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Dalbergia tonkinensis is very similar to Dalbergia odorifera in material, texture, and other macroscopic characteristics, and a comparison of the commonalities and differences in the chemical composition of the extractives may help to distinguish the two. However, the chemical composition of Dalbergia tonkinensis heartwood is unknown. The total flavonoid content of Dalbergia tonkinensis heartwood was determined to range between 49.67 to 101.95 mg, which indicated that Dalbergia tonkinensis is as equally rich in flavonoids as Dalbergia odorifera. Thirty-one flavonoids were identified via ultra-performance liquid chromatography-mass spectrometry in Dalbergia tonkinensis. Among them, the contents of 15 medicinal active flavonoids with were determined, and the liquiritigenin, naringenin, formononetin, pinocembrin, and biochanin A contents were found to be high. The 12 volatile compositions of Dalbergia tonkinensis heartwood identified via gas chromatography-mass spectrometry were very similar to those of Dalbergia odorifera and were dominated by trans-nerolidol, caryophyllene oxide, and eudesmol. The relationship between the chemical composition of Dalbergia tonkinensis and Dalbergia odorifera heartwood extracts was determined via a principal component analysis, and the results indicated that there was no significant difference in chemical composition between the two. This suggested that Dalbergia tonkinensis could be used as a potential substitute for Dalbergia odorifera.

Abstract Background CT-based abdominal skeletal muscle area (SMA) serves as a standard for assessing muscle mass in patients with cirrhosis. Few studies have used MR imaging to measure SMA in cirrhotic patients. The purpose of this study was to investigate the agreement and correlation of the SMA measured by MRI and CT in cirrhotic patients. Methods CT and MR images from 38 cirrhotic patients were analyzed using the Slice-O-Matic V5.0 software. One observer independently measured SMA at the mid-third lumbar vertebral (L3) level on CT and MR images. The intraclass correlation coefficient (ICC), Pearson correlation coefficient, and Bland–Altman plot were used to evaluate the agreement and correlation between CT and MRI SMA and their relationship with the sarcopenia severity and Child–Pugh grades. Results CT and MRI had a high intraobserver agreement, with ICCs ranging from 0.991 to 0.996. CT and MRI measurements were closely correlated (r = 0.991–0.998, all for P

Abstract Background The prognosis of thymic epithelial tumors (TETs) currently relies on the commonly adopted WHO classification and Masaoka staging system, which cannot reflect the undefined biological behaviors limiting them as prognostic factors. Methods In this study, we first identified 40 genes and 179 genes, respectively that were epigenetically upregulated and silenced, corresponding to a total of 509 functionally methylated CpG sites between thymomas and thymic carcinomas by using the TCGA dataset. Results The methylation β‐values of cg20068620 in MAPK4 and cg18770944 in USP51 were significantly associated with recurrence‐free survival (RFS). In the independent validation cohort, only WHO classification and methylation β‐values of cg20068620 in MAPK4 were independent prognostic factors for RFS in Chinese patients with TETs. A linear weighted model including these two factors was used to calculate the recurrence risk score (RRS). Time‐dependent ROC curve analysis revealed that RRS was overwhelmingly superior to WHO classification for predicting 3‐, 5‐, and 10‐year RFS and Masaoka stage for 3‐ and 5‐year RFS. Conclusions These results suggested that the methylation site cg20068620 in MAPK4 can improve the accuracy of the WHO classification alone regarding the prognostic value of TETs recurrence.

Generation of TNF-α in response to chemotherapy has been associated with chemo-resistance and metastasis propagation. Here the authors show that the combination of an anti-TNF antibody and cisplatin doublet chemotherapy increases anti-tumor efficacy in lung cancer preclinical models and report the results of a phase I clinical trial of the anti-TNF-α antibody certolizumab in combination with chemotherapy in patients with stage IV lung adenocarcinomas.

AIM: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification. METHODS: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit. RESULTS: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion. CONCLUSION: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is.

Abstract This cross-sectional study aimed to explore the combined effects of depression and obesity on ischemic heart disease and its subtypes. Data from the National Health and Nutrition Examination Survey 2007–2018 were used. A total of 29,050 participants aged 20 years or older were included in the analyses. Logistic regression models and restricted cubic spline models were applied to evaluate the associations between depression symptom and ischemic heart disease. There were significant correlations between depressive symptoms and ischemic heart disease [OR and 95% CI 2.44 (1.91, 3.10)] and its subtypes: coronary heart disease [2.32 (1.67, 3.23)], heart attack [2.18 (1.71, 2.78)], and angina [2.72 (1.96, 3.79)].The synergistic effects of depression with obesity (BMI ≥ 30) and central obesity (waist ≥ 102/88 cm for men/women) on ischemic heart disease were estimated and expressed using the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP). The RERI and AP with 95% CIs of depression and central obesity for ischemic heart disease were 1.10 (0.01, 2.19) and 0.35 (0.06, 0.64). When we analysed the other three subtypes of ischemic heart disease, we only found depressive symptoms and central obesity could have a meaningful synergistic effect on heart attack (RERI: 0.84 (− 0.28, 1.96) AP: (0.31 (0.00, 0.69)).

Acute kidney injury (AKI) is characterized by a rapid decrease in renal function with high mortality and risk of progression to chronic kidney disease (CKD). Ischemia and reperfusion injury (IRI) is one of the major causes of AKI. However, the cellular and molecular responses of the kidney to IRI are complex and not fully understood. Herein, we conducted unbiased proteomics and bioinformatics analyses in an IRI mouse model on days 3, 7, and 21, and validated the results using IRI, unilateral ureteral obstruction (UUO), and biopsies from patients with AKI or CKD. The results indicated an obvious temporal expression profile of differentially expressed proteins and highlighted impaired lipid metabolism during the progression of AKI to CKD. Acyl-coenzyme A oxidase 1 (Acox1), the first rate-limiting enzyme of peroxisomal fatty acid beta-oxidation, was then selected, and its disturbed expression in the two murine models validated the proteomic findings. Accordingly, Acox1 expression was significantly downregulated in renal biopsies from patients with AKI or CKD, and its expression was negatively correlated with kidney injury score. Furthermore, in contrast to the decreased Acox1 expression, lipid droplet accumulation was remarkably increased in these renal tissues, suggesting dysregulation of fatty acid oxidation. In conclusion, our results suggest that defective peroxisomal fatty acid oxidation might be a common pathological feature in the transition from AKI to CKD, and that Acox1 is a promising intervention target for kidney injury and repair.

