Search

Abstract Objective: This study aims to gain a deeper understanding of the patterns of allergen detection positivity rates among different age and gender groups, and to explore cross-reactivity patterns among allergens. Methods: We conducted a retrospective analysis of patients who underwent allergen testing at our hospital. The sample for this study included all patients who underwent allergen testing. We utilized immune blotting to detect specific IgE antibodies to 20 allergens in patient sera. Results: The study results showed a higher proportion of female samples (72.35%) compared to male samples (27.65%). Among all participants, the age distribution was primarily concentrated in the 25–35 age group, accounting for 37.43% of the total sample, followed by the 45 years and older age group, accounting for 27.00%. This indicates that allergic symptoms may occur not only in children and adolescents but also at any time after adulthood. We further observed significant influences of factors such as gender and age on individual sensitivity to specific allergens. For example, compared to males, females were found to be more sensitive to certain allergens such as cat hair, dust mites, and dog epithelium. Similarly, we also found variations in sensitivity to specific allergens among different age groups. Conclusion: Close monitoring of allergen distribution in populations facilitates active engagement of allergic individuals in self-management, while gender and age may be important factors influencing individual sensitivity to specific allergens. These findings provide valuable insights for understanding the pathogenesis of allergic diseases and designing more effective prevention and treatment strategies.

Abstract Background Psychiatric nurses often encounter patients with mental health disorders and consequently experience prolonged periods of high stress, increased workload, and frequent incidents of workplace violence. These aspects can lead to a higher incidence of poor sleep quality. This study examined the interplay between workplace violence and emotional labour (surface and deep acting) to suggest measures for enhancing sleep quality among psychiatric nurses. Methods A total of 300 completed and valid online questionnaires were collected. The Pittsburgh Sleep Quality Index was used to measure sleep quality, Workplace Violence Scale (WVS) to measure the occurrence of workplace violence, and Emotional Labour Scale to measure surface and deep acting. The data were analysed using Hayes’ PROCESS macro with SPSS. Independent samples t-tests and one-way ANOVA were used to compare differences in sleep quality and emotional labour (surface and deep acting) between psychiatric nurses with different demographics. Results The prevalence of poor sleep quality (PSQI > 5) was 55% among the nurses. Surface acting in emotional labour partially mediated the relationship between workplace violence and sleep quality(a1*b1=0.035,95%CI: 0.002, 0.079), whereas deep acting had a suppressive effect(a2*b2=-0.033,95%CI: -0.071, -0.003). Occupational identity had a positive moderating effect on the relationship between workplace violence and surface acting(Effect=0.091,95%CI: 0.004, 0.179). Conclusions The relationship between workplace violence and poor sleep quality was partially mediated by surface acting and suppressed by deep acting. Moreover, nurses with higher occupational identity engaged in more surface acting after workplace violence. Workplace violence, surface acting, and deep acting emerged as significant factors influencing sleep quality among psychiatric nurses. Deep acting can reduce the impact of workplace violence on sleep quality. The results provide a new and expanded view of the interplay between workplace violence and emotional labour concerning sleep quality. Interprofessional collaboration with clinicians, administrators, educators, and spiritual leaders can contribute to the development of related education and training. Trial registration Chinese Clinical Trial Registry ChiCTR2200062347. https://www.chictr.org.cn/showproj.html?proj=173264

Abstract Erectile Dysfunction (ED) is a form of sexual dysfunction in males that imposes significant health and financial burdens globally. Despite its high prevalence, diagnosing ED remains challenging due to the limitations of current diagnostic methods and patients’ reluctance to seek medical help. Currently, some studies have used machine learning techniques for developing ED prediction models, but the performance and interpretability of existing models need to be further improved. This study utilized data from the National Health and Nutrition Examination Survey (NHANES) for the years 2001 to 2004, adhering to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) statement. After excluding male respondents who did not meet the study criteria, a total of 3,869 participants were included. Gradient boosting decision tree (GBDT) algorithms (XGBoost, CatBoost, LightGBM) were used to develop the ED prediction model. Data preprocessing, feature selection, model evaluation, and interpretability analysis were performed to ensure the reliability and effectiveness of the model. The model evaluation results revealed that the AUC values are XGBoost: 0.887 ± 0.016; LightGBM: 0.879 ± 0.016; CatBoost: 0.871 ± 0.019. The F1-Scores are XGBoost: 0.695 ± 0.023; LightGBM: 0.681 ± 0.025; CatBoost: 0.681 ± 0.025. The Recall values are XGBoost: 0.789 ± 0.026; LightGBM: 0.739 ± 0.030; CatBoost: 0.711 ± 0.030. These results confirmed that the XGBoost model is the best-performing ED prediction model in this study. Interpretability analysis results of the XGBoost model showed that age, obesity, cardiovascular risk factors, prostate-related diseases, and socioeconomic status are key features for predicting ED, playing a significant role in the ED mechanism. Therefore, we believe the ED prediction model trained in this study has strong predictive performance and high interpretability. This model can help to expand the diagnostic options for ED, improve the diagnosis rate of ED, and assist doctors in early intervention for patients with ED, ultimately improving patient prognosis.

Abstract Background New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH. Methods The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features. Results T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression. Conclusions Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores.

Objective Clarifying paraspinal muscle (PM) change in degenerative lumbar scoliosis (DLS) is positive to evaluate the progression of scoliosis. This research compares the characteristic of PM change among different coronal sub‐types of DLS and explores its potential clinical significance. Methods A total of 84 DLS patients between June 2019 to December 2021 were retrospectively analyzed. Patients were classified into three types based on the coronal balance distance (CBD): Type A, CBD 3 cm; Type C: C7PL shifted to the convex side of the curve, and CBD >3 cm. Fat infiltration rates in the multifidus (MS) and erector spinae (ES) at the apex of the main and fractional curves, and spinopelvic parameters were analyzed statistically. Pearson's or Spearman's correlation was applied to analyze the correlation between asymmetric degree of PM change and these parameters in three types. Results There were 62 cases with coronal sub‐Type A, 6 cases with Type B, and 16 cases with Type C. Patients in Type B and C demonstrated higher fat infiltration in MS on the concave side of both the main and fractional curves when compared to those in Type A. The asymmetric degree of ES change was positively correlated with CBD at the apex of the main curve in Type B and at the apex of the fractional curve in Type C respectively, and that of MS was positively correlated with apical vertebral rotation, while negatively strong‐correlated with pelvic incidence and sacral slope in Type C. Conclusion PM fatty infiltration presented difference among varied coronal sub‐types of DLS patients. The CBD in Type B and C patients was correlated with the asymmetric degree of ES change.

Abstract Proton-exchange-membrane fuel cells demand highly efficient catalysts for the oxygen reduction reaction, and core-shell structures are known for maximizing precious metal utilization. Here, we reported a controllable “carbon defect anchoring” strategy to prepare Pt1Ni1@Pt/C core-shell nanoparticles with an average size of ~2.6 nm on an in-situ transformed defective carbon support. The strong Pt–C interaction effectively inhibits nanoparticle migration or aggregation, even after undergoing stability tests over 70,000 potential cycles, resulting in only 1.6% degradation. The stable Pt1Ni1@Pt/C catalysts have high oxygen reduction reaction mass activity and specific activity that reach 1.424 ± 0.019 A/mgPt and 1.554 ± 0.027 mA/cmPt 2 at 0.9 V, respectively, attributed to the optimal compressive strain. The experimental results are generally consistent with the theoretical predictions made by our comprehensive microkinetic model which incorporates essential kinetics and thermodynamics of oxygen reduction reaction. The consistent results obtained in our study provide compelling evidence for the high accuracy and reliability of our model. This work highlights the synergy between theory-guided catalyst design and appropriate synthetic methodologies to translate the theory into practice, offering valuable insights for future catalyst development.

