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Yu-Hsiang Shih, Lou Sun, Shih-Tien Hsu, Ming-Jer Chen, Chien-Hsing Lu Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, TaiwanCorrespondence: Chien-Hsing Lu, Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, Taiwan, Tel +886-4-23592525, Email chlu@vghtc.gov.twObjective: This study investigated whether random urine (RU) samples can be used to accurately identify human papillomavirus (HPV) and whether these samples can replace self-collected vaginal samples in HPV tests.Methods: A total of 167 patients with abnormal Pap smears were recruited. The patients provided self-collected vaginal and RU samples for HPV testing. Clinicians obtained cervical samples from the patients. Colposcopy examination and cervical biopsy were performed. Hybrid Capture II (HC II) and Cervista tests were used to detect HPV in the RU samples.Results: The results of tests on clinician-collected cervical samples were used as the benchmark. The sensitivities of the Cervista tests on vaginal samples and the HC II and Cervista tests on RU samples were 75.00%, 49.07%, and 44.44%, respectively. After we adjusted the HPV detection cutoff value for urine samples based on values in the receiver operating characteristic curve, the sensitivities of the HC II and Cervista tests increased to 63.89% and 58.33%, respectively. In 167 patients, 59 had cervix biopsies showing CIN2 or worse (CIN2+). For CIN2+, the sensitivity was 47.5% and 50.8% in the HC II and Cervista tests on RU samples, respectively.Conclusion: HPV tests on RU samples had approximately 60% sensitivity to HPV tests on clinician-collected cervical samples after the cutoff values were adjusted. For CIN2+, the sensitivity was only approximately 50%. Further studies and improvements in urine-based HPV testing are needed to establish it as a more convenient and accessible method for detecting HPV and cervical dysplasia in patients.Keywords: HPV, random urine, vaginal HPV test, cervical intraepithelial lesion, Hybrid Capture II, Cervista

Cheng-Hsiu Lu,1– 3 Yi-An Chen,4,5 Chien-Chih Ke,6– 8 Sain-Jhih Chiu,5 Fong-Shya Jeng,5 Chao-Cheng Chen,4 Ya-Ju Hsieh,6– 8 Bang-Hung Yang,4,9 Chi-Wei Chang,9 Feng-Sheng Wang,2,3,10,11 Ren-Shyan Liu1,4,9,12 1Industrial Ph.D. Program of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan; 2Core Facility for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 4Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan; 6Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 9PET Center, Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 10Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 11Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 12Department of Nuclear Medicine, Cheng Hsin Hospital, Taipei, TaiwanCorrespondence: Chien-Chih Ke; Ren-Shyan Liu Email ccke@kmu.edu.tw; rsliuvgh@gmail.comIntroduction: Osteoporosis is a result of an imbalance in bone remodeling. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been considered as a potentially promising treatment for osteoporosis. However, the therapeutic effect, genetic alterations, and in vivo behavior of exogenous EVs for osteoporosis in mice models remain poorly understood.Methods: A multiplexed molecular imaging strategy was constructed by micro-positron emission tomography (μPET)/computed tomography (CT), μCT, and optical imaging modality which reflected the osteoblastic activity, microstructure, and in vivo behavior of EVs, respectively. RNA sequencing was used to analyze the cargo of EVs, and the bone tissues of ovariectomized (OVX) mice post EV treatment.Results: The result of [18F]NaF μPET showed an increase in osteoblastic activity in the distal femur of EV-treated mice, and the bone structural parameters derived from μCT were also improved. In terms of in vivo behavior of exogenous EVs, fluorescent dye-labeled EVs could target the distal femur of mice, whereas the uptakes of bone tissues were not significantly different between OVX mice and healthy mice. RNA sequencing demonstrated upregulation of ECM-related genes, which might associate with the PI3K/AKT signaling pathway, in line with the results of microRNA analysis showing that mir-21, mir-29, mir-221, and let-7a were enriched in Wharton’s jelly-MSC-EVs and correlated to the BMP and PI3K/AKT signaling pathways.Conclusion: The therapeutic effect of exogenous WJ-MSC-EVs in the treatment of osteoporosis was successfully assessed by a multiplexed molecular imaging strategy. The RNA sequencing demonstrated the possible molecular targets in the regulation of bone remodeling. The results highlight the novelty of diagnostic and therapeutic strategies of EV-based treatment for osteoporosis.Keywords: Wharton’s jelly mesenchymal stem cells, extracellular vesicles, osteoporosis, [18F]NaF, RNA sequencing

Wen-Chi Chou,1 Yen-Yang Chen,2 Chia-Yen Hung,1,3 Jen-Shi Chen,1 Chang-Hsien Lu,4 Pei-Hung Chang5 1Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan; 2Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan; 3Division of Hematology-Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 4Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan; 5Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan Background: Only 5-fluorouracil (5-FU), cisplatin, and gemcitabine have been reimbursed for metastatic pancreatic cancer (mPC) treatment in Taiwan since 2003. It is uncertain whether the reimbursement of S-1 in June 2014 might change the treatment pattern and improve the survival of mPC patients in Taiwan. Patients and methods: A total of 645 patients with newly diagnosed mPC who received palliative chemotherapy between 2010 and 2016 in Taiwan were analyzed retrospectively. Patients were stratified according to year at diagnosis of mPC for analysis of chemotherapeutic treatment pattern and survival. Results: Overall, the most common chemotherapeutic agents used for the treatment of mPC were gemcitabine (94.8%), followed by cisplatin (52.4%), S-1 (38.1%), and 5-FU (29.7%). The percentage of patients treated with S-1 between 2010 and 2016 increased from 2.6% to 74.0% (P

Yong-hong Pan, Lin Jiao, Cai-yu Lin, Cong-hua Lu, Li Li, Heng-yi Chen, Yu-bo Wang, Yong He Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China Aim: Although EGFR tyrosine kinase inhibitors (TKIs) have shown dramatic effects against sensitizing EGFR mutations in non-small cell lung cancer (NSCLC), ~20%–30% of NSCLC patients with EGFR-sensitive mutation exhibit intrinsic resistance to EGFR-TKIs. The purpose of the current study was to investigate the enhanced antitumor effect of metformin (Met), a biguanide drug, in combination with gefitinib (Gef) in primary resistant human lung cancer cells and the associated molecular mechanism.Experimental design: H1975 cell line was treated with Met and/or Gef to examine the inhibition of cell growth and potential mechanism of action by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Ki67 incorporation assay, flow cytometry analysis, small interfering RNA technology, Western blot analysis and xenograft implantation.Results: Insulin-like growth factor-1 receptor (IGF-1R) signaling pathway was markedly activated in EGFR-TKI primary resistant H1975 cells as compared to EGFR-TKI acquired resistance cells (PC-9GR, H1650-M3) and EGFR-TKI sensitivity cells (PC-9, HCC827). Inhibition of IGF-1R activity by AG-1024 (a small molecule of IGF-1R inhibitor), as well as downregulation of IGF-1R by siRNA, significantly enhanced the ability of Gef to suppress proliferation and induce apoptosis in H1975 cells via the inhibition of AKT activation and subsequent upregulation of Bcl-2-interacting mediator of cell death (BIM). Interestingly, the observation showed that Met combined with Gef treatment had similar tumor growth suppression effects in comparison with the addition of AG-1024 to therapy with Gef. A clear synergistic antiproliferative interaction between Met and Gef was observed with a combination index (CI) value of 0.65. Notably, IGF-1R silencing mediated by RNA interference (RNAi) attenuated anticancer effects of Met without obviously resensitizing H1975 cells to Gef. Finally, Met-based combinatorial therapy effectively blocked tumor growth in the xenograft with TKI primary resistant lung cancer cells.Conclusion: Our findings demonstrated that Met combined with Gef would be a promising strategy to overcome EGFR-TKI primary resistance via suppressing IGF-1R signaling pathway in NSCLC. Keywords: metformin, gefitinib, IGF-1R, primary resistance, lung cancer

