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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 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.

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 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.

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.

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.

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.

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.

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.

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.

The primary cause of the decrease in thermal conductivity of conventional thermal conductive magnesium alloys is electron scattering brought on by solute atoms. However, the impact of phase interface on thermal conductivity of magnesium alloys is usually disregarded. This study has developed a Mg-Si-Zn-Cu alloy with high thermal conductivity that is distinguished by having a very low solute atom content and a significant number of phase interfaces. The thermal conductivity of the Mg-1.38Si-0.5Zn-0.5Cu alloy raises from its untreated value of 133.2 W/(m·K) to 142.2 W/(m·K), which is 91% of the thermal conductivity of pure Mg. This is accomplished by subjecting the alloy to both 0.8wt% Ce modification and T6 heat treatment. The morphology of eutectic Mg2Si phase is changed by Ce modification and heat treatment, and as a result, the scattering of electrons at the Mg2Si/Mg interface is reduced, resulting in increase of the alloy's thermal conductivity.

Abstract Background There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. Methods The China Kadoorie Biobank cohort was followed up from the 2004–08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively. Results Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all P trend

Abstract RNA-binding proteins (RBPs) modulate all aspects of RNA metabolism, but a comprehensive picture of RBP expression across tissues is lacking. Here, we describe our development of the method we call HARD-AP that robustly retrieves RBPs and tightly associated RNA regulatory complexes from cultured cells and fresh tissues. We successfully use HARD-AP to establish a comprehensive atlas of RBPs across mouse primary organs. We then systematically map RNA-binding sites of these RBPs using machine learning-based modeling. Notably, the modeling reveals that the LIM domain as an RNA-binding domain in many RBPs. We validate the LIM-domain-only protein Csrp1 as a tissue-dependent RNA binding protein. Taken together, HARD-AP is a powerful approach that can be used to identify RBPomes from any type of sample, allowing comprehensive and physiologically relevant networks of RNA-protein interactions.

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.

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.

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.

Traditional Chinese villages, as rural settlements shaped over extensive historical evolution in agrarian societies, have lacked a systematic method for quantitatively analysing and understanding the historical spatial forms. This study takes a morphological research perspective, using Lohong Village, Su’er Village, and Shangyue Village in Guangdong Province as case studies of typical Cantonese traditional villages. It focuses on three key spatial texture elements: roads, plots, and architecture, employing parametric modelling techniques to investigate their combination patterns and quantitative characteristics. The findings indicate that: (1) Parametric analysis techniques can comprehensively, quantitatively, and accurately reveal the patterns of village spatial texture; (2) Comparing optimized parametric simulation results with original villages shows high similarity in spatial texture, demonstrating the method’s high fidelity and practical value; (3) The study explores a research approach suitable for the computer era – “data collection – parametric feature extraction and optimization – simulation and data calibration” – to study the spatial texture of traditional villages. Furthermore, it establishes a parametric-based platform for rural planning and construction management, providing a digital design pathway and management basis to preserve and inherit the historical village aesthetics.

Abstract Purpose To investigate the correlation between whole eye movement (WEM) parameters measured using Corvis ST and axial length (AL) to explore whether AL affects WEMs. Methods This single-center, cross-sectional study included data from healthy subjects and patients preparing for refractive surgery at the Qingdao Eye Hospital of Shandong First Medical University. Data were collected from July 2021 to April 2022. We first determined the correlations of WEMs at the time of corneal first applanation (A1_WEM), highest concavity (HC_WEM), and second applanation (A2_WEM), as well as the maximum value of WEM (WEM_Max) with AL. Subsequently, we established a series of regression models to analyze the relationships between different WEM values and AL. Results AL was negatively correlated with HC_WEM, A2_WEM, and WEM_Max (r = − 0.28, − 0.23, and − 0.22, respectively; P

Abstract This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis.

