Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma.

BACKGROUND: Belzutifan, a hypoxia-inducible factor 2α inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies. METHODS: In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response). RESULTS: A total of 374 participants were assigned to belzutifan, and 372 to everolimus. At the first interim analysis (median follow-up, 18.4 months), the median progression-free survival was 5.6 months in both groups; at 18 months, 24.0% of the participants in the belzutifan group and 8.3% in the everolimus group were alive and free of progression (two-sided P = 0.002, which met the prespecified significance criterion). A confirmed objective response occurred in 21.9% of the participants (95% confidence interval [CI], 17.8 to 26.5) in the belzutifan group and in 3.5% (95% CI, 1.9 to 5.9) in the everolimus group (P<0.001, which met the prespecified significance criterion). At the second interim analysis (median follow-up, 25.7 months), the median overall survival was 21.4 months in the belzutifan group and 18.1 months in the everolimus group; at 18 months, 55.2% and 50.6% of the participants, respectively, were alive (hazard ratio for death, 0.88; 95% CI, 0.73 to 1.07; two-sided P = 0.20, which did not meet the prespecified significance criterion). Grade 3 or higher adverse events of any cause occurred in 61.8% of the participants in the belzutifan group (grade 5 in 3.5%) and in 62.5% in the everolimus group (grade 5 in 5.3%). Adverse events led to discontinuation of treatment in 5.9% and 14.7% of the participants, respectively. CONCLUSIONS: Belzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. Belzutifan was associated with no new safety signals. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; LITESPARK-005 ClinicalTrials.gov number, NCT04195750.).

The somatic genome of Eptatretus okinoseanus reveals the adaptation to deep-sea oligotrophic environment.

BACKGROUND: Hagfishes are fascinating creatures that typically inhabit the deep sea. The deep sea is characterized by its lack of sunlight, primary productivity, and diminishing biomass with increasing ocean depth. Therefore, hagfishes living in this environment must develop effective survival strategies to adapt to the limited food supply. Deep-sea hagfishes have been observed to survive without food intake for up to one year. In this study, we have assembled a high-quality somatic genome of the deep-sea hagfish (Eptatretus okinoseanus) captured below 1,000 m. We compared the genome of E. okinoseanus with the genomes of inshore hagfish, lampreys, and other related species to investigate the genetic factors underlying the deep-sea hagfish adaptations to the environment. RESULTS: The E. okinoseanus somatic genome was estimated to be 1.89 Gb and assembled into 17 pseudochromosomes. Phylogenetic analysis showed that shallow-sea and deep-sea hagfishes diverged approximately 58.8 million years ago. We found Perilipin gene family was significantly expanded in deep sea E. okinoseanus, which promotes triacylglycerol storage. Furthermore, a series of genes involved in fatty acid synthesis and metabolism, blood glucose regulation, and metabolic rate regulation were also expanded, rapid evolution or positive selection, and these changes contribute to their efficiency in energy utilization. Among these genes, the positively selected gene JNK may play an important role in energy metabolism. In addition, the olfactory receptors of the deep-sea hagfish were significantly expanded to 86, and three conserved motifs present only in hagfishes olfactory receptors were identified, which may facilitate the rapid localization of carrion. CONCLUSIONS: This study provides valuable genomic resources for insights into the survival strategies of deep-sea hagfishes in oligotrophic environments.

Incorporation of Chest Computed Tomography Quantification to Predict Outcomes for Patients on Hemodialysis with COVID-19.

Introduction: Patients undergoing maintenance hemodialysis are vulnerable to coronavirus disease 2019 (COVID-19), exhibiting a high risk of hospitalization and mortality. Thus, early identification and intervention are important to prevent disease progression in these patients. Methods: This was a two-center retrospective observational study of patients on hemodialysis diagnosed with COVID-19 at the Lingang and Xuhui campuses of Shanghai Sixth People's Hospital. Patients were randomized into the training (130) and validation cohorts (54), while 59 additional patients served as an independent external validation cohort. Artificial intelligence-based parameters of chest computed tomography (CT) were quantified, and a nomogram for patient outcomes at 14 and 28 days was created by screening quantitative CT measures, clinical data, and laboratory examination items, using univariate and multivariate Cox regression models. Results: The median dialysis duration was 48 (interquartile range, 24-96) months. Age, diabetes mellitus, serum phosphorus level, lymphocyte count, and chest CT score were identified as independent prognostic indicators and included in the nomogram. The concordance index values were 0.865, 0.914, and 0.885 in the training, internal validation, and external validation cohorts, respectively. Calibration plots showed good agreement between the expected and actual outcomes. Conclusion: This is the first study in which a reliable nomogram was developed to predict short-term outcomes and survival probabilities in patients with COVID-19 on hemodialysis. This model may be helpful to clinicians in treating COVID-19, managing serum phosphorus, and adjusting the dialysis strategies for these vulnerable patients to prevent disease progression in the context of COVID-19 and continuous emergence of novel viruses.

