Surface display of the COE antigen of porcine epidemic diarrhoea virus on Bacillus subtilis spores.

Porcine epidemic diarrhoea virus (PEDV) infects pigs of all ages by invading small intestine, causing acute diarrhoea, vomiting, and dehydration with high morbidity and mortality among newborn piglets. However, current PEDV vaccines are not effective to protect the pigs from field epidemic strains because of poor mucosal immune response and strain variation. Therefore, it is indispensable to develop a novel oral vaccine based on epidemic strains. Bacillus subtilis spores are attractive delivery vehicles for oral vaccination on account of the safety, high stability, and low cost. In this study, a chimeric gene CotC-Linker-COE (CLE), comprising of the B. subtilis spore coat gene cotC fused to the core neutralizing epitope CO-26 K equivalent (COE) of the epidemic strain PEDV-AJ1102 spike protein gene, was constructed. Then recombinant B. subtilis displaying the CLE on the spore surface was developed by homologous recombination. Mice were immunized by oral route with B. subtilis 168-CLE, B. subtilis 168, or phosphate-buffered saline (PBS) as control. Results showed that the IgG antibodies and cytokine (IL-4, IFN-γ) levels in the B. subtilis 168-CLE group were significantly higher than the control groups. This study demonstrates that B. subtilis 168-CLE can generate specific systemic immune and mucosal immune responses and is a potential vaccine candidate against PEDV infection.

The role of cytolethal distending toxin in Glaesserella parasuis JS0135 strain infection: Cytotoxicity, phagocytic resistance and pathogenicity.

Glaesserella parasuis is an important porcine pathogen that commonly colonizes the upper respiratory tract of pigs and is prone to causing Glässer's disease under complex conditions. As yet, the disease has led to serious economic losses to the swine industry worldwide. Studies so far have found that several virulence factors are associated with the pathogenicity of G. parasuis, but the pathogenic mechanism is still not fully understood. Cytolethal distending toxin (CDT), a potential virulence factor in G. parasuis, is involved in cytotoxicity, serum resistance, adherence to and invasion of host cells in vitro. Here, to further investigate the pathogenic role of CDT during G. parasuis infection in vitro and in vivo, a double cdt1 and cdt2 deletion mutant (Δcdt1Δcdt2) without selectable marker was first generated in G. parasuis JS0135 strain by continuous natural transformations and replica plating. Morphological observation and lactate dehydrogenase assay showed that the Δcdt1Δcdt2 mutant was defective in cytotoxicity. Additionally, the Δcdt1Δcdt2 mutant was more susceptible to phagocytosis caused by 3D4/2 macrophages compared to the wild-type JS0135 strain. Moreover, by focusing on clinical signs, necropsy, bacterial recovery and pathological observation, we found that the deletion of cdt1 and cdt2 genes led to a significant attenuation of virulence in G. parasuis. Taken together, these findings suggest that as an important virulence factor, CDT can significantly affect the pathogenicity of G. parasuis.

Bone Marrow Adipose Tissue as a Critical Regulator of Postmenopausal Osteoporosis - A Concise Review.

Postmenopausal osteoporosis (PMOP) is a major health problem affecting millions of women worldwide. PMOP patients are often accompanied by abnormal accumulation of bone marrow adipose tissue (BMAT). BMAT is a critical regulator of bone homeostasis, and an increasing BMAT volume is negatively associated with bone mass reduction or fracture. BMAT regulates bone metabolism via adipokines, cytokines and the immune system, but the specific mechanisms are largely unknown. This review emphasizes the impact of estrogen deficiency on bone homeostasis and BMAT expansion, and the mechanism by which BMAT regulates PMOP, providing a promising strategy for targeting BMAT in preventing and treating PMOP.

Towards sustainable upcycling of side streams of purple bread wheat using dry fractionation: Enhancing bioactive compounds and reducing harmful elements.