Abstract Purpose This study evaluated and compared the clinical support capabilities of ChatGPT 4o and ChatGPT 4o mini in diagnosing and treating lumbar disc herniation (LDH) with radiculopathy. Methods Twenty-one questions (across 5 categories) from NASS Clinical Guidelines were input into ChatGPT 4o and ChatGPT 4o mini. Five orthopedic surgeons assessed their responses using a 5-point Likert scale for accuracy and completeness, and a 7-point scale for reliability. Flesch Reading Ease scores were calculated to assess readability. Additionally, ChatGPT 4o analyzed lumbar images from 53 patients, comparing its recognizable agreement with orthopedic surgeons using Kappa values. Results Both models demonstrated strong clinical support capabilities with no significant differences in accuracy or reliability. However, ChatGPT 4o provided more comprehensive and consistent responses. The Flesch Reading Ease scores for both models indicated that their generated content was “very difficult to read,” potentially limiting patient accessibility. In evaluating lumbar disc herniation images, ChatGPT 4o achieved an overall accuracy of 0.81, with LDH recognition precision, recall, and F1 scores exceeding 0.80. The AUC was 0.80, and the Kappa value was 0.61, indicating moderate agreement between the model’s predictions and actual diagnoses, though with room for improvement. Conclusion While both models are effective, ChatGPT 4o offers more comprehensive clinical responses, making it more suitable for high-integrity medical tasks. However, the difficulty in reading AI-generated content and occasional use of misleading terms, such as “tumor,” indicate a need for further improvements to reduce patient anxiety.

Objective‍ To explore the roles of transfer RNA-derived small RNAs （tsRNAs） in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma. Methods‍ The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center. The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas （TCGA） database （TCGA-LUAD）. The target genes were predicted based on TRFtarget2.0 and tRFTar databases. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were performed based on DAVID and KOBA KEGG online websites. The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal （UALCAN） database. In vitro cell proliferation， migration， and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.Results‍ ‍Compared with the normal tissues， tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues （log2FC=4.28， FDR

ObjectiveTo explore the effect of slit guidance ligand 3 （Slit3） on rats with diabetic kidney disease （DKD）-induced fibrosis.MethodsA DKD rat model was established by multiple low-dose injections of streptozotocin combined with high-sugar high-fat diet. Forty Sprague-Dawley （SD） rats were randomly divided into the blank control group （control）， diabetes mellitus （DM） group， 4-week DKD group and 8-week DKD group， with 10 rats in each group by random number table method. After successful modeling， there were 8 rats in the control group， and 6 in each of the remaining groups. The 24 h urinary protein content was detected. Total cholesterol （TC）， triglyceride （TG）， blood urea nitrogen （BUN）， serum creatinine （Scr）， and albumin （Alb） were analyzed after abdominal aorta blood collection. Hematoxylin and eosin （H&E） staining was used to observe the histopathological changes of the kidney. Kidney fibrosis degree was examined by Masson’s trichrome staining. The reverse-transcription quantitative real-time polymerase chain reaction （RT-qPCR） was performed to detect mRNA levels of Slit3， α-smooth muscle actin （α-SMA）， and transforming growth factor-β1 （TGF-β1） in kidney tissues， and their protein levels were detected by Western blot. The expression and localization of Slit3 in kidney tissues were detected by immunohistochemical staining.ResultsCompared with the control group， 24-hour urinary protein content ［（37.18 ± 5.55）mg、（47.38 ± 18.19）mg vs （10.66 ± 4.87）mg］， BUN ［（19.18 ± 7.97）mmol/L、（21.01 ± 6.74）mmol/L vs （6.86 ± 1.15）mmol/L］ and Scr ［（58.02 ± 12.49）μmol/L、（61.18 ± 20.76）μmol/L vs （28.34 ± 3.35）μmol/L］ of 4-week and 8-week DKD groups were significantly higher （P0.05）.ConclusionSlit3 can significantly aggravate kidney fibrosis in DKD rats.

Abstract The ubiquitin-proteasome system (UPS) is essential for cellular homeostasis, regulating the degradation of proteins involved in key processes such as cell cycle, apoptosis, and DNA repair. Dysregulation of the UPS is implicated in hepatocellular carcinoma (HCC), contributing to tumor progression and therapeutic resistance. The cereblon (CRBN) E3 ubiquitin ligase complex is a crucial component of the UPS, particularly in modulating protein degradation in response to small-molecule modulators like thalidomide. However, the endogenous substrates of CRBN in solid tumors like HCC remain poorly characterized. Here, we identify MORF4L1, a member of the MRG family involved in chromatin remodeling and DNA damage response, as a substrate of CRBN. Using proteomic analysis, co-immunoprecipitation, and structural modeling, we demonstrate that CRBN promotes MORF4L1 degradation under physiological conditions, which is further enhanced by the modulator CC-885. Importantly, MORF4L1 is upregulated in multiple cancers, including HCC, suggesting a broader role in tumorigenesis. Our findings reveal MORF4L1 as a physiological CRBN substrate and highlight the therapeutic potential of targeting CRBN substrates in cancer.

Abstract Separation of multi-component mixtures in an energy-efficient manner has important practical impact in chemical industry but is highly challenging. Especially, targeted simultaneous removal of multiple impurities to purify the desired product in one-step separation process is an extremely difficult task. We introduced a pore integration strategy of modularizing ordered pore structures with specific functions for on-demand assembly to deal with complex multi-component separation systems, which are unattainable by each individual pore. As a proof of concept, two ultramicroporous nanocrystals (one for C2H2-selective and the other for CO2-selective) as the shell pores were respectively grown on a C2H6-selective ordered porous material as the core pore. Both of the respective pore-integrated materials show excellent one-step ethylene production performance in dynamic breakthrough separation experiments of C2H2/C2H4/C2H6 and CO2/C2H4/C2H6 gas mixture, and even better than that from traditional tandem-packing processes originated from the optimized mass/heat transfer. Thermodynamic and dynamic simulation results explained that the pre-designed pore modules can perform specific target functions independently in the pore-integrated materials.