Surgical outcomes of sacrospinous hysteropexy and hysteropreservation for pelvic organ prolapse: a systematic review of randomized controlled trials.

Objective: In several randomized controlled trials (RCTs), sacrospinous hysteropexy and other forms of hysteropreservation have been compared. Nevertheless, there is no definitively best treatment. This study summarized RCT evidence for various uterine preservation surgical procedures. Methods: From each database inception to August 2023, we searched PubMed, Embase, Cochrane Library, and Web of Science for eligible RCTs. A comparison was made between sacrospinous hysteropexy and other hysteropreservation, including vaginal and abdominal surgery. For categorical and continuous variables, relative risks (RRs) and mean differences (MDs) were calculated using random-effects models. Results: We reviewed a total 1,398 studies and ultimately included five RCTs that met all inclusion criteria. These five studies included a total of 1,372 uterine POP cases all of whom received transvaginal surgery and had a follow-up period for assessment of recurrence from 12 months to 5 years. There were no significant differences between sacrospinous hysteropexy and other hysteropreservation for the incidences of recurrence (RR,1.24; 95% CI, 0.58 to 2.63; p = 0.58) or hematoma (RR,0.70; 95% CI, 0.17 to 2.92; p = 0.62). Moreover, neither sacrospinous hysteropexy nor hysteropreservation had any significant effect on the risk of mesh exposure (RR,0.34; 95% CI, 0.03 to 4.31; p = 0.41), dyspareunia (RR,0.45; 95% CI, 0.13 to1.6; p = 0.22), urinary tract infection (RR,0.66; 95% CI, 0.38 to 1.15; p = 0.15), bothersome bulge symptoms (RR,0.03; 95% CI, -0.02 to 0.08; p = 0.24), operative time (MD, -4.53; 95% CI, -12.08 to 3.01; p = 0.24), and blood loss (MD, -25.69; 95% CI, -62.28 to 10.91; p = 0.17). However, sacrospinous hysteropexy was associated with a lower probability of pain (RR,4.8; 95% CI, 0.79 to 29.26; p = 0.09) compared with other hysteropreservation. Conclusion: There was no difference between sacrospinous hysteropexy and hysteropreservation in terms of recurrence, hematoma, mesh exposure, dyspareunia, urinary tract infection, bothersome bulge symptoms, operative time, pain, and blood loss. Systematic Review Registration: PROSPERO [CRD42023470025].

Does the Angulation of the Screws in the Zero-P Implant Affect the Clinical and Radiological Outcomes of Patients?

OBJECTIVE: When implanting the Zero-P device, the screws of Zero-P form a bone wedge with a 40 ± 5° cranial and caudal angle (CCA). However, no study has been performed in the optimal CCA of the Zero-P implant. To investigate whether the cranial/caudal angles (CCA) of the screws affect the clinical and radiological outcomes in patients undergoing ACDF with the Zero-P implant. METHODS: From January 2016 to December 2023, we retrospectively analyzed 186 patients who underwent 1-level ACDF with the Zero-P device. The patients were divided into four groups: group A (cranial angle ≤40°, caudal angle ≤40°); group B (cranial angle ≤40°, caudal angle >40°); group C (cranial angle >40°, caudal angle ≤40°); and group D (cranial angle >40°, caudal angle >40°). The clinical outcomes, including Japanese Orthopaedic Association (JOA), neck disability index (NDI), and visual analogue scale (VAS) scores, the radiological parameters, including cervical lordosis (CL), cervical lordosis of operated segments (OPCL), intervertebral space height (ISH) and fusion rate (FR), and the complications, were evaluated and compared. Parametric tests, non-parametric tests, and chi-square tests were conducted to analyze the data. RESULTS: The OPCL of group A was significantly less than that of the other groups at the final follow-up (p < 0.05). The ISH of group D was significantly less than that of group A at the final follow-up (p < 0.05). The subsidence rate of group A was significantly less than that of group D at the final follow-up (p < 0.05). At the final follow-up, the upper adjacent-level degeneration (ASD) of group D was significantly less severe than that of groups A and B (p < 0.05). The clinical outcomes do not differ among groups (p > 0.05). CONCLUSION: A larger CCA of the screws (cranial angle >40°, caudal angle >40°) was better for maintaining OPCL and reducing the incidence of ASD. A smaller CCA of the screws (cranial angle ≤40°, caudal angle ≤40°) was better for maintaining ISH and reducing the rate of subsidence.

