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The current study analyzed the chromosomal karyotype of Quasipaa spinosa David, 1875 from Hunan Province, China. The karyotype, C-banding, BrdU-banding pattern were characterized using direct preparation of bone-marrow cells and hemocyte cultures. The findings indicated that Q. spinosa was a diploid species (2n = 26) that lacked heteromorphic chromosomes and secondary constrictions. C-banding analysis revealed an abundance of positive signals in the centromere regions, while the BrdU-banding pattern showed three phases in both male and female, occurring consistently and in chronological sequence during S-phase. Notably, there was no asynchronous replication in the late phase. This study enhanced our understanding of the karyotypic structure of Q. spinosa by conventional cytogenetic techniques, thus providing essential scientific insights into the cytogenetics of Q. spinosa.

Abstract Background Patients receiving PD-(L)1 inhibitors frequently encounter unusual side effects known as immune-related adverse events (irAEs). However, the correlation of irAEs development with clinical response in small cell lung cancer (SCLC) is unknown. Method This retrospective study enrolled 244 stage IV SCLC patients who receiving PD-(L)1 inhibitors from 3 cancer centers. The correlation of irAEs with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results 140 in 244 (57%) patients experienced irAEs, with 122 (87.1%) experiencing one and 18 (12.9%) experiencing two or more. Compared to patient without irAEs, those developing irAEs had higher ORR (73.6% vs. 52.9%, P

Abstract As urban areas expand globally, human activities are leading to a sustained increase in non-methane volatile organic compound (NMVOC) emissions, escalating both environmental and health-related concerns. Given their diverse origins, estimating anthropogenic NMVOC emissions levels from global urban areas remains challenging. Here, we integrate TROPOspheric Monitoring Instrument (TROPOMI) formaldehyde (HCHO) column data, Visible Infrared Imaging Radiometer Suite (VIIRS) nighttime light (NTL) radiance data, and the Emission Database for Global Atmospheric Research (EDGAR) to develop a method for estimating global anthropogenic NMVOC emissions. Furthermore, we construct a linear model to analyze the relationship between urbanization and anthropogenic NMVOC emissions. Our research reveals that meticulously filtered TROPOMI HCHO columns have a high Pearson correlation coefficient (r = 0.91) with anthropogenic NMVOC emissions, indicating its reliability as an indicator reflecting the levels of anthropogenic NMVOC emissions. We establish linear models at various scales, including global, continental, and national, linking HCHO columns (as indicators of anthropogenic NMVOC emissions) and NTL radiance (as an indicator of urbanization). The global-scale linear model exhibits an r of 0.81, with a slope of 0.42 × 1015 molec. cm−2 nanoWatts−1 cm2 sr and an intercept of 9.26 × 1015 molec. cm−2. This linear model reflects a positive correlation between urbanization and anthropogenic NMVOC emissions, also serving as a tool for estimating the levels of anthropogenic NMVOC emissions in urban areas. This study offers valuable insights for real-time monitoring of extensive anthropogenic NMVOC emissions.

Abstract Background Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils. Methods Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. MPN parameters as blood counts, splenomegaly and bone marrow histology were compared to wild-type mice. Megakaryocyte differentiation was investigated using lineage-negative bone marrow cells upon in vitro incubation with TPO/IL-1β. Cytokine concentrations in serum of mice were determined by Mouse Cytokine Array. IL-1α expression in various hematopoietic cell populations was determined by intracellular FACS analysis. RNA-seq to analyse gene expression of inflammatory cytokines was performed in isolated neutrophils from JAK2-V617F and CALR-mutated mice and patients. Bioenergetics of neutrophils were recorded on a Seahorse extracellular flux analyzer. Cell motility of neutrophils was monitored in vitro (time lapse microscopy), and in vivo (two-photon microscopy) upon creating an inflammatory environment. Cell adhesion to integrins, E-selectin and P-selection was investigated in-vitro. Statistical analysis was carried out using GraphPad Prism. Data are shown as mean ± SEM. Unpaired, two-tailed t-tests were applied. Results Strikingly, neutrophil-specific expression of JAK2-V617F, but not CALRdel, was sufficient to induce pro-inflammatory cytokines including IL-1 in serum of mice. RNA-seq analysis in neutrophils from JAK2-V617F mice and patients revealed a distinct inflammatory chemokine signature which was not expressed in CALR-mutant neutrophils. In addition, IL-1 response genes were significantly enriched in neutrophils of JAK2-V617F patients as compared to CALR-mutant patients. Thus, JAK2-V617F positive neutrophils, but not CALR-mutant neutrophils, are pathogenic drivers of inflammation in MPN. In line with this, expression of JAK2-V617F or CALRdel elicited a significant difference in the metabolic phenotype of neutrophils, suggesting a stronger inflammatory activity of JAK2-V617F cells. Furthermore, JAK2-V617F, but not CALRdel, induced a VLA4 integrin-mediated adhesive phenotype in neutrophils. This resulted in reduced neutrophil migration in vitro and in an inflamed vessel. This mechanism may contribute to the increased thrombotic risk of JAK2-V617F patients compared to CALR-mutant individuals. Conclusions Taken together, our findings highlight genotype-specific differences in MPN-neutrophils that have implications for the differential pathophysiology of JAK2-V617F versus CALR-mutant disease.

As an important component of sea cucumber viscera, sea cucumber ovum contains polypeptides, polysaccharides, saponins, and so on, which has biological activities such as enhancing immunity, antioxidant, antitumor, and improving reproductive function, and has high protein, polysaccharide and phospholipid contents. Although rich in nutrition, sea cucumber ovum is discarded as a byproduct of sea cucumber processing. In this article, the nutritional components, the composition, extraction and purification of bioactive substances in sea cucumber ovum are summarized. The biological activities and the current status of the development and utilization of sea cucumber ovum are reviewed, which will provide a scientific basis for the comprehensive utilization of sea cucumber ovum.

Abstract Background The contact plate method is widely accepted and used in various fields where hygiene and contamination levels are crucial. Evidence regarding the applicability of the contact plate method for sampling fabric microbial contamination levels in real medical environments was limited. This study aimed to assess the applicability of the contact plate method for detecting microbial contamination on medical fabrics in a real healthcare environment, thereby providing a benchmark for fabric microbial sampling methods. Methods In a level three obstetrics ward of a hospital, twenty-four privacy curtains adjacent to patient beds were selected for this study. The contact plate and swab method were used to collect microbial samples from the privacy curtains on the 1st, 7th, 14th, and 28th days after they were hung. The total colony count on each privacy curtain surface was calculated, and microbial identification was performed. Results After excluding the effects of time, room type, and curtain location on the detected microbial load, the linear mixed-effects model analysis showed that contact plate method yielded lower colony counts compared to swab method (P

Abstract Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.

Abstract The striatum plays a crucial role in providing input to the basal ganglia circuit and is implicated in the pathological process of Parkinson’s disease (PD). Disruption of the dynamic equilibrium in the basal ganglia loop can be attributed to the abnormal functioning of the medium spiny neurons (MSNs) within the striatum, potentially acting as a trigger for PD. Exercise has been shown to mitigate striatal neuronal dysfunction through neuroprotective and neurorestorative effects and to improve behavioral deficits in PD model mice. In addition, this effect is offset by the activation of MSNs expressing dopamine D2 receptors (D2-MSNs). In the current study, we investigated the underlying neurobiological mechanisms of this effect. Our findings indicated that exercise reduces the power spectral density of the beta-band in the striatum and decreases the overall firing frequency of MSNs, particularly in the case of striatal D2-MSNs. These observations were consistent with the results of molecular biology experiments, which revealed that aerobic training specifically enhanced the expression of striatal dopamine D2 receptors (D2R). Taken together, our results suggest that aerobic training aimed at upregulating striatal D2R expression to inhibit the functional activity of D2-MSNs represents a potential therapeutic strategy for the amelioration of motor dysfunction in PD.