Side streams from milling result in significant food wastage. While highly nutritious, their harmful elements raise concerns. To repurpose these side streams safely, this study designed a dry fractionation technique for anthocyanin-rich purple bread wheat. Four fractions - from inner to outer layers: flour, middlings, shorts and bran - alongside whole-wheat flour were obtained and examined by microstructure, antioxidant activity, anthocyanin profiles, and essential and harmful minerals. Across the four investigated cultivars, both anthocyanin content and antioxidant capacity increased from inner to outer layers. In comparison to flour, cyanidin-3-glucoside concentrations in middlings, shorts and bran were 2-5 times, 3-9 times, and 6-19 times, respectively. Concentrations of Cr, Ni, Sr and Ba progressively increased from inner to outer layers, Pb and Se exhibited uniform distribution, while Al was more concentrated in inner layers. These findings indicate that the fractionation technique is effective in deriving valuable ingredients from underexploited side streams, especially bran.

Reduced field-of-view DWI based on deep learning reconstruction improving diagnostic accuracy of VI-RADS for evaluating muscle invasion.

OBJECTIVES: To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. METHODS: Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). RESULTS: The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p < 0.05). The mean ADC of all cases of rFOVSTA DWI and rFOVDLR DWI was significantly lower than that of fFOV DWI (all p < 0.05). There was no difference in mean ADC value and the AUC for evaluating muscle invasion between rFOVSTA DWI and rFOVDLR DWI (p > 0.05). CONCLUSIONS: rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. CRITICAL RELEVANCE STATEMENT: The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. KEY POINTS: Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI.

Gut microbiome is associated with personality traits of free-ranging Tibetan macaques (Macaca thibetana).

Recent studies have emphasized that there is a strong link between the gut microbiome and the brain that affects social behavior and personality in animals. However, the interface between personality and the gut microbiome in wild primates remains poorly understood. Here, we used high-throughput sequencing and ethological methods in primate behavioral ecology to investigate the relationship between gut microbiome and personality in Tibetan macaques (Macaca thibetana). The behavioral assessment results indicated three personality dimensions including socialization, shyness, and anxiety. There was significant variation in alpha diversity only for shyness, with a significantly lower alpha diversity indices (including Shannon, Chao1, and PD) for bold individuals than for shy individuals. Using regression models to control for possible confounding factors, we found that the relative abundance of three genera, Akkermansia, Dialister, and Asteroleplasma, was significantly and positively correlated with the sociability scores in the macaques. In addition, Oscillospiraceae exhibited a positive correlation with scores for Shy Dimension. Furthermore, we found that the predicted functional genes for propionate and pyruvate, porphyrin and chlorophyll metabolic pathways related to animal behavior, were significant enriched in shyness group. We propose that the gut microbiome may play an important role in the formation of personality of Tibetan macaques.

Examining trends and variability of PM2.5-associated organic and elemental carbon in the megacity of Beijing, China: Insight from decadal continuous in-situ hourly observations.

Organic carbon (OC) and elemental carbon (EC) in fine particulate matter (PM2.5) play pivotal roles in impacting human health, air quality, and climate change dynamics. Long-term monitoring datasets of OC and EC in PM2.5 are indispensable for comprehending their temporal variations, spatial distribution, evolutionary patterns, and trends, as well as for assessing the effectiveness of clean air action plans. This study presents and scrutinizes a comprehensive 10-year hourly dataset of PM2.5-bound OC and EC in the megacity of Beijing, China, spanning from 2013 to 2022. Throughout the entire study period, the average concentrations of OC and EC were recorded at 8.8 ± 8.7 and 2.5 ± 3.0 µg/m3, respectively. Employing the seasonal and trend decomposition methodology, specifically the locally estimated scatter plot smoothing method combined with generalized least squares with the autoregressive moving average method, the study observed a significant decline in OC and EC concentrations, reducing by 5.8 % yr-1 and 9.9 % yr-1 at rates of 0.8 and 0.4 µg/m3 yr-1, respectively. These declining trends were consistently verified using Theil-Sen method. Notably, the winter months exhibited the most substantial declining trends, with rates of 9.3 % yr-1 for OC and 10.9 % yr-1 for EC, aligning with the positive impact of the implemented clean air action plan. Weekend spikes in OC and EC levels were attributed to factors such as traffic regulations and residential emissions. Diurnal variations showcased higher concentrations during nighttime and lower levels during daytime. Although meteorological factors demonstrated an overall positive impact with average reduction in OC and EC concentrations by 8.3 % and 8.7 %, clean air action plans including the Air Pollution Prevention and Control Action Plan (2013-2017) and the Three-Year Action Plan to Win the Blue Sky War (2018-2020) have more contributions in reducing the OC and EC concentrations with mass drop rates of 87.1 % and 89.2 % and 76.7 % and 96.7 %, respectively. Utilizing the non-parametric wind regression method, significant concentration hotspots were identified at wind speeds of ≤2 m/s, with diffuse signals recorded in the southwestern wind sectors at wind speeds of approximately 4-5 m/s. Interannual disparities in potential source regions of OC and EC were evident, with high potential source areas observed in the southern and northwestern provinces of Beijing from 2013 to 2018. In contrast, during 2019-2022, potential source areas with relatively high values of potential source contribution function were predominantly situated in the southern regions of Beijing. This analysis, grounded in observational data, provides insights into the decadal changes in the major atmospheric composition of PM2.5 and facilitates the evaluation of the efficacy of control policies, particularly relevant for developing countries.

