Comparative evaluation of physiological and molecular responses of blackcurrant varieties to powdery mildew infection.

The black currant (Ribes nigrum L.), a member of the Saxifragaceae family's Ribes genus, has gained consumer and grower acceptance due to its high nutritional value and economic potential. However, powdery mildew, the primary leaf disease affecting black currants, significantly impacts growers and the industry. Developing varieties highly resistant to powdery mildew is currently considered the most scientifically sound solution. However, the black currant's physiological and disease resistance mechanisms post-infection by powdery mildew remain understudied, thereby impeding further breeding efforts. Therefore, this study aimed to elucidate the pathogenesis of powdery mildew in various susceptible varieties, post-infection physiological changes, and molecular mechanisms related to powdery mildew. This was achieved through phenotypic observation, physiological data analysis, transcriptomic analysis, and qRT-PCR-mediated gene expression analysis.

Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma.

Background: It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status. Methods: In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis. Results: The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%. Conclusion: Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.

Corrigendum to "Numerical simulation of the magnetically gain-switched chemical oxygen-iodine laser" [Heliyon 8(9) September 2022, Article e10530].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10530.].

The glutamate receptor antagonist ifenprodil inhibits hepatitis E virus infection.

Infection with hepatitis E virus (HEV) represents a global problem, with over 20 million people infected annually. No specific antiviral drugs are available for treating HEV infection, necessitating the development of novel targeted therapeutics. Here, we report that the N-methyl-D-aspartate receptor (NMDAR) antagonist ifenprodil, a clinically approved drug used to treat idiopathic pulmonary fibrosis (IPF), is an HEV inhibitor in liver-derived cells. In vitro investigation demonstrates that ifenprodil suppresses viral protein expression in a dose-dependent manner in human hepatoma cells by inhibiting early stages of viral infection. We also found that ifenprodil modulates host cell intrinsic biological processes distinct from virus-induced innate immunity, inhibiting HEV RNA accumulation in primary human hepatocytes. Finally, the inhibitory effect of ifenprodil in vivo was also tested in rabbits challenged with the HEV-3ra CHN-BJ-R14 strain. Fecal virus shedding was below the limit of detection in two animals for both ribavirin-treated and ifenprodil-treated rabbits compared to vehicle-treated control animals. Our data demonstrate that ifenprodil is an effective anti-HEV compound with potential as a therapeutic candidate for the treatment of HEV infection.

Study on medical dispute prediction model and its clinical-application effectiveness based on machine learning.

BACKGROUND: Medical dispute is a global public health issue, which has been garnering increasing attention. In this study, we used machine learning (ML) method to establish a dispute prediction model and explored the clinical-application efficiency of this model in effectively reducing the occurrence of medical disputes. METHODS: Retrospective study of All disputes filed by Gansu Medical Mediation Committee from 2019 to 2021 and patients with the same hospital level as that of the dispute group and hospitalization year were randomly selected as the control group in 1:1 ratio. SPSS software was used for univariate feature selection of the 14 factors that may cause disputes, and factors with statistical differences were selected. The data were divided into training and test sets in a 7:3 ratio. Six ML models were selected, and Python was used to establish a dispute prediction model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC), sensitivity, specificity, accuracy, precision, average precision (AP), and F1 score were used to characterize the fitting and accuracy of the models, while decision curve analysis (DCA) was used to evaluate their clinical utility. RESULTS: A total of 1189 patients in the dispute and control groups were extracted. Following 11 influencing factors were selected: the inpatient department, doctor title, patient age, patient gender, patient occupation, payment method, hospitalization days, hospitalization times, discharge method, blood transfusion volume, and hospitalization espenses. Compared to other models, the AUC (0.945, 95% CI 0.913-0.981), Sensitivity (0.887), Accuracy (0.887), AP (0.834), and F1 score (0.880) of the random forest model were higher than those of other models, while the DCA curve indicated its high clinical benefits. CONCLUSIONS: Inpatient department, hospitalization expenses, and discharge type are the primary influencing factors of dispute. Random forest exhibited high dispute prediction and clinical-application value and is expected to be promoted for offline dispute prediction.

Establishment of enterically transmitted hepatitis virus animal models using lipid nanoparticle-based full-length viral genome RNA delivery system.