Effect of Replacing Alfalfa Hay with Common Vetch Hay in Sheep Diets on Growth Performance, Rumen Fermentation and Rumen Microbiota.

The aim of this study was to determine whether the inclusion of 40% of common vetch (CV) hay as a feed ingredient in place of alfalfa hay (AH) would improve performance and ruminal fermentation and microbiota in fattening lambs. Twenty lambs were equally divided into two groups: control group (fed 40% AH with 20% rice straw) and CV group (fed 40% CV hay with 20% rice straw). Concerning hay quality, CV hay had greater in vitro digestibility of dry matter and neutral detergent fiber (p < 0.05) than AH. Lambs fed the CV diet had a higher average daily gain (ADG) and efficiency of feed and economy than lambs fed the control group. The NH3-N content and estimated methane produced per unit of ADG of the CV diet group were significantly lower (p < 0.05) than control group. Multiple differential microbial genera were identified, with Prevotella being the most dominant genus and a tendency towards higher (p = 0.095) in lambs offered CV diet. The higher Ruminococcus abundance (p < 0.05) was found in animals of the CV group compared to the control group. In summary, CV can be incorporated into lamb diets as a low-cost forage alternative to AH to improve feed efficiency and animal performance and to reduce methane produced per unit of ADG.

Presence of sputum IgG against eosinophilic inflammatory proteins in asthma.

Background: Sputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma. Methods: This study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation. Results: The levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%). Conclusion: This study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

Allopolyploidization from two dioecious ancestors leads to recurrent evolution of sex chromosomes.

Polyploidization presents an unusual challenge for species with sex chromosomes, as it can lead to complex combinations of sex chromosomes that disrupt reproductive development. This is particularly true for allopolyploidization between species with different sex chromosome systems. Here, we assemble haplotype-resolved chromosome-level genomes of a female allotetraploid weeping willow (Salix babylonica) and a male diploid S. dunnii. We show that weeping willow arose from crosses between a female ancestor from the Salix-clade, which has XY sex chromosomes on chromosome 7, and a male ancestor from the Vetrix-clade, which has ancestral XY sex chromosomes on chromosome 15. We find that weeping willow has one pair of sex chromosomes, ZW on chromosome 15, that derived from the ancestral XY sex chromosomes in the male ancestor of the Vetrix-clade. Moreover, the ancestral 7X chromosomes from the female ancestor of the Salix-clade have reverted to autosomal inheritance. Duplicated intact ARR17-like genes on the four homologous chromosomes 19 likely have contributed to the maintenance of dioecy during polyploidization and sex chromosome turnover. Taken together, our results suggest the rapid evolution and reversion of sex chromosomes following allopolyploidization in weeping willow.

Decision fatigue experience of front-line nurses in the context of public health emergency: an interpretative phenomenological analysis.

BACKGROUND: Decision fatigue is a new concept in the field of psychology and refers to a state of fatigue alongside impaired cognitive processing and emotional regulation ability. Previous studies have confirmed that nurses are prone to decision fatigue, and nurses who experience decision fatigue may implement nursing measures that are inconsistent with clinical evidence, thus affecting patients' benefits. COVID-19, as a large-scale global public health emergency, increased the workload and burden of nurses and aggravated decision fatigue. However, the factors leading to decision fatigue among nurses have not yet been identified. METHODS: This study is guided by interpretative phenomenology. During the epidemic period of COVID-19: From November 2022 to February 2023, a one-to-one, semi-structured in-depth interview was conducted among nurses with decision fatigue experience who were participating in front-line work in Jilin Province using homogenous sampling. The interview recordings and related data were transcribed into text within 24 h, and data analysis was assisted by NVivo 12.0 software. RESULTS: After a total of 14 front-line nurses were analyzed in this study, The thematic level reaches saturation, the findings present a persuasive and coherent narrative, and the study is terminated, and finally extracted and formed three core themes: "Cognition, influence and attitude of decision fatigue", "Approaching factors of decision fatigue" and "Avoidant factors of decision fatigue". CONCLUSION: This study confirmed that decision fatigue was widespread in the work of front-line nurses, affecting the physical and psychological health of nurses, the quality of nursing work, the degree of benefit of patients and the clinical outcome. However, nursing staff do not know enough about decision fatigue, so the popularization and research of decision fatigue should be strengthened. Improve the attention of medical institutions, nursing managers and nursing staff.Some suggestions are put forward for the intervention of decision fatigue through personnel, task, tool and technology, organization and environment.