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver diseases. In most cases, NAFLD progresses from benign steatosis to steatohepatitis (NASH), and then to cirrhosis. No treatment is currently approved for NAFLD/NASH in the clinic. Fenofibrate (FENO) has been clinically used to treat dyslipidemia for more than a half century, but its effects on NASH are not established. FENO’s half-life is quite different between rodent and human. The aim of this study was to investigate the potential of pharmacokinetic-based FENO regime for NASH treatment and the underlying mechanisms.Methods: Two typical mouse NASH models, methionine-choline deficient (MCD) diet-fed mice and choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-fed mice, were used. MCD model was designed as therapeutic evaluation in experiment 1 and CDAHFD model was designed as preventive in experiment 2. Three doses of FENO (5, 25, 125 mg/kg), two times a day (BID), were administered to the above models. Serum markers of liver injury, cholestasis, and the histology of liver tissues were investigated. Normal mice were used as a model in experiment 3 for toxicity evaluation, Quantitative-PCR and Western Blot assays were used to investigate the inflammatory responses, bile acid synthesis as well as lipid catabolism.Results: Mice on the MCD and CDAHFD diets developed steatohepatitis as expected. Treatment with FENO (25 mg/kg·BID) significantly decreased hepatic steatosis, inflammation and fibrosis in both therapeutic and preventive models. In the MCD model, the therapeutic action of FENO (25 mg/kg·BID) and 125 mg/kg·BID on histopathology and the expression of inflammatory cytokines were comparable. In reducing macrophage infiltration and bile acid load, FENO (25 mg/kg·BID) was superior to 125 mg/kg·BID. In all the aspects mentioned above, FENO (25 mg/kg·BID) was the best among the 3 doses in the CDAHFD model. In a third experiment, the effects of FENO (25 mg/kg·BID) and 125 mg/kg·BID on lipid catabolism were comparable, but 125 mg/kg·BID increased the expression of inflammatory factors and bile acid load. In both models, FENO (5 mg/kg·BID) showed little effect in hepatic steatosis and inflammation, neither the adverse effects. FENO (125 mg/kg·BID) aggravated liver inflammation, increased bile acid synthesis, and promoted the potential of liver proliferation. In toxicity risk assay, FENO (25 mg/kg·BID) treatment showed low potential to trigger bile acid synthesis, inflammation and hepatocyte proliferation.Conclusion: A new regime, FENO (25 mg/kg·BID) is potentially a therapeutic strategy for the NASH treatment. Translational medicine is warranted to prove its effectiveness in the clinic.

In the original publication [...]

Abstract Apoptotic resistance leads to persistent accumulation of senescent cells and sustained expression of a senescence-associated secretory phenotype, playing an essential role in the progression of tissue fibrosis. However, whether senescent renal tubular epithelial cells (RTECs) exhibit an apoptosis-resistant phenotype, and the role of this phenotype in diabetic nephropathy (DN) remain unclear. Our previous study was the first to demonstrate that decoy receptor 2 (DcR2) is associated with apoptotic resistance in senescent RTECs and renal fibrosis. In this study, we aimed to further explore the mechanism of DcR2 in apoptosis-resistant RTECs and renal fibrosis in DN. DcR2 was co-localized with fibrotic markers (α-SMA, collagen IV, fibronectin), senescent marker p16, and antiapoptotic proteins FLIP and Bcl2 but rarely co-localized with caspase 3 or TUNEL. DcR2 overexpression promoted renal fibrosis in mice with streptozotocin (STZ)-induced DN, as evidenced by augmented Masson staining and upregulated expression of fibrotic markers. DcR2 overexpression also enhanced FLIP expression while reducing the expression of pro-apoptotic proteins (caspases 8 and 3) in senescent RTECs, resulting in apoptotic resistance. In contrast, DcR2 knockdown produced the opposite effects in vitro and in vivo. Moreover, quantitative proteomics and co-immunoprecipitation experiments demonstrated that DcR2 interacted with glucose-related protein 78 kDa (GRP78), which has been shown to promote apoptotic resistance in cancer. GRP78 exhibited co-localization with senescent and antiapoptotic markers but was rarely co-expressed with caspase 3 or TUNEL. Additionally, GRP78 knockdown decreased the apoptosis resistance of HG-induced senescent RTECs with upregulated cleaved caspase 3 and increased the percentage of apoptotic RTECs. Mechanistically, DcR2 mediated apoptotic resistance in senescent RTECs by enhancing GRP78–caspase 7 interactions and promoting Akt phosphorylation. Thus, DcR2 mediated the apoptotic resistance of senescent RTECs and renal fibrosis by interacting with GRP78, indicating that targeting the DcR2–GRP78 axis represents a promising therapeutic strategy for DN.

AIM: To investigate the role of procollagen C-proteinase enhancer 1 (PCPE1) in retinal angiogenesis and relevant mechanisms. METHODS: The Pcolce1-knockout (KO) mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo. Pcolce1 siRNA were designed, cell count kit 8 (CCK8) assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells (hRMECs) in vitro. Mouse embryo fibroblasts (MEF) cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage. RESULTS: In vivo studies showed that the retinal vascular density of Pcolce1-/- mice was significantly lower than that of the control group. Furthermore, silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of hRMECs in vitro. Additionally, much more pro-collagen was found in Pcolce1-/- MEF cells, compared to wild type MEF cells. CONCLUSION: PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen, which may provide a potential therapeutic target of retinal vascular disease.

Abstract Drug resistance is responsible for castration-resistant prostate cancer (CRPC)-associated mortality. While ATP binding cassette subfamily C member 5 (ABCC5) has been reported to regulate multiple drug resistance, its drug-efflux function may not be the main reason underlying resistance to enzalutamide, an androgen receptor inhibitor. Here, we aimed to determine whether the non-drug efflux function of ABCC5 affects enzalutamide resistance. The ABCC5 expression data in patients with prostate cancer (PCa) were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus, and their correlation with disease prognosis was analyzed. Immunohistochemical staining was performed on a cohort of 80 patient samples. Proliferation of enzalutamide-resistant 22RV1 and C4-2B cells was investigated using CCK-8, EdU, and colony formation assays. The effect of ABCC5 silencing on enzalutamide resensitization was evaluated in vitro and in vivo. Functional assays indicated that ABCC5 depletion resensitized enzalutamide-resistant cells to inhibit cell growth and impeded xenograft tumor proliferation. Mechanistically, luciferase and ChIP assays confirmed that P65 regulated AR expression and activity by binding to its promoter, while ABCC5-mediated resistance effected by AR-V7 (one of the widely studied AR splicing variants that meditate AR antagonist resistance) upregulation could be reversed by P65 knockdown. Furthermore, activation of the NF-κB pathway reversed the effects of ABCC5 knockdown by extra AR-V7 expression. Thus, ABCC5 might be a novel target for enzalutamide-resistant CRPC treatment.

BackgroundSkin regeneration is a challenging issue worldwide. Increasing research has highlighted the role of immune cells in healing and the underlying regulatory mechanism. The purpose of this study was to identify the hotspots and trends in skin regeneration and inflammation research through bibliometrics and to provide insights into the future development of fundamental research and disease treatment.MethodsPublications were collected from the Web of Science Core Collection on March 1, 2022. Articles and reviews published in English from January 1, 1999, to December 31, 2022, were selected, and statistical analyses of countries, institutions, authors, references, and keywords were performed using VOSviewer 1.6.18 and CiteSpace 5.8.ResultsA total of 3,894 articles and reviews were selected. The number of publications on skin inflammation and regeneration showed an increasing trend over time. Additionally, authors and institutions in the United States, United Kingdom, Canada, and China appeared to be at the forefront of research in the field of skin inflammation and regeneration. Werner Sabine published some of the most cited papers. Wound Repair and Regeneration was the most productive journal, while Journal of Investigative Dermatology was the most cited journal. Angiogenesis, diamonds, collagen, cytokine, and keratinocytes were the five most commonly used keywords.ConclusionThe number of publications on skin inflammation and regeneration show an increasing trend. Moreover, a series of advanced technologies and treatments for skin regeneration, such as exosomes, hydrogels, and wound dressings, are emerging, which will provide precise information for the treatment of skin wounds. This study can enhance our understanding of current hotspots and future trends in skin inflammation and regeneration research, as well as provide guidelines for fundamental research and clinical treatment.