BACKGROUND: Enterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and HEV infection are lacking. OBJECTIVE: This study aimed to establish HAV and HEV infections in multiple small animals by intravenously injecting lipid nanoparticle (LNP)-encapsulated full-length viral RNAs (LNP-vRNA). DESIGN: In vitro transcribed and capped full-length HAV RNA was encapsulated into LNP and was intravenously inoculated to Ifnar-/- mice, and HEV RNA to rabbits and gerbils. Virological parameters were determined by RT-qPCR, ELISA and immunohistochemistry. Liver histopathological changes were analysed by H&E staining. Antiviral drug and vaccine efficacy were further evaluated by using the LNP-vRNA-based animal model. RESULTS: On intravenous injection of LNP-vRNA, stable viral shedding was detected in the faeces and infectious HAV or HEV was recovered from the livers of the inoculated animals. Liver damage was observed in LNP-vRNA (HAV)-injected mice and LNP-vRNA (HEV)-injected rabbits. Mongolian gerbils were also susceptible to LNP-vRNA (HEV) injections. Finally, the antiviral countermeasures and in vivo function of HEV genome deletions were validated in the LNP-vRNA-based animal model. CONCLUSION: This stable and standardised LNP-vRNA-based animal model provides a powerful platform to investigate the pathogenesis and evaluate countermeasures for enterically transmitted hepatitis viruses and can be further expanded to other viruses that are not easily cultured in vitro or in vivo.

Mechanism exploration and model construction for small cell transformation in EGFR-mutant lung adenocarcinomas.

Small-cell lung cancer (SCLC) transformation accounts for 3-14% of resistance in EGFR-TKI relapsed lung adenocarcinomas (LUADs), with unknown molecular mechanisms and optimal treatment strategies. We performed transcriptomic analyses (including bulk and spatial transcriptomics) and multiplex immunofluorescence on pre-treated samples from LUADs without transformation after EGFR-TKI treatment (LUAD-NT), primary SCLCs (SCLC-P) and LUADs with transformation after EGFR-TKI treatment (before transformation: LUAD-BT; after transformation: SCLC-AT). Our study found that LUAD-BT exhibited potential transcriptomic characteristics for transformation compared with LUAD-NT. We identified several pathways that shifted during transformation, and the transformation might be promoted by epigenetic alterations (such as HDAC10, HDAC1, DNMT3A) within the tumor cells instead of within the tumor microenvironment. For druggable pathways, transformed-SCLC were proved to be less dependent on EGF signaling but more relied on FGF signaling, while VEGF-VEGFR pathway remained active, indicating potential treatments after transformation. We also found transformed-SCLC showed an immuno-exhausted status which was associated with the duration of EGFR-TKI before transformation. Besides, SCLC-AT exhibited distinct molecular subtypes from SCLC-P. Moreover, we constructed an ideal 4-marker model based on transcriptomic and IHC data to predict SCLC transformation, which obtained a sensitivity of 100% and 87.5%, a specificity of 95.7% and 100% in the training and test cohorts, respectively. We provided insights into the molecular mechanisms of SCLC transformation and the differences between SCLC-AT and SCLC-P, which might shed light on prevention strategies and subsequent therapeutic strategies for SCLC transformation in the future.

Effects of a new continuous nursing program on the short-term and long-term low back pain in patients after UBED: a retrospective study based on 282 patients.

Background: Unilateral biportal endoscopic discectomy (UBED) is a widely accepted minimally invasive surgery for the treatment of lumbar degenerative diseases. However, some patients continue to have persistent low back pain (LBP) symptoms in the short and long term after surgery, which may be related to improper postoperative nursing and rehabilitation of patients. Further research is needed to determine whether continuous nursing can improve the symptoms of patients after UBED. Methods: This study retrospectively enrolled 282 lumbar disc herniation (LDH) patients who underwent UBED in our hospital from January 2019 to January 2022. The patients were divided into two groups according to whether they accepted the continuous nursing program: 147 patients in the traditional nursing group and 135 patients in the continuous nursing group. Demographic characteristics, radiological parameters, and follow-up data of the patients were collected. Finally, the risk factors of LBP after UBED were analyzed. Results: The visual analog scale (VAS) score of LBP in the continuous nursing group was 0.97 ± 1.159 at 3 months and 0.61 ± 0.954 at 12 months after operation, and VAS of leg pain was 0.23 ± 0.421 at 12 months after operation, which were better than those in the traditional nursing group (1.51 ± 1.313, 1.10 ± 1.076, 0.68 ± 0.788, respectively, p < 0.001) The Oswestry disability index (ODI) score of the continuous nursing group was lower than that of the traditional nursing group at 12 months after operation (7.36 ± 6.526 vs. 12.43 ± 6.942, p < 0.001). The rehabilitation completion (7.98 ± 1.857), efficacy satisfaction (9.13 ± 1.101), and re-herniation worry scores (1.97 ± 1.217) in the continuous nursing group were better than those in the traditional nursing group (4.14 ± 3.066, 8.28 ± 1.240, 2.79 ± 1.973, respectively, P < 0.001). The re-herniation rate within 1 year was similar between the two groups (3/135 vs. 2/147, p = 0.673). No incision infection occurred. Multivariate regression analysis showed that risk factors for persistent LBP at 3-month follow-up were degenerative disc [odds ratio (OR): 2.144, CI: 1.306-3.519, p = 0.03], Pfirrmann grade (OR: 3.073, CI: 1.427-6.614, p = 0.04), and surgical time (OR: 0.969, CI: 0.937-1.003, p = 0.74). At the 12-month follow-up, the risk factors for persistent LBP were preoperative VAS of the legs (OR: 1.261, CI: 1.000-1.591, p = 0.05) and Pfirrmann grade (OR: 3.309, CI: 1.460-7.496, p = 0.04). Conclusion: Continuous nursing programs can improve the symptoms of short-term and long-term persistent LBP in patients after UBED, enhance the completion of rehabilitation training after UBED, alleviate patients' concerns about recurrence, and improve patients' satisfaction.