Abstract Background The incidence of chronic diseases is on the rise worldwide, with a high mortality rate in China, posing a serious threat to the health-related quality of life (HRQoL) of middle-aged and older adults. This study explores the association between chronic diseases and the HRQoL of middle-aged and older adults, as well as the role of physical activity (PA) and degree of digitization in this relationship. Methods The data used in this study was obtained from the 2018 China Health and Retirement Longitudinal Study (CHARLS), which included 13,620 middle-aged and older Chinese adults (≥ 45 years). The study utilized correlation analysis, and bootstrapping to investigate the mediating role of PA and the moderating influence of the degree of digitization. Data analysis was conducted using SPSS 26.0. Results The study findings indicate that the severity of chronic disease has a significant negative predictive effect on HRQoL (PCS, physical component summary; MCS, mental component summary) (PCS: β = -2.515, p

Abstract So far, a variety of metabolite components of kiwifruit have been elucidated. However, the identification and analysis of flavonoids in different tissues of kiwifruit are rarely carried out. In this study, we performed transcriptome and metabolome analyses of roots (Gkf_R), stems (Gkf_T), leaves (Gkf_L), and fruits (Gkf_F) to provide insights into the differential accumulation and regulation mechanisms of flavonoids in kiwifruit. Results showed that a total of 301 flavonoids were identified, in four tissues with different accumulation trends, and a large proportion of flavonoids had high accumulation in Gkf_L and Gkf_R. A total of 84 genes have been identified involved in the flavonoid biosynthesis pathway, and the expression levels of five LAR, two DFR, and one HCT were significantly correlated with the accumulation of 16 flavonoids and co-localized in the flavonoid biosynthesis pathway. In addition, a total of 2362 transcription factor genes were identified, mainly MYBs, bHLHs, ERFs, bZIPs and WRKYs, among which the expression level of bHLH74, RAP2.3L/4L/10L, MYB1R1, and WRKY33 were significantly correlated with 25, 56, 43, and 24 kinds of flavonoids. Our research will enrich the metabolomic data and provide useful information for the directed genetic improvement and application in the pharmaceutical industry of kiwifruit.

Abstract Background Transposition of the great arteries (TGA) is the most common cyanotic congenital heart defect in neonates but with low prenatal detection rate. This study sought to review the prenatal diagnosis, associated abnormalities, and mid-term postnatal outcomes of fetuses with TGA and investigate the integrated prenatal and postnatal management for TGA neonates. Methods A total of 134 infants prenatally diagnosed with TGA in Guangdong Provincial People’s Hospital, China, from January 2009 to December 2022 were included in the study. The prenatal ultrasound data and neonatal records were reviewed to assess the accuracy of prenatal diagnosis. Univariate and multivariate logistic and Cox analyses were used to identify risk factors associated with prognosis in such individuals. Results The population originated from 40 cities in 10 provinces in China, with integrated antenatal and postnatal management rate reaching 94.0% (126/134) and a high accuracy rate (99.3%) of prenatal primary diagnosis. The median period of follow-up was 1.6 [interquartile range (IQR) 0.1–4.3] years. There were 3 (2.2%) postnatal deaths, 118 (88.1%) patients undergoing arterial switch operation (ASO), 3 (2.2%) undergoing Rastelli operations and 5 (3.7%) doing stage operations. Of 118 patients receiving ASO, the major morbidity occurred in 64 patients (54.2%), and right ventricular outflow tract obstruction (RVOTO) in 31 (26.3%). In the multivariate logistic analysis, gestational ages at birth (OR = 0.953, 95% CI 0.910–0.991; p = 0.025) and cardiopulmonary bypass (CPB) time (OR = 1.010, 95% CI 1.000–1.030; p = 0.038) were identified as independent risk factors associated with major morbidity. In the Cox multivariate analysis, aortic cross-clamping time (HR = 1.030, 95% CI 1.000–1.050; p = 0.017) was identified as independent risk factor associated with RVOTO. Conclusion Earlier gestational ages at birth and longer CPB time are significantly associated with increased morbidity. Integrated prenatal and postnatal management is recommended for patients with prenatal diagnosis of TGA.

