomes included pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and muscle strength. Meta-analysis was conducted using RevMan (version 5.4) and Stata (version 14.0). The bias risk of included studies was assessed using the Cochrane RoB 2.0 tool, while the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.ResultsThis meta-analysis and systematic review included nine studies involving 456 KOA patients. The results indicated that VR exercise significantly improved pain scores (SMD, −1.53; 95% CI: −2.50 to −0.55; p = 0.002), WOMAC total score (MD, −14.79; 95% CI: −28.26 to −1.33; p = 0.03), WOMAC pain score (MD, −0.93; 95% CI: −1.52 to −0.34; p = 0.002), knee extensor strength (SMD, 0.51; 95% CI: 0.14 to 0.87; p = 0.006), and knee flexor strength (SMD, 0.65; 95% CI: 0.28 to 1.01; p = 0.0005), but not significantly for WOMAC stiffness (MD, −0.01; 95% CI: −1.21 to 1.19; p = 0.99) and physical function (MD, −0.35; 95% CI: −0.79 to −0.09; p = 0.12).ConclusionVR exercise significantly alleviates pain, enhances muscle strength and WOMAC total score in KOA patients, but improvements in joint stiffness and physical function are not significant. However, the current number of studies is limited, necessitating further research to expand on the present findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024540061, identifier CRD42024540061

Abstract Background Ovarian cancer is a common gynecological tumor with high malignant potential and poor prognosis. TRIM8, is involved in the development of various tumors, but its precise regulatory role in ovarian cancer is still unknown. Aims The aim of this study was to explore the specific mechanism by which TRIM8 regulates ovarian cancer. Materials and Methods We used bioinformatics analysis to screen for high expression of TRIM8 in ovarian cancer. The expression of TRIM8 in healthy and cancerous ovarian tissues was assessed by immunofluorescence. TRIM8 was silenced or overexpressed in ovarian cancer cell lines, with cell proliferation and migration evaluated by CCK8, transwell and clonal formation assays. The effect of TRIM8 on ovarian cancer cells in vivo was assessed by subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified by mass spectrometry. The mechanism underlying TRIM8 regulation of VDAC2 was evaluated by co‐immunoprecipitation and western blotting. Results TRIM8 was overexpressed in ovarian cancer. TRIM8 promoted the proliferation and migration of ovarian cancer cells in vitro and the growth of subcutaneous tumors in mice in vivo. TRIM8 interacted with VDAC2, weakened the stability of the protein, and promoted its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of ovarian cancer cells to iron death, whereas overexpression of VDAC2 attenuated ovarian cancer progression induced by TRIM8 overexpression. Discussion TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation, these finding may provide new targets for the treatment of ovarian cancer. Conclusion TRIM8 degraded VDAC2 through the ubiquitination pathway, increased the resistance of ovarian cancer cells to iron death, and promoted the proliferation and migration of ovarian cancer.

Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated.Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups.Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues.Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.

Abstract Background Ovarian cancer (OC) has the highest mortality rate among all gynecological malignancies. A hypoxic microenvironment is a common feature of solid tumors, including ovarian cancer, and an important driving factor of tumor cell survival and chemo- and radiotherapy resistance. Previous research identified the hypoxia-associated gene angiopoietin-like 4 (ANGPTL4) as both a pro-angiogenic and pro-metastatic factor in tumors. Hence, this work aimed to further elucidate the contribution of ANGPTL4 to OC progression. Methods The expression of hypoxia-associated ANGPTL4 in human ovarian cancer was examined by bioinformatics analysis of TCGA and GEO datasets. The CIBERSORT tool was used to analyze the distribution of tumor-infiltrating immune cells in ovarian cancer cases in TCGA. The effect of ANGPTL4 silencing and overexpression on the proliferation and migration of OVCAR3 and A2780 OC cells was studied in vitro, using CCK-8, colony formation, and Transwell assays, and in vivo, through subcutaneous tumorigenesis assays in nude mice. GO enrichment analysis and WGCNA were performed to explore biological processes and genetic networks associated with ANGPTL4. The results obtained were corroborated in OC cells in vitro by western blotting. Results Screening of hypoxia-associated genes in OC-related TCGA and GEO datasets revealed a significant negative association between ANGPTL4 expression and patient survival. Based on CIBERSORT analysis, differential representation of 14 distinct tumor-infiltrating immune cell types was detected between low- and high-risk patient groups. Silencing of ANGPTL4 inhibited OVCAR3 and A2780 cell proliferation and migration in vitro and reduced the growth rate of xenografted OVCAR3 cells in vivo. Based on results from WGCNA and previous studies, western blot assays in cultured OC cells demonstrated that ANGPTL4 activates the Extracellular signal-related kinases 1 and 2 (ERK1/2) pathway and this results in upregulation of c-Myc, Cyclin D1, and MMP2 expression. Suggesting that the above mechanism mediates the pro-oncogenic actions of ANGPTL4T in OC, the pro-survival effects of ANGPTL4 were largely abolished upon inhibition of ERK1/2 signaling with PD98059. Conclusions Our work suggests that the hypoxia-associated gene ANGPTL4 stimulates OC progression through activation of the ERK1/2 pathway. These findings may offer a new prospect for targeted therapies for the treatment of OC.