Objective: To explore the effects of single-session transcranial direct current stimulation (tDCS) on aerobic performance and explosive force in the one-arm pull-down of long-term trained rock climbers.Method: Twenty athletes (twelve male and eight female) from the Rock Climbing Team of Hunan province (Hunan, China) were selected for a randomized double-blind crossover study. After baseline tests, All subjects visited laboratories twice to randomly receive either sham or a-tDCS at a current intensity of 2 mA for 20 min. The two visits were more than 72 h apart. Immediately after each stimulation, subjects completed a 9-min 3-level-load aerobic test and a one-arm pull-down test.Results: Differences in the heart rate immediately after 9-min incremental aerobic exercises revealed no statistical significance between each group (p > 0.05). However, the decrease in heart rate per unit time after exercise after real stimulation was significantly better than before stimulation (p < 0.05), and no statistical significance was observed between after sham stimulation and before stimulation (p > 0.05). One-arm pull-down explosive force on both sides after real stimulation was improved by a-tDCS compared with before stimulation, but with no significant difference (p > 0.05). Real stimulation was significantly improved, compared with sham stimulation on the right side (p < 0.05).Conclusion: Single-session tDCS could potentially benefit sports performance in professional athletes.

Composting is a sustainable strategy to deal with organic waste. Our research aimed to study the influence of an amendment of 10% matured compost (MC) during Chinese herb residue (CHR) compost. Here, a 60-day CHR compost was performed, and MC application was able to reduce the nitrogen loss and enhance the humic acid accumulation during the composting as compared with the non-inoculated control (NC), by 25 and 19%, respectively. Furthermore, the matured compost amendment improved the diversity of the bacterial community, increased the complexity of the co-occurrence network, and changed the keystone and module hub bacteria during composting. The increased abundance levels of Thermopolyspora, Thermobispora, and Thermosporomyces, which were significantly higher in MC than in NC, may contribute to the degradation of cellulose and the formation of humic acid. Overall, this study extends our understanding of the effects of matured compost reflux on compost quality and the bacterial community.

Background: Evidence indicates that chronic stress promotes progression of colorectal liver metastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood. Methods: To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-α) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy. Results: CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-β1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM. Conclusion: MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.

BackgroundGlaucoma is the first irreversible and second blindness disease, which is characterized by the death of retinal ganglion cells (RGCs) and degeneration of the optic nerve. Previous works have indicated that apoptosis is the main reason for RGC death in glaucoma. Although many studies have investigated the mechanism of apoptosis and different strategies targeting apoptosis to protect the RGCs and finally recover the impaired vision in the glaucoma. However, the global trend and hotspots of apoptosis in glaucoma have not been well illustrated and discussed.MethodsDocuments were extracted from the Web of Science Core Collection on November 2, 2022. We selected articles and reviews published in English from January 1, 1999 to November 1, 2022 to perform visual analysis and statistical analysis of countries, institutions, authors, references and keywords by VOSviewer 1.6.18 and CiteSpace 5.8.ResultsThe publications about apoptosis in glaucoma show an increasing trend over time. Besides, the authors, institutions in the US and China published the most numbers of articles with the highest citation, which may be leading the research in the field of apoptosis in glaucoma. Last, series of advanced research results, technology and treatment for glaucoma, such as the discovery of key regulatory mechanisms on RGC apoptosis are emerging and will provide precise strategies for the treatment of glaucoma.ConclusionThis research will broaden our comprehension about the role of apoptosis in the process of glaucoma, and provide guidelines for us in basic research and disease treatment in the further.

Abstract The Global Positioning System (GPS) radio occultation (RO) data provided by the Fengyun-3C (FY-3C) mission during January 2015 to December 2019 are used to detect the existence of sporadic E (Es) layers over the globe, based on which the spatial and temporal distributions of the Es occurrence rates (ORs) are presented and analyzed. The results are compared with the Es morphology obtained using the RO data from the Constellation Observing System for the Meteorology, Ionosphere, and Climate (COSMIC) mission. It is found that the seasonal variation patterns of the spatial distributions of Es ORs derived from the FY-3C RO data, which show clearly the effects of wind shear mechanism and the Earth’s magnetic field on the formation of Es layers, are basically consistent with those derived from the COSMIC RO data. While the limited local time distribution of the FY-3C RO-detected Es occurrences makes it impossible to resolve the complete diurnal variations of Es layers. Detailed comparisons of the Es morphologies derived from the two different RO missions reveal that the magnitudes of the Es ORs derived by FY-3C data are slightly smaller than those derived by COSMIC data in the middle and low latitudes, which is due to that the top heights of the 50 Hz RO data of FY-3C mission are generally lower than those of the COSMIC mission. In the polar regions, the distinctly low ratio of the FY-3C RO 50 Hz measurements which reach the height of 90 km reduces the capability of these observations for Es-layer detections. Graphical Abstract

Isolated pillars in underground mines are subjected to uniaxial stress, and the load bearing cross-section of pillars is commonly rectangularly shaped. In addition, the uniaxial compression test (UCT) is widely used for determining the basic mechanical properties of rocks and revealing the mechanism of isolated pillar disasters under unidimensional stress. The shape effects of rock mechanical properties under uniaxial compression are mainly quantitatively reflected in the specific shape ratios of rocks. Therefore, it is necessary to study the detailed shape ratio effects on the mechanical properties of rectangular prism rock specimens and isolated pillars under uniaxial compressive stress. In this study, granite, marble and sandstone rectangular prism specimens with various height to width ratios (r) and width to thickness ratios (u) were prepared and tested. The study results show that r and u have a great influence on the bearing ability of rocks, and thin or high rocks have lower uniaxial compressive strength. Reducing the level of r can enhance the u effect on the strength of rocks, and increasing the level of u can enhance the r effect on the strength of rocks. The lateral strain on the thickness side of the rock specimen is larger than that on the width side, which implies that crack growth occurs easily on the thickness side. Considering r and u, a novel strength prediction model of isolated pillars was proposed based on the testing results, and the prediction model was used for the safety assessment of 179 isolated pillars in the Xianglu Mountain Tungsten Mine.

It has been recently recognized that the DNA sensing innate immune cGAS-STING pathway exerts an IFN-independent antiviral function; however, whether and how chicken STING (chSTING) exerts such an IFN-independent antiviral activity is still unknown. Here, we showed that chSTING exerts an antiviral activity in HEK293 cells and chicken cells, independent of IFN production. chSTING was able to trigger cell apoptosis and autophagy independently of IFN, and the apoptosis inhibitors, rather than autophagy inhibitors, could antagonize the antiviral function of chSTING, suggesting the involvement of apoptosis in IFN-independent antiviral function. In addition, chSTING lost its antiviral function in IRF7-knockout chicken macrophages, indicating that IRF7 is not only essential for the production of IFN, but also participates in the other activities of chSTING, such as the apoptosis. Collectively, our results showed that chSTING exerts an antiviral function independent of IFN, likely via apoptosis.