Abstract Gastric cancer (GC) is a highly heterogeneous and aggressive malignant tumor that seriously affects the life safety of people all over the world. Its early manifestations are subtle. The present study aimed to investigate the clinical significance of serum lipid profiles, insulin resistance markers including the triglyceride-glucose (TyG) index and the atherosclerotic index (AI), in GC patients. A retrospective analysis encompassed 215 GC patients and 827 healthy individuals. The study results show that the total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein levels, and the TyG index of GC patients were significantly lower than those of the control group before and after propensity score matching analysis. In the GC group, the levels of CEA, CA199, CA125, and CA724 tumor markers were higher than those in the healthy control group. Patients in advanced stages exhibited lower serum levels of serum lipids and TyG index compared to those in early stages. ROC analysis revealed that the TyG index, CA125, and CA199 combination yielded the highest positive prediction rate for GC at 98.6%. TyG index is significantly associated with the risk of adverse reactions after chemotherapy (OR = 1.104, 95% CI 1.028–1.186, P

Abstract Background The family Lauraceae is subdivided into six main lineages: Caryodaphnopsideae, Cassytheae, Cryptocaryeae, Hypodaphnideae, Laureae, and Neocinnamomeae. However, phylogenetic relationships among these lineages have been debatable due to incongruence between trees constructed using nuclear ribosomal DNA (nrDNA) sequences and chloroplast (cp) genomes. As with cp DNA, the mitochondrial (mt) DNA of most flowering plants is maternally inherited, so the phylogenetic relationships recovered with mt genomes are expected to be consistent with that from cp genomes, rather than nrDNA sequences. Results The mitogenome of Machilus yunnanensis, with a length of 735,392 bp, has a very different genome size and gene linear order from previously published magnoliid mitogenomes. Phylogenomic reconstructions based on 41 mt genes from 92 Lauraceae mitogenomes resulted in highly supported relationships: sisterhood of the Laureae and a group containing Neocinnamomeae and Caryodaphnopsideae, with Cassytheae being the next sister group, followed by Cryptocaryeae. However, we found significant incongruence among the mitochondrial, chloroplast, and nuclear phylogenies, especially for the species within the Caryodaphnopsideae and Neocinnamomeae lineages. Time-calibrated phylogenetic analyses showed that the split between Caryodaphnopsideae and Neocinnamomeae dated to the later Eocene, around 38.5 Ma, Laureae originated in the Late Cretaceous, around 84.9 Ma, Cassytheae originated in the mid-Cretaceous around 102 Ma, and Cryptocaryeae originated in the Early Cretaceous around 116 Ma. From the Late Cretaceous to the Paleocene, net diversification rates significantly increased across extant clades of major lineages, and both speciation rates and net diversification rates continued steady growth towards the present. Conclusions The topology obtained here for the first time shows that mt genes can be used to support relationships among lineages of Lauraceae. Our results highlight that both Caryodaphnopsideae and Neocinnamomeae lineages are younger than previously thought, likely first diversifying in the Eocene, and species in the other extant lineages of Lauraceae dates in a long-time span from the Early Cretaceous to the Eocene, and the climate of a period of about 90 million years was relatively warm, while the extant species of Lauraceae then continuously diversified with global cooling from the Eocene to the present day.

Nonalcoholic steatohepatitis (NASH) may soon become the leading cause of end-stage liver disease worldwide with limited treatment options. Liver fibrosis, which is driven by chronic inflammation and hepatic stellate cell (HSC) activation, critically determines morbidity and mortality in patients with NASH. Pyruvate kinase M2 (PKM2) is involved in immune activation and inflammatory liver diseases; however, its role and therapeutic potential in NASH-related fibrosis remain largely unexplored. Bioinformatics screening and analysis of human and murine NASH livers indicated that PKM2 was upregulated in nonparenchymal cells (NPCs), especially macrophages, in the livers of patients with fibrotic NASH. Macrophage-specific PKM2 knockout (PKM2FL/FLLysM-Cre) significantly ameliorated hepatic inflammation and fibrosis severity in three distinct NASH models induced by a methionine- and choline-deficient (MCD) diet, a high-fat high-cholesterol (HFHC) diet, and a western diet plus weekly carbon tetrachloride injection (WD/CCl4). Single-cell transcriptomic analysis indicated that deletion of PKM2 in macrophages reduced profibrotic Ly6Chigh macrophage infiltration. Mechanistically, PKM2-dependent glycolysis promoted NLR family pyrin domain containing 3 (NLRP3) activation in proinflammatory macrophages, which induced HSC activation and fibrogenesis. A pharmacological PKM2 agonist efficiently attenuated the profibrotic crosstalk between macrophages and HSCs in vitro and in vivo. Translationally, ablation of PKM2 in NPCs by cholesterol-conjugated heteroduplex oligonucleotides, a novel oligonucleotide drug that preferentially accumulates in the liver, dose-dependently reversed NASH-related fibrosis without causing observable hepatotoxicity. The present study highlights the pivotal role of macrophage PKM2 in advancing NASH fibrogenesis. Thus, therapeutic modulation of PKM2 in a macrophage-specific or liver-specific manner may serve as a novel strategy to combat NASH-related fibrosis.

Abstract Diabetic encephalopathy (DE) is a severe complication of diabetes, but its pathogenesis remains unclear. This study aimed to investigate the roles and underlying mechanisms of high glucose (HG)- and advanced glycosylation end product (AGE)-induced oxidative stress (OS) in the cognitive decline in DE. The DE mouse model was established using a high-fat diet and streptozotocin, and its cognitive functions were evaluated using the Morris Water Maze, novel object recognition, and Y-maze test. The results revealed increased reactive oxygen species (ROS) generation, mitophagy inhibition, and decreased prohibitin 2 (PHB2) expression in the hippocampal neurons of DE mice and HG- or AGE-treated HT-22 cells. However, overexpression of PHB2 reduced ROS generation, reversed mitophagy inhibition, and improved mitochondrial function in the HG- or AGE-treated HT-22 cells and ameliorated cognitive decline, improved mitochondrial structural damage, and reversed mitophagy inhibition of hippocampal neurons in DE mice. Further analysis revealed that the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was involved in the HG- or AGE-mediated downregulation of PHB2 in HT-22 cells. These results demonstrate that HG- or AGE-induced OS inhibits the mitophagy of hippocampal neurons via the Keap1–Nrf2–PHB2 pathway, thereby contributing to the cognitive decline in DE.