Blockchain is gaining popularity as a technology that provides secure data sharing and management for the Internet of vehicles (IoV). The current research on cross-chaining between blockchains is still inefficient, and how to perform efficient cross-chain data communication has not been well studied. This paper studies the cross-chain protocol in the IoV environment, and designs a lightning-c cross-chain protocol based on the lightning network. The protocol consists of three steps. The user opens the cross-chain channel through election of nodes, and conducts transactions in the cross-chain channel, then the cross-chain channel is closed and the transaction is broadcasted to the blockchain. Our proposed approach enables efficient interoperability between heterogeneous blockchains. Compared with the traditional cross-chain protocol BTCRelay, it is proved that the lightning-c cross-chain mechanism can greatly improve the throughput of cross-chain transactions. The experimental results show that the method proposed in this paper is more efficient.

This study investigates the potential of Particle Swarm Optimization (PSO)-based Neural Network (NN) training to enhance the efficacy of English language instruction. Recognizing English as a global language vital for international communication and economic interaction, effective language training is imperative. Leveraging PSO as a guiding mechanism for NN training presents a novel approach to refine instructional strategies. This study critically examines existing literature and identifies shortcomings in conventional algorithms employed in English teaching methodologies. Subsequently, a sophisticated algorithmic framework integrating PSO with NN is proposed to address these deficiencies and augment instructional outcomes. The adaptability of this methodology to conventional teaching models in English language education is explored. Experimentation and simulation validate the effectiveness of this innovative approach, illustrating its potential to revolutionize English education by optimizing learning outcomes. The findings underscore the significance of PSO-driven NN training in enhancing teaching effectiveness, paving the way for advancing English language education methodologies.

Abstract Background Components of excretory/secretory products (ESPs) of helminths have been proposed as vaccine targets and shown to play a role in modulating host immune responses for decades. Such research interest is further increased by the discovery of extracellular vesicles (EVs) in the ESPs of parasitic worms. Although efforts have been made to reveal the cargos of EVs, little is known about the proteomic differences between EVs and canonical ESPs released by parasitic worms from animals. Methods The total ESPs of Haemonchus contortus (barber’s pole worm) were obtained by short-term in vitro culturing of young adult worms, and small EVs were isolated from ESPs using an ultracentrifugation method. Data-dependent acquisition (DDA) label-free Nano-LC–MS/MS was used to quantify the proteomic difference between small EVs and EV-depleted ESPs of H. contortus. Functional annotation and enrichment of the differential proteins were performed regarding cellular components, molecular functions, pathways, and/or biological processes. Results A total of 1697 proteins were identified in small EVs and EV-depleted ESPs of H. contortus adult worms, with 706 unique proteins detected in the former and 597 unique proteins in the latter. It was revealed that proteins in small EVs are dominantly cytoplasmic, whereas proteins in EV-depleted ESPs are mainly extracellular; canonical ESPs such as proteases and small GTPases were abundantly detected in small EVs, and SCP/TAP-, DUF-, and GLOBIN domain-containing proteins were mainly found in EV-depleted ESPs. Compared with well-characterised proteins in small EVs, about 50% of the proteins detected in EV-depleted ESPs were poorly characterised. Conclusions There are remarkable differences between small EVs and EV-depleted ESPs of H. contortus in terms of protein composition. Immune modulatory effects caused by nematode ESPs are possibly contributed mainly by the proteins in small EVs. Graphical Abstract