Abstract Background TG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes. Methods In this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18–75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103. Results A total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 μg*h/mL, and AUC0-inf ranged from 159 to 340 μg*h/mL. TG103 had a half-life of 110–116 h, with a median Tmax of 36–48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p

Abstract Testosterone has complex effects on psychological traits and behavior; it is associated with social dominance and competition and is a potential human sex pheromone. This study aimed to investigate the associations between testosterone levels, aggressive behavior, and manic symptoms using a network analysis among bipolar disorder (BD) patients in psychiatric emergency departments (PED). Data from January 2021 and March 2022 BD patients in PED were analyzed. Manic symptoms were assessed using the Young Mania Rating Scale (YMRS). Aggression was assessed with subscale of the PANSS scale (PANSS-AG). The undirected network structures of testosterone levels, aggressive behavior, and manic symptoms were estimated, and centrality and bridge centrality indices were examined. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. We recruited a total of 898 BD patients, with the mean YMRS score as 13.30 ± 9.58. The prevalence of level II aggression was 35.6% (95%CI = 32.5%–38.7%), level III aggression was 29.5% (95%CI = 26.3%–32.6%), and level VI aggression was 7.0% (95%CI = 5.4%–8.8%). The male participants had a mean testosterone level of 391.71 (Standard Deviation (SD):223.39) compared to 36.90 (SD:30.50) for female participants in the whole sample. Through network analysis, “Increased motor activity-energy” emerged as the central symptom, with the highest centrality expected influence, followed by “Emotional Instability” and “Disruptive/aggression behavior”. Notably, “Emotional Instability” appeared to be the bridge symptom linking manic symptoms to aggressive behavior. Within the flow network model, “Speech rate and amount” exhibited the strongest positive correlation with testosterone levels, followed closely by “Disruptive/aggression behavior”. The constructed network model demonstrated robust stability, with gender showing no significant impact on the structure. In this study, “Increased motor activity-energy” stood out as the most influential symptom, and “Speech rate and amount” acted as the main bridge symptom linking testosterone levels, aggressive behavior, and manic symptoms. Targeting the central and bridge symptoms may improve the outcomes of aggression interventions implemented among BD patients in psychiatric emergency care.

Abstract Background High-efficiency prime editing (PE) is desirable for precise genome manipulation. The activity of mammalian PE systems can be largely improved by inhibiting DNA mismatch repair by coexpressing a dominant-negative variant of MLH1. However, this strategy has not been widely used for PE optimization in plants, possibly because of its less conspicuous effects and inconsistent performance at different sites. Results We show that direct RNAi knockdown of OsMLH1 in an ePE5c system increases the efficiency of our most recently updated PE tool by 1.30- to 2.11-fold in stably transformed rice cells, resulting in as many as 85.42% homozygous mutants in the T0 generation. The high specificity of ePE5c is revealed by whole-genome sequencing. To overcome the partial sterility induced by OsMLH1 knockdown of ePE5c, a conditional excision system is introduced to remove the RNAi module by Cre-mediated site-specific recombination. Using a simple approach of enriching excision events, we generate 100% RNAi module-free plants in the T0 generation. The increase in efficiency due to OsMLH1 knockdown is maintained in the excised plants, whose fertility is not impaired. Conclusions This study provides a safe and reliable plant PE optimization strategy for improving editing efficiency without disturbing plant development via transient MMR inhibition with an excisable RNAi module of MLH1.

In this study, 304 antimicrobial stainless steel coatings were prepared by the electron beam melting of antimicrobial stainless steel powder, in an attempt to enhance the surface properties of Q345R steel. Besides, the effect of Cu-containing 304 powder coatings on the microstructure, mechanical properties, and electrochemical properties of the Q345R surface was investigated. The results indicated that the coating grain was refined, the dislocation density was increased, and both the plasticity and toughness were enhanced after the electron beam surface coating (EBSC) treatment. Additionally, the hardness of coatings was also enhanced under the three beam currents due to grain refinement and dislocation strengthening. At a beam current of 28 mA, the coating hardness reached a maximum of 384.078 HV, representing a two-fold increase compared with the base material (BM) hardness of 131.048 HV. Moreover, the abrasion resistance of the coating was superior to that of the BM. At a beam current of 28 mA, the wear volume and wear rate were minimized to only 10 % of the wear volume of substrates. In galvanic corrosion measurements, the coatings displayed better corrosion resistance than the substrates, and these samples at a beam current of 28 mA exhibited the best corrosion resistance. Overall, the E-beam surface melting 304 stainless steel coating can effectively improve the properties of Q345R carbon steel.

Abstract Most proteins exert their functions by interacting with other proteins, making the identification of protein-protein interactions (PPI) crucial for understanding biological activities, pathological mechanisms, and clinical therapies. Developing effective and reliable computational methods for predicting PPI can significantly reduce the time-consuming and labor-intensive associated traditional biological experiments. However, accurately identifying the specific categories of protein-protein interactions and improving the prediction accuracy of the computational methods remain dual challenges. To tackle these challenges, we proposed a novel graph neural network method called GNNGL-PPI for multi-category prediction of PPI based on global graphs and local subgraphs. GNNGL-PPI consisted of two main components: using Graph Isomorphism Network (GIN) to extract global graph features from PPI network graph, and employing GIN As Kernel (GIN-AK) to extract local subgraph features from the subgraphs of protein vertices. Additionally, considering the imbalanced distribution of samples in each category within the benchmark datasets, we introduced an Asymmetric Loss (ASL) function to further enhance the predictive performance of the method. Through evaluations on six benchmark test sets formed by three different dataset partitioning algorithms (Random, BFS, DFS), GNNGL-PPI outperformed the state-of-the-art multi-category prediction methods of PPI, as measured by the comprehensive performance evaluation metric F1-measure. Furthermore, interpretability analysis confirmed the effectiveness of GNNGL-PPI as a reliable multi-category prediction method for predicting protein-protein interactions.

Abstract Background Coccidiosis is one of the most frequently reported diseases in chickens, causing a significant economic impact on the poultry industry. However, there have been no previous studies evaluating the prevalence of this disease in broiler farms in Guangdong province. Therefore, this study aims to conduct an epidemiological investigation into the occurrence of Eimeria species and associated risk factors in intensive management conditions across four regions in Guangdong province, China. A total of 394 fecal samples were collected from 89 broiler farms in Guangdong province. The prevalence of Eimeria species infection was determined using PCR, and the occurrence of Clostridium perfringens type A was assessed using quantitative real-time PCR. Results The results showed an overall prevalence of 98.88% (88/89) at the farm level and 87.06% (343/394) at the flock level. All seven Eimeria species were identified, with E. acervulina (72.53%; 64/89), E. tenella (68.54%; 61/89), and E. mitis (66.29%; 59/89) at the farm level, and E. acervulina (36.55%; 144/394), E. mitis (35.28%; 139/394), and E. tenella (34.01%; 134/394) at the flock level. The predominant species combination observed was a co-infection of all seven Eimeria species (6.74%; 6/89), followed by a combination of E. acervulina, E. tenella, E. mitis, E. necatrix, E. brunetti, and E. maxima (5.62%, 5/89). A combination of E. acervulina, E. tenella, E. mitis, E. necatrix, E. brunetti, and E. praecox (4.49%; 4/89) was also observed at the farm level. Furthermore, the study identified several potential risk factors associated with the prevalence of Eimeria species, including farm location, chicken age, drinking water source, control strategy, and the presence of C. perfringens type A were identified as potential risk factors associated with prevalence of Eimeria species. Univariate and multivariate analyses revealed a significant association between E. necatrix infection and both grower chickens (OR = 10.86; 95% CI: 1.92–61.36; p

ABSTRACT Objective Chronic kidney disease (CKD) is increasingly recognized as a risk factor for alterations in brain function. However, detecting early‐stage symptoms and structural changes remains challenging, potentially leading to delayed treatment. In our study, we aimed to investigate spontaneous brain activity changes in CKD patients using resting‐state functional magnetic resonance imaging (fMRI). Additionally, we explored the correlation between common biomarkers reflecting CKD severity and brain activity. Methods We recruited a cohort of 22 non–dialysis‐dependent CKD patients and 22 controls for resting‐state fMRI scans. Amplitude of low‐frequency fluctuations (ALFFs) and regional homogeneity (ReHo) were calculated to evaluate brain activity. Regression analysis was conducted to explore the correlations between biomarkers reflecting the severity of CKD and brain activity. Results CKD patients exhibited reduced z‐scored ALFF (zALFF) and mean ALFF (mALFF) in the bilateral putamen, right caudate nucleus, left anterior cingulate, and right precuneus. Changes in bilateral putamen were also found in smCohe‐ReHo and szCohe‐ReHo analyses. Urine albumin‐to‐creatinine ratio (UACR), urine protein‐to‐creatinine ratio (UPCR), and serum albumin levels were associated with attenuated putamen activity. Conclusion Non–dialysis‐dependent CKD patients had changes in zALFF, mALFF, smCohe‐ReHo, and szCohe‐ReHo values in specific brain regions, especially bilateral putamen. UACR, UPCR, and serum albumin levels are associated with putamen activity attenuation in rs‐fMRI.