Abstract Background The enhancement of nurses’ disaster literacy is crucial for effective disaster emergency management, especially for clinical nurses with no prior experience in disaster rescue. This study aims to explore the perspectives of nurses who have been involved in disaster rescue operations on strategies to advance nurses’ disaster literacy. Methods A qualitative descriptive study, which follows unified qualitative study reporting guidelines. Thirty disaster rescue nurses were recruited to participate in this study, who came from 30 third-class hospitals in China. From October to December 2021, information was acquired by conducting semi-structured telephone interviews with participants. Qualitative content analysis was used to examine the data. Results Six categories and eleven subcategories were created. Strengthening disaster education and training was the main focus, and its subcategories included continuing education, nursing curriculum development, and disaster rescue experience guide. The second focus, which included scene simulation, actual combat/military simulation, and virtual reality simulation, was strengthening disaster simulation and drill. The third focus was on providing psychosocial support, which included improving self-psychological adjustment, developing resilience, and engaging in active coping. The fourth category was to strengthen nurse/hospital managers roles and leadership, which included enhancing professional identity and policies/leadership support. The fifth category was disaster preparedness, and the sixth was enhancing knowledge transformation. Conclusions Government agencies or healthcare organizations should actively promote the formation of nurses’ disaster literacy from multiple viewpoints. Disaster education and training, simulation exercises, and psychosocial support should be prioritized.

Abstract Inflammation plays a crucial role in cancer development. The neutrophil-to-lymphocyte ratio (NLR), a measure of inflammation, is obtained from a complete blood count. However, little is known about the association between NLR and cancer in the general adult population in the United States. This study aimed to evaluate whether NLR is associated with cancer in American adults. This retrospective cross-sectional study included 28,016 adult participants from the National Health and Nutrition Examination Survey (NHANES) dataset spanning 2005 to 2018. Data on demographics (age, sex, race, marital status, Poverty-Income Ratio, education level), lifestyle factors (smoking, alcohol consumption, body mass index), medical conditions (hypertension, diabetes, cardiovascular disease), and laboratory parameters (hemoglobin, platelet count, alanine aminotransferase, creatinine, albumin, and lactate dehydrogenase), were collected. Logistic regression analysis was used to investigate the research objectives. Of the total 28,016 participants, 2639 had cancer. The mean age was 49.6 ± 17.6 years, and 50% were male. A positive association between NLR and cancer risk was observed after multivariate adjustment (OR = 1.20, 95% confidence interval (CI) = 1.05–1.36, p = 0.006). Similar patterns were observed in subgroup analyses (all p-values for interaction > 0.05). A higher NLR was directly correlated with an increased risk of developing cancer in adults.

Abstract Total Knee Arthroplasty (TKA) is a surgery that is commonly performed on older adults to improve their quality of life. However, the increasing use of knee joint prostheses has led to a rise in the incidence of Prosthetic Joint Infections (PJI) in patients after TKA. Different clinical studies have looked at the occurrence of PJI after TKA in different regions, but they have drawn varying conclusions. To better understand this topic, we conducted a meta-analysis and bibliometric study using data from multiple databases. Our research found that the estimated prevalence of PJI after TKA is approximately 1.08% across different regions, but there is still considerable variation. Additionally, our regression analysis of sub-groups shows significant differences in follow-up periods. Furthermore, our comprehensive bibliometric analysis identifies current research trends, “hotspots” related to TKA-related PJI, influential nations, organizations, and noteworthy publications. Our analysis provides valuable insights to guide future research in this area.

Abstract Many studies have focused on the effects of small molecules, such as amino acids, on metabolism under hypoxia. Recent findings have indicated that phenylalanine levels were markedly elevated in adaptation to chronic hypoxia. This raises the possibility that phenylalanine treatment could markedly improve the hypoxic endurance. However, the importance of hypoxia-regulated phenylalanine is still unclear. This study investigates the role of phenylalanine in hypoxia adaptation using a hypoxic zebrafish model and multi-omics analysis. We found that phenylalanine-related metabolic pathways are significantly up-regulated under hypoxia, contributing to enhanced hypoxic endurance. Phenylalanine treatment reduced ROS levels, improved mitochondrial oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) in hypoxic cells. Western blotting revealed increased phenylalanine uptake via L-type amino transporters (LAT1), activating the LKB1/AMPK signaling pathway. This activation up-regulated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and the Bcl-2/Bax ratio, while down-regulating uncoupling protein 2 (UCP2), thereby improving mitochondrial function under hypoxia. This is the first comprehensive multi-omics analysis to demonstrate phenylalanine’s crucial role in hypoxia adaptation, providing insights for the development of anti-hypoxic drugs. Graphical Abstract

Abstract Background Despite the explicit biomechanical advantages associated with FNS, it is currently inconclusive, based on the existing literature, whether Femoral Neck System (FNS) outperforms Cannulated cancellous screws (CSS) in all aspects. Due to variances in bone morphology and bone density between the elderly and young cohorts, additional research is warranted to ascertain whether the benefits of FNS remain applicable to elderly osteoporosis patients. This study aimed to investigate the biomechanical properties of FNS in osteoporotic femoral neck fractures and propose optimization strategies including additional anti-rotation screw. Methods The Pauwels type III femoral neck fracture models were reconstructed using finite element numerical techniques. The CSS, FNS, and modified FNS (M-FNS) models were created based on features and parameterization. The various internal fixations were individually assembled with the assigned normal and osteoporotic models. In the static analysis mode, uniform stress loads were imposed on all models. The deformation and stress variations of the femur and internal fixation models were recorded. Simultaneously, descriptions of shear stress and strain energy were also incorporated into the figures. Results Following bone mass reduction, deformations in CSS, FNS, and M-FNS increased by 47%, 52%, and 40%, respectively. The equivalent stress increments for CSS, FNS, and M-FNS were 3%, 43%, 17%, respectively. Meanwhile, variations in strain energy and shear stress were observed. The strain energy increments for CSS, FNS, and M-FNS were 4%, 76%, and 5%, respectively. The shear stress increments for CSS, FNS, and M-FNS were 4%, 65% and 44%, respectively. Within the osteoporotic model, M-FNS demonstrated the lowest total displacement, shear stress, and strain energy. Conclusion Modified FNS showed better stability in the osteoporotic model (OM). Using FNS alone may not exhibit immediate shear resistance advantages in OM. Concurrently, the addition of one anti-rotation screw can be regarded as a potential optimization choice, ensuring a harmonious alignment with the structural characteristics of FNS.

Abstract In this work, we revisit the one-loop renormalization group equations (RGEs) among non-degenerate seesaw scales, i.e., threshold effects in the canonical seesaw mechanism, which have been obtained for more than two decades. Different from the previous work only focusing on the Weinberg operator, we derive the complete one-loop RGEs of all three dimension-five operators in the Standard Model effective field theory with right-handed neutrinos (νSMEFT) and apply them to threshold effects in the canonical seesaw mechanism. We find some contributions from the Weinberg operator to its Wilson coefficient, the neutrino Yukawa coupling matrix, and the Higgs quartic coupling absent in the previous calculations. Based on the updated one-loop RGEs, we derive the RGE of the effective neutrino mass matrix’s determinant without any approximation. Then, for the first time, we provide a strict proof that the one-loop RG running effects among non-degenerate seesaw scales can not generate a non-zero mass for the initial massless neutrino in the minimal type-I seesaw mechanism or in the canonical one with a rank-degenerate neutrino Yukawa coupling matrix. One has to include two- or higher-loop corrections to achieve a non-zero mass for the massless neutrino.