Abstract Background The large-scale application of pyrethroids and organophosphorus pesticides has great benefits for pest control. However, the increase of cancer incidence rate in recent years has also caused public concern about the health risks of pesticides. Hence, we utilized data from the National Health and Nutrition Examination Survey (NHANES) to assess the association and risk between pesticide exposure and several cancers, along with the comprehensive impact of oxidative stress. In this study, six cancers and six common pesticides were included to analyze their correlation and risk. And the levels of eight oxidative stress marks and two inflammatory markers were used for stratified analysis. Multiple logistic regression analysis was applied to estimate the odds ratio and 95% confidence intervals. Machine learning prediction models were established to evaluate the importance of different exposure factors. Results According to the data analyzed, each pesticide increased the risk of three to four out of six cancers on average. Iron, aspartate aminotransferase (AST), and gamma glutamyl transferase levels positively correlated with cancer risk in most cases of pesticide exposure. Except for demographic factors, factors such as AST, iron, and 3-phenoxybenzoic acid showed high contributions to the random forest model, which was consistent with our expectations. The receiver operating characteristic curve showed that the prediction model had sufficient accuracy (74.2%). Conclusion Our results indicated that specific pesticide exposure increased the risk of cancer, which may be mediated by various oxidative stress mechanisms. Additionally, some biochemical indicators have the potential to be screened for cancer prevention.

The electrochemical hydrogen evolution reaction (HER) stands as a burgeoning clean energy prospect. This work synthesized composite materials (CMOxCNT), exhibiting exceptional electrocatalytic prowess, emerged from the fusion of cobalt molybdate (CMO) and carbon nanotubes (CNT). The outcomes of characterization established the CMO as a hydrated cobalt molybdate mineral, the theoretical molecular formula CoMoO4·nH2O. The CMO particles demonstrated a distinctive rod-shaped morphology. Notably, under the optimal mass ratio (CMO/CNT=7/3), carbon nanotubes exhibited partial coverage of the CMO particle surface. Electrochemical hydrogen evolution experiments decisively illuminated the catalytic potency of the CMO-CNT composites, which effectively improved the HER efficiency. The CMO3CNT, distinguished by elevated electrochemically active surface area, yielded a lower HER overpotential of 171.5 mV (at 10 mA·cm−2) and Tafel slope of 69.9 mV dec−1. Importantly, the material demonstrated commendable catalytic stability across a 30-hour span of i-t tests and 3000 CV cycles. Density Functional Theory (DFT) analyses unveiled at the adept electron transfer capabilities in CNT and favorable catalytic ability exhibited in CMO contributed substantively to the composite's overall efficacy. The remarkable catalytic proficiency of CMO stemmed from the synergistic interplay between cobalt and molybdenum atoms. The amalgamation of both inherent advantages engendered the composite's pronounced electrocatalytic performance.

Abstract. Background. Bladder cancer (BLCA) is the most common malignancy of the urinary system. Muscle-invasive bladder cancer (MIBC), which constitutes approximately 25% of all BLCA cases, is characterized by frequent recurrence and early onset of metastasis. Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging. However, the prognostic value of age-related genes in BLCA, especially in MIBC, remains unclear. Materials and methods. Training and testing sets were obtained from The Cancer Genome Atlas BLCA project. Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures, followed by the construction of a risk score model and nomogram. Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power. An independent BLCA cohort of 165 samples was included for external validation. The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment. Results. Seven genes (IGF1, NGF, GCLM, PYCR1, EFEMP1, APOC3, and IFNB1) were identified by Cox and least absolute shrinkage and selection operator analyses. After combining the gene signature with the clinical parameters of patients with BLCA, a risk-prognosis model and nomogram were constructed and validated with the testing set. Bladder cancer cases with high 7-gene signature scores (high-risk group) and low scores (low-risk group) showed distinct prognoses. Furthermore, 7 types of immune cells were significantly altered between the low- and high-risk groups. Conclusions. Collectively, our data provide a 7-gene signature that serves as a potential biomarker for BLCA, especially MIBC. Moreover, this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1–based immunotherapy.

Bolted joints, with their advantages of simple structure and convenient disassembly and assembly, are widely used in complex equipment fields such as aerospace systems and weaponry. Subject to complex mechanical loads, the contact surfaces may undergo nonlinear behaviors such as contact–separation and viscous slip, leading to the nonlinear degradation of the connection stiffness, which severely threatens the safety and reliability. These have driven research on bolted joints to span multiple disciplines, from interfacial micro-friction to macro-structural dynamics. Therefore, from the field of micro-friction to macro-dynamics, this review summarizes and analyzes three major degradation models, outlines the experimental development in connected structures, and provides an overview of the numerical analysis methods for degradation simulation. This paper also looks forward to the development directions for future research on the degradation of connected structures.

