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Abstract Background The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear. Methods A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index). Results Among the 4,109 HF patients, FFA levels exceeding 0.4–0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11–1.58) for CV death & HHP, 1.45 (95% CI: 1.16–1.82) for CV death, and 1.39 (95% CI: 1.15–1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P

Abstract Background Prader-Willi syndrome (PWS) is a rare multisystemic hereditary illness. Recombinant human growth hormone (rhGH) therapy is widely recognized as the primary treatment for PWS. This study aimed to examine how different PWS genotypes influence the outcome of rhGH treatment in children with PWS. Methods A review was conducted on 146 Chinese children with PWS, genetically classified and monitored from 2017 to 2022. Unaltered and modified generalized estimating equations (GEE) were employed to examine the long-term patterns in primary outcomes (growth metrics) and secondary outcomes (glucose metabolism metrics and insulin-like growth factor-1 (IGF-1)) during rhGH therapy. The study also evaluated the prevalence of hypothyroidism, hip dysplasia, and scoliosis before and after rhGH treatment. Results Children with PWS experienced an increase in height/length standard deviation scores (SDS) following rhGH administration. The impact of rhGH therapy on growth measurements was similar in both the deletion and maternal uniparental diploidy (mUPD) cohorts. Nevertheless, the deletion group was more prone to insulin resistance (IR) compared to the mUPD group. No significant variations in growth metrics were noted between the two groups (P > 0.05). At year 2.25, the mUPD group showed a reduction in fasting insulin (FINS) levels of 2.14 uIU/ml (95% CI, -4.26, -0.02; P = 0.048) and a decrease in homeostasis model assessment of insulin resistance (HOMA-IR) of 0.85 (95% CI, -1.52, -0.17; P = 0.014) compared to the deletion group. Furthermore, there was a decrease in the IGF standard deviation scores (SDS) by 2.84 (95% CI, -4.84, -0.84; P = 0.005) in the mUPD group during the second year. The frequency of hip dysplasia was higher in the mUPD group compared to the deletion group (P

Abstract Malignant pleural effusion (MPE) is a common occurrence in advanced cancer and is often linked with a poor prognosis. Eosinophils were reported to involve in the development of MPE. However, the role of eosinophils in MPE remains unclear. To investigate this, we conducted studies using both human samples and mouse models. Increased eosinophil counts were observed in patients with MPE, indicating that the higher the number of eosinophils is, the lower the LENT score is. In our animal models, eosinophils were found to migrate to pleural cavity actively upon exposure to tumor cells. Intriguingly, we discovered that a deficiency in eosinophils exacerbated MPE, possibly due to their anti-tumor effects generated by modifying the microenvironment of MPE. Furthermore, our experiments explored the role of the C-C motif chemokine ligand 11 (CCL11) and its receptor C-C motif chemokine receptor 3 (CCR3) in MPE pathology. As a conclusion, our study underscores the protective potential of eosinophils against the development of MPE, and that an increase in eosinophils through adoptive transfer of eosinophils or increasing their numbers improved MPE.

Abstract The aim of this study was to evaluate the accuracy of the single upper‐arm cuff oscillometric blood pressure (BP) monitor RBP‐9801 developed for office and home BP measurement in the general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060–2:2018). Subjects were recruited to fulfil the age, gender, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method. A total of 105 subjects were recruited and 85 were analyzed. For validation criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 2.3 ± 6.4/3.1 ± 5.8 mmHg (systolic/diastolic). For criterion 2, the SD of the mean BP differences between the test device and reference BP per subject was 5.24/5.03 mmHg (systolic/diastolic). The conclusion is that the RBP‐9801 oscillometric device for office and home BP measurement fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060–2:2018) in the general population and can be recommended for clinic and self‐use at home.