Abstract Background The high prevalence of sensory impairment and functional limitations in older adults is a significant concern, yet there is limited understanding of the relationship between these two conditions. Therefore, the objective of this study was to investigate the pathways connecting sensory impairment and functional limitations by examining serial multiple mediating effects of social isolation and cognition in older adults. Methods Using the China Health and Retirement Longitudinal Study dataset, a sample of 4871 older adults was selected. The study variables included sensory impairment, functional limitations, social isolation and cognition, and other covariates. A hierarchical multiple linear regression model was used to assess the association between sensory impairment and functional limitations. Mediation analysis was conducted to explore the sequential multiple mediating effects of social isolation and cognitive function in the relationship between sensory impairment and functional limitations. Results Our findings revealed a significant and positive association between sensory impairment and functional limitations (B = 0.615, 95% CI: 0.397, 0.834). After adjusting for social isolation and cognitive function, the impact of sensory impairment on functional limitations accounted for 87.19% of the total effect. Additionally, approximately 12.81% of the significant relationship between dual sensory impairment and functional limitations was mediated by social isolation and cognitive function. A serial multiple mediating pathway (sensory impairment → social isolation → cognition → functional limitations) was identified, with a coefficient of 0.013 (95% CI: 0.006, 0.020). Conclusions Our study provides evidence for the mediating effects of social isolation and cognition in the relationship between sensory impairment and functional limitations. Given the prevalence of functional limitations among older adults with sensory impairment, it is crucial to consider social isolation and cognitive function in efforts to reduce the burden of disability care. Future validation of these findings through longitudinal studies is necessary.

In this study, we have found two new species—Stropharia subrugosoannulata and Stropharia microaeruginosa. Phylogenetic analyses, based on the internal transcribed spacer regions (ITS) and the nuclear ribosomal RNA gene (nrLSU), suggest that the two new species are distinct and monophyletic. S. subrugosoannulata is distinguished from other species of the genus Stropharia by the pileus covered with greyish-orange squamules in the centre, stipe light brown and surface covered with white triangular squamules. S. microaeruginosa differs from other species in its pileus bluish-grey when young becoming lighter towards margins, later greyish-turquoise lightens towards the edges and surface radially striate when young, lamellae adnate to subdecurrent, stipe with white squamules at the base, acanthocytes absent. The new record species from Jilin Province, Clitolyophyllum umbilicatum was also confirmed, based on morphological and molecular study. Here, we have given full descriptions of each species, colour images, illustrations and two phylogenetic trees that show the placement and relationship of the two new species and the new record are provided.

Abstract The redox state of a planetary mantle affects its thermal evolution. The redox evolution of lunar mantle, however, remains unclear due to limited oxygen fugacity (fO2) constraints from young lunar samples. Here, we report vanadium (V) oxybarometers on olivine and spinel conducted on 27 Chang’e-5 basalt fragments from 2.0 billion years ago. These fragments yield an average fO2 of ΔIW -0.84 ± 0.65 (2σ), which closely aligns with the Apollo samples from 3.6–3.0 billion years ago. This temporal uniformity indicates the lunar mantle remained reduced. This observation reveals that the processes responsible for oxidizing mantles of Earth and Mars either did not occur or had negligible oxidizing effects on the Moon. The long-term reduced mantle may lead to a distinctive volatile degassing pathway for the Moon. It could also make the lunar mantle more difficult to melt, preventing internal heat dissipation and consequently resulting in a slow cooling rate.

Abstract Background Major salivary duct carcinomas (MSDCs) often involve the regional lymph nodes (LNs). However, the clinical value of LN parameters in patients with MSDCs is unclear. We aimed to investigate the optimal cut‐off points for number of positive LNs (PLNN) and ratio of positive LNs (PLNRs) and their prognostic value in patients with MSDC. Study Design Retrospective cohort. Methods We retrospectively reviewed relevant data extracted from the Surveillance, Epidemiology, and End Results database on patients with MSDC who had undergone surgery between 2004 and 2016. The optimal PLNN and positive lymph node ratio (PLNR) cut‐off points were identified using the X‐tile program. Kaplan–Meier and Cox regression analyses were performed to determine prognostic factors. Results Overall, 290 patients were enrolled, 57.6% of whom had LN metastases. Advanced T stage in the submandibular gland and unpaired lesions were associated with LN involvement. Positive LNs, late T stage, and submandibular gland location were associated with poor overall survival (OS). The 5‐year OS rates of patients with negative and positive LNs were 74.3% and 36.5%, respectively. PLNN > 16 and PLNR > 0.48 were the best cut‐off points. The 5‐year OS of patients with PLNN ≤ 16 and PLNN > 16 was 42.8% and 15.4%, respectively. The 5‐year OS rates were 46.8% for patients with PLNR ≤ 0.48 and 26.3% for patients with PLNR > 0.48. PLNR was a strong prognostic factor for patients with MSDC with LN metastases. Conclusions PLNR reflects both the effects of LN dissection and PLNN. Furthermore, its prognostic value in patients with MSDC exceeds that of PLNN. Patients with high PLNRs should be followed closely after surgery.

Objective: To analyze the impact of global population aging on cancer epidemiology, with a focus on the incidence and mortality rates among individuals aged 60 years and above. Methods: We utilized open-source data, retrieving population age estimates from the United Nations Population Division website. The GLOBOCAN 2020 database provided estimates for cancer cases and deaths in 2020 and 2040, while the Global Burden of Disease 2019 database supplied estimates of new cancer cases worldwide from 2000 to 2019. Inclusion criteria considered individuals aged 60 years and over, focusing on the top five deadliest cancers. The cohort-component method was employed for population prediction, with age-specific incidence and mortality rates estimated for 2020 used to forecast the cancer burden. Results: In 2021, the global population aged over 60 years accounted for 13.7%, with Europe/North America and Australia/New Zealand having the highest proportions. The older population is predicted to reach 19.2% by 2040. In 2020, of the 19.3 million new cancer cases worldwide, 64% occurred in individuals aged 60 and above, contributing to 71.3% of cancer-related deaths. The five most common cancer sites were the lung, colorectum, prostate, breast, and stomach. Cancer incidence and deaths are projected to rise significantly among older individuals, reaching 20.7 million new cases and 12.7 million deaths by 2040. Older age, tobacco use, dietary factors, alcohol consumption, and high body mass index (BMI) were identified as major risk factors for various cancers in this demographic. Conclusions: This study reveals a significant rise in cancer incidence and mortality among the elderly due to global population aging. The urgency for targeted interventions in cancer prevention, screening, and treatment for older individuals is emphasized. Despite acknowledged limitations, these findings contribute valuable insights to inform strategies for managing cancer in the elderly amidst evolving demographic trends.

ABSTRACT: Lactococcus lactis, widely used in the manufacture of dairy products, encounters various environmental stresses both in natural habitats and during industrial processes. It has evolved intricate machinery of stress sensing and defense to survive harsh stress conditions. Here, we identified a novel TetR/AcrR family transcription regulator, designated AcrR1, to be a repressor for acid and antibiotic tolerance that was derepressed in the presence of vancomycin or under acid stress. The survival rates of acrR1 deletion strain ΔAcrR1 under acid and vancomycin stresses were about 28.7-fold (pH 3.0, HCl), 8.57-fold (pH 4.0, lactic acid) and 2.73-fold (300 ng/mL vancomycin) greater than that of original strain F44. We also demonstrated that ΔAcrR1 was better able to maintain intracellular pH homeostasis and had a lower affinity to vancomycin. No evident effects of AcrR1 deletion on the growth and morphology of strain F44 were observed. Subsequently, we characterized that the transcription level of genes associated with amino acids biosynthesis, carbohydrate transport and metabolism, multidrug resistance, and DNA repair proteins significantly upregulated in ΔAcrR1 using transcriptome analysis and quantitative reverse transcription-PCR assays. Additionally, AcrR1 could repress the transcription of the nisin post-translational modification gene, nisC, leading to a 16.3% increase in nisin yield after AcrR1 deletion. Our results not only refined the knowledge of the regulatory mechanism of TetR/AcrR family regulator in L. lactis, but presented a potential strategy to enhance industrial production of nisin.