Abstract Achieving a synergy of biocompatibility and extreme environmental adaptability with excellent mechanical property remains challenging in the development of synthetic materials. Herein, a “bottom-up” solution-interface-induced self-assembly strategy is adopted to develop a compressible, anti-fatigue, extreme environment adaptable, biocompatible, and recyclable organohydrogel composed of chitosan-lignosulfonate-gelatin by constructing noncovalent bonded conjoined network. The ethylene glycol/water solvent induced lignosulfonate nanoparticles function as bridge in chitosan/gelation network, forming multiple interfacial interactions that can effectively dissipate energy. The organohydrogel exhibits high compressive strength (54 MPa) and toughness (3.54 MJ/m3), 100 and 70 times higher than those of pure chitosan/gelatin hydrogel, meanwhile, excellent self-recovery and fatigue resistance properties. Even when subjected to severe compression up to a strain of 0.5 for 500,000 cycles, the organohydrogel still remains intact. This organohydrogel also demonstrates notable biocompatibility both in vivo and vitro, environment adaptability at low temperature, as well as recyclability. Such all natural organohydrogel provides a promising route towards the development of high-performance load-bearing materials.

Abstract Selective catalytic oxidation (SCO) of NH3 to N2 is one of the most effective methods used to eliminate NH3 emissions. However, achieving high conversion over a wide operating temperature range while avoiding over-oxidation to NOx remains a significant challenge. Here, we report a bi-metallic surficial catalyst (PtSCuO/Al2O3) with improved Pt atom efficiency that overcomes the limitations of current catalysts. It achieves full NH3 conversion at 250 °C with a weight hourly space velocity of 600 ml NH3·h−1·g−1, which is 50 °C lower than commercial Pt/Al2O3, and maintains high N2 selectivity through a wide temperature window. Operando XAFS studies reveal that the surface Pt atoms in PtSCuO/Al2O3 enhance the redox properties of the Cu species, thus accelerating the Cu2+ reduction rate and improving the rate of the NH3-SCO reaction. Moreover, a synergistic effect between Pt and Cu sites in PtSCuO/Al2O3 contributes to the high selectivity by facilitating internal selective catalytic reduction.

Abstract Hepatitis E virus (HEV) infection is a major cause of acute viral hepatitis worldwide. The efficacy and safety of the HEV239 vaccine have been validated, with protection lasting at least 10 years. This study extended the phase 3 trial of HEV239 (NCT01014845), presenting data on the durability of the anti-HEV IgG response elicited by one or two doses in the participants with different baseline serostatus. Over half of baseline seronegative individuals retained detectable antibodies at month 91 after two doses, with geometric mean concentration levels above the detection limit at month 67 (no available data for month 91). Seropositive individuals exhibited more prolonged and higher anti-HEV IgG response. After a single dose, individuals with pre-existing immunity achieved high and sustained antibody levels for over 103 months, comparable to the two-dose regimen. Both single-dose and two-dose HEV239 regimens demonstrated notable immunogenicity and persistence, potentially offering substantial protective benefits.

Abstract Spaceflight-associated neuro-ocular syndrome (SANS) has been well documented in astronauts. However, its pathogenesis is not fully understood. New findings indicate the impaired outflow of the optic nerve cerebrospinal fluid may participate or contribute to some changes in SANS. In this perspective, we generated a hypothesis that the outflow of cerebrospinal fluid through the optic nerve sheath may be impaired under micro-gravity and then may potentially lead to SANS-related alterations.

Abstract Background Intercropping increases land use efficiency and farmland ecological diversity. However, little is understood about whether and how soil biota, metabolites, and nutrients change under interspecific competition among plants. Thus, this study aimed to explore the changes in the physicochemical properties, microbial communities, and metabolites of rhizosphere and bulk soils of pepper monocropping and pepper–maize intercropping systems. Results Intercropping significantly increased the contents of available phosphorus (AP) and available potassium (AK), and decreased the pH value, whereas it had little effect on the total nitrogen (TN) and organic matter (OM) in the rhizosphere and bulk soils, compared with those in monocropping pepper. Moreover, the OM content was higher in rhizosphere soil than in bulk soil. The microbial community structures and metabolite profiles also differed between the two systems. The diversity of bacteria and fungi increased in intercropped pepper. The relative abundances of Actinobacteria, Chloroflexi, Cyanobacteria, and Ascomycota were higher while those of Proteobacteria, Planctomycetes, Mucoromycota, and Basidiomycota were significantly lower in the rhizosphere and bulk soils from the intercropping system than in those from the monocropping system. Linear discriminant analysis revealed that the predominant bacteria and fungi in the rhizosphere soil from the intercropping system belonged to the order Sphingomonadales and genera Nitrospira, Phycicoccus and Auricularia, whereas those in the bulk soil from the intercropping system belonged to the phylum Acidobacteria and genera Calocera, Pseudogymnoascus, and Trichosporon. Intercropping promoted the secretion of flavonoids, alkaloids, and nucleotides and their derivatives in the rhizosphere soil and significantly increased the contents of organoheterocyclic compounds in the bulk soil. Furthermore, the AP and AK contents, and pH value had strong positive correlations with bacteria. In addition, co-occurrence network analysis also showed that asebogenin, trachelanthamidine, 5-methyldeoxycytidine, and soil pH were the key factors mediating root-soil-microbe interactions. Conclusion Intercropping can alter microbial community structures and soil metabolite composition in rhizosphere and bulk soils, enhancing soil nutrient contents, enriching soil beneficial microbes and secondary metabolites (flavonoids and alkaloids) of intercropped pepper, and provided a scientific basis for sustainable development in the pepper-maize intercropping system.

ABSTRACT Importance Umbilical venous catheterization (UVC) is a common procedure for critically ill newborn infants. The insertion depth was estimated before the procedure using various formulae. Objective To compare the accuracy of five published formulae based on birth weight (BW). Methods This is a secondary retrospective analysis using data collected in a previous study, in which the actual final insertion depth of UVC was recorded. Predicted insertion depths were calculated by five published formulae based on BW. Then the actual depth and predicted depth were compared. Accurate position was defined as predicted depth being within ± 10% of actual depth. The accuracy rate calculated as “(accurately positioned UVCs/ all UVCs) × 100%” and the ratio of difference calculated as “(|predicted depth − actual depth|/ actual depth)” were compared among five formulae. Results Totally 1298 were enrolled, with gestational age 29.8 ± 2.3 weeks and BW 1215 ± 273 g. The accuracy rates were: Tambasco formula (67.2%), Shukla formula (65.0%), JSS formula (64.4%), BW formula (48.9%), and revised Shukla formula (26.9%). Tambasco formula had the highest accuracy rate in newborns with BW ≥ 1000 g. JSS formula had the highest accuracy rate in newborns with BW

Abstract Monkeypox (MPOX) is a zoonotic disease caused by Orthopoxvirus monkeypox (MPXV), belonging to the Orthopoxvirus genus, and exhibits symptoms similar to smallpox. In 2024, the monkeypox outbreak in the Democratic Republic of the Congo continued to develop, raising widespread global public health concerns. In September 2023, the first local monkeypox outbreak was reported in Nantong, Jiangsu Province, China. Whole-genome sequencing of samples from seven confirmed patients identified a new lineage, C.1.1, which may be related to imported cases from Japan. Evolutionary analysis of MPXV showed fewer mutations mediated by Apolipoprotein B mRNA Editing Catalytic polypeptide-like 3 (APOBEC3). Additionally, mutations in the N2L protein disrupted transcription initiation, while changes in the Cytomegalovirus-encoded immunomodulatory protein B (CrmB) led to structural instability of the protein. It is hoped that these findings will provide insights for future research on the evolutionary mechanisms of the monkeypox virus and the development of vaccines.