Unveiling the toxicological effects and risks of prometryn on red swamp crayfish (Procambarus clarkii): Health assessments, ecological, and molecular insights.

Prometryn is commonly used in agricultural and non-agricultural settings. However, possible harm to aquatic organisms remains a persistent concern. Prometryn was also the only one of the 26 triazine herbicides detected in this study. Numerous studies have assessed the harmful effects of prometryn in teleost fish and shrimp. There is a lack of information regarding the ecological and human health risks, as well as the toxic mechanisms affecting crayfish. In this study, human health risk assessment (THQ) and ecological risk assessment (RQ) were conducted on P. clarkii in the rice-crayfish co-culture (IRCC) farming model. The 96 h of exposure to 0.286 mg/L and 1.43 mg/L prometryn was conducted to investigate the potential effects and molecular mechanisms of hepatopancreatic resistance to prometryn in P. clarkii. The original sample analysis revealed that the THQ calculated from the prometryn levels in the muscle and hepatopancreas was below 0.1, suggesting no threat to human health. However, the calculated RQ values were >0.1, indicating a risk to P. clarkii. Histological analysis and biochemical index detection of the experimental samples revealed that the hepatopancreatic injury and oxidative damage in P. clarkii were caused by prometryn. Moreover, transcriptome analysis identified 2512 differentially expressed genes (DEGs) after 96 h of prometryn exposure. Prometryn exposure caused significant changes in metabolic pathways, including oxoacid metabolic processes and cytochrome P450-associated drug metabolism. Further hub gene analysis via PPI indicated that exposure to prometryn may inhibit lipid synthesis, storage, and amino acid transport and affect glucose metabolic pathways and hormone synthesis. Additionally, we hypothesized that prometryn-triggered cell death could be linked to the PI3K-Akt signaling cascade. This study's findings have significant meaning for the efficient and logical application of herbicides in IRCC, ultimately aiding in advancing a highly productive agricultural system.

[Effects of Long-term Biochar Addition on Denitrification N2O Emissions from Bacteria and Fungi in Paddy Soil].

Denitrification driven by bacteria and fungi is the main source of nitrous oxide （N2O） emissions from paddy soil. It is generally believed that biochar reduces N2O emissions by influencing the bacterial denitrification process, but the relevant mechanism of its impact on fungal denitrification is still unclear. In this study, the long-term straw carbonization returning experimental field in Changshu Agricultural Ecological Experimental Base of the Chinese Academy of Sciences was taken as the object. Through indoor anaerobic culture and molecular biology technology, the relative contributions of bacteria and fungi to denitrifying N2O production in paddy soil and the related microorganism mechanism were studied under different long-term biochar application amounts （blank, 2.25 t·hm-2, and 22.5 t·hm-2, respectively, expressed by BC0, BC1, and BC10）. The results showed that compared with that in BC0, biochar treatment significantly reduced N2O emission rate, denitrification potential, and cumulative N2O emissions, and the contribution of bacterial denitrification was greater than that of fungal denitrification in all three treatments. Among them, the relative contribution rate of bacterial denitrification in BC10 （62.9%） was significantly increased compared to BC0 （50.8%）, whereas the relative contribution rate of fungal denitrification in BC10 （37.1%） was significantly lower than that in BC0 （49.2%）. The application of biochar significantly increased the abundance of bacterial denitrification functional genes （nirK, nirS, and nosZ） but reduced the abundance of fungal nirK genes. The contribution rate of fungal denitrification was significantly positively correlated with the N2O emission rate and negatively correlated with soil pH, TN, SOM, and DOC. Biochar may have inhibited the growth of denitrifying fungi by increasing pH and carbon and nitrogen content, reducing the abundance of related functional genes, thereby weakening the reduction ability of NO to N2O during fungal denitrification process. This significantly reduces the contribution rate of N2O production during the fungal denitrification process and the denitrification N2O emissions from paddy soil. This study helps to broaden our understanding of the denitrification process in paddy soil and provides a theoretical basis for further regulating fungal denitrification N2O emissions.