The high temperature oxidation behavior of Fe–36Ni Invar alloy in the forged billet stage and hot rolled rod stage in the compressed air atmosphere has been systematically studied. The results show that the oxide layer can be divided into the external oxide layer composed of Fe2O3, Fe3O4 and NiO, and the inner transition oxide layer composed of FeO, Fe2O3, Fe3O4 and NiO. In addition, hot rolled rod samples treated by solution and rolling have higher oxidation resistance. The mechanism of O diffusion during oxidation is analyzed, and it is found that the O atom adsorbed on the surface of the substrate diffuses into the grain along the grain boundary. The grain boundary is the optimal path for O diffusion to the interior of the material, which results in the degree of intergranular oxidation of the alloy being greater than the degree of intragranular oxidation. In summary, the oxidation resistance of Invar alloy can be improved by proper solution treatment and avoiding the formation of grain boundary cracks during production.

AbstractContext Chinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain.Objective To assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP).Materials and methods Randomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR).Results Forty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively.Conclusions The optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

Abstract Background Casein kinase 1α (CK1α), expressed in both ovarian germ and somatic cells, is involved in the initial meiosis and primordial follicle formation of mouse oocytes. Using in vitro and in vivo experiments in this study, we explored the function and mechanism of CK1α in estrogen synthesis in mice ovarian granulosa cells. Methods A CK1α knockout (cKO) mouse model, targeted specifically to ovarian granulosa cells (GCs), was employed to establish the influence of CK1α on in vivo estrogen synthesis. The influence of CK1α deficiency on GCs was determined in vivo and in vitro by immunofluorescence analysis and Western blot assay. Transcriptome profiling, differentially expressed genes and gene functional enrichment analyses, and computation protein–protein docking, were further employed to assess the CK1α pathway. Furthermore, wild-type female mice were treated with the CK1α antagonist D4476 to elucidate the CK1α's role in estrogen regulation. Results Ovarian GCs CK1α deficiency impaired fertility and superovulation of female mice; also, the average litter size and the estradiol (E2) level in the serum of cKO female mice were decreased by 57.3% and 87.4% vs. control mice, respectively. This deficiency disrupted the estrous cycle and enhanced the apoptosis in the GCs. We observed that CK1α mediated the secretion of estradiol in mouse ovarian GCs via the cytochrome P450 subfamily 19 member 1 (CYP19A1). Conclusions These findings improve the existing understanding of the regulation mechanism of female reproduction and estrogen synthesis. Trial registration Not applicable.

Abstract Background Offspring consistently exhibit similar imaging features as their parents in cases of degenerative lumbar scoliosis (DLS). Nevertheless, the role of genetic factors in the pathogenesis of DLS remains uncertain. Methods A prospective analysis was conducted on 35 patients with DLS and their 36 offspring. Genomic DNA was extracted from 71 blood samples for gene mutation analysis using whole exome sequencin. Various demographic and imaging parameters were compared. Results In 11 pedigrees of the 35 family members with DLS, 13 suspected pathogenic genes were identified. Among the 35 DLS patients, 11/35(31.5%) exhibited susceptibility gene mutations (mutant group), while 24/35(68.5%) had no pathogenic gene mutations (non-mutant group). AVR was more severe in mutant group than that in no-mutant group (p

Abstract Background Chronic cough in children is closely related to gastroesophageal reflux (GER). However, this association has not been adequately studied due to a lack of diagnostic tools. Combined esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring is considered the most accurate method for evaluating the association between symptoms and reflux, but data on its use in children with chronic cough are still lacking. We aimed to assess the association between chronic cough and GER in children through MII-pH monitoring. Methods Children with chronic cough (> 4 weeks) who were suspected gastroesophageal reflux disease(GERD) were selected to undergo 24 h MII-pH monitoring at our hospital. Patients were divided into groups according to their age, body position, reflux index (RI) or total reflux events, and the differences between the groups were analyzed. Then the significance and value of 24 h pH and impedance monitoring in chronic cough and the relationship between chronic cough and reflux were discussed. Results Overall, 426 patients were included. The median age was 12 months (interquartile range: 6–39.5 months), 129 (30.3%) patients had RI > 7% detected by pH-metry, and 290 (68.1%) patients had positive diagnosis based on the impedance data. GER predominantly occurred in the upright position and mostly involved weakly acidic reflux and mixed gas–liquid reflux. There were 14.1% of children in non-acid GER group were SAP positive showing no difference in acid GER group 13.2% (P = 0.88), whereas patients with SAP > 95% in MII positive group (47[16.2%]) is higher than in MII negative group (P

In the process of CO2-enhanced coalbed methane recovery, the behaviours of coal seam fractures significantly affect sequestration and extraction. To address the unclear impact of fracture roughness evolution on engineering efficiency under multi-physical field coupling effects, we developed an innovative interdisciplinary mathematical model. This model introduces a parameter to quantitatively describe coal seam fracture roughness and couples it with the gas flow control equations under multi-field effects in the coal seam. We investigated the thermo-hydro-mechanical (THM) coupling effects and fracture network characteristics in the coal seam gas extraction process. Results show that the mathematical model aligns well with field data and effectively characterizes coal seam fracture roughness. Fracture roughness significantly influences the residual gas pressure in the coal seam and the injection pressure of CO2. When the roughness parameter decreases from 0.24 to 0.18, the maximum methane content decreases by 32.5% and the maximum CO2 pressure increases by 26.7%, the maximum gas adsorption capacity of coal seam decreased by 31.7%, and the maximum CO2 adsorption capacity increased by 12.1%.

ObjectiveTo investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α (RORA) in the proliferation and progression of colorectal cancer (CRC) cells. MethodsThe expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR, FISH, and IHC. Cell proliferation capability was detected through EdU and CFSE assay, cell apoptosis by flow cytometry assay, and cell migration and invasion abilities by cell scratch and Transwell invasion assays, respectively. The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay, cell function rescue test, RT-PCR, and Western blot assay. Finally, bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation, invasion, and progression of CRC via regulating RORA. ResultsmiR-18a-5p exhibited a high expression in CRC tissues and cells (P

Abstract Salmonella, the prevailing zoonotic pathogen within the Enterobacteriaceae family, holds the foremost position in global bacterial poisoning incidents, thereby signifying its paramount importance in public health. Consequently, the imperative for expeditious and uncomplicated detection techniques for Salmonella in food is underscored. After more than two decades of development, loop-mediated isothermal amplification (LAMP) has emerged as a potent adjunct to the polymerase chain reaction, demonstrating significant advantages in the realm of isothermal amplification. Its growing prominence is evident in the increasing number of reports on its application in the rapid detection of Salmonella. This paper provides a systematic exposition of the technical principles and characteristics of LAMP, along with an overview of the research progress made in the rapid detection of Salmonella using LAMP and its derivatives. Additionally, the target genes reported in various levels, including Salmonella genus, species, serogroup, and serotype, are summarized, aiming to offer a valuable reference for the advancement of LAMP application in Salmonella detection. Finally, we look forward to the development direction of LAMP and expect more competitive methods to provide strong support for food safety applications.