Abstract Objective This study aimed to examine the associations between knowledge, social support, and physical activity and explore the mediating role of physical activity self-efficacy in pregnant women with a high risk for gestational diabetes mellitus (GDM). Methods A cross-sectional study was conducted in Guangzhou, China, from July 2022 to May 2023. Five hundred thirty-seven pregnant women with a high risk for GDM completed the Pregnancy Physical Activity Questionnaire, Pregnancy Physical Activity Self-Efficacy Scale, Pregnancy Physical Activity Knowledge Scale, Physical Activity Social Support Scale, and a socio-demographic data sheet. The mediation effect was tested using structural equation modeling (SEM) and the bootstrap method. Results 42.5% of pregnant women did not meet the current physical activity guidelines. Physical activity self-efficacy (β, 0.16; P

To address the high-dimensional complexity of wind farm scenario data， a generation method based on spectral normalization generative adversarial networks and spectral clustering is proposed. First， adversarial training is performed on two deep neural networks of the generator and discriminator， with spectral normalization applied to the convolutional layers of the discriminator to enhance the Lipschitz continuity constraint， thereby improving the stability of data training and the quality of generated wind farm scenarios. Next， an improved Gaussian kernel-based spectral clustering method is used to extract wind power features and reduce the dimensionality of the data， transforming the generated scenarios into a set of typical wind farm scenarios. Finally， simulations are conducted using the publicly available WIND dataset. The simulation results indicate that the proposed method significantly reduces the mean squared errors of generated samples， accurately capturing the spatiotemporal correlations of wind power generation； the spectral clustering based on Gaussian kernel function effectively clusters the sample space.

The rapid advancement of gas sensitive properties in metal oxides is crucial for detecting hazardous gases in industrial and coal mining environments. However, the conventional experimental trial and error approach poses significant challenges and resource consumption for the high throughput screening of gas sensitive materials. Consequently, this paper introduced a novel screening approach that integrates first principles with machine learning (ML) to rapidly predict the gas sensitivity of materials. Initially, a comprehensive database of multi-physical parameters was established by modeling various adsorption sites on the surface of WO3, which serves as a representative material. Since density functional theory (DFT) is one of the first principles, DFT calculations were conducted to derive essential multi-physical parameters, including bandgap, density of states (DOS), Fermi level, adsorption energy, and structural modifications resulting from adsorption. The collected data was subsequently utilized to develop a correlation model linking the multi-physical parameters to gas sensitive performance using intelligent algorithms. The model’s performance was assessed through receiver operating characteristic (ROC) curves, confusion matrices, and other evaluation metrics, ultimately achieving a prediction accuracy of 90% for identifying key features influencing gas adsorption performance. This proposed strategy for predicting the gas sensitive characteristics of materials holds significant potential for application in identifying additional gas sensitive properties across various materials.

Abstract The CCCTC-binding factor (CTCF) is pivotal in orchestrating diverse biological functions across the human genome, yet the mechanisms driving its cell type-active DNA binding affinity remain underexplored. Here, we collected ChIP-seq data from 67 cell lines in ENCODE, constructed a unique dataset of cell type-active CTCF binding sites (CBS), and trained convolutional neural networks (CNN) to dissect the patterns of CTCF binding activity. Our analysis reveals that transcription factors RAD21/SMC3 and chromatin accessibility are more predictive compared to sequence motifs and histone modifications. Integrating them together achieved AUPRC values consistently above 0.868, highlighting their utility in deciphering CTCF transcription factor binding dynamics. This study provides a deeper understanding of the regulatory functions of CTCF via machine learning framework.

Traditional Low Probability of Intercept (LPI) array radars that use phased array or Multiple-Input Multiple-Output (MIMO) systems face limitations in terms of controlling radiation energy only at specific angles and cannot achieve energy control over specific areas of range and angle. To address these issues, this paper proposes an LPI waveform design method for Frequency Diverse Array (FDA)-MIMO radar utilizing neural networks. This method jointly designs the transmit waveform and receive beamforming in FDA-MIMO radars to ensure target detection probability while uniformly distributing radar energy across the spatial domain. This minimizes energy directed toward the target, thereby reducing the probability of the radar signal being intercepted. Initially, we formulate an optimization objective function aimed at LPI performance for transmitting waveform design and receiving beamforming by focusing on minimizing pattern matching errors. This function is then used as the loss function in a neural network. Through iterative training, the neural network minimizes this loss function until convergence, resulting in optimized transmit signal waveforms and solving the corresponding receive weighting vectors. Simulation results indicate that our proposed method significantly enhances radar power distribution control. Compared to traditional methods, it shows a 5 dB improvement in beam energy distribution control across nontarget regions of the transmit beam pattern. Furthermore, the receiver beam pattern achieves more concentrated energy, with deep nulls below −50 dB at multiple interference locations, demonstrating excellent interference suppression capabilities.

Abstract Background Inflammatory bowel disease (IBD), a persistent gastrointestinal disease, is featured with impaired gut immunity. Previous studies have demonstrated that tuft cells can regulate the intestinal type 2 immune response by activating downstream ILC2 and Th2 cells and repair gut barrier upon invasion of parasitic helminths, bacteria, protozoans, and enteritis through different chemo-sensing receptors, such as bitter taste receptors. Berberine is a widely used in the treatment of diarrhea in clinic, however the mechanism underlying this effect is not clear. In this study, we aim to explore the relationship between berberine and tuft cells in dextran sulfate sodium (DSS) -induced colitis. Results Our data showed that berberine significantly ameliorated DSS-induced colitis and regulating type 2 innate immune lymphocytes (ILC2) and Th2 immune cells via tuft cells in the gut. Furthermore, the effect of berberine on colitis was partially abolished by U73122, a bitter taste receptor inhibitor, suggesting that bitter taste signalling pathway played an important role in the effect of berberine on relieving colitis. Conclusions Berberine ameliorates dextran sulfate sodium -induced colitis through tuft cells and bitter taste signalling. Our study reveals the unique pharmacological mechanisms of berberine in the context of colitis, laying the foundation for further clinical applications of this compound.