Integrated Comparative Transcriptome and Weighted Gene Co-Expression Network Analysis Provide Valuable Insights into the Mechanisms of Pinhead Initiation in Chinese Caterpillar Mushroom Ophiocordyceps sinensis (Ascomycota).

The initiation and formation of the "pinhead" is the key node in growth process of Ophiocordyceps sinensis (Chinese Cordyceps). The research on the mechanism of changes in this growth stage is the basis for realizing the industrialization of its artificial cultivation. Clarifying the mechanisms of pinhead initiation is essential for its further application. Here, we performed a comprehensive transcriptome analysis of pinhead initiation process in O. sinensis. Comparative transcriptome analysis revealed remarkable variation in gene expression and enriched pathways at different pinhead initiation stages. Gene co-expression network analysis by WGCNA identified 4 modules highly relevant to different pinhead initiation stages, and 23 hub genes. The biological function analysis and hub gene annotation of these identified modules demonstrated that transmembrane transport and nucleotide excision repair were the topmost enriched in pre-pinhead initiation stage, carbohydrate metabolism and protein glycosylation were specially enriched in pinhead initiation stage, nucleotide binding and DNA metabolic process were over-represented after pinhead stage. These key regulators are mainly involved in carbohydrate metabolism, synthesis of proteins and nucleic acids. This work excavated the candidate pathways and hub genes related to the pinhead initiation stage, which will serve as a reference for realizing the industrialization of artificial cultivation in O. sinensis.

Soluble ST2: A Novel Biomarker for Diagnosis and Prognosis of Cardiovascular Disease.

The increasing incidence of cardiovascular disease (CVD) is a significant global health concern, affecting millions of individuals each year. Accurate diagnosis of acute CVD poses a formidable challenge, as misdiagnosis can significantly decrease patient survival rates. Traditional biomarkers have played a vital role in the diagnosis and prognosis of CVDs, but they can be influenced by various factors, such as age, sex, and renal function. Soluble ST2 (sST2) is a novel biomarker that is closely associated with different CVDs. Its low reference change value makes it suitable for continuous measurement, unaffected by age, kidney function, and other confounding factors, facilitating risk stratification of CVDs. Furthermore, the combination of sST2 with other biomarkers can enhance diagnostic accuracy and prognostic value. This review aims to provide a comprehensive overview of sST2, focusing on its diagnostic and prognostic value as a myocardial marker for different types of CVDs and discussing the current limitations of sST2.

Pseudo-Elevation of Anti Double Stranded DNA IgG Antibody Caused by Rheumatoid Factor.

BACKGROUND: The examination of anti-double stranded DNA (ds-DNA) IgG antibody is of great significance for the diagnosis, differential diagnosis, assessment of disease activity, and prognosis of disease recurrence in SLE. METHODS: We used a chemiluminescence method to detect ds-DNA IgG and found that the levels of ds-DNA IgG antibody in the patient's serum were significantly increased and the indirect immunofluorescence (IIF) test result was negative. Laboratory tests show that the patient's RF level far exceeds the upper limit of their reference range. RESULTS: RF 110.6 IU/mL, ds-DNA IgG 753 IU/mL; After PEG6000 treatment, the RF was 108.7 IU/mL, and then the ds-DNA IgG was measured at 23.5 IU/mL. CONCLUSIONS: The RF IgM subtype is the main cause of RF interference in IgG antibody detection, mainly due to the binding of the Fc region of RF to the Fab segment of IgG. Combining with capture antibodies and labeled antibodies leads to the formation of non-specific detection signals, or directly reacting with the detected substance, resulting in false positive test results.

Gender differences in the relationship between nicotine exposure and symptoms of depression.