ABSTRACT Aim This cross‐sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near‐infrared spectroscopy (fNIRS). Methods Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. Results Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale‐24 (HAMD‐24). Conclusions Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.

Background The purpose of this study was to estimate the effect of remote nursing guidance based on WeChat platform for female patients receiving subcutaneous anticoagulation during the COVID-19 epidemic. Methods Retrospective analysis of clinical data, including demographic data and anticoagulation complications, of 126 female patients who received subcutaneous anticoagulation therapy and received remote nursing guidance using WeChat platform in our hospital from January 2022 to December 2022. The Anti-Clot Treatment Scale (ACTS) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale were used to evaluate patients’ satisfaction with anticoagulation and quality of life at the beginning of anticoagulation, half a month after anticoagulation, and after three months of anticoagulation. Results In total, 126 patients were involved in this study, all of them were female, 115 cases were natural pregnancy, 11 cases were assisted reproduction. This study included seven cases of lower extremity deep vein thrombosis, 100 cases of hypercoagulable state, 10 cases of antiphospholipid syndrome, and eight cases of protein S deficiency, one case of hyperhomocysteinemia. During the follow-up period, four patients (3.17%) had subcutaneous injection complications, including three cases of subcutaneous hemorrhage and one case of liquid leakage. A total of 123 patients had completed the planned anticoagulation therapy or were receiving anticoagulation therapy as planned, and three patients did not receive anticoagulation therapy as planned (zero cases lost contact, two cases changed treatment units, and one case refused treatment). ACTS score (55.03 ± 1.73) and WHOQOL-BREF score (62.18 ± 3.17) after three months of anticoagulation, ACTS score (54.18 ± 1.20) and WHOQOL-BREF score (60.37 ± 2.25) after half a month of anticoagulation was significantly higher than the ACTS score (47.81 ± 1.69) and WHOQOL-BREF score (55.25 ± 1.85) at the beginning of anticoagulation, and the difference was statistically significant (P value < 0.01). Conclusions During the COVID-19 pandemic, remote nursing instruction via the WeChat platform for female patients receiving subcutaneous anticoagulation can increase anticoagulation compliance, satisfaction, and quality of life.

The composition and size distribution of particles in the ocean control their optical (scattering and absorption) properties, as well as a range of biogeochemical and ecological processes. Therefore, they provide important information about the pelagic ocean ecosystem’s structure and functioning, which can be used to assess primary production, particle sinking, and carbon sequestration. Due to its harsh environment and remoteness, the particulate bio-optical properties of the Southern Ocean (SO) remain poorly observed and understood. Here, we combined field measurements from hydrographic casts from two research voyages and from autonomous profiling floats (BGC-Argo) to examine particulate bio-optical properties and relationships among several ecologically and optically important variables, namely the phytoplankton chlorophyll a concentration (Chl), the particulate absorption coefficient (ap), the particulate backscattering coefficient (bbp), and the particulate organic carbon (POC) concentration. In the clearest waters of the SO (Chl < 0.2 mg m−3), we found a significant contribution to absorption by non-algal particles (NAP) at 442 nm, which was up to 10 times greater than the absorption by phytoplankton. This makes the particulate bio-optical properties there remarkably different from typical oceanic case 1 water. A matchup analysis confirms the impact of this larger NAP absorption on the retrieval of Chl from satellite ocean colour observations. For waters with Chl > 0.2 mg m−3, no significant differences are observed between the SO and temperate waters. Our findings also demonstrate consistency in predicting phytoplankton carbon from either Chl or bbp, suggesting that both methods are applicable in the SO.

BackgroundEpidemiological and observational studies demonstrate a comorbid relationship between hypothyroidism and atherosclerotic cardiovascular disease (ASCVD). The nature and direction of this causal relationship, however, remain unclear.ObjectiveThis study aims to elucidate the causal relationship between hypothyroidism and ASCVD using a bidirectional Mendelian randomization approach.MethodSingle nucleotide polymorphisms (SNPs) associated with hypothyroidism were identified and selected as genetic instrumental variables from aggregated data of genome-wide association studies (GWAS). The outcome of interest, ASCVD, included seven conditions: coronary artery disease (CAD), angina pectoris (AP), myocardial infarction (MI), ischemic stroke (IS), and subtypes IS-large artery atherosclerosis (IS-LAA), IS-small vessels (IS-SV), and peripheral artery disease (PAD). MR analysis employed multiple methods—chiefly inverse variance weighting (IVW), along with MR Egger, weighted median, and weighted mode—to assess causality. Cochrane's Q test was utilized to evaluate heterogeneity in the MR findings. Causal association reliability was assessed using the MR-Egger intercept, MR-PRESSO tests, and leave-one-out analysis. Reverse MR analysis ensued if forward MR identified a positive exposure-outcome association. Moreover, the DAVID database facilitated GO functional and KEGG pathway enrichment analyses of neighboring genes to instrumental variables, exploring potential disease mechanisms.ResultGWAS pooled data yielded 122 SNPs as potential instrumental variables for hypothyroidism. Forward MR analysis, using the IVW method, indicated hypothyroidism as a risk factor for CAD (OR = 2.34, 95% CI = 1.39–3.94, P = 0.001), AP (OR = 2.01, 95% CI = 1.28–3.16, P = 0.002), MI (OR = 1.02, 95% CI = 1.01–1.04, P = 0.004), and IS-SV (OR = 6.92, 95% CI = 2.45–19.55, P

BackgroundWe developed a new predictive staging system to explore the heterogeneity of survival in newly diagnosed multiple myeloma (NDMM) patients in the real world.MethodsIn this retrospective study, we evaluated the predictive value of cytogenetic abnormal and clinical data in 375 patients with NDMM at our center. Established a weighted MM prognostic scoring system risk model and validated its predicted PFS and OS by external cohort.ResultsElevated lactate dehydrogenase levels (1 point), international staging system stage II/III (1 point), 1q21+ ≥ 52.75% (0.5 point), del (17p) ≥ 3.5% (0.5 point), and t (14;16) ≥ 35.25% (1 point) had independent prognostic significance. Patients were further divided into three risk groups: low (I) (score 0–0.5, 16.5%), intermediate (II) (score 1, 46.7%), and high (III) (score 1.5–3, 36.8%). In the training cohort, the 3-year PFS was 79.5% vs. 65.3% vs. 40.3% (p < 0.001), and the 3-year OS was 87.7% vs.70.1% vs. 55% (p < 0.001) for the three risk groups. In the external validation cohort, the 3-year PFS was 85.5% vs.61.2% vs. 43.1% (p < 0.001) and the 3-year OS was 91.4% vs.83.5% vs. 56.9% (p < 0.001) for the three risk groups.ConclusionThe risk stratification of this model shows good discrimination and calibration, and its application in clinical practice can improve the risk assessment of patients with NDMM and guide personalized treatment strategies.