R2R3-MYB transcription factors (TFs) form one of the most important TF families involved in regulating various physiological functions in plants. The heartwood of Dalbergia odorifera is a kind of high-grade mahogany and valuable herbal medicine with wide application. However, the role of R2R3-MYB genes in the growth and development of D. odorifera, especially their relevance to heartwood formation, has not been revealed. A total of 126 R2R3-MYBs were screened from the D. odorifera genome and named DodMYB1-126 based on their location on 10 chromosomes. The collinearity results showed that purification selection was the main driving force for the evolution of the R2R3-MYB TFs family, and whole genome/fragment replication event was the main form for expanding the R2R3-MYB family, generating a divergence of gene structure and function. Comparative phylogenetic analysis classified the R2R3-MYB TFs into 33 subfamilies. S3-7,10,12-13,21 and N4-7 were extensively involved in the metabolic process; S9,13,16-19,24-25 and N1-3,8 were associated with the growth and development of D. odorifera. Based on the differential transcriptional expression levels of R2R3-MYBs in different tissues, DodMYB32, DodMYB55, and DodMYB89 were tentatively screened for involvement in the regulatory process of heartwood. Further studies have shown that the DodMYB89, localized in the nucleus, has transcriptional activation activity and is involved in regulating the biosynthesis of the secondary metabolites of heartwood by activating the promoters of the structural genes DodI2’H and DodCOMT. This study aimed to comprehensively analyze the functions of the R2R3-MYB TFs and screen for candidate genes that might be involved in heartwood formation of D. odorifera.

C9~C33 n-alkane standard solution and Smart Database Pesticides database were used to establish a rapid analytical method for the determination of 32 fungicides in strawberry based on retention index. Thirty-two fungicides were selected as the target, the samples were extracted and purified by QuEChERS method. Gas chromatography tandem mass spectrometry was used for qualitative and quantitative analysis. Results showed that, the 32 fungicides showed good linear relationship in the range of 5~200 μg/L, and the correlation coefficients were greater than 0.9982. The recoveries of 32 fungicides spiked at 10, 50, 100 μg/kg were 70.3%~117.8% and therelative standard deviations were 0.01%~8.50%. The limits of detection were 0.01~2.91 μg/kg, and the limits of quantitative were 0.04~9.71 μg/kg. This method was rapid, simple, accurate, steady, and achieved good performance in strawberry sample analyses, and was suitable for monitoring fungicides using in strawberry, and provided reliable date and technical support for determination of multi-component pesticide residues studies．

In the past decade, object localization and object classification using correlation filters, especially large margin correlation filters which combine with support vector machine (SVM), have become a hotspot. However, the large margin correlation filters do not consider the class distribution and the structural features within the class during training, which is easily affected by noise. This paper presents two methods to overcome this drawback: minimum class variance large margin correlation filter (MCVLMCF) and minimum class locality preserving variance correlation filter (MCLPVCF). First, the overall structure information of the target is obtained by the within-class scatter with MCVLMCF, and the spatial features of the sample are extracted by the intrinsic manifold structure of data with MCLPVCF. Then, we embed these two types of information into the optimal function of the large margin correlation filter, fuse the sample spatial features with the large margin principle and correlation filtering, and convert it to solve the filter in the frequency domain. Finally, object localization experiments in actual environments and classification experiments on different datasets demonstrate that our proposed methods can adapt to complex object changes and achieve better performances than some state-of-the-art methods.

Abstract Prostate cancer (PCa) is the fifth leading cause of death from cancer in men worldwide. Its treatment remains challenging due to the heterogeneity of the tumor, mainly because of the lack of effective and targeted prognostic markers at the system biology level. First, the data were retrieved from TCGA dataset, and valid samples were obtained by consistent clustering and principal component analysis; next, key genes were analyzed for prognosis of PCa using WGCNA, MEGENA, and LASSO Cox regression model analysis, while key genes were screened based on disease-free survival significance. Finally, TIMER data were selected to explore the relationship between genes and tumor immune infiltration, and GSCAlite was used to explore the small-molecule targeted drugs that act with them. Here, we used tumor subtype analysis and an energetic co-expression network algorithm of WGCNA and MEGENA to identify a signal dominated by the ROMO1 to predict PCa prognosis. Cox regression analysis of ROMO1 was an independent influence, and the prognostic value of this biomarker was validated in the training set, the validated data itself, and external data, respectively. This biomarker correlates with tumor immune infiltration and has a high degree of infiltration, poor prognosis, and strong correlation with CD8+T cells. Gene function annotation and other analyses also implied a potential molecular mechanism for ROMO1. In conclusion, we putative ROMO1 as a portal key prognostic gene for the diagnosis and prognosis of PCa, which provides new insights into the diagnosis and treatment of PCa.

Abstract Red yeast rice is consumed as a medicinal food to lower blood lipids. Besides, it is used to color food, make wine, etc. In this study, water‐soluble oligosaccharides in red yeast rice were extracted by ultrasonic‐assisted extraction method. The parameters to extract oligosaccharides from red yeast rice were optimized by the Box‐Behnken design under the following optimal extraction conditions: extraction temperature, 60°C; extraction time, 97 min; and liquid/material ratio, 25 ml/g. The structure and the antioxidant activity of the new oligosaccharide were preliminarily investigated. Total carbohydrates extracted from red yeast rice with 80% ethanol–water solution (v/v) were first removed from pigments using D101 macroporous adsorption resin. The total sugar contents were then purified by DE52 resins and Sephadex G‐25 resins to obtain red yeast rice oligosaccharides, coded as RYRO1. Structural characterization experiments indicated that RYRO1 is an oligosaccharide with a weight average molecular weight of 874 Da and a theoretical degree of polymerization of 4.86. RYRO1 is composed of mannose, glucosamine, glucose, and galactose with a molar ratio of 0.248:0.019:1:0.026. The ABTS, DPPH, and hydroxyl free radical scavenging assays showed antioxidant nature of RYRO1.

Abstract Background Frail patients with chronic obstructive pulmonary disease (COPD) face a higher risk of adverse outcomes, but there is no clear consensus on which frailty measures are most suitable for COPD patients. Herein we evaluated the ability of frailty measurements in predicting 1-year acute exacerbation, hospitalization, and mortality in older patients with COPD. Methods A total of 302 patients [median age: 86 years (IQR: 80–90), 22.2% female] were admitted to the Department of Geriatric Medicine were prospectively enrolled in this study. Frailty status was assessed using the Fried Frailty Phenotype (FFP), Clinical Frailty Scale (CFS), Frailty Index of Accumulative Deficits (FI-CD), and Short Physical Performance Battery (SPPB). Cox proportional hazard regression and Poisson regression were used to evaluating the association of the adverse outcomes with frailty as assessed using the four instruments. The discrimination accuracy of these tools in predicting the 1-year all-cause mortality was also compared. Results Prevalence of frailty ranged from 51% (using FFP) to 64.2% (using CFS). The four frail instruments were associated with 1-year mortality. After an average follow-up time of 2.18 years (IQR: 1.56–2.62 years), frailty as defined by four instruments (except for FI-CD), was associated with death [FFP: Hazard ratio (HR) = 3.11, 95% confidence interval (CI) 1.30–7.44; CFS: HR = 3.68, 95% CI 1.03–13.16; SPPB: HR = 3.74, 95% CI 1.39–10.06). Frailty was also associated with acute exacerbation (using FFP) and hospitalization (using FFP, CFS, and FI-CD). Frail showed a moderate predictive ability [area under the curve ranging (AUC) 0.70–0.80] and a high negative predictive value (0.98–0.99) for 1-year mortality. Conclusions With the four different frailty assessment tools, frailty was associated with poor prognosis in older patients with stable COPD. The FFP, CFS, FI-CD, and SPPB instruments showed similar performance in predicting 1-year mortality.