Objective Imperfect fitting of the navigation template leads to prolonged surgery time and increased blood loss. These problems have not been effectively addressed in previous research. This study explores the efficacy of a novel 5‐point positioning point‐contact pedicle navigation template in complex pedicle situations in scoliosis. Methods This study employed a retrospective controlled design. From November 2019 to November 2023, 28 patients with scoliosis and complex pedicle were selected and underwent scoliosis correction surgery. A 5‐point positioning point‐contact pedicle navigation template was used intraoperatively to guide pedicle screw placement. Matched with 56 historical cases as a control group. The analysis included screw placement time, screw placement bleeding volume, fluoroscopy frequency, manual repositioning frequency, screw placement accuracy and grade, screw placement complications, and main curve correction rate. Continuous variables were compared using the independent samples t‐test. Categorical data were analyzed with the chi‐square test. Results All 28 patients successfully underwent surgery, with a total of 268 pedicle screws placed. The surgery duration ranged from 220 to 410 min, with an average of (283.16 ± 51.26) min. Intraoperative blood loss ranged from 630 to 1900 mL, with an average of (902.17 ± 361.25) mL. Pedicle screw placement time ranged from 60 to 130 min, with an average of (85.24 ± 24.65) min. Pedicle screw placement bleeding volume ranged from 40 to 180 mL, with an average of (76.47 ± 42.65) mL. Fluoroscopy frequency ranged from 3 to 7 times, with an average of (4.31 ± 1.14) times. Manual repositioning frequency ranged from 0 to 2 times, with an average of (0.46 ± 0.58) times. Pedicle screw placement grades: Grade I: 237 screws; Grade II: 25 screws; Grade III: 6 screws; Grade IV: 0 screws. There were no screw‐related complications. The correction rate ranged from 46% to 68%, with an average of (55.83 ± 9.22)%. Compared to the experienced screw group, the differences in screw placement time, screw placement bleeding volume, fluoroscopy procedures, and manual redirections were statistically significant (p

Mathematical models supported by a robust automated data pipeline proved to be useful tools for a data-driven and science-based response and policy-making during the COVID-19 pandemic in the Philippines. In the first year of the pandemic, FASSSTER (Feasibility Analysis on Syndromic Surveillance using Spatio-Temporal Epidemiological modeleR) used a compartmental model to generate scenario-based projections of COVID-19 cases. The emergence of the Delta variant, however, and the administration of vaccines over the second half of 2021 caused significant changes in the Philippine pandemic landscape. This necessitated making adjustments to the model to better capture the local disease transmission dynamics and address policy questions posed by stakeholders regarding COVID-19 over that period. The extended model was then utilized to generate case projections by applying different intervention scenarios, specifically, scenarios involving vaccination coverage, compliance to public health standards and active detection of cases. The new model demonstrated reliability in terms of capturing historical data and in producing relatively accurate short-term projections. In turn, most of the projections generated by the model had been used in support of case monitoring and policy-making in the country. This paper illustrates the significance of enhancing mathematical models in response to the dynamic nature of the COVID-19 pandemic.

Only a few studies on large sports tourism explore motorsport events such as the Moto Grand Prix. The present study addresses this gap by examining the factors influencing visitors’ satisfaction and intention to revisit related to the large sports event of MotoGP, Indonesia. The data were collected from visitors who had attended the MotoGP event in Indonesia using an online questionnaire with purposive sampling. The partial Least Square-Structural Equation Modeling (PLS-SEM) analysis was applied in this study to analyze the data. The findings indicate that hospitality, accessibility, and attraction significantly influenced visitor satisfaction at the MotoGP sports event in Mandalika, Indonesia. However, the factors of hospitality, infrastructure, accessibility, and attraction are insignificant where it concerns visitors’ intention to revisit. Moreover, satisfaction successfully influences visitors to revisit the MotoGP event in Indonesia. This study contributes to research on sports event management in large sports events by examining the factors that influence satisfaction and intention to revisit in the context of the MotoGP sports event, and contributes both theoretically and practically to research on sports events and tourism.

Authoritative-side domain hijacking is characterized by abnormal changes in resource records. To enable timely warnings for authoritative-side domain hijacking incidents, a monitoring system for authoritative-side resource records was established, targeting significant domains in key sectors such as government and education, as well as high-traffic popular domains. The system actively captured and continuously monitored 7.5 million important domains globally. An algorithm was developed to filter abnormal changes in resource records, identifying abnormal changes in 896 significant domains within a one-month analysis period. Manual verification results indicate that the causes included misconfigurations by domain administrators, phishing attacks, and the display of illegal content.

To evaluate whether the current flood control capacity of the Shenzhen River Basin meets design standards, a one-dimensional hydrodynamic mathematical model was employed to simulate the flood process during "9·7" torrential rainfall. Additionally, simulations were conducted to analyze the flood control capacity of the basin under different topographies and roughness conditions. The simulation results indicate that the dredging projects carried out between 2016 and 2020 have enhanced the flood control capacity of the main stream of the Shenzhen River from less than a 20-year return period in some sections to a 50-year return period overall. However, rapid sedimentation and vegetation growth in the riverbed after dredging increase roughness, preventing the upstream section of the Liantang River tributary from meeting the 50-year flood control standard. Currently, the Shenzhen River faces unfavorable underlying conditions, including a fan-shaped catchment topography combined with urban development, significant sedimentation following dredging, and continuous expansion of mangroves at the river mouth, as well as challenges such as frequent extreme weather events and significant urban waterlogging risks. Therefore, to enhance flood control capacity, it is necessary to develop a comprehensive strategy from a basin-wide perspective. A combination of measures including storage, retention, diversion, discharge, and blocking can be used to further reduce peak flood discharges and increase river flood conveyance capacity.

Abstract The mucosal immune response plays a crucial role in the prevention of respiratory viruses. Given the risk of recurrent SARS-CoV-2 infections in the population, the rapid development of next-generation intranasal COVID-19 vaccines with high safety and efficacy is paramount. In the current study, we developed a protein-based intranasal vaccine comprising the XBB.1.5 receptor binding domain (RBD)-derived trimeric recombinant protein (RBDXBB.1.5-HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBDXBB.1.5-HR vaccine elicited robust and sustained humoral immune responses in mice and rats, resulting in high levels of neutralizing antibodies against XBB-lineage subvariants, with protection lasting for at least six months. The intranasal RBDXBB.1.5-HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (TRM) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBDXBB.1.5-HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBDXBB.1.5-HR vaccine as a heterologous booster shot showed more effective boosting effects after mRNA administration compared to homologous vaccination, as evidenced by the induction of superior systemic and extra mucosal immune response. Importantly, the intranasal RBDXBB.1.5-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBDXBB.1.5-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.