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent malignancy with a pressing need for improved therapeutic response and prognosis prediction. This study delves into a novel predictive model related to ferroptosis, a regulated cell death mechanism disrupting metabolic processes. Results Single-cell sequencing data analysis identified subpopulations of HCC cells exhibiting activated ferroptosis and distinct gene expression patterns compared to normal tissues. Utilizing the LASSO-Cox algorithm, we constructed a model with 10 single-cell biomarkers associated with ferroptosis, namely STMN1, S100A10, FABP5, CAPG, RGCC, ENO1, ANXA5, UTRN, CXCR3, and ITM2A. Comprehensive analyses using these biomarkers revealed variations in immune infiltration, tumor mutation burden, drug sensitivity, and biological functional profiles between risk groups. Specific associations were established between particular immune cell subtypes and certain gene expression patterns. Treatment response analyses indicated potential benefits from anti-tumor immune therapy for the low-risk group and chemotherapy advantages for the high-risk group. Conclusions The integration of this single-cell level model with clinicopathological features enabled accurate overall survival prediction and effective risk stratification in HCC patients. Our findings illuminate the potential of ferroptosis-related genes in tailoring therapy and prognosis prediction for HCC, offering novel insights into the intricate interplay among ferroptosis, immune response, and HCC progression.

Background Central retinal artery occlusion (CRAO) has been identified as an acute emergency resulting in vision loss, with its pathogenesis potentially involving systemic inflammation and abnormal lipid metabolism. Over recent years, it has been established that peripheral blood inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), the systemic immunoinflammatory index (SII), and the monocyte-to-high-density lipoprotein ratio (MHR), play significant roles in assessing systemic inflammation and lipid metabolism. However, the role of these indices in assessing the severity of CRAO has rarely been explored. This study aimd to investigate the relationship between these inflammatory indices and the severity of CRAO. Methods This was a retrospective clinical study with a total of 49 CRAO patients and 50 age- and sex-matched controls involved. The patients with CRAO were divided into three groups (13 with incomplete CRAO, 16 with subtotal CRAO and 20 with total CRAO). Data were compared across these groups, and additionally, correlation analysis, restricted cubic spline plots, and receiver operating characteristic curve analysis were performed. Results The values of NLR, SII and MHR were significantly higher in the CRAO group compared to controls (NLR: 2.49(1.71,3.44) vs 1.60(1.24,1.97), P

IntroductionFetal membrane inflammation is an integral event of parturition. However, excessive pro-inflammatory cytokines can impose threats to the fetus. Coincidentally, the fetal membranes express abundant 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which generates biologically active cortisol to promote labor through induction of prostaglandin synthesis. Given the well-recognized anti-inflammatory actions of glucocorticoids, we hypothesized that cortisol regenerated in the fetal membranes might be engaged in restraining fetus-hazardous pro-inflammatory cytokine production for the safety of the fetus, while reserving pro-labor effect on prostaglandin synthesis to ensure safe delivery of the fetus.MethodsThe hypothesis was examined in human amnion tissue and cultured primary human amnion fibroblasts as well as a mouse model.Results11β-HSD1 was significantly increased in the human amnion in infection-induced preterm birth. Studies in human amnion fibroblasts showed that lipopolysaccharide (LPS) induced 11β-HSD1 expression synergistically with cortisol. Cortisol completely blocked NF-κB-mediated pro-inflammatory cytokine expression by LPS, but STAT3-mediated cyclooxygenase 2 expression, a crucial prostaglandin synthetic enzyme, remained. Further studies in pregnant mice showed that corticosterone did not delay LPS-induced preterm birth, but alleviated LPS-induced fetal organ damages, along with increased 11β-HSD1, cyclooxygenase 2, and decreased pro-inflammatory cytokine in the fetal membranes.DiscussionThere is a feed-forward cortisol regeneration in the fetal membranes in infection, and cortisol regenerated restrains pro-inflammatory cytokine expression, while reserves pro-labor effect on prostaglandin synthesis. This dual role of cortisol regeneration can prevent excessive pro-inflammatory cytokine production, while ensure in-time delivery for the safety of the fetus.

Abstract N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC–MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. With a favorable bioavailability of 24.0%, N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs. Graphical Abstract

Abstract Aims Red blood cell distribution width‐to‐albumin ratio (RAR), an innovate biomarker of inflammation, can independently predict adverse cardiovascular outcomes. However, the association between RAR and prognosis in patients with non‐ischaemic heart failure (NIHF) remains unclear. Methods and results A total of 2077 NIHF patients admitted to the Heart Failure Care Unit, Fuwai Hospital, were consecutively enrolled from December 2006 to October 2017 in this retrospective study. The primary endpoint was a composite outcome of all‐cause mortality and heart transplantation. The correlation between RAR and the composite outcome was assessed by the Kaplan–Meier survival analysis and the Cox regression analysis. Incremental predictive values and the clinical performance of RAR for all‐cause mortality or heart transplantation were also assessed based on a 12‐variable traditional risk model. The median follow‐up time in this study was 1433 (1341, 1525) days. As the gender no longer satisfied the Cox proportional risk assumption after 1150 days, we set 1095 days as the follow‐up time for analysis. A total of 500 patients reached the composite outcome. Multivariable Cox regression showed that per log2 increase of RAR was significantly associated with a 132.9% [hazard ratio 2.329, 95% confidence interval (CI) 1.677–3.237, P