Flower bud differentiation represents a crucial transition from vegetative growth to reproductive development. Carya cathayensis (hickory) is an important economic species in China, with a long juvenile period that hinders its commercial development. In recent years, circular RNAs (circRNAs) have been widely studied and identified as sponges for miRNA regulation of mRNA expression. However, little is known regarding the role of circRNAs in flower buds. In this study, we sequenced circRNAs at three developmental stages (undifferentiated, differentiating, and fully differentiated) in both female and male buds. A total of 6,931 circRNAs were identified in the three developmental stages and 4,449 and 2,209 circRNAs were differentially expressed in female and male buds, respectively. Gene ontology demonstrated that many circRNA host genes participated in various processes, for example, cellular and intracellular pH regulation. Function annotation identified 46 differentially expressed circRNAs involved in flowering regulation, with 28 circRNAs found only in female buds, 4 found only in male buds, and 11 found in both female and male buds. A circRNA-miRNA-mRNA network was predicted based on 13 flowering-related circRNAs and their seven putative interacting miRNAs to describe the regulatory mechanism. Our preliminary results demonstrated a potential involvement of circRNA in bud differentiation. They provided a preliminary theoretical basis for how circRNA might participate in flower development in hickory, perhaps in woody plants.

Abstract The S4max data retrieved from the Constellation Observing System for the Meteorology, Ionosphere, and Climate (COSMIC) radio occultation (RO) measurements during 2007 to 2015 is adopted to investigate the global distribution and seasonal variation of the sporadic E (Es) layers in the present work. The long-term and short-term global Es occurrence maps are presented and the spatial and temporal distributions of Es occurrence rates (ORs) are further confirmed and studied. The International Geomagnetic Reference Field model (IGRF12) is used to calculate the horizontal intensity and inclination of the Earth’s magnetic field. The analysis shows that the Earth’s magnetic field is one of the fundamental reasons for the global distribution of the Es layers. In addition, the Horizontal Wind Field model HWM14 and the IGRF12 model were employed to calculate the vertical ion convergence (VIC) to examine the role of neutral wind shear in the global distribution of the Es ORs. The results reveal that the middle latitude distribution of simulated vertical concentration of Fe+ is similar to that of Es ORs, which indicates that the VIC induced by the neutral wind shear is an important factor in determining the geographical distribution, summer maximum (or winter minimum) and diurnal characteristics of Es ORs in middle latitudes. The new findings mainly include the following two aspects: (1) in summer over mid-latitudes, VIC peaks in the morning and afternoon to evening, which explains the semidiurnal behavior of Es ORs; (2) VIC reaches its minimum value in low-altitude (100 km) areas, which is the reason for the significant decrease in Es ORs in low-altitude areas. The disagreements between the VIC and Es ORs indicate that other processes, such as the meteor influx rate, the ionospheric electric fields and atmospheric tides, should also be considered as they may have an important impact on the variation of Es layers. Graphical Abstract

ObjectiveLenvatinib and sorafenib are first-line oral multikinase inhibitors approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the primary therapeutic agent among these two remains controversial. This meta-analysis aimed to estimate the efficacy and safety of lenvatinib and sorafenib in patients with advanced HCC.MethodsPubMed, Cochrane Library, Web of Science, and Embase databases were searched for relevant research published up to June 30, 2022. After quality assessment and data extraction of the included studies, RevMan 5.3 software was used for analysis. Odds ratio (OR) and hazard ratio (HR) with a 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model.ResultsFifteen studies containing 3908 patients were included after final scrutiny. Our meta-analysis showed that there was no significant difference in overall survival (OS) between the lenvatinib and sorafenib groups (HR = 0.86; 95% CI: 0.72–1.02; p = 0.09); however, the progression-free survival (PFS) (HR = 0.63; 95% CI: 0.53–0.74; p < 0.00001), complete response (CR) (OR = 5.61; 95% CI: 2.71–11.64; p < 0.00001), partial response (PR) (OR = 4.62; 95% CI: 3.06–6.98; p < 0.00001), objective response rate (ORR) (OR = 5.61; 95% CI: 3.90–8.09; p < 0.00001), and disease control rate (DCR) (OR = 2.42; 95% CI: 1.79–3.28; p < 0.00001) in the lenvatinib group were significantly better than those in the sorafenib group. In terms of treatment safety, lenvatinib had similar incidences of any grade adverse events (AEs) (OR = 0.99; 95% CI: 0.47–2.09; p = 0.98) and grade ≥ 3 AEs (OR = 1.17, 95% CI; 1.00–1.37; p = 0.05) compared to sorafenib. Besides, lenvatinib was significantly associated with a higher incidence of hypertension, proteinuria, fatigue, decreased appetite, and weight loss, whereas sorafenib was associated with a higher incidence of diarrhea and hand-foot skin reaction (p < 0.05).ConclusionGiven its potential survival benefit and good tolerability, lenvatinib is an appropriate and promising alternative to sorafenib as first-line systemic therapy in patients with advanced HCC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD 42022327398.

To report potential vaccine-induced inflammatory ocular adverse events following inactivated COVID-19 vaccination. Retrospective study of patients with uveitis and other ocular complications following inactivated coronavirus disease 2019 (COVID-19) vaccination at a tertiary referral center between May 2021 and August 2021. Data collection consisted of demographic and clinical data. The study included 8 eyes of 5 patients (4 females, 1 male), with a mean age of 37.2 ± 12.5 years (range 28–59 years). Mean time between vaccination and ocular complications onset was 13.2 ± 11.9 days (range 3–30 days), including two patients after the first dose of the vaccine and 3 patients after the second dose. The cases reported were three anterior uveitis, one herpetic keratitis and iridocyclitis, and one posterior uveitis. Patients received treatment with local and/or systemic steroids and all the patients had good visual outcomes. Ocular inflammatory events may occur after vaccination with possible gender preponderance. However, they are rare and manageable. Overall, the efficacy and safety of vaccination should be emphasized.

Customers have obvious occupational gender stereotypes for service employees. In recent years, intelligent service robots have been widely used in the hospitality industry and have also been given gender characteristics to attract customers to use them. However, whether and when the usage of gendered service robots is effective remains to be explored. This research focuses on customers' occupational gender stereotypes and the gender of service robots, examining the influences of their consistency on customers' willingness to use service robots through three scenario studies. The findings suggest that: (1) The consistency between occupational gender stereotypes and service robot gender positively affects customers' willingness to use service robots. (2) Performance expectancy and trust are two psychological mechanisms underlying the above effect. (3) In the context of service failures, the consistency backfires and brings negative effects on willingness to use. This research extends the literature on customers' acceptance of anthropomorphized robots from the perspective of gender stereotypes and identifies the mechanisms behind the stereotype consistency effect. For practical implications, hotels should design and deploy gendered robots consistent with corresponding occupational gender stereotypes.