Soybean [Glycine max (L.) Merr.], as a globally commercialized crop, is an important source of protein and oil for both humans and livestock. With more frequent extreme weather disasters, abiotic stress has become one of the critical factors restricting soybean production. Proline (Pro) is a well-known substance in plants that responds to abiotic stress. To identify potential effector genes involved in soybean resistance to abiotic stress, we focused on the pyrroline-5-carboxylate dehydrogenase (P5CDH) which is a key enzyme in the degradation process of Pro. Through homologous sequence alignment, phylogenetic tree, and predicted expression, we chose GmP5CDH1 (Glyma.05G029200) for further research. Tissue-specific expression assay showed that GmP5CDH1 had higher expression levels in soybean seed and cotyledon development. Subcellular localization assay revealed that GmP5CDH1 was a nuclear-membrane-localized protein. As the result of the predicted cis-acting regulatory element indicates, the expression level of GmP5CDH1 was induced by low temperature, drought, salt stress, and ABA in soybean. Next, we constructed transgenic Arabidopsis overexpressing GmP5CDH1. The results showed that GmP5CDH1 also strongly responded to exogenous Pro, and overcame the toxicity of abiotic stress on plants by regulating the endogenous concentration of Pro. The interaction between GmP5CDH1 and GmSAM1 was validated through yeast two-hybrid, LUC fluorescence complementary, and BIFC. In conclusion, overexpression of a soybean pyrroline-5-carboxylate dehydrogenase GmP5CDH1 regulates the development of Arabidopsis thaliana by altering proline content dynamically under salt stress, especially improving the growth of plants under exogenous Pro.

Hail poses a significant meteorological hazard in China, leading to substantial economic and agricultural damage. To enhance the detection of hail and mitigate these impacts, this study presents an ensemble machine learning model (BPNN+Dtree) that combines a backpropagation neural network (BPNN) and a decision tree (Dtree). Using FY-4A satellite and ERA5 reanalysis data, the model is trained on geostationary satellite infrared data and environmental parameters, offering comprehensive, all-day, and large-area hail monitoring over China. The ReliefF method is employed to select 13 key features from 29 physical quantities, emphasizing cloud-top and thermodynamic properties over dynamic ones as input features for the model to enhance its hail differentiation capability. The BPNN+Dtree ensemble model harnesses the strengths of both algorithms, improving the probability of detection (POD) to 0.69 while maintaining a reasonable false alarm ratio (FAR) on the test set. Moreover, the model’s spatial distribution of hail probability more closely matches the observational data, outperforming the individual BPNN and Dtree models. Furthermore, it demonstrates improved regional applicability over overshooting top (OT)-based methods in the China region. The identified high-frequency hail areas correspond to the north-south movement of the monsoon rain belt and are consistent with the northeast-southwest belt distribution observed using microwave-based methods.

Objectives The objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs).Design This was a prospective cohort study.Setting This study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China.Primary and secondary outcome measures A cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model.Results The adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP.Conclusions As independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.

ObjectiveTo investigate the prevalence of chronic kidney disease (CKD) and the association of obesity with CKD among hypertension patients registered at community health service centers in suburb of Shanghai. MethodsThe participants of the study were 3 600 hypertensive patients randomly recruited from chronic disease patients registered at two community health service centers in a suburban district of Shanghai city. Face-to-face interview with a self-designed questionnaire and the International Physical Activity Questionnaire, physical examination, laboratory tests were conducted among the participants during October – December 2021. Unconditional multivariate logistics regression model was adopted to analyze the association between body mass index [BMI] and CKD. ResultsOf the 2 991 participants finally included in the analysis, 1 037 (34.67%) were identified as having CKD and the number (proportion) of the participants with decreased estimated glomerular filtration (eGFR), proteinuria, and hematuria were 464 (15.51%), 677 (22.63%), and 99 (3.31%), respectively. After adjusting for age, sex, education, smoking, alcohol drinking, physical activity, diabetes, blood lipids and blood pressure control, unconditional multivariate logistic regression analysis revealed that the participants with obesity (BMI ≥ 28.0) were at a significantly increased risk of having CKD (odds ratio [OR] = 1.498，95% confidence interval [95%CI]: 1.203 – 1.866), decreased estimated glomerular filtration (OR = 1.340，95%CI: 1.001 – 1.793), and proteinuria (OR = 1.388，95%CI: 1.088 – 1.771) compared to those with normal or low body weight (≤ 23.9). Conclusion The prevalence of CKD was high and positively correlated with obesity among hypertension patients registered at community health service centers in suburb of Shanghai.