Dictyophora indusiata polysaccharide attenuated LPS-induced intestinal inflammation of mice via the TLR4/JNK signaling pathway.

BACKGROUND: Dictyophora indusiata polysaccharide is an important bioactive component of D. indusiata, playing an important role in alleviating inflammation. The present study aimed to investigate the anti-inflammatory effect and mechanism of D. indusiata polysaccharide on lipopolysaccharide (LPS)-induced intestinal inflammation in mice. RESULTS: Our results indicated that D. indusiata polysaccharide ameliorated intestinal inflammation of mice by increasing the body weight, the number of goblet cells and decreasing inflammatory cell infiltration. In addition, D. indusiata polysaccharide significantly up-regulated expression of ZO-1, Occuldin mRNA, which were 2.55-fold and 2.28-fold higher than the LPS group, respectively. In particular, D. indusiata polysaccharide effectively inhibited the Toll-like receptor 4 (TLR4)/ c-Jun NH2-terminal kinase (JNK) signalling pathway which was 0.34-fold and 0.49-fold of gene expression and 0.41-fold and 0.39-fold of protein expression in the LPS group, respectively. CONCLUSION: The results of the present study suggested that D. indusiata polysaccharide exerted anti-inflammatory and intestinal protective effects by inhibiting the TLR4/JNK signaling pathway, which will provide a basis for the potential value of D. indusiata polysaccharide as prebiotics in food applications. © 2024 Society of Chemical Industry.

Isolation and characterization of a multidrug-resistant Staphylococcus aureus infecting phage and its therapeutic use in mice.

In recent years, the emergence of multidrug-resistant bacteria has limited the selection of drugs for treating bacterial infections, reduced clinical efficacy, and increased treatment costs and mortality. It is urgent to find alternative antibiotics. In order to explore a new method for controlling methicillin resistant Staphylococcus aureus (S. aureus) , this study isolated and purified a multi drug resistant S. aureus broad-spectrum phage JPL-50 from wastewater. JPL-50 belongs to the Siphoviridae family after morphological observation, biological characterization, and transmission electron microscopy (TEM) fragmentation spectrum analysis. It can cleave 84% of tested S. aureus (168/200) , in which 100% of tested mastitis-associated strains (48/48) and 72.04% of MRSA strains (67/93) were lysed. In addition, it has an optimal growth temperature of about 30°C, a high activity within a wide pH range (pH 3-10) , and an optimal multiplicity of infection of 0.01. The one-step growth curve shows a latent time of 20 minutes, an explosive time of 80 minutes. JPL-50 was 16, 927 bp in length and was encoded by double-stranded DNA, with no genes associated with bacterial resistance or virulence factors detected. In a therapeutic study, injection of the phage JPL-50 once and for 7 times in 7 days protected 40% and 60% of the mice from fatal S.aureus infection, respectively. More importantly, JPL-50-doxycycline combination could effectively inhibit host S.aureus in vitro and reduce the use of doxycycline within 8 hours. In conclusion, the bacteriophage JPL-50 has a wide lysis spectrum, high lysis rate, high tolerance to extreme environments, and moderate in vivo activity, providing ideas for developing multidrug-resistant S. aureus infections.