Abstract Cisplatin is a widely used chemotherapeutic drug that can induce ovarian damage. Icariin (ICA), a natural antioxidant derived from Epimedium brevicornum Maxim., has been found to protect against organ injury. The aim of the present study was to investigate whether ICA can exert an ovarian-protective effect on cisplatin induced premature ovarian failure (POF) and the underlying mechanism involved. The preventive effect of ICA was evaluated using body weight, the oestrous cycle, ovarian histological analysis, and follicle counting. ICA treatment increased body weight, ovarian weight, and the number of follicles and improved the oestrous cycle in POF mice. ICA reduced cisplatin-induced oxidative damage and upregulated the protein expression levels of Nrf2, GPX4 and HO-1. Moreover, ICA reduced the expression levels of Bax and γH2AX and inhibited ovarian apoptosis. In addition, ICA activated the Nrf2 pathway in vitro and reversed changes in the viability of cisplatin-induced KGN cells, reactive oxygen species (ROS) levels, lipid peroxidation, and apoptosis, and these effects were abrogated when Nrf2 was knocked down or inhibited. Molecular docking confirmed that ICA promotes the release of Nrf2 by competing with Nrf2 for binding to Keap1. The inhibitory effects of ICA on cisplatin-induced oxidative stress, ferroptosis, and apoptosis may be mediated by its modulatory effects on the Nrf2 pathway, providing a novel perspective on the potential mechanisms by which ICA prevents POF.

Abstract C–H bond activation enables the facile synthesis of new chemicals. While C–H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C–H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C–C coupling mediated by 2D TMDCs to promote C–H activation and carbon dots synthesis. Our results shed light on 2D materials for C–H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.

Low temperature heating process of the slab has become the mainstream process for producing high quality oriented silicon steel due to its environmental protection, low cost, and high yield. For this process, the number of inhibitors is less and the size is large, resulting in insufficient inhibition, coarsen grains during primary recrystallization, and insufficient driving force for secondary recrystallization, which reduces the magnetic properties of the product. These shortcomings can be improved by optimizing the inhibitors and normalizing processes. The effects of normalizing processes on the microstructure, texture, and precipitations of low-temperature oriented silicon steel containing Sn were studied by OM, SEM, TEM, and EBSD with Fe–3%Si hot-rolled plate as initial material. The experimental results show that the sample has the best performance in terms of microstructure, texture, and precipitations with the two-stage boiling water cooling normalizing process that the heating temperature is 1150 °C, and the normalizing intermediate temperature is 850 °C. With the above parameters, the microstructure is inhomogeneous along thickness. There are more {111} textures, which are favorable to the growth of Goss texture. The proportion of high energy grain boundary reached 54.2%. The precipitates are significantly refined, which enhances the ability to inhibit primary recrystallization. The sub-surface thickness of the hot rolled plate increases from 40.6% to 62.1% with increasing Sn content from 0.01% to 0.11%. The degree of tin segregation at grain boundary increases with the increase of normalizing temperature and the decrease of medium soaking temperature.

Abstract Background Caryodaphnopsis, a group of tropical trees (ca. 20 spp.) in the family Lauraceae, has an amphi-Pacific disjunct distribution: ten species are distributed in Southeast Asia, while eight species are restricted to tropical rainforests in South America. Previously, phylogenetic analyses using two nuclear markers resolved the relationships among the five species from Latin America. However, the phylogenetic relationships between the species in Asia remain poorly known. Results Here, we first determined the complete mitochondrial genome (mitogenome), plastome, and the nuclear ribosomal cistron (nrDNA) sequences of C. henryi with lengths of 1,168,029 bp, 154,938 bp, and 6495 bp, respectively. We found 2233 repeats and 368 potential SSRs in the mitogenome of C. henryi and 50 homologous DNA fragments between its mitogenome and plastome. Gene synteny analysis revealed a mass of rearrangements in the mitogenomes of Magnolia biondii, Hernandia nymphaeifolia, and C. henryi and only six conserved clustered genes among them. In order to reconstruct relationships for the ten Caryodaphnopsis species in Asia, we created three datasets: one for the mitogenome (coding genes and ten intergenic regions), another for the plastome (whole genome), and the other for the nuclear ribosomal cistron. All of the 22 Caryodaphnopsis individuals were divided into four, five, and six different clades in the phylogenies based on mitogenome, plastome, and nrDNA datasets, respectively. Conclusions The study showed phylogenetic conflicts within and between nuclear and organellar genome data of Caryodaphnopsis species. The sympatric Caryodaphnopsis species in Hekou and Malipo SW China may be related to the incomplete lineage sorting, chloroplast capture, and/or hybridization, which mixed the species as a complex in their evolutionary history.

Abstract Objective The insula is an important part of the posttraumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) neuropathological activity pattern. It is composed of functionally different subdivisions and each of which plays different role in PTH neuropathology. Methods Ninety-four mTBI patients were included in this study. Based on perfusion imaging data obtained from arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI), this study evaluated the insular subregion perfusion-based functional connectivity (FC) and its correlation with clinical characteristic parameters in patients with PTH after mTBI and non-headache mTBI patients. Results The insular subregions of mTBI + PTH (mTBI patients with PTH) and mTBI-PTH (mTBI patients without PTH) group had positive perfusion-based functional connections with other insular nuclei and adjacent discrete cortical regions. Compared with mTBI-PTH group, significantly increased resting-state perfusion-based FC between the anterior insula (AI) and middle cingulate cortex (MCC)/Rolandic operculum (ROL), between posterior insula (PI) and supplementary motor area (SMA), and decreased perfusion-based FC between PI and thalamus were found in mTBI + PTH group. Changes in the perfusion-based FC of the left posterior insula/dorsal anterior insula with the thalamus/MCC were significant correlated with headache characteristics. Conclusions Our findings provide new ASL-based evidence for changes in the perfusion-based FC of the insular subregion in PTH patients attributed to mTBI and the association with headache features, revealing the possibility of potential neuroplasticity after PTH. These findings may contribute to early diagnosis of the disease and follow-up of disease progression.

Abstract The challenge of spatial resource allocation is pervasive across various domains such as transportation, industry, and daily life. As the scale of real-world issues continues to expand and demands for real-time solutions increase, traditional algorithms face significant computational pressures, struggling to achieve optimal efficiency and real-time capabilities. In recent years, with the escalating computational power of computers, the remarkable achievements of reinforcement learning in domains like Go and robotics have demonstrated its robust learning and sequential decision-making capabilities. Given these advancements, there has been a surge in novel methods employing reinforcement learning to tackle spatial resource allocation problems. These methods exhibit advantages such as rapid solution convergence and strong model generalization abilities, offering a new perspective on resolving spatial resource allocation problems. Despite the progress, reinforcement learning still faces hurdles when it comes to spatial resource allocation. There remains a gap in its ability to fully grasp the diversity and intricacy of real-world resources. The environmental models used in reinforcement learning may not always capture the spatial dynamics accurately. Moreover, in situations laden with strict and numerous constraints, reinforcement learning can sometimes fall short in offering feasible strategies. Consequently, this paper is dedicated to summarizing and reviewing current theoretical approaches and practical research that utilize reinforcement learning to address issues pertaining to spatial resource allocation. In addition, the paper accentuates several unresolved challenges that urgently necessitate future focus and exploration within this realm and proposes viable approaches for these challenges. This research furnishes valuable insights that may assist scholars in gaining a more nuanced understanding of the problems, opportunities, and potential directions concerning the application of reinforcement learning in spatial resource allocation.