Abstract Fluorouracil-based chemotherapy responses in colorectal cancer (CRC) patients vary widely, highlighting the role of pharmacogenomics in developing better predictive models. We analyzed 379 CRC patients receiving fluorouracil-based chemotherapy, collecting data on fluorouracil metabolism-related SNPs (TYMS, MTHFR, DPYD, RRM1), blood inflammatory markers, and clinical status. Six machine learning models—K-nearest neighbors, support vector machine, gradient boosting decision trees (GBDT), eXtreme Gradient Boosting (XGBoost), LightGBM, and random forest—were compared against multivariate logistic regression and a deep learning model (i.e., multilayer perceptron, MLP). Feature importance analysis highlighted seven predictors: histological grade, N and M staging, monocyte count, platelet-to-lymphocyte ratio, MTHFR rs1801131, and RRM1 rs11030918. In a five-fold cross-validation, XGBoost and GBDT exhibited superior performance, with Area Under Curve (AUC) of 0.88 ± 0.02. XGBoost excelled in identifying favorable prognosis (recall = 0.939). GBDT demonstrated balance in recognizing both categories, with a recall for favorable prognosis of 0.908 and a precision for unfavorable prognosis of 0.863. MLP had a similar AUC (0.87) with high precision for favorable prognosis (recall = 0.946). In external validation, XGBoost model achieved an accuracy of 0.79. An online prognostic tool based on XGBoost was developed, integrating metabolism-related SNPs and inflammatory markers, enhancing CRC treatment precision and supporting tailored chemotherapy.

Introduction: Surgical ventricular reconstruction (SVR) is an alternative therapeutic approach in patients with refractory heart failure (HF), but residual remodeling after SVR limits the improvement of HF. Recently, we reported that SVR may act as an environmental cue to reactivate endogenous proliferation of cardiomyocytes; however, it is unclear whether enhancing endogenous cardiomyocyte regeneration further improves HF after SVR. Objectives: We aimed to explore whether circular RNAs (circRNAs) would involved in SVR and their mechanisms. Methods: Male C57BL/6 mice were subjected to myocardial infarction (MI) or sham surgery. Four weeks later, MI mice with a large ventricular aneurysm underwent SVR or a second open-chest operation only. Echocardiography and histological analysis were used to evaluate heart function, cardiac remodeling, and myocardial regeneration. Sequencing of circular RNAs, RNA immunoprecipitation, RNA pulldown, and luciferase reporter assay were used to explore the underlying mechanisms. Results: SVR markedly attenuated cardiac remodeling and induced cardiomyocyte regeneration, as evidenced by positive staining of Ki-67, phospho-histone H3 (pH3), and Aurora B in the plication zone, but significant residual remodeling still existed in comparison with the sham group. Sequencing results showed that SVR altered the expression profile of cardiac circRNAs, and circMap4k2 was identified as the most upregulated one. After characterizing circMap4k2, we noted that overexpression of circMap4k2 significantly promoted proliferation of cardiomyocytes in cultured neonatal rat cardiomyocytes and silencing of circMap4k2 significantly inhibited it; similar results were obtained in SVR-treated MI mice but not in MI mice without SVR treatment. Residual cardiac remodeling after SVR was further attenuated by circMap4k2 overexpression. CircMap4k2 bound with miR-106a-3p and inhibited cardiomyocyte proliferation by targeting a downstream effector of the antizyme inhibitor 1 (Azin1) gene. Conclusions: CircMap4k2 acts as an environmental cue and targets the miR-106a-3p/Azin1 pathway to increase cardiac regeneration in the plication zone and attenuate residual remodeling after SVR.

Abstract We investigated the Strong Cosmic Censorship (SCC) conjecture in Einstein–Power–Maxwell–de Sitter (EPMdS) black holes by analyzing the quasinormal modes (QNMs) of a massless neutral scalar field perturbation. Using the pseudospectral method, we calculated the QNM frequencies across various cosmological constants and nonlinear electromagnetic parameters. Our results show that for black holes far from extremality, the lowest QNM frequency $$-\text {Im} (\omega )/\kappa _-$$ - Im ( ω ) / κ - remains below 1/2. However, as the black holes approach extremality, the lowest mode’s $$-\text {Im} (\omega )/\kappa _-$$ - Im ( ω ) / κ - consistently exceeds 1/2, leading to a violation of SCC. Moreover, with a fixed cosmological constant, as the nonlinearity parameter $$\alpha $$ α increases, the interval of SCC violation under the charge extremality ratio narrows. Considering that $$k = 1/2 + 1/\alpha $$ k = 1 / 2 + 1 / α is inversely proportional to $$\alpha $$ α , our results indicate that increasing the order k of the non-linear electromagnetic field can effectively mitigate SCC violations.

Abstract The dynamic crack propagation trajectories play a crucial role in enhancing our understanding of spatial mechanisms involved in crack expansion. However, visualization of internal cracks under complex crack conditions has always been a challenge. Biological networks have been honed by many cycles of evolutionary selection pressure and are likely to yield reasonable solutions to such combinatorial optimization problems. This study applied the slime mould algorithm to improve the accuracy of internal crack localization in rocks and employed Minimum spanning tree and Gaussian mixture model to construct the crack propagation trajectories. By introducing the concept of bond length, the evolution characteristics of crack levels were effectively characterized. Research results showed that this approach effectively preserves essential crack localization information while mitigating the influence of interfering parameters, providing crack characterization results that exhibit high consistency with actual fracture patterns. The curves of cumulative bond length and relative bond length over time conform to the trend of a Growth/Sigmoidal curve. The strength of the bond was correlated with the temporal process of crack propagation. This result could be helpful for analyzing crack trajectories and predicting rock stability.

Outliers are typically identified using frequentist methods. The data are classified as “outliers” or “not outliers” based on a test statistic that measures the magnitude of the difference between a value and the majority part of the data. The threshold for a data value to be an outlier is typically defined by the user. However, a subjective choice of the threshold increases the uncertainty associated with outlier status for each data value. A cellwise outlier detection algorithm named FuzzyHRT is used to automate the editing process in repeated surveys. This algorithm uses Bienaymé–Chebyshev’s inequality and fuzzy logic to detect four different types of outliers resulting from format inconsistencies, historical, tail, and relational anomalies. However, fuzzy logic is not suited for probabilistic reasoning behind the identification of anomalous cells. Bayesian methods are well suited for quantifying the uncertainty associated with the identification of outliers. Although, as suggested by the literature, there exist well-developed Bayesian methods for record-level outlier detection, Bayesian methods for identifying outliers within individual records (i.e., at the cell level) remain unexplored. This paper presents two approaches from the Bayesian perspective to study the uncertainty associated with identifying outliers. A Bayesian bootstrap approach is explored to study the uncertainty associated with the output scores from the FuzzyHRT algorithm. Empirical likelihoods in a Bayesian setting are also considered for probabilistic reasoning behind the identification of anomalous cells. NASS survey data for livestock and major crop yield (such as corn) are considered for comparing the performances of the two proposed approaches with recent cellwise outlier methods.