GhPME36 aggravates susceptibility to Liriomyza sativae by affecting cell wall biosynthesis in cotton leaves.

BACKGROUND: Cotton is an important economic crop and a host of Liriomyza sativae. Pectin methylesterase (PME)-mediated pectin metabolism plays an indispensable role in multiple biological processes in planta. However, the pleiotropic functions of PME often lead to unpredictable effects on crop resistance to pests. Additionally, whether and how PME affects susceptibility to Liriomyza sativae remain unclear. RESULTS: Here, we isolated GhPME36, which is located in the cell wall, from upland cotton (Gossypium hirsutum L.). Interestingly, the overexpression of GhPME36 in cotton caused severe susceptibility to Liriomyza sativae but increased leaf biomass in Arabidopsis. Cytological observations revealed that the cell wall was thinner with more demethylesterified pectins in GhPME36-OE cotton leaves than in WT leaves, whereas the soluble sugar content of GhPME36-OE cotton leaf cell walls was accordingly higher; both factors attracted Liriomyza sativae to feed on GhPME36-OE cotton leaves. Metabolomic analysis demonstrated that glucose was significantly differentially accumulated. Transcriptomic analysis further revealed DEGs enriched in glucose metabolic pathways when GhPME36 was overexpressed, suggesting that GhPME36 aggravates susceptibility to Liriomyza sativae by affecting both the structure and components of cell wall biosynthesis. Moreover, GhPME36 interacts with another pectin-modifying enzyme, GhC/VIF1, to maintain the dynamic stability of pectin methyl esterification. CONCLUSIONS: Taken together, our results reveal the cytological and molecular mechanisms by which GhPME36 aggravates susceptibility to Liriomyza sativae. This study broadens the knowledge of PME function and provides new insights into plant resistance to pests and the safety of genetically modified plants.

Correlation between the Systemic Immunoinflammatory Index and Platelet-Lymphocyte Ratio in Patients with Adenomyosis.

Background: The chronic inflammatory immune response is a significant factor in the pathogenesis of benign gynecological diseases. The systemic immunoinflammatory index (SII) and the platelet-to-lymphocyte ratio (PLR) are commonly available biomarkers of inflammation. However, evidence of the relationship between SII and PLR in patients with adenomyosis is limited. This study aimed to investigate the relationship between SII and PLR in patients with adenomyosis. Methods: This cross-sectional study included 483 patients with adenomyosis who were first diagnosed at our institution between January 2019 and December 2021. Basic patient clinical information and inflammatory factors were collected for univariate analysis, smoothed curve fitting, and multivariate segmented linear regression. Results: The results of the univariate analysis showed a significant positive correlation between PLR levels and SII (P < 0.001). In addition, a nonlinear relationship between PLR and SII was tested using a smoothed curve fit after adjusting for potential confounders. Multiple segmented linear regression models showed a significant relationship between SII and PLR in both SII < 1,326.47 (ß 0.14, 95% CI: 0.12, 0.16; P < 0.0001) and >1,326.47 (ß 0.02, 95% CI: -0.01, 0.05; P = 0.2461). Conclusions: In conclusion, this study showed a nonlinear relationship between SII and PLR in patients with uterine adenomyosis. An increase in serum PLR levels correlates with an increase in SII before SII levels reach an inflection point.

Jintiange capsule ameliorates glucocorticoid-induced osteonecrosis of the femoral head in rats by regulating the activity and differentiation of BMSCs.

Background and aim: A surplus of glucocorticoids (GC) is a main cause of non-traumatic osteonecrosis of the femoral head (ONFH), and Jintiange (JTG), as one of the traditional Chinese medicines (TCM), also plays an instrumental role in the alleviation of bone loss simultaneously. Therefore, JTG was thought to be able to reverse GC-induced ONFH (GC-ONFH) to a certain extent. Experimental procedure: In vivo, the effect of JTG on trabeculae in the subchondral bone of the femoral head was investigated using micro-computed tomography (micro-CT), TdT-mediated dUTP nick end labeling (TUNEL) and histological staining; in vitro, proliferation, viability, apoptosis, and senescence of purified bone mesenchymal stem cells (BMSCs) were examined to demonstrate the direct impact of JTG on these cells. Meanwhile after using a series of interventions, the function of JTG on BMSC differentiation could be assessed by measuring of osteogenic and adipogenic markers at levels of protein and mRNA. Results: Our final results demonstrated that with the involvement of Wnt/ß-catenin pathway, JTG was able to significantly promote osteogenesis, restrain adipogenesis, delay senescence in BMSCs, reduce osteoclast number, weaken apoptosis, and enhance proliferation of osteocytes, all of which could mitigate the progression of subchondral osteonecrosis. Conclusion: According to the results of experiments in vitro and vivo, JTG was deemed to relieve the early GC-ONFH using the prevention of destruction of subchondral bone, which was contributed to regulating the differentiation of BMSCs and the number of osteoclasts.