Abstract Optical Kerr effect, in which input light intensity linearly alters the refractive index, has enabled the generation of optical solitons, supercontinuum spectra, and frequency combs, playing vital roles in the on-chip devices, fiber communications, and quantum manipulations. Especially, terahertz Kerr effect, featuring fascinating prospects in future high-rate computing, artificial intelligence, and cloud-based technologies, encounters a great challenge due to the rather low power density and feeble Kerr response. Here, we demonstrate a giant terahertz frequency Kerr nonlinearity mediated by stimulated phonon polaritons. Under the influences of the giant Kerr nonlinearity, the power-dependent refractive index change would result in a frequency shift in the microcavity, which was experimentally demonstrated via the measurement of the resonant mode of a chip-scale lithium niobate Fabry-Pérot microcavity. Attributed to the existence of stimulated phonon polaritons, the nonlinear coefficient extracted from the frequency shifts is orders of magnitude larger than that of visible and infrared light, which is also theoretically demonstrated by nonlinear Huang equations. This work opens an avenue for many rich and fruitful terahertz Kerr effect based physical, chemical, and biological systems that have terahertz fingerprints.

Abstract Emerging evidence highlights cellular senescence’s pivotal role in chronic kidney disease (CKD). Proximal tubule epithelial cells (PTECs) and fibroblasts are major players in CKD and serve as cellular sources of senescence. The generation of a conditionally immortalized human kidney cell model would allow to better understand the specific mechanisms and factors associated with cellular senescence in a controlled setting, devoid of potential confounding factors such as age and comorbidities. In addition, the availability of human kidney cell lines for preclinical research is sparse and most cell lines do not reflect their in vivo counterparts due to their altered behavior as immortalized cancer-like cells. In this study, PTECs and fibroblasts from human kidneys were isolated and transduced with doxycycline-inducible simian virus 40 large T antigen (SV40LT) vector. By comparing their gene expression with single-cell RNA sequencing data from human kidneys, the newly produced human kidney cell lines demonstrated significant resemblances to their in vivo counterparts. As predicted, PTECs showed functional activity and fibroblasts responded to injury with fibrosis. Withdrawal of the immortalizing factor doxycycline led to p21+ cell-cycle arrest and the key hallmarks of senescence. The obtained senescence gene set largely overlapped between both cell lines and with the previously published SenMayo set of senescence-associated genes. Furthermore, crosstalk experiments showed that senescent PTECs can cause a profibrotic response in fibroblasts by paracrine actions. In 76 human kidney sections, the number of p21+ cells correlated with the degree of fibrosis, age and reduced glomerular filtration, validating the role of senescence in CKD. In conclusion, we provide a novel cellular ex vivo model to study kidney senescence which can serve as a platform for large scale compounds testing.

Abstract Background Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement. Case presentation This paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis. Conclusions These findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

Abstract Background Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents into the esophagus. Despite its widespread prevalence worldwide, the causal link between GERD and various cancer risks has not been fully established, and past medical research has often underestimated or overlooked this relationship. Methods This study performed Mendelian randomization (MR) to investigate the causal relationship between GERD and 19 different cancers. We leveraged data from 129,080 GERD patients and 473,524 controls, along with cancer-related data, obtained from the UK Biobank and various Genome-Wide Association Studies (GWAS) consortia. Single nucleotide polymorphisms (SNPs) associated with GERD were used as instrumental variables, utilizing methods such as inverse variance weighting, weighted median, and MR-Egger to address potential pleiotropy and confounding factors. Results GERD was significantly associated with higher risks of nine types of cancer. Even after adjusting for all known risk factors—including smoking, alcohol consumption, major depression, and body mass index (BMI)—these associations remained significant, with higher risks for most cancers. For example, the adjusted risk for overall lung cancer was (OR, 1.23; 95% CI: 1.14–1.33), for lung adenocarcinoma was (OR, 1.18; 95% CI: 1.03–1.36), for lung squamous cell carcinoma was (OR, 1.35; 95% CI: 1.19–1.53), and for oral cavity and pharyngeal cancer was (OR, 1.73; 95% CI: 1.22–2.44). Especially noteworthy, the risk for esophageal cancer increased to (OR, 2.57; 95% CI: 1.23–5.37). Mediation analyses further highlighted GERD as a significant mediator in the relationships between BMI, smoking, major depression, and cancer risks. Conclusions This study identifies a significant causal relationship between GERD and increased cancer risk, highlighting its role in cancer development and underscoring the necessity of incorporating GERD management into cancer prevention strategies.