ABSTRACT Crustaceans are important food sources worldwide and possess significant ecological status in the marine ecosystem. However, our understanding of the diversity and evolution of RNA viruses in crustaceans, especially in economic crustaceans, is still limited. Here, 106 batches of economic crustaceans including 13 species were collected from 24 locations in China during 2016–2021. We identified 90 RNA viruses, 69 of which were divergent from the known viruses. Viral transcripts were assigned to 18 different viral families/clades and three unclassified groups. Among the identified viruses, five were double-stranded RNA viruses, 74 were positive-sense single-stranded RNA (+ssRNA) viruses, nine were negative-sense single-stranded RNA (−ssRNA) viruses, and two belonged to an unclassified RNA virus group. Phylogenetic analyses showed that crustacean viruses were often clustered with viruses identified from invertebrates. Remarkably, most crustacean viruses were closely related to those from different host species along the same food chain or ecological aquatic niche. In addition, the genome structures of the newly discovered picornaviruses exhibited remarkable diversity. Our study significantly expands the diversity of viruses in important economic crustaceans and provides essential data for the risk assessment of the pathogens spreading in the global aquaculture industry.IMPORTANCEThe study delves into the largely uncharted territory of RNA viruses in crustaceans, which are not only vital for global food supply but also play a pivotal role in marine ecosystems. Focusing on economic crustaceans, the research uncovers 90 RNA viruses, with 69 being potentially new to science, highlighting the vast unknown viral diversity within these marine organisms. The findings reveal that these viruses are often related to those found in other invertebrates and tend to share close relationships with viruses from species within the same food web or habitat. This suggests that viruses may move between different marine species more frequently than previously thought. The discovery of such a wide variety of viruses, particularly the diverse genome structures of newly identified picornaviruses, is a significant leap forward in understanding the crustacean virology. This knowledge is crucial for managing disease risks in aquaculture and maintaining the balance of marine ecosystems.

BackgroundGrowing evidence emphasizes the importance of xanthophyll carotenoids and omega-3 fatty acids in eye health. However, the beneficial effects of such supplementation have not been thoroughly discussed among adults with high screen exposure. Current trial evidence on lutein bioavailability is contradictory, and the interactions of dietary intervention with host-related factors remain elusive. This study aims to investigate the comparative effectiveness of supplementation with macular xanthophylls and omega-3 fatty acids on macular pigment optical density (MPOD) and visual function, access the bioavailability of free lutein and lutein ester, and explore the complex interplay between genetic variations, intestinal microbiota, and the dietary intervention in Chinese adults with long-term exposure to digital devices.MethodsThe Lutein, Zeaxanthin, and Omega-3 (LZO) clinical trial is a 24-week multicenter, randomized, double-blind, placebo-controlled trial of 600 participants recruited from research centers, universities, and communities. Individuals are eligible to participate if they are aged over 18 years and use digital devices for over 8 h daily in the last 2 years, and will be randomized to six arms. A total of three visits will be scheduled at baseline, 12 and 24 weeks. The primary outcome is the change in MPOD over the 24-week intervention. The secondary outcomes are changes in visual function (visual acuity, best-corrected visual acuity, contrast and glare sensitivity, critical flicker fusion, reaction time, visuognosis persistence, symptoms and signs of dry eye, retinal thickness, and optical quality), and changes in serum lutein and zeaxanthin concentrations, and erythrocyte membrane omega-3 fatty acids. Genetic variations will be determined using genome-wide genotyping at baseline. 16S rRNA gene sequencing will be utilized to assess microbiome compositional changes before and after intervention.DiscussionThe trial is anticipated to establish early interventions to prevent photochemical ocular damage and delay the onset of vision impairment in young adults with long-term repeated exposure to screen-based electronic devices, and provide valuable insights for the development of precision nutrition strategies for maintaining eye health.Clinical trial registrationwww.clinicaltrials.in.th, Identifier, TCTR20220904002.

BackgroundPrevious research has indicated that engagement in social activities has proven advantageous for diminishing the likelihood of cognitive decline. However, no study has examined whether such cognitive benefits were to a similar extent for the young-old, the old–old, and the oldest-old groups. The purpose of this research was to determine whether aging would have an impact on the changes in cognitive function that would occur in older adults with varying degrees of social involvement.MethodsThe sample for this study comprised 4,481 older adults who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) during the waves spanning from 2008 to 2018. At baseline, participants were classified into the young-old (60–69 years; Mage = 66.66; SD = 1.87), the old–old (70–79 years; Mage = 74.21; SD = 2.82), and the oldest-old (80 years or older; Mage = 86.46; SD = 5.71) groups.ResultsThe level of cognitive function decreased as participants aged. Importantly, compared to those lacking social activities, individuals who were got involved in social engagement at baseline had slower rates of cognitive decline over time. Furthermore, compared with the young-old group and the old–old group, the impact of social activity engagement on slowing cognitive decline was more salient for the oldest-old group.ConclusionActive engagement in social activities can slow age-related cognitive decline, particularly for the oldest-old group. To preserve cognitive function with aging, attention and resources should be allocated to encourage social activity engagement.

BackgroundThe oxidative balance score (OBS) is a composite indicator that evaluates the balance between pro-oxidants and antioxidants in one’s diet and lifestyle. However, the relationship between OBS and circadian syndrome (CircS) has remained unexplored. This investigation aimed to determine a correlation between OBS and CircS.MethodsThis population-based study examined 7,202 participants from the 2005 to 2018 National Health and Nutrition Examination Survey (NHANES), 1,433 of whom had CircS. We utilized weighted multivariate logistic regression, trend tests, subgroup analysis, and interaction tests to evaluate the correlation between OBS (total OBS, dietary OBS, and lifestyle OBS) and CircS. Restricted cubic splines (RCS) models and threshold effect analysis were used to explore nonlinear relationships.ResultsMultivariate logistic regression analysis indicated that the protective factor for CircS was a high OBS level (total OBS: Odds ratio (OR) = 0.95, 95% Confidence interval (CI): 0.93-0.97; dietary OBS: OR = 0.98, 95% CI: 0.96-1.00; lifestyle OBS: OR = 0.65, 95% CI: 0.61-0.69). Compared to the quartile 1 group, OBS (total OBS, dietary OBS, and lifestyle OBS) was negatively and statistically significantly associated with the risk of developing Circs in the quartile 4 group (total OBS: OR = 0.47, 95% CI: 0.32-0.70; dietary OBS: OR = 0.69, 95% CI: 0.48-0.99; lifestyle OBS: OR = 0.07, 95% CI: 0.04-0.11). According to subgroup analysis and interaction tests, there was an interaction effect between the association of lifestyle OBS and CircS in terms of education level (p for interaction = 0.01). Furthermore, we observed a nonlinear negative relationship between lifestyle OBS and CircS prevalence, with inflection points at 6 (p for nonlinearity = 0.002).ConclusionThe results showed a substantial negative connection between OBS and CircS. Encouraging foods filled with antioxidants and antioxidant-rich lifestyles may reduce the risk of CircS.

Silicosis is one of the most severe occupational diseases characterized by inflammatory cell infiltration, fibroblasts activation, and fibrosis in the lung. However, specific drug treatments are lacking. Cardamonin (CDM) has been reported to possess antitumor, anti-inflammatory/fibrotic effects. While, the effect of CDM on the progression of silicosis remains unknown. In this study, we established a SiO2-M stimulated fibroblast cell model, and explored the antifibrotic effect of CDM and the related molecular mechanism using WB, RT-qPCR, and immunofluorescence. The results indicate that CDM inhibits SiO2-M-induced fibroblast activation, proliferation, and migration. Furthermore, a silicosis mouse model was established through injecting silica suspension intratracheally. The results revealed that CDM retards the progression of pulmonary fibrosis. The RNA sequencing results suggest that the antifibrotic effect of CDM may be mediated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. In conclusion, the results of this study demonstrate that CDM inhibits the development of silicosis via the PI3K-AKT signaling pathway, which could provide guidance for the development of drugs for silicosis treatment.

It is known that asymmetrical maternal transcripts play an important role in the cell fate of the early embryo, but few studies are available in mammal oocytes especially in pig. To investigate the spatial factors in pig oocytes, the oriented bisection was established for collecting karyoplasts (NSOs) and cytoplasts (SSOs) with more than 95% efficiency. Subsequently, RNA-Seq and LC-MS/MS analysis were performed on NSOs and SSOs. Although no differentially expressed genes (DEGs) could be detected between NSOs and SSOs, 89 of the differentially expressed proteins (DEPs) were detected, that 58 proteins higher expressed but 31 proteins lower expressed in NSOs compared with SSOs. These DEPs mainly participated in the ‘cell cycle’ and ‘ribosome’ pathway, while the up-regulated DEPs were mainly GO in ‘spindle’ and ‘positive regulation of translation’, and the down-regulated DEPs were in ‘cytosolic small ribosomal subunit’ and ‘mRNA binding’. The up-regulated DEP SIRT5 which are related to the regulation of gene expression, epigenetic were further detected and revealed. A spatial asymmetry of maternal factors at the protein level was firstly detected in pig mature oocytes.