To overcome the concurrency of multi-mode and multi-position failures of composite structures, this paper explores the application of the branch-bound method (BBM) to the multi-mode and multi-position reliability analysis and combines the Monte Carlo method to solve the multi-mode reliability. Firstly, "branch" is carried out by combining structural composition with loading state to identify all possible potential failure modes; "boundary" is carried out by combining structural characteristics with stress state to determine main failure modes and failure positions, thus establishing a multi-mode reliability analysis model. Secondly, by translating the unequal failure criterion to safe boundary equations, a framework for the reliability analysis of composite materials was established, and the Monte Carlo method was used to solve the reliability of multi-mode and multi-position failures. Finally, a reliability analysis case was used to validate the composite T-type reinforced plate under axial compressive load. The use of the BBM reduces the computational scale by 75%. The multi-mode reliability of the reinforced plate under axial compressive load is 0.998.

A novel Qingke Baijiu was produced by the process of light-aroma Baijiu combined with high-temperature stacking process and using highland barley of Tibet as material. Three kinds of Qingke Baijiu samples were evaluated by quantitative descriptive analysis, and analyzed by liquid-liquid extraction combined with gas chromatography-mass spectrometry and gas chromatography-olfactometry-mass spectrometry and analyzed by partial least squares regression analysis to clarify the aroma characteristic of the novel Qingke Baijiu and to investigate the influence of different manufacturing process. A total of 139 volatile compounds and 57 aroma compounds were detected in three samples, which included 11 aroma active compounds with odor active value (OAV) greater than 1. The total concentration of volatile compounds was 1.4 times higher after secondary fermentation. The sorghum and Zao aromas increased in the samples after secondary fermentation, where ethyl caprylate, ethyl caproate, ethyl isovalerate, and guaiacol were the corresponding key differential compounds. The sorghum and Zao aromas decreased after high-temperature stacking process, while floral aroma increased. Compared with the samples without high-temperature stacking process, the OAV of isoamyl acetate, guaiacol and 4-methylguaiacol increased, while the OAV of ethyl butyrate, ethyl caproate, and ethyl caprylate declined. After high-temperature stacking process, the concentration of isoamyl acetate increased, which lead to stronger floral aroma, and the concentration of butyric acid, ethyl caproate, ethyl caprylate, and ethyl decanoate declined, which lead to weaker sorghum aroma.

Chlorophorus fainanensis Pic, 1918 is redescribed. Four species, C. coniperda Holzschuh, 1992, C. diversicolor Holzschuh, 2016, C. orbatus Holzschuh, 1991 and C. pinguis Holzschuh, 1992 are newly reported from China. A new synonymy, Chlorophorus arciferus (Chevrolat, 1863) = Chlorophorus semisinuatus Pic, 1949, syn. nov. is proposed.

Abstract Value co-creation can be defined as the joint benefit that is created by patients and medical service providers through the integration of their respective resources. Participation and interaction between doctors and patients can generate an outcome that benefits both sides. Relevant studies of value co-creation in the healthcare field are limited. This study established hypotheses to explore the association between doctor interaction behavior, patient participation in value co-creation, and patient satisfaction. A cross-sectional survey was conducted with 637 patients (outpatients and inpatients) at a tertiary-level hospital in Guangzhou, China. The analysis result indicated that doctor interaction behavior could stimulate patient participation in value co-creation then increase patient satisfaction. The standardized total effect, direct effect, and indirect effect were 0.641 (95%CI: 0.055 ~ 0.067), 0.546 (95%CI: 0.044 ~ 0.059), and 0.095 (95%CI: 0.032 ~ 0.166), respectively. Patient participation in value co-creation mediated the relationship between doctor interaction behavior and patient satisfaction. Among the different dimensions of doctor interaction behavior, access, risk assessment and transparency dimensions were associated with positive patient participation in value co-creation. During the treatment process, doctor interaction and patient participation can get satisfying results.

Abstract Functional dyspepsia (FD) is known to be influenced by gut microbiota (GM) and circulating inflammatory proteins (CIPs), however, the causal relationship between GM, CIPs and FD haven’t been investigated. This study employed two-sample Mendelian Randomization (TSMR) to investigate their associations using data from Genome-Wide Association Studies (GWAS). In this study, Inverse-variance weighted (IVW) method was employed as the primary analysis, with supplementary approaches including weighted median, weighted mode, simple mode, and MR-Egger. Heterogeneity and pleiotropy were assessed using the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test. Totally, 196 GM traits and 91 CIPs were analyzed, and the results uncovered the causal impact of 12 GM taxa and 5 proteins on functional dyspepsia (FD). 9 GM genera were linked to a reduced risk of FD, while 3 GM genera were associated with an increased risk of FD.Additionally, reverse analysis revealed no FD-GM causation. Furthermore, IL-12, IL-10, CXCL10, CXCL9 and VEGFA were significantly correlated with FD, with CXCL9 and VEGFA acting as mediators in the association between GM traits and FD. Taken together, our findings established a link between specific GM and CIPs in the pathogenesis of FD, offering novel insights for its diagnosis and treatment.

Abstract Pseudorabies virus (PRV) can establish lifelong latent infection in peripheral nervous ganglion, and persistent infections in peripheral blood lymphocytes. Establishing an infection in the lymphocytes does not only enable the PRV to escape host immune surveillance but pass through the placental barrier, leading to fetal death and abortion. Due to the pathogenicity of the PRV, it poses a huge challenge in its prevention and control. The PRV escapes host immunity through downregulation of swine leukocyte antigen class I (SLA I) molecules on infected cells. However, data on the molecular mechanisms of the SLA I suppression remains scant. Here, in order to verify the effect of candidate proteins PRV pUL44 and pUS6 on PRV immune escape related molecules SLA I and peptide loading complex (PLC), we detected the expression of SLA I and PLC components after expressing PRV pUL44 and pUS6. The effects of pUS6 and pUL44 on SLA I and PLC were analyzed by qRT-PCR and Western blot at mRNA and protein level, respectively. Cells expressing pUS6 or pUL44 genes showed a significantly suppressed expression of surface and total SLA I molecules. In addition, unlike UL44, the US6 gene was shown to downregulate the transporter associated with antigen processing 1 (TAP1), TAP2 and Tapasin molecules. The results show that PRV pUS6 may participate in virus immune escape by directly regulating the SLA I, TAP dimer and Tapasin molecules, thus blocking the transportation of TAP-bound peptides to the ER to bind SLA I molecules. We provide a theoretical basis on the mechanism of TAP mediated immune escape by the PRV.