BACKGROUND: Tobacco-derived nicotine exposure is linked to depression. However, the associations of nicotine and its metabolites with symptoms of depression, particularly concerning gender differences, remain underexplored. METHODS: The characteristics and total nicotine equivalents (TNE) of 1001 subjects were determined. The association between the TNE and symptoms of depression, accounting for gender differences, was investigated using generalized linear models and subgroup analyses. RESULTS: Men exhibited significantly greater levels of the nicotine exposure indicators TNE2, TNE3, TNE6, and TNE7 (P < 0.005). A significantly greater percentage of women (23.45 %) than men (9.81 %) exhibited symptoms of depression (P < 0.0001). In women, the relationship between the TNE and depression was reflected by a U-shaped curve with significant inflection points, particularly for TNE3, TNE6, and TNE7. Furthermore, in women, concentrations above 48.98 nmol/mL for TNE3, 53.70 nmol/mL for TNE6, and 57.54 nmol/mL for TNE7 were associated with 154 %, 145 %, and 138 % increases in the risk of depression, respectively. In contrast, these associations did not reach significance among men. LIMITATIONS: The cross-sectional design limits the ability to infer causality between nicotine exposure and depressive symptoms. Larger-scale studies are needed to confirm these findings. CONCLUSIONS: Gender could be a significant factor influencing the relationship between nicotine exposure levels and symptoms of depression. The impact of nicotine exposure on symptoms of depression should be particularly considered among women. IMPLICATIONS: This study revealed the complex relationship between tobacco-related nicotine exposure and depressive symptoms, with a particular focus on gender differences. Our results revealed a distinct U-shaped correlation between total nicotine equivalents and depression in women, which differed from that in men. These findings emphasize the importance of tailoring clinical approaches to address nicotine exposure and manage depressive symptoms based on gender.

Enhanced dielectric constant and breakdown strength of sandwiched polymer nanocomposite film for excellent energy storage.

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

Sex chromosome turnover plays an important role in the maintenance of barriers to post-speciation introgression in willows.

Almost all species in the genus Salix (willow) are dioecious and willows have variable sex-determining systems, the role of this variation in maintaining species barriers is relatively untested. We first analyzed the sex determination systems (SDS) of two species, Salix cardiophylla and Salix interior, whose positions in the Salix phylogeny make them important for understanding a sex chromosome turnover that has been detected in their relatives, and that changed the system from male (XX/XY) to female (ZW/ZZ) heterogamety. We show that both species have male heterogamety, with sex-linked regions (SLRs) on chromosome 15 (termed a 15XY system). The SLRs occupy 21.3% and 22.8% of the entire reference chromosome, respectively. By constructing phylogenetic trees, we determined the phylogenetic positions of all the species with known SDSs. Reconstruction of ancestral SDS character states revealed that the 15XY system is likely the ancestral state in willows. Turnovers of 15XY to 15ZW and 15XY to 7XY likely contributed to early speciation in Salix and gave rise to major groups of the Vetrix and Salix clades. Finally, we tested introgression among species in the phylogenetic trees based on both autosomes and SLRs separately. Frequent introgression was observed among species with 15XY, 15ZW, and 7XY on autosomes, in contrast to the SLR datasets, which showed less introgression, and in particular no gene flow between 15ZW and 7XY species. We argue that, although SDS turnovers in willow speciation may not create complete reproductive barriers, the evolution of SLRs plays important roles in preventing introgression and maintaining species boundaries.

The galactomannan-EGCG physical complex: Effect of branching degree and molecular weight on structural and physiological properties.

Polysaccharides and polyphenols are bioactive components that co-exist in many plant foods. Their binary interaction in terms of the structure-function relationships, however, has not been well clarified. This study elucidated the correlation between the structural and physiological properties of galactomannan (GM) -catechin monomer complexes and GM with different branching or molecular weight (Mw). Results indicated that locus bean gum with lower branching degree (Gal/Man is 0.259) bound more readily to EGCG with adsorption rate of 19.42 %. EGCG and ECG containing galloyl groups were more inclined to form hydrogen bonds with GMs, significantly improving the adsorption by GMs. The introduction of EGCG could enhance the antioxidant activity and starch digestion inhibition of GM, which positively correlated with the adsorption capacity of EGCG. The guar gum (GG) with higher Mw (7384.3 kDa) could transport 71.51 % EGCG into the colon, while the retention rate of EGCG reaching the colon alone was only 46.33 %. Conversely, GM-EGCG complex with lower Mw (6.9 kDa) could be readily utilized by gut microbiota, and increased production of short-chain fatty acids (SCFAs). This study elucidated the structure-properties relationship of GM-EGCG complexes, and provide a new idea for the development and precision nutrition of polysaccharides-polyphenol complexes fortified functional foods.