Abstract Background Human trafficking is a serious global challenge associated with a complex array of health inequities for individuals, families, and communities. Consequently, in addition to a conventional criminal justice approach, anti-trafficking scholars have increasingly called for a public health approach to address this global challenge. Such calls have emphasized that a comprehensive, robust, and social justice-informed public health strategy for anti-trafficking must include services to facilitate survivors’ HT exit and recovery, and to prevent their re-victimization. Fortunately, many community-based organizations and non-governmental organizations worldwide have heeded these calls and developed anti-trafficking programs for survivors. Unfortunately, despite the growing numbers of organizations providing anti-trafficking services, research concerning these programs’ effectiveness remains nascent overall, and even more scant when filtered through an equity focus. Methods To advance the field by developing guidance concerning how best to evaluate anti-human trafficking programs, an ongoing research project aims to conduct a mixed methods evaluability assessment of a prominent anti-trafficking program using a social justice framework. Guided by well-established evaluability assessment frameworks, the study activities include four sequential steps: (a) focusing the assessment, (b) developing the program theory and logic, (c) gathering feedback, and (d) applying the assessment findings. Activities will include qualitative interviews and focus groups, observations, and quantitative analysis of program data among others. Human subjects and ethical review for the evaluability assessment has been granted by the Office of Human Subjects Research at The University of North Carolina at Chapel Hill. Discussion Once completed, evaluability assessment results will provide evidence and products that have the potential to guide both evaluation research and service provision not only for the specific organization under study, but also for other anti-human trafficking programs worldwide. Findings will be developed into a variety of dissemination products tailored for both practice professionals and researchers. In the interim, this protocol manuscript offers research strategies and recommendations that can help inform the development of other studies in the developing field of anti-trafficking program evaluation research.

Abstract Background Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, OVs could activate the host innate immunity, then impair the viral propagation in tumor cells. In this study, we explored the effect of propranolol, a non-selective β-blocker, on the antitumor efficacy of T1012G virus in gastric cancer models. Methods The proliferation of gastric cancer cells treated with monotherapy or combination treatment was detected by CCK8 cell proliferation assay. The effect of propranolol was further evaluated by in vitro viral replication assays. In vivo tumor xenograft experiments were used to observe the effect of combination therapy on gastric cancer growth in mice. The expression levels of viral proteins and interferon responsive genes were detected in the gastric cancer cell lines treated with combined treatment by western blot. The impact of propranolol on IFN-α/β-mediated inhibition of viral propagation and the expression of antiviral gene PKR was detected by viral replication assays and western blot. Results Cell viability assay detected a 97.9% decrease of T1012G IC50 in HGC-27 when it was pretreated with propranolol along with a sevenfold increase of virus titers compared with T1012G only group (P

Abstract Background With the emergence of three-dimensional (3D) integration technology, analysis of soft tissue displacement and morphological changes after maxillary full-arch implant-supported fixed prostheses can be performed. The aim of this study was to verify the feasibility of the 3D integration method for constructing the relative position of the prostheses and facial soft tissue, evaluate the displacement and morphological variation of the upper lips after maxillary full-arch implant-supported fixed prostheses. Methods Twenty-five maxillary edentulous patients were recruited in this study. At the time of final prosthesis delivery, the 3D prostheses data and three 3D facial profiles were integrated. After method validation, the 3D position changes of seven soft tissue landmarks were used to reflect the 25 upper lips. The variation of four morphological distances were analyzed to reflect the morphological alteration of the upper lips. Two pairs of dentofacial landmarks were used to analyze the sagittal relative position of the prostheses and soft tissue. The included patients were also grouped to determine the impact of sex, upper lip thickness, and length on lip support changes. Results The average distance of the two matched relative reliable forehead regions was only 0.32 mm. The sagittal shifts of labrale superius (LS), stomion (STO), crista philtri left (CPHL) and crista philtri right (CPHR) were 3.44 ± 1.39 mm, 2.52 ± 1.38 mm, 3.04 ± 1.18 mm, and 3.12 ± 1.21 mm, respectively. With the exception of the decrease in the length of subnasale (SN)-LS, the length of cheilion right (CHR)-cheilion left (CHL), CPHR-CPHL, and LS-STO significantly increased. The two pairs of dentofacial landmarks had strong positive movement correlations along the sagittal direction. Patients with thinner and longer lips showed more lip support than those with thicker and shorter lips by a clinically insignificant amount. Conclusions The integration method of 3D facial and dental data showed high repeatability in constructing the dentofacial relative position. The linear equations reflecting dentofacial relative position could aid clinicians in evaluating the restoration effect and estimate the upper lip variation.

Objective Investigation of muscle growth at different developmental stages is an appropriate strategy for studying the mechanisms underlying muscle development and differences in phenotypes. In particular, the muscle development mechanisms and the difference between the fastest and slowest growth rates. Methods In this study, we used a growth curve model to fit the growth inflection point (IP) of QingYu pigs and compared differences in the long non-coding RNA (lncRNA) transcriptome of muscle both at the growth IP and plateau phase (PP). Results The growth curve of the QingYu pig had a good fit (R2 = 0.974) relative to a typical S-curve and reached the IP at day 177.96. At the PP, marbling, intramuscular fat, and monounsaturated fatty acids had increased significantly and the percentage of lean muscle and polyunsaturated fatty acids had decreased. A total of 1,199 mRNAs and 62 lncRNAs were differentially expressed at the IP compared with the PP. Additional to gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses, these differentially expressed protein coding genes were principally related to muscle growth and lipid metabolism. Conclusion Our results suggest that the identified differentially expressed lncRNAs, could play roles in muscle growth, fat deposition and regulation of fatty acid composition at the IP and PP.

Background: Regulation of cell death plays a key role in numerous diseases. As a proline isomerase, prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is important for the regulation of signaling pathways. An in-depth understanding of how Pin1 participates in the process of cell death, which affects the occurrence and development of diseases, will aid in the discovery of new disease mechanisms and therapeutic methods. Thus, the purpose of our study was to discover the research trends and hotspots of Pin1 and cell death through bibliometric analyses and to provide insights for understanding the future development of basic research and treatment of diseases.Methods: Documents were extracted from the Web of Science Core Collection on 7 May 2022. We selected articles and reviews published in English from 2000 to 2021, and visual and statistical analyses of countries, institutions, authors, references and keywords were performed using VOSviewer 1.6.18 and CiteSpace 5.8.Results: A total of 395 articles and reviews were selected. Since 2001, the number of articles on Pin1 and cell death has increased annually. Publications come from 43 countries, with the US having the most publications and citations. We identified 510 authors, with Giannino Del Sal having the most articles and Paola Zacchi having the most co-citations. The Journal of Biological Chemistry is the most researched journal, and Nature and its subjournals are the most cited journals. Apoptosis, phosphorylation, and breast cancer were the three most common keywords.Conclusion: The number of documents showed an increasing trend from 2001 to 2014. Stagnant growth after 2014 may be related to the absence of new research hotspots. Cooperative links between core institutions need to be strengthened, and the institution with the highest citation count in recent years is Fujian Medical University in China. The role of Pin1 in cell death requires further research to discover new research hotspots. Before breakthroughs in molecular mechanism or signaling pathway research, future research will focus more on the treatment of diseases represented by Pin1 inhibitors.

Familial exudative vitreoretinopathy (FEVR) is an important cause of childhood blindness and is clinically characterized by phenotypic heterogeneity. FEVR patients harboring the same genetic mutation vary widely in disease severity. The purpose of this study was to explore non-genetic factors that regulate FEVR phenotypic heterogeneity. We detected methylation levels of 21 CpG sites located at the FZD4 exon 1 region of 11 probands, 12 asymptomatic/paucisymptomatic carriers and 11 non-carriers from 10 unrelated FZD4-associated FEVR families using bisulfite amplicon sequencing (BSAS). Our results showed reduced methylation level of FZD4 exon 1 in probands, suggesting that FZD4 exon 1 methylation level may be negatively linked with FEVR disease severity. It provided a new research direction for follow-up research, helping us better understand the complexity of the FEVR-causing mechanism.