Abstract Atomic clocks with higher frequency stability and accuracy than traditional space-borne atomic clocks are the cornerstone of long-term autonomous operation of space-time-frequency systems. We proposed a space cold atoms clock based on an intracavity cooling scheme, which captures cold atoms at the center of a microwave cavity and then executes in situ interactions between the cold atoms and microwaves. As a result of the microgravity environment in space, the cold atoms can interact with the microwaves for a longer time, which aids in realizing a high-precision atomic clock in space. This paper presents the overall design, operational characteristics, and reliability test results of the space atomic clock based on the intracavity cooling scheme designed for the operation onboard the China space station. In addition, the engineering prototype performance of the space cold atoms microwave clock is also presented. The ground test results for the clock show a fractional frequency stability of 1.1 × 10−12 τ−1/2 reaching 2.5 × 10−15 at 200,000 s, providing solid technical and data support for its future operation in orbit.

Abstract N 6-methyladenosine (m6A) plays critical roles in regulating mRNA metabolism. However, comprehensive m6A methylomes in different plant tissues with single-base precision have yet to be reported. Here, we present transcriptome-wide m6A maps at single-base resolution in different tissues of rice and Arabidopsis using m6A-SAC-seq. Our analysis uncovers a total of 205,691 m6A sites distributed across 22,574 genes in rice, and 188,282 m6A sites across 19,984 genes in Arabidopsis. The evolutionarily conserved m6A sites in rice and Arabidopsis ortholog gene pairs are involved in controlling tissue development, photosynthesis and stress response. We observe an overall mRNA stabilization effect by 3’ UTR m6A sites in certain plant tissues. Like in mammals, a positive correlation between the m6A level and the length of internal exons is also observed in plant mRNA, except for the last exon. Our data suggest an active m6A deposition process occurring near the stop codon in plant mRNA. In addition, the MTA-installed plant mRNA m6A sites correlate with both translation promotion and translation suppression, depicting a more complicated regulatory picture. Our results therefore provide in-depth resources for relating single-base resolution m6A sites with functions in plants and uncover a suppression-activation model controlling m6A biogenesis across species.

Drug resistance poses a significant challenge in the treatment of breast cancer. In recent years, a variety of nanomaterials have been discovered and synthesized that can selectively target tumor cells and play a crucial role in the advancement of breast cancer therapies. As our understanding of tumor heterogeneity deepens, the emerging potential of nanomaterials in addressing drug resistance has garnered considerable attention. These materials not only selectively target tumor cells but also possess unique properties that make them promising options for cancer treatment, including low toxicity, excellent biocompatibility, ease of preparation, the ability to carry antitumor drugs, and customizable surface functions. In this review, we will comprehensively summarize two key developments in breast cancer treatment: the application of antitumor drugs and nanomaterials. We will explore the mechanisms by which nanomaterials improve drug resistance in breast cancer, targeted nanotherapy strategies to mitigate this resistance, and recent research advancements in anticancer nanomaterials. This overview aims to highlight the significant role of nanomaterials in breast cancer treatment and provide a theoretical framework for identifying optimal treatment strategies in the future.

Endometrial cancer is a common tumor of the female reproductive system. In recent years, as the age of onset of the disease has gradually become younger, this has caused distress to some young patients with reproductive needs, and the active search for methods of preserving reproductive function has gradually attracted attention. In this paper, we will systematize the current status of progestin-based pharmacotherapy in combination with other drug therapies in the conservative management of early-stage endometrial cancer. With the expectation of providing a reference for the treatment of early stage endometrial cancer patients in China and for the in-depth development of related research in this field.

Background: Membranous nephropathy (MN) is characterized by immune complex deposition in the glomerular basement membrane, leading to proteinuria and potentially progressive renal dysfunction. Fibroblasts have been implicated in the pathogenesis of MN through their involvement in tissue remodeling and immune modulation. Methods: We employed integrated bioinformatics analyses to identify fibroblast-associated biomarkers and molecular subtypes in MN. The xCell algorithm was used to assess fibroblast infiltration, and weighted gene co-expression network analysis (WGCNA) identified fibroblast-related gene modules. Differentially expressed fibroblast-associated genes (DEFAGs) were screened between MN and healthy controls (HC) using differential expression analysis and protein-protein interaction (PPI) network construction. Consensus clustering categorized MN patients into distinct subtypes based on DEFAG expression profiles. Results: Fibroblast scores were a significant elevation in MN compared to HC, indicating increased fibroblast involvement in MN pathogenesis. WGCNA identified 13 fibroblast-related gene modules, with the brown and turquoise modules showing strong correlation with fibroblast scores (correlation coefficient = 0.79 and 0.75, respectively, p

Mechanical metamaterials signify a groundbreaking leap in material science and engineering. The intricate and experience-dependent design process poses a challenge in uncovering architectural material sequences with exceptional mechanical properties. This study introduces inverse-designed 3D sequential metamaterials with outstanding mechanical attributes, achieved through a novel computational framework. The explored sequences based on Schoen's I-graph–wrapped package (IWP) and Schwarz Primitive (Schwarz P) surpass the Hashin-Shtrikman upper bound of Young's modulus at relative densities of 0.24 and 0.43, outperforming previous records. Optimized Body-Centered-Cubic (BCC) truss-based sets outperform traditional ones by 72.7%. This innovative approach can be extended for metamaterial customization, involving the optimization of multi-directional Young's modulus, total stiffness, and the addition of isotropy constraints. The paper explores the characteristics and implications of this innovation, emphasizing the impact of geometric and topological variations on mechanical performance. These metamaterial sequences offer unparalleled adaptability, and hold significant potential in structural engineering and adaptive mechanical systems, opening avenues for technological advancements.

In this study, glutathione (GSH)-responsive magnetic mesoporous silica nanoparticles grafted by disulfide organosilicon (SMNPs) were synthesized, characterized, and evaluated as controlled drug carriers. The nanoparticles exhibited consistent dispersion, considerable drug-loading capacity, and high saturation magnetization. Importantly, they demonstrated the ability to release doxorubicin (DOX) by up to 43% in a reducing tumor microenvironment, highlighting their potential for targeted therapy. In addition, the SMNPs displayed favorable biocompatibility, making them suitable for biomedical applications. Most notably, the SMNPs loaded with DOX effectively killed both HepG2 and HeLa cancer cells, while also showing efficient cellular uptake in HeLa cells. These findings suggest that SMNPs are a promising platform for magnetic-targeted and GSH-responsive delivery of therapeutic agents.

Abstract Immunotherapy shows great promise for treating advanced cancers, but its effectiveness varies widely among different patients and cancer types. Identifying biomarkers and developing robust predictive models to discern which patients are most likely to benefit from immunotherapy is of great importance. In this context, we have developed the tumor immunotherapy gene expression R package (tigeR 1.0) to address the increasing need for effective tools to explore biomarkers and construct predictive models. tigeR encompasses four distinct yet closely interconnected modules. The Biomarker Evaluation module enables researchers to evaluate whether the biomarkers of interest are associated with immunotherapy response via built‐in or custom immunotherapy gene expression data. The Tumor Microenvironment Deconvolution module integrates 10 open‐source algorithms to obtain the proportions of different cell types within the tumor microenvironment, facilitating the investigation of the association between immune cell populations and immunotherapy response. The Prediction Model Construction module equips users with the ability to construct sophisticated prediction models using a range of built‐in machine‐learning algorithms. The Response Prediction module predicts the immunotherapy response for the patients from gene expression data using our pretrained machine learning models or public gene expression signatures. By providing these diverse functionalities, tigeR aims to simplify the process of analyzing immunotherapy gene expression data, thus making it accessible to researchers without advanced programming skills. The source code and example for the tigeR project can be accessed at http://github.com/YuLab-SMU/tigeR.