Deciphering the inhibitory mechanisms of betanin and phyllocactin from Hylocereus polyrhizus peel on protein glycation, with insights into their application in bread.

Protein glycation closely intertwines with the pathogenesis of various diseases, sparking a growing interest in exploring natural antiglycation agents. Herein, high-purity betacyanins (betanin and phyllocactin) derived from Hylocereus polyrhizus peel were studied for their antiglycation potential using an in vitro bovine serum albumin (BSA)-glucose model. Notably, betacyanins outperformed aminoguanidine, a recognized antiglycation agent, in inhibiting glycation product formation across different stages, especially advanced glycation end-products (AGEs). Interestingly, phyllocactin displayed stronger antiglycation activity than betanin. Subsequent mechanistic studies employing molecular docking analysis and fluorescence quenching assay unveiled that betacyanins interact with BSA endothermically and spontaneously, with hydrophobic forces playing a dominant role. Remarkably, phyllocactin demonstrated higher binding affinity and stability to BSA than betanin. Furthermore, the incorporation of betacyanins into bread dose-dependently suppressed AGEs formation during baking and shows promise for inhibiting in vivo glycation process post-consumption. Overall, this study highlights the substantial potential of betacyanins as natural antiglycation agents.

Circ_100549 promotes tumor progression in lung adenocarcinoma through upregulation of BIRC6.

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with high incidence and mortality globally. Emerging evidence suggests that circular RNAs (circRNAs) exert critical functions in human cancers, including LUAD. CircRNA_100549 (circ_100549) has been reported to be significantly upregulated in non-small cell lung cancer (NSCLC) samples, while its role in modulating LUAD progression remains to be explored. The current study aims at investigating the functional roles of circ_100549 in LUAD and its downstream molecular mechanism. First, we found that the expression of circ_100549 was higher in LUAD cell lines. Loss-of-function assays verified that depletion of circ_100549 repressed LUAD cell proliferation but accelerated cell apoptosis. Furthermore, in vivo experiments demonstrated that silencing of circ_100549 suppressed tumor growth. Subsequently, based on database analysis, we carried out a series of experiments to explore the mechanisms and effects of circ_100549 underlying LUAD progression, including RNA-binding protein immunoprecipitation (RIP), RNA/DNA pull-down, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays. The results indicated that circ_100549 serves as a ceRNA by sponging miR-95-5p to upregulate BPTF expression, thus upregulating BIRC6 expression at a transcriptional level in LUAD. In summary, our study demonstrated that circ_100549 facilitates LUAD progression by upregulating BIRC6 expression.

Bladder MRI with deep learning-based reconstruction: a prospective evaluation of muscle invasiveness using VI-RADS.