Abstract Objective To enhance the detection, management and monitoring of Chinese children afflicted with sitosterolemia by examining the physical characteristics and genetic makeup of pediatric patients. Methods In this group, 26 children were diagnosed with sitosterolemia, 24 of whom underwent genetic analysis. Patient family medical history, physical symptoms, tests for liver function, lipid levels, standard blood tests, phytosterol levels, cardiac/carotid artery ultrasounds, fundus examinations, and treatment were collected. Results The majority (19, 73.1%) of the 26 patients exhibited xanthomas as the most prevalent manifestation. The second most common symptoms were joint pain (7, 26.9%) and stunted growth (4, 15.4%). Among the 24 (92.3%) patients whose genetics were analyzed, 16 (66.7%) harbored ABCG5 variants (type 2 sitosterolemia), and nearly one-third (8, 33.3%) harbored ABCG8 variants (type 1 sitosterolemia). Additionally, the most common pathogenic ABCG5 variant was c.1166G > A (p.Arg389His), which was found in 10 patients (66.7%). Further analysis did not indicate any significant differences in pathological traits among those carrying ABCG5 and ABCG8 variations (P > 0.05). Interestingly, there was a greater abundance of nonsense variations in ABCG5 than in ABCG8 (P = 0.09), and a greater frequency of splicing variations in ABCG8 than ABCG5 (P = 0.01). Following a change in diet or a combination of ezetimibe, the levels of cholesterol and low-density lipoprotein were markedly decreased compared to the levels reported before treatment. Conclusion Sitosterolemia should be considered for individuals presenting with xanthomas and increased cholesterol levels. Phytosterol testing and genetic analysis are important for early detection. Managing one’s diet and taking ezetimibe can well control blood lipids.

Abstract Background Ecosystems are brimming with myriad compounds, including some at very low concentrations that are indispensable for insect survival and reproduction. Screening strategies for identifying active compounds are typically based on bioassay-guided approaches. Results Here, we selected two candidate odorant receptors from a major pest of cruciferous plants—the diamondback moth Plutella xylostella—as targets to screen for active semiochemicals. One of these ORs, PxylOR16, exhibited a specific, sensitive response to heptanal, with both larvae and adult P. xylostella displaying heptanal avoidance behavior. Gene knockout studies based on CRISPR/Cas9 experimentally confirmed that PxylOR16 mediates this avoidance. Intriguingly, rather than being involved in P. xylostella–host plant interaction, we discovered that P. xylostella recognizes heptanal from the cuticular volatiles of the parasitoid wasp Cotesia vestalis, possibly to avoid parasitization. Conclusions Our study thus showcases how the deorphanization of odorant receptors can drive discoveries about their complex functions in mediating insect survival. We also demonstrate that the use of odorant receptors as a screening platform could be efficient in identifying new behavioral regulators for application in pest management.

There is a worldwide agreement to proactively enhance public health (PH) to mitigate potential challenges posed by future health crises. Alterations in social factors, including financial policy, serve as determinants of PH. Green finance policy (GFP) represents a groundbreaking innovation in financial policy. GFP addresses the shortcomings of traditional finance and serves as a key driver in promoting PH. This study establishes a theoretical framework on GFP’s impact on PH and employs the differences-in-differences method for validation. First, GFP has a significant positive impact on PH. Second, the impact mechanisms are green industry development, green governance investment, and green food supply. Third, the benchmark results are pronounced in regions with a high level of financial development and none ‘Atmospheric Ten’ policy pilot. This study explores the significant impact of GFP on PH, examining theoretical frameworks and empirical evidence. It offers valuable empirical insights and policy recommendations for governments. Governments should persist in refining green financial policies while pursuing economic development. Simultaneously, society should prioritise the construction of green PH facilities, widely promote the concept of green living, and cultivate a sustainable living environment.