ABSTRACT: Myocyte enhancer factor 2A (MEF2A) is a transcription factor that plays a critical role in cell proliferation, differentiation and apoptosis. In contrast to the wide characterization of its regulation mechanism in mammalian skeletal muscle, its role in chickens is limited. Especially, its wide target genes remain to be identified. Therefore, we utilized Cleavage Under Targets and Tagmentation (CUT&Tag) technology to reveal the genome-wide binding profile of MEF2A in chicken primary myoblasts thus gaining insights into its potential role in muscle development. Our results revealed that MEF2A binding sites were primarily distributed in intergenic and intronic regions. Within the promoter region, although only 8.87% of MEF2A binding sites were found, these binding sites were concentrated around the transcription start site (TSS). Following peak annotation, a total of 1903 genes were identified as potential targets of MEF2A. Gene Ontology (GO) enrichment analysis further revealed that MEF2A target genes may be involved in the regulation of embryonic development in multiple organ systems, including muscle development, gland development, and visual system development. Moreover, a comparison of the MEF2A target genes identified in chicken primary myoblasts with those in mouse C2C12 cells revealed 388 target genes are conserved across species, 1515 target genes are chicken specific. Among these conserved genes, ankyrin repeat and SOCS box containing 5 (ASB5), transmembrane protein 182 (TMEM182), myomesin 2 (MYOM2), leucyl and cystinyl aminopeptidase (LNPEP), actinin alpha 2 (ACTN2), sorbin and SH3 domain containing 1 (SORBS1), ankyrin 3 (ANK3), sarcoglycan delta (SGCD), and ORAI calcium release-activated calcium modulator 1 (ORAI1) exhibited consistent expression patterns with MEF2A during embryonic muscle development. Finally, TMEM182, as an important negative regulator of muscle development, has been validated to be regulated by MEF2A by dual-luciferase and quantitative real-time PCR (qPCR) assays. In summary, our study for the first time provides a wide landscape of MEF2A target genes in chicken primary myoblasts, which supports the active role of MEF2A in chicken muscle development.

Lytic bacteriophages (phages) are promising clinically viable therapeutic options against carbapenem-resistant Klebsiella pneumoniae (CRKP). In China, the predominant strains are those assigned to sequence type 11 and capsular type 64 (ST11-KL64). The emergence of phage resistance is a major bottleneck hindering effective phage therapy, requiring more new phages to provide the flexibility for creating different phage cocktails. However, the majority of phages against ST11-KL64 CRKP belong to the genus Przondovirus of the family Autographiviridae, which limits the options for constructing cocktails. We recovered a novel lytic phage of the genus Taipeivirus within the family Ackermannviridae against ST11-KL64 CRKP from a river in China. We phenotypically characterized this phage and obtained its genome sequence for analysis. This phage can inhibit the growth of ST11-KL64 CRKP for 6.5 h at a 0.1 multiplicity of infection and exhibits a narrow host range, being unable to attack CRKP strains of the other 30 capsular types. This phage carries no genes encoding antimicrobial resistance, virulence, or lysogeny. It is stable across a wide range of temperatures and pH values, making it suitable for phage therapy. Unlike other Taipeivirus phages, P01 has two tail spike proteins and a unique tail fiber protein. The distinct tail composition of this phage contributes to its activity against ST11-KL64 CRKP and its narrow host range. Taken together, we recovered a phage of a novel viral species with the potential for therapy, which expands the phage biobank against CRKP.

Background: Epilepsy is a chronic neurological disorder characterized by recurrent seizures that significantly impact patients’ quality of life. Identifying predictors is crucial for early intervention. Objective: Electroencephalography (EEG) microstates effectively describe the resting state activity of the human brain using multichannel EEG. This study aims to develop a comprehensive prediction model that integrates clinical features with EEG microstates to predict drug-refractory epilepsy (DRE). Design: Retrospective study. Methods: This study encompassed 226 patients with epilepsy treated at the epilepsy center of a tertiary hospital between October 2020 and May 2023. Patients were categorized into DRE and non-DRE groups. All patients were randomly divided into training and testing sets. Lasso regression combined with Stepglm [both] algorithms was used to screen independent risk factors for DRE. These risk factors were used to construct models to predict the DRE. Three models were constructed: a clinical feature model, an EEG microstate model, and a comprehensive prediction model (combining clinical-EEG microstates). A series of evaluation methods was used to validate the accuracy and reliability of the prediction models. Finally, these models were visualized for display. Results: In the training and testing sets, the comprehensive prediction model achieved the highest area under the curve values, registering 0.99 and 0.969, respectively. It was significantly superior to other models in terms of the C-index, with scores of 0.990 and 0.969, respectively. Additionally, the model recorded the lowest Brier scores of 0.034 and 0.071, respectively, and the calibration curve demonstrated good consistency between the predicted probabilities and observed outcomes. Decision curve analysis revealed that the model provided significant clinical net benefit across the threshold range, underscoring its strong clinical applicability. We visualized the comprehensive prediction model by developing a nomogram and established a user-friendly website to enable easy application of this model ( https://fydxh.shinyapps.io/CE_model_of_DRE/ ). Conclusion: A comprehensive prediction model for DRE was developed, showing excellent discrimination and calibration in both the training and testing sets. This model provided an intuitive approach for assessing the risk of developing DRE in patients with epilepsy.

Abstract Integration of solar cell and secondary battery cannot only promote solar energy application but also improve the electrochemical performance of battery. Lithium–sulfur battery (LSB) is an ideal candidate for photoassisted batteries owing to its high theoretical capacity. Unfortunately, the researches related the combination of solar energy and LSB are relatively lacking. Herein, a freestanding photoelectrode is developed for photoassisted lithium–sulfur battery (PALSB) by constructing a heterogeneous structured Au@N‐TiO2 on carbon cloths (Au@N‐TiO2/CC), which combines multiple advantages. The Au@N‐TiO2/CC photoelectrode can produce the photoelectrons to facilitate sulfur reduction during discharge process, while generating holes to accelerate sulfur evolution during charge process, improving the kinetics of electrochemical reactions. Meanwhile, Au@N–TiO2/CC can work as an electrocatalyst to promote the conversion of intermediate polysulfides during charge/discharge process, mitigating induced side reactions. Benefiting from the synergistic effect of electrocatalysis and photocatalysis, PALSB assembled with an Au@N‐TiO2/CC photoelectrode obtains ultrahigh specific capacity, excellent rate performance, and outstanding cycling performance. What is more, the Au@N‐TiO2/CC assembled PALSB can be directly charged under light illumination. This work not only expands the application of solar energy but also provides a new insight to develop advanced LSBs.

Abstract Radiated tumor cell‐derived extracellular vesicles (RT‐EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT‐EVs, thus the low abundance of DNA fragments limits immune responses of RT‐EVs. Here, this study found that different radiations affected fates of DNA fragments in RT‐EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT‐EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high‐linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs‐educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti‐tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long‐term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.

Abstract Chemodynamic therapy (CDT) is a novel tumor treatment method by using hydroxyl radicals (•OH) to kill cancer cells. However, its therapeutic effects are strictly confined by the short lifespan of •OH and reduced •OH generation speed. Herein, an effective CDT is achieved by both improving •OH lifetime and long‐lasting generating •OH through intraparticle electron transfer within heterogeneous nanoparticles (NPs). These heterogeneous NPs are composed of evenly distributed Cu and Fe3O4 (CFO NPs) with large interaction interfaces, and electrons tend to transfer from Cu to Fe3O4 for the appearance of ≡Cu2+ and increase in ≡Fe2+. The generated ≡Cu2+ can interact with GSH, which prolongs the lifespan of •OH, produces ≡Cu+ for higher speed •OH generation with H2O2, and induces cell ferroptosis for tumor therapy. The improved ≡Fe2+ can also improve the •OH release under H2O2 until Cu is depleted. As a result, a sustainable •OH generation is achieved to promote cell apoptosis for effective tumor therapy. Since H2O2 and GSH are only overexpressed at tumor, and CFO NPs can degrade in the tumor microenvironment, these NPs are with high biosafety and can be metabolized by urine. This work provides a novel biomaterial for effective cancer CDT through intraparticle electron transfer.