PURPOSE: To investigate the influence of deep learning reconstruction (DLR) on bladder MRI, specifically examination time, image quality, and diagnostic performance of vesical imaging reporting and data system (VI-RADS) within a prospective clinical cohort. METHODS: Seventy participants with bladder cancer who underwent MRI between August 2022 and February 2023 with a protocol containing standard T2-weighted imaging (T2WIS), standard diffusion-weighted imaging (DWIS), fast T2WI with DLR (T2WIDL), and fast DWI with DLR (DWIDL) were enrolled in this prospective study. Imaging quality was evaluated by measuring signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and qualitative image quality scoring. Additionally, the apparent diffusion coefficient (ADC) of bladder lesions derived from DWIS and DWIDL was measured and VI-RADS scoring was performed. Paired t-test or paired Wilcoxon signed-rank test were performed to compare image quality score, SNR, CNR, and ADC between standard sequences and fast sequences with DLR. The diagnostic performance for VI-RADS was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Compared to T2WIS and DWIS, T2WIDL and DWIDL reduced the acquisition time from 5:57 min to 3:13 min and showed significantly higher SNR, CNR, qualitative image quality score of overall image quality, image sharpness, and lesion conspicuity. There were no significant differences in ADC and AUC of VI-RADS between standard sequences and fast sequences with DLR. CONCLUSIONS: The application of DLR to T2WI and DWI reduced examination time and significantly improved image quality, maintaining ADC and the diagnostic performance of VI-RADS for evaluating muscle invasion in bladder cancer.

Resveratrol triggers autophagy-related apoptosis to inhibit the progression of colorectal cancer via inhibition of FOXQ1.

Colorectal cancer (CRC) is a significant health problem with elevated mortality rates, prompting intense exploration of its complex molecular mechanisms and innovative therapeutic avenues. Resveratrol (RSV), recognised for its anticancer effects through SIRT1 activation, is a promising candidate for CRC treatment. This study focuses on elucidating RSV's role in CRC progression, particularly its effect on autophagy-related apoptosis. Using bioinformatics, protein imprinting and immunohistochemistry, we established a direct correlation between FOXQ1 and adverse CRC prognosis. Comprehensive in vitro experiments confirmed RSV's ability to promote autophagy-related apoptosis in CRC cells. Plasmids for SIRT1 modulation were used to investigate underlying mechanisms. Molecular docking, glutathione-S-transferase pull-down experiments and immunoprecipitation highlighted RSV's direct activation of SIRT1, resulting in the inhibition of FOXQ1 expression. Downstream interventions identified ATG16L as a crucial autophagic target. In vivo and in vitro studies validated RSV's potential for CRC therapy through the SIRT1/FOXQ1/ATG16L pathway. This study establishes RSV's capacity to enhance autophagy-related cell apoptosis in CRC, positioning RSV as a prospective therapeutic agent for CRC within the SIRT1/FOXQ1/ATG16L pathway.

Porcine epidemic diarrhea virus E protein induces formation of stress granules and attenuates protein translation through activation of the PERK/eIF2α signaling pathway.

Porcine epidemic diarrhea virus (PEDV) envelope protein (E) has been characterized as an important structural protein that plays critical roles in the interplay with its host to affect the virus life cycle. Stress granules (SGs) are host translationally silent ribonucleoproteins, which are mainly induced by the phosphorylation of eIF2α in the PERK/eIF2α signaling pathway. Our previous study found that PEDV E protein caused endoplasmic reticulum stress response (ERS)-mediated suppression of antiviral proteins' translation. However, the link and the underlying mechanism by which PEDV induces SGs formation and suppresses host translation remain elusive. In this study, our results showed that PEDV E protein significantly elevated the expression of GRP78, CANX, and phosphorylation of PERK and eIF2α, indicating that the PERK/eIF2α branch of ERS was activated. PEDV E protein localized to the ER and aggregated into puncta to reconstruct ER structure, and further induced SGs formation, which has been caused through upregulating the G3BP1 expression level. In addition, a significant global translational stall and endogenous protein translation attenuation were detected in the presence of E protein overexpression, but the global mRNA transcriptional level remained unchanged, suggesting that the shutoff of protein translation was associated with the translation, not with the transcription process. Collectively, this study demonstrates that PERK/eIF2α activation is required for SGs formation and protein translation stall. This study is beneficial for us to better understand the mechanism by which PEDV E suppresses host protein synthesis, and provides us a new insight into the host translation regulation during virus infection.