Three patients with new mutations in the EPCAM variant gene for congenital tufting enteropathy and a mutation review in China: a case report.

Background: Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. Case Description: We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. Conclusions: CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

Machine learning prediction of no reflow in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Background: No-reflow (NRF) phenomenon is a significant challenge in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Accurate prediction of NRF may help improve clinical outcomes of patients. This retrospective study aimed at creating an optimal model based on machine learning (ML) to predict NRF in these patients, with the additional objective of guiding pre- and intra-operative decision-making to reduce NRF incidence. Methods: Data were collected from 321 STEMI patients undergoing pPCI between January 2022 and May 2023, with the dataset being randomly divided into training and internal validation sets in a 7:3 ratio. Selected features included pre- and intra-operative demographic data, laboratory parameters, electrocardiogram, comorbidities, patients' clinical status, coronary angiographic data, and intraoperative interventions. Post comprehensive feature cleaning and engineering, three logistic regression (LR) models [LR-classic, LR-random forest (LR-RF), and LR-eXtreme Gradient Boosting (LR-XGB)], a RF model and an eXtreme Gradient Boosting (XGBoost) model were developed within the training set, followed by performance evaluation on the internal validation sets. Results: Among the 261 patients who met the inclusion criteria, 212 were allocated to the normal flow group and 49 to the NRF group. The training group consisted of 183 patients, while the internal validation group included 78 patients. The LR-XGB model, with an area under the curve (AUC) of 0.829 [95% confidence interval (CI): 0.779-0.880], was selected as the representative model for logistic regression analyses. The LR model had an AUC slightly lower than XGBoost model (AUC 0.835, 95% CI: 0.781-0.889) but significantly higher than RF model (AUC 0.731, 95% CI: 0.660-0.802). Internal validation underscored the unique advantages of each model, with the LR model demonstrating the highest clinical net benefit at relevant thresholds, as determined by decision curve analysis. The LR model encompassed seven meaningful features, and notably, thrombolysis in myocardial infarction flow after initial balloon dilation (TFAID) was the most impactful predictor in all models. A web-based application based on the LR model, hosting these predictive models, is available at https://l7173o-wang-lyn.shinyapps.io/shiny-1/. Conclusions: A LR model was successfully developed through ML to forecast NRF phenomena in STEMI patients undergoing pPCI. A web-based application derived from the LR model facilitates clinical implementation.

The effects of ambient temperature on non-accidental mortality in the elderly hypertensive subjects, a cohort-based study.

BACKGROUND: The association between ambient temperature and mortality has yielded inconclusive results with previous studies relying on in-patient data to assess the health effects of temperature. Therefore, we aimed to estimate the effect of ambient temperature on non-accidental mortality among elderly hypertensive patients through a prospective cohort study conducted in northeastern China. METHODS: A total of 9634 elderly hypertensive patients from the Kailuan research who participated in the baseline survey and follow-up from January 1, 2006 to December 31, 2017, were included in the study. We employed a Poisson generalized linear regression model to estimate the effects of monthly ambient temperature and temperature variations on non-accidental mortality. RESULTS: After adjusting for meteorological parameters, the monthly mean temperature (RR = 0.989, 95% CI: 0.984-0.993, p < 0.001), minimum temperature (RR = 0.987, 95% CI: 0.983-0.992, p < 0.001) and maximum temperature (RR = 0.989, 95% CI: 0.985-0.994, p < 0.001) exhibited a negative association with an increased risk of non-accidental mortality. The presence of higher monthly temperature variation was significantly associated with an elevated risk of mortality (RR = 1.097, 95% CI:1.051-1.146, p < 0.001). Further stratified analysis revealed that these associations were more pronounced during colder months as well as among male and older individuals. CONCLUSIONS: Decreased temperature and greater variations in ambient temperature were observed to be linked with non-accidental mortality among elderly hypertensive patients, particularly notable within aging populations and males. These understanding regarding the effects of ambient temperature on mortality holds clinical significance for appropriate treatment strategies targeting these individuals while also serving as an indicator for heightened risk of death.