ObjectivesThe purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the effectiveness, safety, and tolerability of psilocybin in adult patients with major depressive disorder (MDD).MethodsA systematic search (up to September 14, 2023) was conducted for RCTs that examined the efficacy, safety, and tolerability of psilocybin in physically healthy adult patients with MDD. Three independent researchers extracted data from publications where the primary outcome was a change in depressive symptoms, and key secondary outcomes were changes in anxiety symptoms and suicidal ideation, discontinuation rates for any reason, and adverse drug reactions (ADRs).ResultsFive RCTs with 472 adult patients with MDD on psilocybin (n = 274) and controls (n = 198) were included. Two of the five RCTs (40%) reported mixed results, while the other three (60%) found that psilocybin had a beneficial effect on MDD treatment. Four RCTs (80%) assessing the anxiolytic effects of psilocybin for treating MDD found that psilocybin was significantly more effective than the control group in improving anxiety symptoms. Psilocybin was more effective than the control group in improving suicidal ideation in one out of five RCTs. Discontinuation rates were similar for any reason between the psilocybin group (2–13%) and the control group (4–21%) (P > 0.05). Four RCTs (80%) reported ADRs in detail. The most common ADR in both groups was headache.ConclusionPsilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD. The long-term efficacy and safety of psilocybin for MDD treatment needs to be further investigated in large RCTs.

Macroautophagy/autophagy is an intracellular degradation pathway that has an important effect on both healthy and diseased pancreases. It protects the structure and function of the pancreas by maintaining organelle homeostasis and removing damaged organelles. A variety of pancreas-related diseases, such as diabetes, pancreatitis, and pancreatic cancer, are closely associated with autophagy. Genetic studies that address autophagy confirm this view. Loss of autophagy homeostasis (lack or overactivation) can lead to a series of adverse reactions, such as oxidative accumulation, increased inflammation, and cell death. There is growing evidence that stimulating or inhibiting autophagy is a potential therapeutic strategy for various pancreatic diseases. In this review, we discuss the multiple roles of autophagy in physiological and pathological conditions of the pancreas, including its role as a protective or pathogenic factor.

BackgroundThe relationship between secondary traumatic stress (STS), empathy, and vicarious post-traumatic growth (VPTG) in oncology nurses is unclear. Understanding these links is crucial for improving nurse well-being and patient care quality.ObjectiveThis study aimed to investigate the relationships between STS, empathy, and VPTG among oncology nurses.MethodsThis cross-sectional study was conducted in a multicentric setting. Data collection involved oncology nurses completing questionnaires assessing STS, empathy, and VPTG levels. Data analysis included correlation analyses, multiple stepwise regression analysis, and structural equation modeling (SEM) to examine the interrelationships between these variables. The study adhered to the STROBE checklist.ResultsA total of 391 oncology nurses participated in the study. They showed moderate to low levels of VPTG and high levels of STS. STS exhibited a negative association with VPTG, while empathy demonstrated a positive direct association with both VPTG and STS. Moreover, SEM indicated that empathy mediated the relationship between STS and VPTG, with a partial mediating effect of 0.127. Factors such as receiving psychological training, educational attainment, STS, and empathy collectively explained 24% of the variance in VPTG.ConclusionOur findings highlighted the negative correlation between STS and VPTG among oncology nurses. Additionally, empathy was found to mediate the relationship between STS and VPTG, suggesting it plays a significant role in influencing VPTG.Implications for practiceTo aid oncology nurses, interventions should focus on reducing STS and enhancing empathy. Strategies like resilience workshops, peer support, and stress management can foster VPTG. Creating a supportive work environment is crucial for nurses’ well-being and quality patient care.

Objectives To appraise the quality of clinical practice guidelines (CPGs) and expert consensus statements on rehabilitation for patients with COVID-19, summarise recommendations of rehabilitation assessments and interventions and evaluate the heterogeneity of the recommendations.Design Systematic review.Data sources PubMed and Embase databases and five online guideline repositories: The National Guideline Clearinghouse, Guidelines International Network, Scottish Intercollegiate Guidelines Network, National Institute for Health and Clinical Excellence and WHO were searched from their inception to August 2024. In addition, we reviewed reference lists of eligible citations and searched the grey literature on the relevant websites.Eligibility criteria for selecting studies We included CPGs and expert consensus statements which provided information about rehabilitation of patients with COVID-19. To be eligible, the CPGs and expert consensus statements were issued in English by a nationally or internationally recognised government authority, medical/academic society or organisation. If there were multiple versions of the guidelines, we included the latest one. The translations, interpretations and abstracts of guidelines were excluded.Data extraction and synthesis All recommendations on rehabilitation assessments and interventions for COVID-19 were extracted and summarised. Two reviewers independently evaluated the methodological quality with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and two other reviewers assessed the reporting quality using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement of included CPGs and expert consensus statements. We used the Measurement Scale of Rate of Agreement to evaluate the heterogeneity of the recommendations in different CPGs and expert consensus statements.Results A total of 31 CPGs and expert consensus statements were included. 14 guidelines provided recommendations for rehabilitation assessments. At the early, development, critical and recovery stages of COVID-19, the most frequently recommended were exercise therapy (25.8%, 35.5%, 25.8% and 58.1%, respectively). According to AGREE II, 17 included guidelines were assessed as low methodological quality (35%–56%), 10 guidelines were rated as moderate quality (46%– 62%) and four had high quality (69%–79%). Among 31 eligible guidelines, the reporting rate of 22 items in the RIGHT checklist ranged from 10% to 100%. The included guidelines were consistent with the reference guidelines (80%–100%). Only one guideline existed minor (60%–80%) disagreements in respiratory muscle training relative to the reference guideline.Conclusions Rehabilitation assessments and interventions should be implemented consistently throughout the entire process of COVID-19. The recommendations should be tailored to each stage of COVID-19. The methodological and reporting qualities of several guidelines remain suboptimal. Therefore, developers should adhere strictly to the AGREE II standard and RIGHT checklist to formulate and publish CPGs and expert consensus statements with high quality.PROSPERO registration number CRD42020190761.

IntroductionHybrid rice demonstrated superior performance in enhancing yield and efficiency in rice production compared to inbred rice. Nevertheless, the underlying mechanism responsible for the increased yield and efficiency of hybrid rice in South China’s double-cropping rice region remains understudied.MethodsField experiments over two consecutive years were conducted. Firstly, yield variations among 20 inbred and 15 hybrid rice cultivars prevalent in South China’s double-cropping rice system were examined. Secondly, selecting representative hybrid and inbred rice cultivars with significant yield disparities were carried out on further analyzing dry-matter production, source-sink relationships, and nutrient absorption and utilization in both rice types.ResultsHybrid rice displayed an average grain yield of 8.07 and 7.22 t hm-2 in the early and late seasons, respectively, which corresponds to a 12.29% and 13.75% increase over inbred rice with statistically significant differences. In comparison to inbred rice, hybrid rice exhibited enhanced nitrogen concentration in leaves at the heading stage (15.48–16.20%), post-heading dry matter accumulation (52.62–73.21%), post-heading dry matter conversion rate (29.23–34.12%), and harvest index (17.31–18.37%). Additionally, grain nitrogen and phosphorus uptake in hybrid rice increased by 11.88–22.50% and 16.38–19.90%. Hybrid rice mainly improved post-heading nitrogen and phosphorus uptake and transport, while not total nitrogen and phosphorus uptake. Internal nitrogen and phosphorus use efficiency enhanced by 9.83%-14.31% and 10.15%-13.66%, respectively. Post-heading dry matter accumulation, harvest index, grain nitrogen and phosphorus uptake, and internal nitrogen and phosphorus use efficiency exhibited significant positive linear correlations with grain yield.DiscussionThe period from heading to maturity is critical for enhancing hybrid rice yield and efficiency. Improving photosynthetic capacity during this period and promoting nutrient transport to grains serve as crucial pathways for increasing grain yield and efficiency. This study is of great significance for further improvement grain yield and breeding rice cultivars with high-yield and high nutrients use efficiency for South China's double-cropped rice system.