Dysregulation of cholesterol metabolism is an important feature of cancer development. There are limited reports on the involvement of lncRNAs in hepatocellular carcinoma (HCC) progression via the cholesterol metabolism pathway. The present study explored the effect of LINC00618 on HCC growth and metastasis, and elucidated the underlying mechanisms involved in cholesterol metabolism. Here, we found that LINC00618 expression was upregulated in cancerous tissues from 30 patients with HCC compared to that in adjacent normal tissues. High expression of LINC00618 was detected in metastatic HCC tissues. LINC00618 is predominantly localized in the nucleus and overexpression of LINC00618 facilitated HCC cell proliferation, migration and EMT progression by promoting cholesterol biosynthesis. Mechanistically, the 1–101nt region of LINC00618 bound to NSUN2. LINC00618 inhibited ubiquitin-proteasome pathway-induced NSUN2 degradation. NSUN2 stabilized by LINC00618 increased m5C modification of SREBP2 and promoted SREBP2 mRNA stability in a YBX1-dependent manner, thereby promoting cholesterol biosynthesis in HCC cells. Moreover, mouse HCC xenograft and lung metastasis models were established by subcutaneous and tail vein injections of MHCC97 cells transfected with or without sh-LINC00618. Silencing LINC00618 impeded HCC growth and metastasis. In conclusion, LINC00618 promoted HCC growth and metastasis by elevating cholesterol synthesis by stabilizing NSUN2 to enhance SREBP2 mRNA stability in an m5C-dependent manner.

Summary: Pain has become a major symptom of long COVID-19 without effective therapy. Apart from viral infection pathological process, SARS-CoV-2 membranal proteins (envelope [S2E], spike [S2S] and membrane [S2M]) also present pro-inflammatory feature independently. Here, we aim to uncover the neuroinflammatory mechanism of COVID-pain induced by SARS-CoV-2 membranal proteins. We detected the three proteins in both peripheral sensory ganglions and spinal dorsal horn of COVID-19 donors. After intradermal and intrathecal injection, only S2E triggered pain behaviors, accompanied with upregulated-phosphorylation nuclear factor kappa B (NF-κB), which was significantly attenuated by minocycline in mice. We further identified Toll-like receptor 2 (TLR2) among TLRs as the target of S2E to evoke inflammatory responses leading to COVID-pain. This study identified the nociceptive effect of S2E through directly interacting with macrophage/microglia TLR2 and inducing the following NF-κB inflammatory storm. Clearing away S2E and inhibiting macrophage/microglia TLR2 served as perspective therapeutic strategies for COVID-19 pain.

Fetomaternal hemorrhage (FMH) is a perplexing obstetric condition that predominantly occurs during the third trimester or at the time of delivery. Its insidious and non-specific onset often leads to diagnostic challenges. The underlying pathophysiology of FMH remains incompletely understood, though it is primarily attributed to compromise of the placental barrier. The severity of the condition is intrinsically associated with the volumn of blood loss, the hemorrhage rate, and the presence of alloimmunity. Upon the occurrence of severe FMH, it can rapidly lead to intrauterine distress, fetal anemia, and the possibility of fetal demise, presenting a considerable threat to both maternal and neonatal well-being. In this article, I present a substantial case of FMH and conduct a systematic review of the current scientific literature regarding the etiology, clinical manifestations, diagnostic approaches, treatment highlights, and prognosis of this condition. The objective of this work is to improve clinicians’ comprehension and diagnostic proficiency concerning FMH.

ABSTRACT Salmonella enterica serovar Typhimurium (ST) is a predominant serovar causing foodborne illnesses worldwide. Traditional detection methods often face challenges, including the need for specialized equipment, skilled operators, and lengthy procedures. To address these limitations, we developed a rapid, sensitive, and specific ST detection method by integrating loop-mediated isothermal amplification (LAMP) with the clustered regularly interspaced short palindromic repeats and associated protein 12b (CRISPR/Cas12b) system, all within a single tube. Our results indicate that the LAMP–CRISPR/Cas12b reaction can be completed isothermally in under 1 h without requiring specialized instruments. The platform’s limit of detection (LoD) is 12.5 copies per reaction. Additionally, the system demonstrated 100% inclusivity and exclusivity when tested against 30 reference strains, highlighting its specificity. In practical applications, the LoDs for ST in pure nucleic acid and contaminated fecal samples were 2.32 and 23.2 CFU/mL, respectively, with higher sensitivity observed in pure nucleic acid samples. Overall, our findings underscore the potential of the one-tube LAMP–CRISPR/Cas12b platform as a rapid, sensitive, and specific tool for ST detection, particularly in resource-limited settings.IMPORTANCEHere, we have provided a novel one-step method for Salmonella Typhimurium detection in one pot by integrating the LAMP assay with the CRISPR/Cas12b system, offering significant advantages in terms of simplicity, speed, and accuracy.

Objectives: Few studies illustrate the mechanism between air temperature and blood pressure (BP) in childhood. This study aims to investigate the associations between air temperature, humidity exposure, and BP trajectories in children and adolescents, and explore the potential mediating roles of lipid profiles in these relationships. Methods: This prospective cohort study included 5,971 children with 10,800 person-times measurements at baseline from the Chongqing Health Cohort, with evaluations conducted in 2014–2015 (baseline) and follow-ups in 2016 (urban areas) and 2019 (urban and rural areas). Multilevel mixed-effects models were used to analyse the impacts of air temperature and humidity on BP levels and the incidence of elevated BP, while accounting for potential confounders. Mediation analyses were performed to evaluate the mediating effects of lipid profiles, including low-density lipoprotein (LDL), total cholesterol (TC), and specific lipid species. Results: After adjusting for covariates, higher air temperature quartiles were associated with both decreased BP levels and elevated BP risk (RR: 0.83; 95 % CIs: 0.78, 0.89; P = 0.028). Conversely, higher humidity quartiles exhibited a U-shaped relationship with BP levels. Greater variability in air temperature was linked to increase BP levels. The cumulative effects of air temperature exposure on BP were significant from pregnancy to age 10, with females exhibiting larger effects (β:-3.291, 95 % CIs: −4.242,-2.340, P

Microbial secondary metabolites are a rich source for pharmaceutical discoveries and play crucial ecological functions. While tools exist to identify secondary metabolite clusters in genomes, precise sequence-to-function mapping remains challenging because neither function nor substrate specificity of biosynthesis enzymes can accurately be predicted. Here, we developed a knowledge-guided bioinformatic pipeline to solve these issues. We analyzed 1928 genomes of Pseudomonas bacteria and focused on iron-scavenging pyoverdines as model metabolites. Our pipeline predicted 188 chemically different pyoverdines with nearly 100% structural accuracy and the presence of 94 distinct receptor groups required for the uptake of iron-loaded pyoverdines. Our pipeline unveils an enormous yet overlooked diversity of siderophores (151 new structures) and receptors (91 new groups). Our approach, combining feature sequence with phylogenetic approaches, is extendable to other metabolites and microbial genera, and thus emerges as powerful tool to reconstruct bacterial secondary metabolism pathways based on sequence data.