Abstract Super-enhancers are a class of DNA cis-regulatory elements that can regulate cell identity, cell fate, stem cell pluripotency, and even tumorigenesis. Increasing evidence shows that epigenetic modifications play an important role in the pathogenesis of various types of cancer. However, the current research is far from enough to reveal the complex mechanism behind it. This study found a super-enhancer enriched with abnormally active histone modifications in pancreatic ductal adenocarcinoma (PDAC), called DKK1-super-enhancer (DKK1-SE). The major active component of DKK1-SE is component enhancer e1. Mechanistically, AP1 induces chromatin remodeling in component enhancer e1 and activates the transcriptional activity of DKK1. Moreover, DKK1 was closely related to the malignant clinical features of PDAC. Deletion or knockdown of DKK1-SE significantly inhibited the proliferation, colony formation, motility, migration, and invasion of PDAC cells in vitro, and these phenomena were partly mitigated upon rescuing DKK1 expression. In vivo, DKK1-SE deficiency not only inhibited tumor proliferation but also reduced the complexity of the tumor microenvironment. This study identifies that DKK1-SE drives DKK1 expression by recruiting AP1 transcription factors, exerting oncogenic effects in PDAC, and enhancing the complexity of the tumor microenvironment.

ObjectiveTo evaluate the efficacy and further analyze the application prospects of the combined multitarget fecal FIT-DNA assay in the early screening of colorectal cancer. MethodsSubjects were selected from a population attending the Inner Mongolia Medical University Hospital. Each subject underwent a combined multi-target fecal FIT-DNA test (experimental group), a serum tumor marker test and enteroscopy (control group). The pathological results were used as the gold standard to evaluate the efficacy of novel fecal molecular testing techniques for colorectal cancer screening with timely intervention given to screen positive individuals. ResultsThe data of 115 individuals were analyzed. Serum tumor markers test had a sensitivity of 63.2% (43/68) and a specificity of 74.5% (35/47). The enteroscopy had a sensitivity of 97.1% (66/68) and a specificity of 80.7% (38/47); the combined multitarget fecal FIT-DNA test had a sensitivity of 89.7% (61/68) and a specificity of 87.2% (41/47). ConclusionThe sensitivity and specificity of multitarget fecal FIT-DNA combined detection are better than those of serum tumor marker detection. Although its sensitivity is lower than enteroscopy, its operation is simpler and can be tested at home.

Abstract Analysis of the spatial–temporal pattern and trend of carbon emissions provides an important scientific basis for the development of a low-carbon economy. Based on the corrected NPP-VIIRS and DMSP/OLS nighttime light data, a carbon emission model for the Chengdu–Chongqing Economic Zone (CCEZ) in China is constructed. Furthermore, the article establishes an integrated qualitative and quantitative research system. The qualitative results show that at the city and county scales, the high carbon emission areas and counties are mainly distributed in Chengdu and Chongqing, while the low carbon emission areas are concentrated in the marginal cities of the CCEZ and the counties with low levels of industrialization around the Sichuan Basin. The high-carbon emission zone tended to expand to the north, and the low-carbon emission zone tended to expand to the south. At the grid scale, the carbon emissions of the CCEZ fluctuated and increased from 2000 to 2020, forming a trend connected with those of the central city, with high carbon emissions at the core and radiating outward expansion. Quantitative analysis revealed that carbon emissions at the county and grid scales exhibited a significant positive global spatial correlation, and the overall correlation degree exhibited an increasing trend.

Plantago major (Plantaginaceae) is a medicinal plant in Chinese folk culture, known for its famous medicinal components such as plantagomain. In this study, we conducted genome sequencing of P. major using Illumina sequencing technology. The assembled complete chloroplast genome had a length of 165,044 bp, comprising a large single-copy regions (82,963 bp), a small single-copy regions (4,633 bp), and a pair of inverted repeat regions (38,724 bp). A total of 140 genes were detected, including 94 CDS, 38 tRNA, and 8 rRNA. Phylogenetic analysis revealed a close genetic relationship between P. major and P. rigida. These findings provide valuable data for a comprehensive understanding of the biological characteristics of P. major.