ObjectiveAmong the disturbing motor symptoms in Parkinson’s disease (PD), freezing of gait (FOG) stands out as one of the most severe challenges. It typically arises during the initiation of gait or when turning. This phenomenon not only impose a heavy burden on patients, but also on their families. We conduct a bibliometric analysis to summarize current research hotspots and trends concerning freezing of gait in Parkinson’s disease (PD-FOG) over past two decades.MethodsWe retrieved articles and reviews published in English about PD-FOG in the Web of science Core Collection database from 2000 to 2023 on November 30,2023. The tools VOSviewer and CiteSpace facilitated a visual analysis covering various aspects such as publications, countries/regions, organizations, authors, journals, cited references, and keywords.ResultThis study includes 1,340 articles from 64 countries/regions. There is a growth in publications related to PD-FOG over the past two decades, maintaining a stable high output since 2018, indicating a promising research landscape in the field of PD-FOG. The United States holds a leading position in this field, with Nieuwboer A and Giladi N being two of the most influential researchers. Over the past two decades, the research hotspots for PD-FOG have primarily encompassed the kinematic characteristics, diagnosis and detection, cognitive deficits and neural connectivity, as well as therapy and rehabilitation of PD-FOG. Topics including functional connectivity, virtual reality, deep learning and machine learning will be focal points of future research.ConclusionThis is the first bibliometric analysis of PD-FOG. We construct this study to summarize the research in this field over past two decades, visually show the current hotspots and trends, and offer scholars in this field concepts and strategies for subsequent studies.

The differentiation of vascular endothelial cells and the formation of new blood vessels are inseparable from the energy supply and regulation of metabolism. The budding of blood vessels is a starting point of glycolysis pathway in angiogenesis. Phosphofructokinase-2/fructose 2,6-biophosphatase 3 (PFKFB3), a key rate-limiting enzyme in glycolysis, exhibits strong kinase activity. Inhibition of PFKFB3 can reduce the rate of glycolysis, thereby inhibiting the budding of blood vessels, resulting in inhibition of pathological angiogenesis. In this review, the role of PFKFB3 in the angiogenesis of inflammatory diseases was summarized, and the endothelial inflammatory diseases associated with PFKFB3 were reviewed.

Purpose: To evaluate if pseudo-continuous arterial spin labeling (pcASL) and territorial ASL (tASL) can assess cerebral perfusion post-revascularization in Moyamoya disease and compare with digital subtraction angiography (DSA) outcomes. Materials and methods: Patients diagnosed with Moyamoya disease who underwent pcASL using two post-labeling delays (short ASL, 1,525 ms; delayed ASL, 2,525 ms), tASL, and DSA 3 months after surgery at a single institution were retrospectively evaluated. Manual delineation on pcASL cerebral blood flow (CBF) maps covered middle cerebral artery (MCA) territory on both sides, and cerebellum. Normalized CBF (nCBF) was calculated. Revascularization in the MCA territory was evaluated with external carotid angiography and tASL, graded on a three-point scale. Intermodality agreement was analyzed with weighted κ statistics. Correlation between pcASL-derived nCBF and tASL-measured revascularization, and revascularization grade from direct angiography, was determined. Diagnostic performance of pcASL and tASL was evaluated using DSA as a reference via receiver operating characteristic (ROC) curve analysis. Results: A total of 32 hemispheres from 31 patients were assessed. On the operated side, sASL and dASL had nCBF values of 1.00 ± 0.30 and 1.31 ± 0.31, respectively. Revascularization area grading showed substantial intermodality agreement (weighted κ = 0.68; 95 % CI: 0.49, 0.87). DSA revascularization moderately correlated with sASL and dASL nCBF values (r = 0.56 and 0.47) and strongly correlated with tASL revascularization area (r = 0.73). ROC analysis revealed that sASL and dASL nCBF values reflected revascularization (area under the curve (AUC) = 0.86 and 0.77) and tASL revascularization area (AUC = 0.91). Combined pcASL and tASL had an AUC of 0.93, comparable to tASL alone, improving diagnostic performance. The diagnostic accuracy of nCBF for sASL was 87.5 %, superior to 75 % for dASL. The diagnostic accuracy of tASL external carotid artery revascularization area was 87.5 %, with sensitivity and specificity of 88 % and 85.7 %, respectively. Conclusion: The combination of pcASL and tASL outperformed pcASL alone in assessing cerebral perfusion post-Moyamoya disease revascularization.

ObjectivesTo examine the impact of receptive music therapy on maternal anxiety both during and after the process of childbirth.MethodsIn this experimental study, 217 women were divided into the receptive music therapy and control groups. The first group were exposed to music at intervals of 20 minutes for a duration of 30 minutes during labor. Data were collected using the Pregnant Information Form, the State Anxiety Inventory (STAI), Visual Analogue Scale and Edinburgh postnatal depression scale.ResultsThe pregnant women who participated in the music group exhibited reduced scores of STAI, both during the active time (46.42 ± 11.69 vs. 50.21 ± 11.14, 44.37 ± 10.38 vs. 47.56 ± 11.46, P

BackgroundDespite its excellent therapeutic efficacy, albumin-bound paclitaxel often leads to peripheral neurotoxicity, significantly affecting patients’ quality of life. This study reported a case of non-small cell lung cancer (NSCLC) with peripheral neurotoxicity induced by albumin-bound paclitaxel.Case presentationA 70-year-old male was admitted to the Hubei Cancer Hospital complaining of left-side limb weakness and numbness for one month following the first cycle of albumin paclitaxel plus cisplatin plus tislelizumab regimen for the right-side NSCLC in December 2021. Chest CT displayed a soft tissue density mass in the apical segment of the right upper lung lobe (5.5×4.9 cm2). Immunohistochemistry results and CT-guided percutaneous lung biopsy confirmed NSCLC stage cT3NXMX. The pain and numbness in both feet were alleviated after the first cycle of this regimen of liposomal paclitaxel 240 mg plus cisplatin 90 mg plus tislelizumab 200 mg. After four treatment cycles, the tumor treatment was evaluated as partial response (PR), and the tumor lesion became 2.9×2.7 cm2.ConclusionThe regimen containing liposomal paclitaxel, cisplatin, and tislelizumab alleviated the symptoms of peripheral neurotoxicity induced by albumin-bound paclitaxel in an NSCLC case, which may be a potential therapeutic option.

Objective: Polyfluoroalkyl substances (PFAS) are known endocrine disruptors, that have been the subject of limited research regarding their impact on human lean body mass. The aim of this study was to investigate the effects of PFAS exposure on lean body mass. Methods: We performed a cross-sectional data analysis involving 1022 adolescents and 3274 adults from the National Health and Nutrition Examination Survey (NHANES) 2011–2018, whose lean body mass was measured by dual-energy X-ray absorptiometry. The lean mass index (LMI) was calculated as lean body mass dividing by the square of height. The association between PFAS and LMI was examined through a multivariate-adjusted weighted generalized linear model. Moreover, weighted quantile sum (WQS) regression models were employed to futher examine the relationship between the mixture of PFAS and LMI. Results: Regression analyses revealed an inverse correlation between PFAS exposure and LMI after adjusting for potential covariates. Adults with higher serum PFAS concentrations manifested a reduction in whole LMI (β = −0.193, 95 % confidence interval (CI): −0.325 to −0.06). Notably, this correlation was particularly significant in adult females and individuals with obesity, and it was observed across diverse anatomical regions, including lower limbs, right arm, trunk, and whole lean body mass. In adult females, the association between PFAS and whole LMI was statistically significant (β = −0.294, 95 % CI: −0.495 to −0.094), and a similar trend was found in obese individuals (β = −0.512, 95 % CI: −0.762 to −0.261). WQS regression analyses supported the results obtained from weighted linear regression analyses. Conclusions: Our study suggests that exposure to PFAS, whether individually or in combination, is associated with decreased lean body mass in specific body areas, with sex and obesity serving as major influencing factors.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) plaques and neurofibrillary tangles composed of tau protein in the brain. These neuropathological hallmarks contribute to cognitive impairment by inducing neuronal loss in the cerebral cortex and hippocampus. Unfortunately, current therapeutic approaches only target symptomatic relief and do not impede disease progression. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), has emerged as a promising candidate for the treatment of age-related neurodegenerative disorders. NMN supplementation could restore NAD+ levels, thereby alleviating neuronal damage and slowing the progression of AD and other aging-associated diseases. AD is closely associated with autophagic impairment and oxidative stress. Our in vivo experiments demonstrated that NMN could ameliorate pathological and behavioral impairments in AD mice. Specifically, NMN enhanced autophagy and promoted p-tau clearance. Meanwhile, NMN could activate the Nrf2/Keap1/NQO1 pathway, thereby reducing the oxidative stress. Immunofluorescence results demonstrated that NMN could alleviate neuronal damage in AD mice. Furthermore, in vitro results showed that the p-tau clearance and antioxidant stress effects of NMN were suppressed by autophagy inhibitor, chloroquine (CQ) or bafilomycin A1 (BafA1), in Aβ-induced PC12 cells. Lastly, when Nrf2 was knocked down, the antioxidant stress, autophagy enhancement, and p-tau clearance effects of NMN were all inhibited. In conclusion, our research indicates that NMN exerts therapeutic effect against AD by activating autophagy and the Nrf2/Keap1/NQO1 pathway through a mutual regulating mechanism of autophagy and antioxidative stress. These findings highlight the promising potential of NMN for the treatment of AD.