Plant-based diet indices and their interaction with ambient air pollution on the ovarian cancer survival: A prospective cohort study.

BACKGROUND: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions. METHODS: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales. RESULTS: Throughout a median follow-up of 37.60 (interquartile: 24.77-50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend < 0.01), whereas no significant associations were found between either overall PDI or hPDI and OC survival. Higher APS (HR for per interquartile range = 1.27, 95 % CI = 1.01, 1.60) was significantly associated with worse OC survival, and the association was exacerbated by adherence to uPDI. Notably, an additive interaction was identified between combined air pollution and uPDI (P < 0.005 for high APS and high uPDI). We also found that adherence to overall PDI aggravated associations of air pollution with OC survival (P-interaction = 0.006). CONCLUSIONS: Joint exposure to various ambient air pollutants was significantly associated with lower survival among patients with OC, particularly for those who predominantly consumed unhealthy plant-based foods.

Revolutionizing early Alzheimer's disease and mild cognitive impairment diagnosis: a deep learning MRI meta-analysis.

BACKGROUND: The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights. OBJECTIVE: A meta-analysis was designed to analyze the diagnostic accuracy of deep learning of MRI images on AD and MCI models. METHODS: A meta-analysis was performed across PubMed, Embase, and Cochrane library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on the diagnostic accuracy of deep learning. Subsequently, methodological quality was assessed using the QUADAS-2 checklist. Diagnostic measures, including sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristic curve (AUROC) were analyzed, alongside subgroup analyses for T1-weighted and non-T1-weighted MRI. RESULTS: A total of 18 eligible studies were identified. The Spearman correlation coefficient was -0.6506. Meta-analysis showed that the combined sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.84, 0.86, 6.0, 0.19, and 32, respectively. The AUROC was 0.92. The quiescent point of hierarchical summary of receiver operating characteristic (HSROC) was 3.463. Notably, the images of 12 studies were acquired by T1-weighted MRI alone, and those of the other 6 were gathered by non-T1-weighted MRI alone. CONCLUSION: Overall, deep learning of MRI for the diagnosis of AD and MCI showed good sensitivity and specificity and contributed to improving diagnostic accuracy.

ANTECEDENTES: O diagnóstico precoce da doença de Alzheimer (DA) e do comprometimento cognitivo leve (CCL) continua sendo um desafio significativo na neurologia, com métodos convencionais frequentemente limitados pela subjetividade e variabilidade na interpretação. A integração da aprendizagem profunda com a inteligência artificial (IA) na análise de imagens de ressonância magnética surge como uma abordagem transformadora, oferecendo o potencial para insights diagnósticos imparciais e altamente precisos. OBJETIVO: Uma metanálise foi projetada para analisar a precisão diagnóstica do aprendizado profundo de imagens de ressonância magnética em modelos de DA e CCL. MéTODOS: Uma metanálise foi realizada nos bancos de dados das bibliotecas PubMed, Embase e Cochrane seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com foco na precisão diagnóstica do aprendizado profundo. Posteriormente, a qualidade metodológica foi avaliada por meio do checklist QUADAS-2. Medidas diagnósticas, incluindo sensibilidade, especificidade, razões de verossimilhança, razão de chances diagnósticas e área sob a curva característica de operação do receptor (area under the receiver operating characteristic curve [AUROC]) foram analisadas, juntamente com análises de subgrupo para ressonância magnética ponderada em T1 e não ponderada em T1. RESULTADOS: Um total de 18 estudos elegíveis foram identificados. O coeficiente de correlação de Spearman foi de -0,6506. A metanálise mostrou que a sensibilidade e a especificidade combinadas, a razão de verossimilhança positiva, a razão de verossimilhança negativa e a razão de chances de diagnóstico foram 0,84, 0,86, 6,0, 0,19 e 32, respectivamente. A AUROC foi de 0,92. O ponto quiescente do resumo hierárquico da característica de operação do receptor (hierarchical summary of receiver operating characteristic [HSROC]) foi 3,463. Notavelmente, as imagens de 12 estudos foram adquiridas apenas por ressonância magnética ponderada em T1, e as dos outros 6 foram obtidas apenas por ressonância magnética não ponderada em T1. CONCLUSãO: Em geral, a aprendizagem profunda da ressonância magnética para o diagnóstico de DA e CCL mostrou boa sensibilidade e especificidade e contribuiu para melhorar a precisão diagnóstica.