Region-specific delamination strength of ascending thoracic aortic aneurysm of elderly hypertensive patients with bicuspid and tricuspid aortic valves.

Both ageing and hypertension are clinical factors that may lead to a higher propensity for dissection or rupture of ascending thoracic aortic aneurysms (ATAAs). This study sought to investigate effect of valve morphology on regional delamination strength of ATAAs in the elderly hypertensive patients. Whole fresh ATAA samples were harvested from 23 hypertensive patients (age, 71 ± 8 years) who underwent elective aortic surgery. Peeling tests were performed to measure region-specific delamination strengths of the ATAAs, which were compared between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). The regional delamination strengths of the ATAAs were further correlated with patient ages and aortic diameters for BAV and TAV groups. In the anterior and right lateral regions, the longitudinal delamination strengths of the ATAAs were statistically significantly higher for BAV patients than TAV patients (33 ± 7 vs. 23 ± 8 mN/mm, p = 0.01; 30 ± 7 vs. 19 ± 9 mN/mm, p = 0.02). For both BAV and TAV patients, the left lateral region exhibited significantly higher delamination strengths in both directions than the right lateral region. Histology revealed that disruption of elastic fibers in the right lateral region of the ATAAs was more severe for the TAV patients than the BAV patients. A strong inverse correlation between longitudinal delamination strength and age was identified in the right lateral region of the ATAAs of the TAV patients. Results suggest that TAV-ATAAs are more vulnerable to aortic dissection than BAV-ATAAs for the elderly hypertensive patients. Regardless of valve morphotypes, the right lateral region may be a special quadrant which is more likely to initiate dissection when compared with other regions.

Three coordination polymers based on 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether: Synthesis, structure and selective fluorescent sensing properties.

Three CPs [Zn2(PDA)2(BMIOPE)2·3H2O]n (1), [Co(Br-BDC)(BMIOPE)]n (2) and [Co(MIP)(BMIOPE)]n (3) were synthesized by solvothermal method based on dual-ligand strategy (H2PDA, Br-H2BDC, BMIOPE and H2MIP are 1,3-phenylenediacetic acid, 5-bromo-isophthalic acid, 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether and 5-methylisophthalic acid, respectively). Complexes 1 and 3 exhibit twofold parallel interwoven sql nets. Complex 2 is 2D layer structure. The luminescence property investigations showed that complexes 1-3 could act as multi-responsive fluorescent sensors to detect UO22+, Cr2O72- and CrO42- and nitrofurantoin (NFT) through fluorescence turn-off process, presenting excellent sensitivity and selectivity. Finally, the possible fluorescent quenching mechanisms of complexes 1-3 toward the above pollutants are also further investigated by employing spectroscopic methods and quantum chemical calculations. The fluorescence lifetime measurements manifest the mechanism of fluorescence quenching is static quenching process.

Purification and characterization of betacyanin monomers from Hylocereus polyrhizus peel: A comparative study of their antioxidant and antidiabetic activities with mechanistic insights.

Betacyanins have garnered escalating research interest for their promising bioactivities. However, substantial challenges in purification and separation have impeded a holistic comprehension of the distinct bioactivities of individual betacyanins and their underlying mechanisms. Herein, betanin and phyllocactin monomers with purity exceeding 95% were successfully obtained from Hylocereus polyrhizus peel using a feasible protocol. These monomers were subsequently employed for comparative bioactivity assessments to uncover underlying mechanisms and illuminate structure-activity relationships. Interestingly, phyllocactin exhibited superior antioxidant activities and 36.1% stronger inhibitory activity on α-glucosidase compared to betanin. Mechanistic studies have revealed that they function as mixed-type inhibitors of α-amylase and competitive inhibitors of α-glucosidase, with interactions predominantly driven by hydrogen bonding. Notably, phyllocactin demonstrated a greater binding affinity with enzymes than betanin, thereby substantiating its heightened inhibitory activity. Overall, our results highlight novel bioactivities of betacyanin monomers and provide profound insights into the intricate interplay between structures and properties.