To explore the quality evaluation indicators of walnut and pecan varieties cultured in Yunnan, the contents of 12 nutritional indicators which included in mineral elements, protein, crude fat, and vitamin C of 27 walnut varieties were determined. 12 indicators were comprehensively explored by correlation analysis, principal component analysis and cluster analysis to reveal variation and comprehensive quality of walnut resources in Yunnan Province. Results showed that the variation of the content of 12 indicators was relatively rich, the variation coefficient ranged from 5% to 83%, among which the variation coefficient of vitamin C was the largest and the variation coefficient of crude fat was the smallest. The order of the average contents of 9 mineral elements was K>P>Mg>Ca>Mn>Na>Fe>Zn>Cu. The average contents of protein, fat and vitamin C were 15.62%, 68.63% and 4.66 mg/100 g, respectively. As demonstrated by the results of correlation analysis on 12 indicators, there was a significant positive correlation between protein and P, Fe, Mg, Ca, and Cu. The principal component analysis was used to comprehensively evaluate, showed that the comprehensive quality of walnut varieties 'Xiangcha' 'Yongping' 'Wanshu' and 'Xiaoyuanguo' were the best and the pecan variety 'Kaduo' was the better. The clustering analysis results showed that it can be divided into two major categories, namely the group rich in mineral elements and the group with high fat content. Subsequently, by combining with cluster analysis, K, Fe, Mg, Ca, Cu, protein and fat were determined as the critical indicators to evaluate the quality of walnut and pecan varieties cultured in Yunnan. Pecan varieties were suitable for extracting oil, and 22 main walnut varieties were suitable for direct consumption or the development of functional beverages rich in mineral elements and protein. The study clarified the critical indicators for evaluating the quality of Yunnan walnut and explored its quality characteristics, providing a scientific classification method, and laying a theoretical basis for the construction of the Yunnan walnut quality evaluation system.

Abstract Objective The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. Methods A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5–10 days after the first evaluation. Results The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p 0.05). The Cronbach’s α of the CNS-BFSC was 0.972. Conclusion The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

AIM: To evaluate the trending visual performance of different intraocular lenses (IOLs) over time after implantation. METHODS: Ninety-one patients received cataract surgery with implantations of monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs, and extended-depth-of-focus (EDoF) IOLs were included. The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared. RESULTS: Most of the visual parameters improved over the postoperative 6mo. The postoperative visual acuity (POVA) of the Mon IOL, SegRef IOL, and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group. Nevertheless, the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo. The optical quality initially improved in the EDoF IOL group, then in the Mon IOL, SegRef IOL, and Dif IOL groups. POVA and objective visual performance of the Mon IOL and EDoF IOL groups, as well as POVA and visual quality of the Dif IOL group, improved in the postoperative 1mo and stabilized. Within the postoperative 6mo, gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group, as well as in the postoperative optical quality of the Dif IOL group. CONCLUSION: The visual performance is different among eyes implanted with different IOLs. The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

AIM: To investigate Omicron's impact on clinical presentation of acute primary angle closure (APAC) in China. METHODS: A consecutive case series with historical controls was conducted at Shenzhen Eye Hospital, the largest specialized hospital in Shenzhen, China. Medical records from a two-month period during the Omicron pandemic (December 1, 2022, to January 31, 2023) were compared with records from two control groups (12/2018–1/2019 and 12/2021–1/2022) before pandemic. Patients with APAC were included, and the prevalence of APAC and demographic characteristics in Omicron-infected and non-infected patients were compared. RESULTS: Seventy-one (23.43%) out of 303 patients were diagnosed with APAC in the pandemic cohort, which was 2.98 and 2.61 times higher than that in control cohorts (7.87% in 2019, 8.96% in 2022, P

The X bill of material (XBOM) of a missile and rocket product is a comprehensive and basic support document produced by a multi-stakeholder that considers structural composition, data information and interactional processes in different life stages. The XBOM data management of missile and rocket products coordinates the data organization and control in the whole life cycle, eliminates the interactional disconnection and one-way transmission between related parties, business and data in different life stages and provides effective data source support for the full digital model supply. To meet the requirements of organic integration and multi-party collaboration, this paper proposes the XBOM data management method based on digital thread. Firstly, the digital thread framework is analyzed, and the XBOM data management architecture based on the digital thread is proposed and established. Secondly, guided by the hierarchy of "data-interaction-modeling-application", the XBOM data management method for the missile and rocket product are developed, including data organization, data relational analysis, data modeling and data application. Finally, the structural system of a certain model of carrier rocket is studied, and the XBOM data management system based on digital thread is developed and its application is validated.