Stability of electrostatically stabilized emulsions and its encapsulation of astaxanthin against environmental stresses: Effect of sodium caseinate-sugar beet pectin addition order.

Two addition orders, i.e., the layer-by-layer (L) and mixed biopolymer (M) orders, were used to generate sodium caseinate - sugar beet pectin electrostatically stabilized o/w emulsions with 0.5% oil and varying sodium caseinate: sugar beet pectin ratios (3:1-1:3) at pH 4.5. Emulsion stability against environmental stresses (i.e., pH, salt addition, thermal treatment, storage and in vitro simulated gastrointestinal digestion) and its astaxanthin encapsulation against degradation during storage and in vitro digestion were evaluated. Results indicated that a total biopolymer concentration of 0.5% was optimal, with the preferred sodium caseinate-sugar beet pectin ratios for L and M emulsions being 1:1 and 1:3, respectively. L emulsions generally exhibited smaller droplet diameters than M emulsions across all ratios, except at 1:3. Lowering the pH to 1.5 substantially reduced the net negative charge of all emulsions, with only L emulsions precipitating at pH 3. M emulsions showed greater tolerance to salt addition, remaining stable up to 500 mM sodium and calcium concentrations, whereas L emulsions destabilized at levels exceeding 50 mM and 30 mM, respectively. All emulsions were stable when heated at 37 °C or 90 °C for 30 min. Astaxanthin degradation rates increased with prolonged storage, reaching 61.66% and 54.08% by day 7 for L and M emulsions, respectively. Encapsulation efficiency of astaxanthin in freshly prepared M emulsions (86.85%) was significantly higher compared to L emulsions (72.82%). M emulsions had 30% and 25% higher encapsulation efficiency of astaxanthin than L emulsions after in vitro digestion for 120 min and 240 min respectively. This study offers suggestions for interface design and process optimization to improve the performance of protein-polysaccharide emulsion systems, such as in beverages and dairy products, as well as their delivery effect of bioactives.

Synergetic effects of chlorinated paraffins and microplastics on microbial communities and nitrogen cycling in deep-sea cold seep sediments.

Chlorinated paraffins (CPs) and microplastics (MPs) are commonly found in deep-sea cold seep sediments, where nitrogen cycling processes frequently occur. However, little is known about their combined effects on sedimentary microbial communities and nitrogen cycling in these environments. This study aimed to investigate the synergistic impacts of CPs and MPs on microbial communities and nitrogen cycling in deep-sea cold seep sediments through microcosm experiments. Our results demonstrated that the presence of CPs and MPs induced significant alterations in microbial community composition, promoting the growth of Halomonas. Furthermore, CPs and MPs were found to enhance nitrification, denitrification and anammox processes, which was evidenced by the higher abundance of genes associated with nitrification and denitrification, as well as increased activity of denitrification and anammox in the CPs and MPs-treatment groups compared to the control group. Additionally, the enhanced influence of CPs and MPs on denitrification was expected to promote nitrate-dependent and sulfate-dependent anaerobic oxidation of methane, thereby resulting in less methane released into the environment. These findings shed light on the potential consequences of simultaneous exposure to CPs and MPs on biogeochemical nitrogen cycling in deep-sea cold seep sediments.

The role of m6A-associated membraneless organelles in the RNA metabolism processes and human diseases.

N6-methyladenosine (m6A) is the most abundant post-transcriptional dynamic RNA modification process in eukaryotes, extensively implicated in cellular growth, embryonic development and immune homeostasis. One of the most profound biological functions of m6A is to regulate RNA metabolism, thereby determining the fate of RNA. Notably, the regulation of m6A-mediated organized RNA metabolism critically relies on the assembly of membraneless organelles (MLOs) in both the nucleus and cytoplasm, such as nuclear speckles, stress granules and processing bodies. In addition, m6A-associated MLOs exert a pivotal role in governing diverse RNA metabolic processes encompassing transcription, splicing, transport, decay and translation. However, emerging evidence suggests that dysregulated m6A levels contribute to the formation of pathological condensates in a range of human diseases, including tumorigenesis, reproductive diseases, neurological diseases and respiratory diseases. To date, the molecular mechanism by which m6A regulates the aggregation of biomolecular condensates associated with RNA metabolism is unclear. In this review, we comprehensively summarize the updated biochemical processes of m6A-associated MLOs, particularly focusing on their impact on RNA metabolism and their pivotal role in disease development and related biological mechanisms. Furthermore, we propose that m6A-associated MLOs could serve as predictive markers for disease progression and potential drug targets in the future.