Association between the quantitative characteristics of dual-energy spectral CT and cytoreduction surgery outcome in patients with advanced epithelial ovarian cancers: A prospective observational study.

This study aimed to explore the association between the quantitative characteristics of dual-energy spectral CT and cytoreduction surgery outcome in patients with advanced epithelial ovarian carcinoma (EOC). In this prospective observational study, patients with advanced EOC (federation of gynecology and obstetrics stage III-IV) treated in the Department of Gynecological Oncology at our Hospital between June 2021 and March 2022 were enrolled. All participants underwent dual-energy spectral computed tomography (DECT) scanning 2 weeks before cytoreductive surgery. The quantitative data included peritoneal cancer index (PCI) determined by DECT, CT value at 70 keV, normalized iodine concentration, normalized water concentration, effective atomic number (effective-Z), and slopes of the spectral attenuation curves (slope λ Hounsfield unit). Fifty-five participants were included. The patients were 57.2 ±â€…9.8 years of age, and 72.7% were menopausal. The maximal diameter of tumors was 8.6 (range, 2.9-19.7) cm, and 76.4% were high-grade serous carcinomas. Optimal cytoreduction was achieved in 43 patients (78.2%). Compared with the optimal cytoreductive group, the suboptimal cytoreductive group showed a higher PCI (median, 21 vs 6, P < .001), higher 70 keV CT value (69.5 ±â€…16.6 vs 57.1 ±â€…13.0, P = .008), and higher slope λ Hounsfield unit (1.89 ±â€…0.66 vs 1.39 ±â€…0.60, P = .015). The multivariable analysis showed that the PCI (OR = 1.74, 95%CI: 1.24-2.44, P = .001) and 70 keV CT value (OR = 1.07, 95%CI: 1.01-1.13, P = .023) were independently associated with a suboptimal cytoreductive surgery. The area under the receiver operating characteristics curve of PCI and 70 keV CT value was 0.903 (95%CI: 0.805-1.000, P = .000) and 0.740 (95%CI: 0.581-0.899, P = .012), respectively. High PCI and 70 keV CT value are independently associated with suboptimal cytoreductive surgery in patients with advanced EOC. The PCI determined by DECT might be a better predictor for suboptimal cytoreduction.

Phosphine-Catalyzed [4 + 3] Annulation of ß'-Acetoxy Allenoates with 1C,3N-Dinucleophiles: Access to Functionalized Azepine Derivatives.

A novel method for the synthesis of functionalized azepine derivatives has been developed through a phosphine-catalyzed [4 + 3] annulation of ß'-acetoxy allenoates with benzimidazole-derived 1C,3N-dinucleophiles. This approach demonstrates high efficiency and yields ranging from moderate to excellent. The reaction exhibits a wide substrate scope under the optimized conditions. Furthermore, an initial exploration of the asymmetric variant of this reaction has been conducted, utilizing phosphine (R)-SITCP as the catalyst.

Dormancy release of seeds of Podophyllum hexandrum Royle accompanied by changes in phytochemicals and inorganic elements.

Podophyllum hexandrum Royle is an alpine medicinal plant of considerable importance, and its seed dormancy severely inhibits population renewal. Although cold stratification can break dormancy to a certain extent, the migration and accumulation of phytochemicals and inorganic elements in the seeds during dormancy release and their functions remain unclear. Changes in phytochemicals and inorganic elements in different seed parts were analyzed during dormancy. The key differential phytochemicals and inorganic elements were screened and their association with dormancy release and their roles in dormancy release were explored. The results showed that dormancy release may have occurred following the decrease in palmitic acid and linoleic acid content in the seeds and the increase in 2,3-dihydro-3,5-dihydro-6-methyl-4 (h)-pyran-4-one content in the endosperm. Meanwhile, 6-propyltridecane and hexadecane in the seed coat may enhance the water permeability of seeds to speed up germination. Mg may migrate from the seed coat to the endosperm and seed embryos, whereas Co may migrate from the seed embryo to the seed coat. Ca, Mn, Mg, and Co are involved in various physiological metabolic processes, which may facilitate the dormancy release of P. hexandrum seeds. These findings have enhanced our understanding of the mechanisms of dormancy release in P. hexandrum seeds and can serve as a reference for the development of more effective dormancy-breaking techniques for the conservation of this endangered medicinal plant.