ABSTRACT: The laying hen is the spontaneous model of ovarian tumor. A comprehensive comparison based on RNA-seq from hens and women may shed light on the molecular mechanisms of ovarian cancer. We performed next-generation sequencing of microRNA and mRNA expression profiles in 9 chicken ovarian cancers and 4 normal ovaries, which has been deposited in GSE246604. Together with 6 public datasets (GSE21706, GSE40376, GSE18520, GSE27651, GSE66957, TCGA-OV), we conducted a comparative transcriptomics study between chicken and human. In the present study, miR-451, miR-2188-5p, and miR-10b-5p were differentially expressed in normal ovaries, early- and late-stage ovarian cancers. We also disclosed 499 up-regulated genes and 1,061 down-regulated genes in chicken ovarian cancer. The molecular signals from 9 cancer hallmarks, 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 369 Gene Ontology (GO) pathways exhibited abnormalities in ovarian cancer compared to normal ovaries via Gene Set Enrichment Analysis (GSEA). In the comparative analysis across species, we have uncovered the conservation of 5 KEGG and 76 GO pathways between chicken and human including the mismatch repair and ECM receptor interaction pathways. Moreover, a total of 174 genes contributed to the core enrichment for these KEGG and GO pathways were identified. Among these genes, the 22 genes were found to be associated with overall survival in patients with ovarian cancer. In general, we revealed the microRNA profiles of ovarian cancers in hens and updated the mRNA profiles previously derived from microarrays. And we also disclosed the molecular pathways and core genes of ovarian cancer shared between hens and women, which informs model animal studies and gene-targeted drug development.

ABSTRACT: Avian leukosis virus (ALV) is an enveloped retrovirus with a single-stranded RNA genome, belonging to the genus Alpharetrovirus within the family Retroviridae. The disease (Avian leukosis, AL) caused by ALV is mainly characterized by tumor development and immunosuppression in chickens, which increases susceptibility to other pathogens and leads to significant economic losses in the Chinese poultry industry. The government and poultry industry have made lots of efforts to eradicate ALV, but the threat of which remains not vanished. This review provides a summary of the updated understanding of ALV in China, which mainly focuses on genetic and molecular biology, epidemiology, and diagnostic methods. Additionally, promising antiviral agents and ALV eradication strategies performed in China are also included.

Di(2-ethylhexyl) phthalate (DEHP) is a widely recognized environmental endocrine disruptor that potentially impacts female reproductive function, although the specific mechanisms leading to such impairment remain unclear. A growing body of research has revealed that the endoplasmic reticulum and mitochondrial function significantly influence oocyte quality. The structure of mitochondria-associated endoplasmic reticulum membranes (MAMs) is crucial for facilitating the exchange of Ca2+, lipids, and metabolites. This study aimed to investigate the alterations in the composition and function of MAMs after DEHP exposure and to elucidate the underlying mechanisms of ovarian toxicity. The female mice were exposed to DEHP at doses of 5 and 500 mg/kg/day for one month. The results revealed that DEHP exposure led to reduced serum anti-Müllerian hormone levels and increased atretic follicles in mice. DEHP induced endoplasmic reticulum stress and disrupted calcium homeostasis in oocytes. Furthermore, DEHP impaired the mitochondrial function of oocytes and reduced their membrane potential, and promoting apoptosis. Similar results were observed in human granulosa cells after exposure to mono-(2-ethylhexyl) phthalate (MEHP, metabolites of DEHP) in vitro. Proteomic analysis and transmission electron microscopy revealed modifications in the functional proteins and structure of the MAMs, and the suppression of oxidative phosphorylation pathways. The findings of this investigation provide a new perspective on the mechanism underlying the reproductive toxicity of DEHP in females.

m6A modification is a crucial epigenetic regulatory mechanism in diffuse large B-cell lymphoma (DLBCL). Low-dose cardiotonic drugs have been shown to induce apoptosis in DLBCL cells through epigenetic modulation. However, the involvement of the cardiotonic drug ouabain in the malignant progression of DLBCL remains unclear. Our study revealed that ouabain indeed contributes to the malignant progression of DLBCL through m6A modification. Through qPCR analysis, we observed a negative correlation between ouabain concentration and the expression levels of the demethylase ALKBH5 and the m6A-binding protein IGF2BP2 in DLBCL cells. Furthermore, high expression levels of ALKBH5 and IGF2BP2 were identified in both the GEO database and DLBCL patient tissue samples. Notably, elevated ALKBH5 and IGF2BP2 promoted cell proliferation both in vitro and in vivo. Inhibition of their expression rendered DLBCL cells more sensitive to ouabain treatment, resulting in significant suppression of cell proliferation, G1/S phase cell cycle arrest, and increased apoptosis. In summary, our results clarify that the demethylase ALKBH5 and the m6A-binding protein IGF2BP2 are involved in the malignant progression of DLBCL, and that the cardiotonic drug ouabain can inhibit the proliferation of DLBCL cells by inhibiting the expression of ALKBH5 and IGF2BP2, which provides new insights into the targeted treatment of DLBCL.

Abstract Hiptage yangshuoensis K.Tan & K.S.Nguyen, a new species of Hiptage collected from a karst cliff close to the Lijiang River, Northeast of Guangxi Zhuang Autonomous Region, China, is described and illustrated based on molecular and morphological data. Hiptage yangshuoensis shares some morphological similarities with the H. multiflora F.N.Wei, but easily distinguished by its long pedicels with articulate at top, one large calyx gland, oblanceolate middle wing and lanceolate lateral wings of samara, and young branch covered rusty sericeous. The new species status is also supported by molecular phylogenetic analyses based on nuclear ribosome internal transcribed spacer (nrITS), which showed distinct systematic distinctiveness from the most morphologically similar species, H. multiflora.

Combination antiretroviral therapy (cART) has dramatically reduced mortality in people with human immunodeficiency virus (HIV), but it does not completely eradicate the virus from the brain. Patients with long-term HIV-1 infection often show neurocognitive impairment, which severely affects the quality of life of those infected. Methamphetamine (METH) users are at a significantly higher risk of contracting HIV-1 through behaviors such as engaging in high-risk sex or sharing needles, which can lead to transmission of the virus. In addition, HIV-1-infected individuals who abuse METH exhibit higher viral loads and more severe cognitive dysfunction, suggesting that METH exacerbates the neurotoxicity associated with HIV-1. Therefore, this review focuses on various mechanisms underlying METH and HIV-1 infection co-induced neurotoxicity and existing interventions targeting the sigma 1 receptor, dopamine transporter protein, and other relevant targets are explored. The findings of this review are envisaged to systematically establish a theoretical framework for METH abuse and HIV-1 infection co-induced neurotoxicity, and to suggest novel clinical treatment targets.