Abstract Background In diabetic wounds, hyperglycemia-induced cytotoxicity and impaired immune microenvironment plasticity directly hinder the wound healing process. Regulation of the hyperglycemic microenvironment and remodeling of the immune microenvironment are crucial. Results Here, we developed a nanozymatic functionalized regenerative microenvironmental regulator (AHAMA/CS-GOx@Zn-POM) for the effective repair of diabetic wounds. This novel construct integrated an aldehyde and methacrylic anhydride-modified hyaluronic acid hydrogel (AHAMA) and chitosan nanoparticles (CS NPs) encapsulating zinc-based polymetallic oxonate nanozyme (Zn-POM) and glucose oxidase (GOx), facilitating a sustained release of release of both enzymes. The GOx catalyzed glucose to gluconic acid and (H₂O₂), thereby alleviating the effects of the hyperglycemic microenvironment on wound healing. Zn-POM exhibited catalase and superoxide dismutase activities to scavenge reactive oxygen species and H₂O₂, a by-product of glucose degradation. Additionally, Zn-POM induced M1 macrophage reprogramming to the M2 phenotype by inhibiting the MAPK/IL-17 signaling diminishing pro-inflammatory cytokines, and upregulating the expression of anti-inflammatory mediators, thus remodeling the immune microenvironment and enhancing angiogenesis and collagen regeneration within wounds. In a rat diabetic wound model, the application of AHAMA/CS-GOx@Zn-POM enhanced neovascularization and collagen deposition, accelerating the wound healing process. Conclusions Therefore, the regenerative microenvironment regulator AHAMA/CS-GOx@Zn-POM can achieve the effective conversion of a pathological microenvironment to regenerative microenvironment through integrated control of the hyperglycemic-immune microenvironment, offering a novel strategy for the treatment of diabetic wounds.

To investigate the differences in volatile components during the processing of Fuling Zhacai, or pickled mustard tuber, with three stacked layers of mustard tuber and salt, gas chromatography-tandem mass spectrometry (GC-MS/MS)-based non-targeted metabolomics combined with multivariate statistical analysis was used to analyze the changes in volatile metabolites and significantly differential metabolic pathways during the spontaneous fermentation of Zhacai. The results showed that a total of 627 volatile compounds were identified from Zhacai samples at different pickling stages, including terpenoids, esters, heterocyclic compounds, terpenoids, aldehydes, ketones, alcohols, phenols, amines, sulfur compounds, acids, halogenated hydrocarbons, and nitrogen compounds. A significant difference was observed in volatile components among pickling stages. A total 157 unique differential metabolites in the 1st pickling stage vs. the control group, 28 in the 2nd vs. the 1st pickling stage, and one in the 3rd vs. 2nd pickling stage were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential metabolites were significantly enriched in metabolic pathways including secondary metabolite biosynthesis, diterpenoid biosynthesis, monoterpenoid biosynthesis, caffeine metabolism, and fatty acid biosynthesis. This study provides a theoretical basis for the standardized production of Fuling Zhacai.

The attention of residents has always been drawn to the courtyard gates of rural residential buildings, this is the basis for evaluating the first impression of the countryside by first-time visitors. Using eye-tracking technology, this study measures the pupil diameter, fixation duration, and fixation point of subjects as objective physiological data, Then combined with the results of the subjective satisfaction questionnaire for a comprehensive analysis. The findings showed that, When the subjects evaluated their satisfaction with the courtyard gates, the proportion and color of the modeling elements led to the subjects’ emotional changes, and the subjects focused mainly on the central axis and the connection of various structures with raised areas. In order to elicit positive emotions in the subjects, village gate designs should therefore adhere to the standard specification’s requirements as well as the following: the width of the gate should be 0.8 times the height, the height should be 5 times the width of the gateposts, and the color should match the material’s color. To meet the emotional needs of the visitors, the final design strategy of the proportion and color of rural courtyard gates in southern Hebei Province is proposed.

Abstract This study focuses on the degradation behaviour of metallised film capacitors, which are the essential components for the stability of converter valves in flexible ultra‐high voltage direct current (HVDC) transmission systems. Through systematic experimentation, we investigated the failure mechanisms of MFCs under HVDC fields with superimposed harmonics, considering both equipment and material perspectives. The experiments subjected capacitors to 500 h of ageing under two conditions: a DC/AC‐superimposed field with a constant DC component of 290 kV/mm and an AC ripple rate varying from 12% to 28%, and a control group aged solely under a DC field. Our findings indicate that capacitors aged under the DC/AC‐superimposed field exhibited shorter lifespans and more significant capacitance loss than those aged under only the DC field. This difference in performance is primarily attributed to the distinct electrode loss behaviours observed under each ageing condition, which are key factors in the capacitors' capacitance decay. Moreover, the biaxially oriented polypropylene films in the DC‐aged samples showed more severe deterioration, characterised by more noticeable molecular chain scission and reduced breakdown strength, compared to those aged under the DC/AC superimposed field. This difference is partly due to the moderate temperature increase caused by harmonics, which benefits the aggregation structure, and partly to the reduced molecular structure damage from the AC field.

Use of nanomaterials (NMs) to improve plant abiotic stress tolerance (AST) is a hot topic in NM-enabled agriculture. Previous studies mainly focused on the physiological and biochemical responses of plants treated with NMs under abiotic stress. To use NMs for improving plant AST, it is necessary to understand how they act on this tolerance at the omics and epigenetics levels. In this review, we summarized the knowledge of NM-improved abiotic stress tolerance in relation to omics (such as metabolic, transcriptomic, proteomic, and microRNA), DNA methylation, and histone modifications. Overall, NMs can improve plant abiotic stress tolerance through the modulation at omics and epigenetics levels.

Objective To understand the establishment and application experience of whole-course management nursing path for lymphoma patients by navigation nurses, and to provide reference for the construction of whole-course management for lymphoma patients. Methods In November 2023, a purposive sampling method was used to select 11 navigation nurses for lymphoma management in the Department of Lymphatic Hematology and Pediatric Medicine at the Guangxi Medical University Cancer Hospital for semi-structured interviews. The Colaizzi 7-step method was used to organize and analyze the dataResults The application experience of navigation nurses can be summarized into three main themes and four sub themes: recognizing the importance of managing nursing paths throughout the entire process (perceiving the value of professional roles), real work emotional experiences (positive feedback, negative psychological feelings), and factors affecting long-term career development (challenges in ensuring the quality of specialized practice). Conclusion Navigation nurses play an indispensable role in the overall management of lymphoma. Valuing their establishment and application experience in the management of nursing paths throughout the entire process can further enhance the value of full-time nursing, thereby increasing their work engagement, initiative, and creativity, and better playing the role of navigation nurses in the overall management of lymphoma; Ultimately achieving high-quality development of the hospital's dedicated nursing team. (目的 了解导航护士对淋巴瘤患者全程管理护理路径建立及应用体验, 为实施淋巴瘤患者全程管理的建设提供参考依据。方法 于2023年11月在广西医科大学附属肿瘤医院淋巴血液及儿童内科采用目的抽样法选取淋巴瘤全程管理的导航护士11名进行半结构式访谈, 并采用Colaizzi的七步资料分析法进行资料整理与分析。结果 导航护士的应用体验可归纳为3大主题4个次主题: 认可全程管理护理路径的重要性(感知专业角色价值), 真实工作情感体验(正性反馈、负性心理感受)和职业长远发展影响因素(专科实践质量保障挑战)。结论 导航护士在全程管理工作中发挥着不可或缺的作用, 重视其在全程管理护理路径的建立及应用体验, 可进一步发挥专职护理价值, 进而增强其工作投入度、主动性与创造力, 更好地发挥导航护士在淋巴瘤全程管理的作用; 最终实现医院专职护理队伍高质量发展。)

Abstract Background Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). Methods PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis. Results TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients. Conclusions In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.

Abstract Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.