The innate immune DNA sensing cGAS-STING signaling pathway has been widely recognized for inducing interferons (IFNs) and subsequent antiviral state. In addition to IFN, the cGAS-STING pathway also elicits other cell autonomous immunity events including autophagy and apoptosis. However, the downstream signaling events of this DNA sensing pathway in livestock have not been well defined. Here, we systematically analyzed the porcine STING (pSTING) induced IFN, autophagy and apoptosis, revealed the distinct dynamics of three STING downstream events, and established the IFN independent inductions of autophagy and apoptosis. Further, we investigated the regulation of autophagy on pSTING induced IFN and apoptosis. Following TBK1-IRF3-IFN activation, STING induced Atg5/Atg16L1 dependent autophagy through LIR motifs. In turn, the autophagy likely promoted the pSTING degradation, inhibited both IFN production and apoptosis, and thus restored the cell homeostasis. Therefore, this study sheds lights on the molecular mechanisms of innate immunity in pigs.

BackgroundThe prevalence of atopic dermatitis (AD) in children has increased substantially in China over past decades. The ongoing rise in the prevalence stresses the important role of the environmental factors in the pathogenesis of AD. However, studies evaluating the effects of air pollution on AD in children are scarce.ObjectiveTo quantitatively assess the association between air pollution and outpatient visits for AD in children.MethodsIn this time-series study, we collected 214,747 children of AD from January 1, 2015 to December 31, 2019 through the electronic data base in the Children's Hospital of Chongqing Medical University. The number of daily visits was treated as the dependent variable, and generalized additive models with a Poisson like distribution were constructed, controlling for relevant potential confounders and performing subgroup analyses.ResultsEach 10 μg/m3 increase in PM2.5, PM10, SO2, NO2 and each 1 mg/m3 increase in CO concentrations was significantly associated with a 0.7% (95% CI: 0.2, 1.3%), 0.9% (95% CI: 0.5, 1.4%), 11% (95% CI: 7.5, 14.7%), 5.5% (95% CI: 4.3, 6.7%) and 10.1% (95% CI: 2.7, 18.2%) increase of AD outpatient visits on the current day, respectively. The lag effect was found in SO2, PM10, and NO2. The effects were stronger in cool season and age 0–3 group.ConclusionsOur study suggests that short-term exposure to ambient air pollution contributes to more childhood AD outpatient visits in Chongqing, China.

Abstract Background Muscular invasive bladder cancer (MIBC) is a common malignant tumor in the world. Because of their heterogeneity in prognosis and response to treatment, biomarkers that can predict survival or help make treatment decisions in patients with MIBC are essential for individualized treatment. Aim We aimed to integrate bioinformatics research methods to identify a set of effective biomarkers capable of predicting, diagnosing, and treating MIBC. To provide a new theoretical basis for the diagnosis and treatment of bladder cancer. Methods and results Gene expression profiles and clinical data of MIBC were obtained by downloading from the Cancer Genome Atlas database. A dataset of 129 MIBC cases and controls was included. 2084 up‐regulated genes and 2961 down‐regulated genes were identified by differentially expressed gene (DEG) analysis. Then, gene ontology analysis was performed to explore the biological functions of DEGs, respectively. The up‐regulated DEGs are mainly enriched in epidermal cell differentiation, mitotic nuclear division, and so forth. They are also involved in the cell cycle, p53 signaling pathway, PPAR signaling pathway, and so forth. The weighted gene co‐expression network analysis yielded five modules related to pathological stages and grading, of which blue and turquoise were the most relevant modules for MIBC. Next, Using Kaplan–Meier survival analysis to identify further hub genes, the screening criteria at p ≤ .05, we found CNKSR1, HIP1R, CFL2, TPM1, CSRP1, SYNM, POPDC2, PJA2, and RBBP8NL genes associated with the progression and prognosis of MIBC patients. Finally, immunohistochemistry experiments further confirmed that CNKSR1 plays a vital role in the tumorigenic context of MIBC. Conclusion The research suggests that CNKSR1, POPDC2, and PJA2 may be novel biomarkers as therapeutic targets for MIBC, especially we used immunohistochemical further to validate CNKSR1 as a therapeutic target for MIBC which may help to improve the prognosis for MIBC.

ObjectiveTo identify less invasive and easily applicable serum cytokine-derived biomarkers which contribute to the diagnostic utility and risk assessment ability of the prostate health index (PHI) based multivariable model in grey zone aggressive prostate cancer (AG PCa) early detection.MethodsSerum 45 cytokines screening was performed in a small training cohort consisting of 10 sera by Luminex liquid array-based multiplexed immunoassays and identified TRAIL and IL-10 as new biomarkers for PHI diagnostic utility adjustment for further validation with a multivariable predictive model in a cohort including 79 aggressive prostate cancer patients and 209 benign prostatic hyperplasia or indolent PCa patients within the PSA grey zone.ResultsTRAIL and IL-10 were identified as potential serum biomarkers for AG PCa detection by the result of multi-cytokines screening in the univariate analysis, while multivariable logistic regression confirmed the AUC of the full risk predictive model (0.915) including tPSA, fPSA, PHI, TRAIL, and IL-10 was higher than various diagnostic strategies. DCA suggested a superior net benefit and indicated a good discriminative ability of the full risk model consistently with the result of the nomogram.ConclusionWe suggest a significant advantage for the PHI-based multivariate combinations of serum TRAIL and IL-10 comparing to PHI or other serum-derived biomarkers alone in the detection and risk stratification of grey zone AG PCa.

PurposeTo construct a dynamic prediction model for BK polyomavirus (BKV) reactivation during the early period after renal transplantation and to provide a statistical basis for the identification of and intervention for high-risk populations.MethodsA retrospective study of 312 first renal allograft recipients with strictly punctual follow-ups was conducted between January 2015 and March 2022. The covariates were screened using univariable time-dependent Cox regression, and those with P

Objectives: The purpose of this study was to quantitatively evaluate the impacts of the”4 + 7” pilot policy on purchase volume, purchase expenditures, and daily cost and to find the changes in the use of SSRIs.Methods: Data was collected covering 31 months, before, during, and after the “4 + 7” pilot policy was implemented in Shenzhen. Interrupted time-series (ITS) analysis was used to examine whether there had been a significant effect with the onset of the “4 + 7” pilot policy in March 2019.Findings: The daily cost of policy-related drugs had a substantial drop of 2.93 yuan under the “4 + 7” pilot policy. The result has shown a 76.70% increase in volume and a 3.39% decrease in the expenditure on policy-related drugs. This study found that the “4 + 7” pilot policy increased the proportion of purchasing winning drugs, with an increment of 85.60 percent. After the implementation of the “4 + 7” pilot policy, policy-related drugs decreased by 443.55thousand Chinese yuan. The study indicated that volume of winning products significantly increased as shown in the regression with a level coefficient (β2) of -224.17 (p < 0.001) and trend coefficient (β3) of 15.74 (p < 0.001). The result revealed that both volume and expenditures on branded products showed a significant decrease in the regression in the post-intervention period (level coefficient of volume: β2 = -57.65, p < 0.01, trend coefficient of volume: β3 = -3.44, p < 0.01; level coefficient of expenditure: β2 = -712.98, p < 0.01, trend coefficient of expenditure: β3 = -40.10, p < 0.01).Conclusion: The volume-based procurement has successfully led to price reductions and improved the affordability of medicines, especially for those with chronic diseases. The volume-based procurement has demonstrated initial success in reshaping the composition of the Chinese pharmaceutical market in favor of generics with high quality and low prices.