【Objective】 Non-pressurized mesh filters are often installed in front of pumps to filter sediments and debris. In this paper, we study the influence of different irrigation water sources and backwash device parameters on hydraulic performance of a new network filter. 【Method】 The water flow rate in the experiment ranged from 120 to 160 m3/h, and the sediment concentration in the water varied from 0.2 to 0.8 g/L. The backwash varied from 1 to 20 m3/h, and the velocity gradient in the filter box changed from 1 to 4 r/min. A multi factor dispersion analysis method was used to analyze the experimental results. 【Result】 ① The initial sediment concentration had minimal impact on hydraulic performance of the mesh filter, contributing only 0.010 8 to the overall effect. However, the influence of water flow duration on the initial sediment concentration was significant, exceeding 159%. ② The fourth model provided the best fit for the overall regression analysis, with a residual value of 0.804 4, significantly higher than other models; its coefficient of determination R2 was 0.986 1. ③ the optimal performance was achieved when flow rate was 120.198 m3/h, velocity was 1.112 r/min, and self-cleaning flow rate was 19.934 m3/h. The associated a minimum energy loss was 16.024 kPa. 【Conclusion】 The model we proposed can accurately predict the impact of operation conditions and sediment concentration in the water on the performance of the non-pressurized mesh filters. Selecting optimal operation conditions can minimize the energy loss across the filter.

Objective: Functional magnetic resonance imaging (fMRI) has been applied to assess the microstructure of the kidney. However, it is not clear whether fMRI could be used in the field of kidney injury in patients with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: This study included 20 patients with AAV. Diffusion kurtosis imaging (DKI) and blood oxygen level-dependent (BOLD) scanning of the kidneys were performed in AAV patients and healthy controls. The mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) parameters of DKI, the R2* parameter of BOLD, and clinical data were further analyzed. Results: In AAV patients, the cortex exhibited lower MD but higher R2* values compared to the healthy controls. Medullary MK values were elevated in AAV patients. Renal medullary MK values showed a positive correlation with serum creatinine levels and negative correlations with hemoglobin levels and estimated glomerular filtration rate. To assess renal injury in AAV patients, AUC values for MK, MD, FA, and R2* in the cortex were 0.66, 0.67, 0.57, and 0.55, respectively, and those in the medulla were 0.81, 0.77, 0.61, and 0.53, respectively. Conclusions: Significant differences in DKI and BOLD MRI parameters were observed between AAV patients with kidney injuries and the healthy controls. The medullary MK value in DKI may be a noninvasive marker for assessing the severity of kidney injury in AAV patients.

Abstract Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.

Abstract Background Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR). Methods To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran’s Q-test and the MR Egger intercept test. Results The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209–2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044–1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062–2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039–1.425, P = 0.015). Conclusions Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.

As a benzoylurea insecticide, diflubenzuron (DFB) has been widely used in the prevention and control of diseases and insect pests in vegetables, fruits, grain cultivation, and other fields in recent years. In addition, because of its low acute toxicity, excellent biological activity, and specific action mechanism, DFB has been widely used in aquaculture to kill bacteria and lice. With its large-scale production and widespread use, its partial residue remains in environmental media, such as water, soil, and the atmosphere, and causes direct or indirect chronic toxicity to aquatic organisms. The residual DFB enters the human body along the food chain and poses a threat to human health when it reaches a certain concentration through chronic exposure and long-term accumulation. At present, research on DFB insecticides has been limited to the usage and dosage, residual metabolism, and its toxicological effects on the environment. There have been no reports, to our knowledge, on the effect of DFB on gene expression in carp liver in China. The purpose of this study was to explore the differential expression of genes in carp liver under DFB stress.In this study, carp (Cyprinus carpio) was selected as the research subject, and three exposure experiments for 15 days under 0.1 and 1.0 mg/L medicated bath concentrations were carried out in parallel for each concentration. High-throughput sequencing of the liver was performed using the Illumina NovaSeq 6000. Differentially expressed genes (DEGs) were screened by Padj < 0.05 and |log2FoldChange| ≥1, and bioinformatics analysis, such as Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, were performed. The transcriptome analysis results showed that 2 406 and 2 688 DEGs changed significantly at 0.1 and 1.0 mg/L exposure concentrations, respectively, and 821 DEGs were co-expressed between the two groups. GO analysis results showed that DEGs in the DFB exposure group were enriched in biological processes, cell compositions, and molecular functions. KEGG enrichment analysis showed that DEGs in the low DFB concentration exposure group were significantly enriched in metabolic pathways, such as biodegradation and metabolism of xenobiotics, lipid metabolism, carbohydrate metabolism, amino acid metabolism, signal molecules and interactions, endocrine system, and immune system. In addition to the above metabolic pathways, DEGs in the high DFB concentration exposure group were significantly enriched in metabolic pathways, such as folding, classification and degradation, transport, and catabolism.Studies have shown that DFB exposure causes the biodegradation and metabolism of xenobiotics, lipid metabolism, carbohydrate metabolism, and amino acid metabolism, and generates endoplasmic reticulum stress, inflammatory response, and immune toxicity. In summary, the results of this study provide basic data and a theoretical basis for further research on the molecular mechanism of DFB stress in carp.