Correlation Between ICU Admission Time and Long-Term Mortality in Elderly Critically Ill Patients.

Objective: The the intensive care unit (ICU), also known as intensive care medicine department and intensive intensive care unit, is a medical place for centralized treatment of critical diseases and continuous monitoring and treatment. To investigate the relationship between the length of intensive care unit (ICU) admission and long-term mortality in elderly critically ill patients. Methods: A total of 2694 critically ill ICU patients admitted to Xianning First People's Hospital from April 2017 to April 2021 were selected. Inclusion criteria including: age ≥ 60 years; meet the diagnostic criteria for critical illness; admission to ICU ≥ 24h. According to admission time, patients were divided into 1684 patients admitted during working hours and 1010 patients admitted during non-working hours. The relationship between the admission time of ICU patients and long-term mortality was taken as the dependent variable. The evaluation was performed using the Acute Physiology and Chronic Health Status Assessment Scale (APACHE II score). Epidemiological questionnaire was used to investigate the status of time to hospital and mortality, and the independent risk factors affecting time to hospital and mortality were analyzed by univariate and multivariate analysis. SPSS 26.0 statistical software was used for analysis and processing. Results: Among 2694 critically ill patients in ICU, 1010 patients were hospitalized during non-working hours, with an admission rate of 37.49%. The acute physiology and chronic health evaluation (APACHE) II score of non-working hours was 19.91±6.62, which is significantly higher than that of working hours (18.21±6.42) (P < .05). The mortality rates of ICU patients hospitalized during non-working hours and during working hours accounted for 30.10 % and 19.71% of all patients, respectively, with statistical significance (P < .05). Comparing the mortality rates of the two groups at different time periods, there was a significant difference between the two groups (P < .05). In order to influence the independent variables of ICU mortality (non-occurrence = 0, occurrence = 1), the significant factors of univariate analysis were included in the logistic regression equation. Time of admission, combined cardiopulmonary disease, APACHE II score, nurse workload and other factors were independent risk factors for ICU mortality. Conclusion: Out-of-hours admission is associated with an increased risk of death and is associated with changes in ICU organizational structure. Therefore, sending patients to ICU in time migh help improve their life.

LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells.

Glaesserella parasuis is an early colonizer of the swine upper respiratory tract and can break through the respiratory barrier for further invasion. However, the mechanisms underlying G. parasuis increases epithelial barrier permeability remain unclear. This study demonstrates that G. parasuis cytolethal distending toxin (CDT) induces p53-dependent apoptosis in new-born piglet tracheal (NPTr) cells. Moreover, we report for the first time that leucine-rich repeat-containing protein 8A (LRRC8A), an essential subunit of the volume-regulated anion channel (VRAC), involves in apoptosis of NPTr cells mediated by G. parasuis CDT. Pharmacological inhibition of VRAC with either PPQ-102 or NS3728 largely attenuated CDT-induced apoptosis in NPTr cells. Additionally, experiments with cells knocked down for LRRC8A using small interfering ribonucleic acid (siRNA) or knocked out LRRC8A using CRISPR/Cas9 technology showed a significant reduction in CDT-induced apoptosis. Conversely, re-expression of Sus scrofa LRRC8A in LRRC8A-/- NPTr cells efficiently complemented the CDT-induced apoptosis. In summary, these findings suggest that LRRC8A is pivotal for G. parasuis CDT-induced apoptosis, providing novel insights into the mechanism of apoptosis caused by CDT.