Artificial intelligence (AI) is a cutting-edge technology that has been widely applied in tourism operations. To enhance tourists' experience, many tourism suppliers introduced AI devices to interact with tourists. Previous studies classified AI devices as task- and social- oriented based on their functions; however, current models that explain customers' intention to use AI devices did not reflect the discrepancy between the two different types. Therefore, this paper attempts to fill this gap by proposing a theoretical model for the use of task-oriented AI devices. Based on the multi-stage appraisal framework and the Structural Equation Modeling analysis, this paper presents the following findings: (1) utilitarian motivation, interaction convenience, and task-technology fit are the factors appraised in the first stage; (2) perceived competence and flow experience are the factors appraised in the second stage; (3) utilitarian motivation, interaction convenience, and task-technology fit are positively associated with perceived competence. (4) Perceived competence positively influences flow experience, which further affects customers' switching intention from task-oriented AI devices to human service; (5) the serial mediating effect of perceived competence and flow experience between the stimulus mentioned in the first appraisal stage and the switching intention is confirmed. This study reveals the underlying psychological mechanism when customers use task-oriented AI devices, and it provides a theoretical framework for task-oriented AI device adoption.

ObjectiveThis study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD).Materials and methodsA total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC.ResultThe subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F(1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [F(1,99) = 8.607, p = 0.004], hippocampal tail [F(1,99) = 4.077, p = 0.046], and molecular layer [F(1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 (p = 0.004). Further analysis found that the SCWT C-B reaction time of SCD was significantly longer than NC no matter whether it is at the normal BMI level [F(1,104) = 4.325, p = 0.040] or the high BMI level [F(1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [F(1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [F(1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [F(1,99) = 7.619, p = 0.007].ConclusionThe BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging.

Porcine epidemic diarrhea virus (PEDV) has caused great damage to the global pig industry. Innate immunity plays a significant role in resisting viral infection; however, the exact role of innate immunity in the anti-PEDV response has not been fully elucidated. In this study, we observed that various porcine innate immune signaling adaptors are involved in anti-PEDV (AJ1102-like strain) activity in transfected Vero cells. Among these, TRIF and MAVS showed the strongest anti-PEDV activity. The endogenous TRIF, MAVS, and STING were selected for further examination of anti-PEDV activity. Agonist stimulation experiments showed that TRIF, MAVS, and STING signaling all have obvious anti-PEDV activity. The siRNA knockdown assay showed that TRIF, MAVS, and STING are also all involved in anti-PEDV response, and their remarkable effects on PEDV replication were confirmed in TRIF−/−, MAVS−/− and STING−/− Vero cells via the CRISPR approach. For further verification, the anti-PEDV activity of TRIF, MAVS, and STING could be reproduced in porcine IPEC-DQ cells treated with siRNAs. In summary, this study reveals that multiple pattern-recognition receptor (PRR) signaling pathways of porcine innate immunity play an important role in the anti-PEDV infection, providing new and useful antiviral knowledge for prevention and control of PEDV spreading.

The use of construction waste for concrete is an effective way to reduce the environmental burden while improving the sustainability of construction materials. Nano-SiO2 (NS) has excellent volcanic ash activity, which can effectively improve the strength of concrete. In this study, the synergistic effects of NS and 30% recycled concrete aggregate (RCA) on the mass loss, compressive strength, ultrasonic sound velocity values and microstructure of RAC after 25, 50, 75 and 100 repetitions of a dry–wet cycle (DWC) of sulfuric acid were investigated. The results show that NS has a significant role in improving RAC performance. The RAC specimens showed the lowest mass loss rate, the highest compressive strength, the lowest ultrasonic velocity value and the best resistance to sulfate erosion when the NS doping was 4%. Meanwhile, under CT and SEM, RAC with NS has lower porosity and higher hydration, which can effectively inhibit the crack generation and has stable volume growth within 0–50 repetitions of DWC. In addition, the addition of NS improves not only the microstructure of the substrate but also the interfacial transition zone (ITZ). When 4% NS was added, the porosity was the lowest and the durability improvement was the best performance. This study not only improves the production performance of RAC but also provides a strong reference for the integrated application of nanomaterials in concrete.

Abstract Poor growth and disease transmission of small sea urchins Strongylocentrotus intermedius in summer greatly hamper the production efficiency of the longline culture. Reducing the adverse effects of high stocking density while maintaining high biomass is essential to address these problems. Here, we conducted a laboratory experiment to simulate the multi-layer culture for sea urchins at ambient high temperatures (from 22.2 to 24.5 °C) in summer for ~ 7 weeks. Survival, body size, lantern growth, gut weight, food consumption, Aristotle's lantern reflex, 5-hydroxytryptamine concentration, pepsin activity and gut morphology were subsequently evaluated. The present study found that multi-layer culture led to significantly larger body size than those without multi-layer culture (the control group). This was probably because of the greater feeding capacity (indicated by lantern growth and Aristotle's lantern reflex) and food digestion (indicated by morphology and pepsin activity of gut) in the multi-layer cultured sea urchins. These results indicate that multi-layer is an effective approach to improving the growth efficiency of sea urchins at high temperatures. We assessed whether eliminating interaction further improve these commercially important traits of sea urchins in multi-layer culture. This study found that eliminating interactions displayed greater body size and Aristotle's lantern reflex than those not separated in the multi-layer culture. This approach also significantly reduced the morbidity compared with the control group. These novel findings indicate that eliminating interactions in multi-layer culture greatly contributes to the growth and disease prevention of sea urchins at high temperatures. The present study establishes a new technique for the longline culture of sea urchins in summer and provides valuable information into the longline culture management of other commercially important species (e.g. scallops, abalones and oysters).

Abstract Musk, the dried secretion from the musk sac gland which is located between the navel and genitals of mature male musk deer, is utilized as oriental medicine in east Asia. It has been utilized to treat conditions such as stroke, coma, neurasthenia, convulsions, and heart diseases in China since ancient times. This paper aims to provide a comprehensive overview of musk in zoology, chemical composition, pharmacology, clinical applications, and quality control according to the up-to-date literature. Studies found that musk mainly contains macrocyclic ketones, pyridine, steroids, fatty acids, amino acids, peptides, and proteins, whilst the main active ingredient is muscone. Modern pharmacological studies have proven that musk possesses potent anti-inflammatory effects, neuroprotective effects, anti-cancer effects, antioxidant effects, etc. Moreover, muscone, the main active ingredient, possesses anti-inflammatory, neuroprotective, antioxidant, and other pharmacological effects. In the quality control of musk, muscone is usually the main detection indicator, and the common analytical method is GC, and researchers have established novel and convenient methods such as HPLC-RI, RP-UPLC-ELSD, and Single-Sweep Polarography. In addition, quality evaluation methods based on steroids and the bioactivity of musk have been established. As for the identification of musk, due to various objective factors such as the availability of synthetic Muscone, it is not sufficient to rely on muscone alone as an identification index. To date, some novel technologies have also been introduced into the identification of musk, such as the electronic nose and DNA barcoding technology. In future research, more in vivo experiments and clinical studies are encouraged to fully explain the pharmacological effects and toxicity of musk, and more comprehensive methods are needed to evaluate and control the quality of musk.