Urban vitality stands as a pivotal metric for evaluating the sustainability and appeal of urban environments. Global experiences underscore the significance of parks and shopping centers as crucial components of urban vitality spaces. However, existing literature predominantly concentrates on the individual impacts of parks or shopping centers on urban vitality, with limited exploration into the vitality relationship between them, often relying on linear correlation analyses. To address this gap, this study, centered on the renowned Park City of Chengdu in China, employs Baidu heatmap and POI data, utilizing a combination of spatial syntax and linear and non-linear analysis methods to examine the influence of road accessibility on the vitality of shopping malls and parks, as well as their correlation. Findings indicate: (1) High-vitality shopping malls primarily cluster within the first ring road, while park utilization is notably higher in the southern urban area. (2) High-vitality parks and shopping centers are situated in regions characterized by elevated global integration and efficiency values, suggesting their vitality is influenced by road accessibility. (3) Linear correlation analysis, with global integration and efficiency values controlled, yields correlation coefficients of 0.797 and 0.795 for high-vitality parks and shopping centers, respectively. Non-linear correlation analysis indicates a correlation coefficient close to 0.7 between park vitality and shopping mall vitality, highlighting a strong correlation between them. This study elucidates the critical relationship between park vitality and commercial vitality in urban layout, offering valuable insights for urban planning strategies aimed at promoting sustainable urban development.

Abstract Objective To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO). Methods Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate. Results Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p

Abstract Background Resident microglia- and peripheric macrophage-mediated neuroinflammation plays a predominant role in the occurrence and development of ischemic stroke. Microglia undergo polarization to M1/M2-like phenotype under stress stimulation, which mediates intracellular inflammatory response. β-elemene is a natural sesquiterpene and possesses potent anti-inflammatory activity. This study aimed to investigate the anti-inflammatory efficacy and mechanism of β-elemene in ischemic stroke from the perspective of balancing microglia M1/M2-like polarization. Methods The middle cerebral artery occlusion (MCAO) model and photothrombotic stroke model were established to explore the regulation effect of β-elemene on the cerebral ischemic injury. The LPS and IFN-γ stimulated BV-2 cells were used to demonstrate the anti-inflammatory effects and potential mechanism of β-elemene regulating M1/M2-like polarization in vitro. Results In C57BL/6 J mice subjected to MCAO model and photothrombotic stroke model, β-elemene attenuated neurological deficit, reduced the infarction volume and neuroinflammation, thus improving ischemic stroke injury. β-elemene promoted the phenotype transformation of microglia from M1-like to M2-like, which prevented neurons from oxygen and glucose deprivation/reoxygenation (OGD/R) injury by inhibiting inflammatory factor release, thereby reducing neuronal apoptosis. Mechanically, β-elemene prevented the activation of TLR4/NF-κΒ and MAPK signaling pathway and increased AKT/mTOR mediated-autophagy, thereby promoting M2-like polarization of microglia. Conclusions These results indicated that β-elemene improved cerebral ischemic injury and promoted the transformation of microglia phenotype from M1-like to M2-like, at least in part, through AKT/mTOR-mediated autophagy. This study demonstrated that β-elemene might serve as a promising drug for alleviating ischemic stroke injury.