Plums (Prunus salicina and Prunus domestica) are prevalent in southwestern China, and have attracted interest owing to their delectable taste and exceptional nutritional properties. Therefore, this study aimed to investigate the nutritional and flavor properties of plum to improve its nutritional utilization. Specifically, we determined the soluble sugars, organic acids, and phenolic components in 86 accessions using high-performance liquid chromatography. Notably, glucose, fructose, malic, and quinic acids were the predominant sweetness and acidity in plums, with sucrose contributing more to the sweetness of the flesh than the peel. Moreover, The peel contains 5.5 fold more phenolics than flesh, epicatechin, gallic acid, and proanthocyanidins C1 and B2 were the primary sources of astringency. Correlation and principal component analyses showed eight core factors for plum flavor rating, and a specific rating criterion was established. Conclusively, these findings provide information on the integrated flavor evaluation criteria and for enhancing optimal breeding of plums.

AURKA, also known as Aurora kinase A, is a key molecule involved in the occurrence and progression of cancer. It plays crucial roles in various cellular processes, including cell cycle regulation, mitosis, and chromosome segregation. Dysregulation of AURKA has been implicated in tumorigenesis, promoting cell proliferation, genomic instability, and resistance to apoptosis. In this study, we conducted an extensive bibliometric analysis of research focusing on Aurora-A in the context of cancer by utilizing the Web of Science literature database. Various sophisticated computational tools, such as VOSviewer, Citespace, Biblioshiny R, and Cytoscape, were employed for comprehensive literature analysis and big data mining from January 1998 to September 2023.The primary objectives of our study were multi-fold. Firstly, we aimed to explore the chronological development of AURKA research, uncovering the evolution of scientific understanding over time. Secondly, we investigated shifting trends in research topics, elucidating areas of increasing interest and emerging frontiers. Thirdly, we delved into intricate signaling pathways and protein interaction networks associated with AURKA, providing insights into its complex molecular mechanisms. To further enhance the value of our bibliometric analysis, we conducted a meta-analysis on the prognostic value of AURKA in terms of patient survival. The results were visually presented, offering a comprehensive overview and future perspectives on Aurora-A research in the field of oncology. This study not only contributes to the existing body of knowledge but also provides valuable guidance for researchers, clinicians, and pharmaceutical professionals. By harnessing the power of bibliometrics, our findings offer a deeper understanding of the role of AURKA in cancer and pave the way for innovative research directions and clinical applications.

Background: There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC. Results: Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34–52 %) with two cycles and 33 % (95%CI, 22–45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28–50 %) and 56 % (95%CI, 44–68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21–50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15–35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates. Conclusion: There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.

Abstract Background Prader-Willi syndrome (PWS) is a rare genetic disease often associated with bone problems, mainly scoliosis and hip dysplasia (HD). This study aimed to analyze the clinical characteristics of orthopedic deformities in patients with PWS. Methods A retrospective study was conducted on 175 patients up to March 2023. The Cobb angle(CA) of the spine, the alpha angle of the hip joint, and the acetabular index (AI) were measured. This study aimed to evaluate the relationship between demographic parameters and bone deformities. Results Scoliosis was found in 66 patients (43.7%), including 52 (78.8%) with mild scoliosis, 10 (15.2%) with moderate scoliosis, and 4 (6.1%) with severe scoliosis. Only seven patients received orthopedic treatment (10.6%). The median age of scoliosis was 4.5 years old, and the prevalence of scoliosis increased rapidly at the age of 5 years and adolescence. The mean CA in this study increased gradually with age. HD was found in 47 patients (38.2%), and 6 patients received orthopedic treatment (12.7%). The median age at HD was 1.8 years old. The mean AI of the study population decreased with age. The prevalence of HD treated with recombinant human growth hormone (rhGH) was low. No significant differences were observed in sex, genotype, body mass index (BMI), obesity rate, or onset of scoliosis and HD. Conclusion The prevalence of scoliosis and HD was higher in patients with PWS. The onset age and developmental trends of the different skeletal malformations were different. Early diagnosis and treatment are important for the prognosis and treatment of orthopedic diseases in patients with PWS.

Abstract Background MiRNAs are involved in the occurrence and development of many diseases. Extensive literature studies have demonstrated that miRNA-disease associations are stratified and encompass ~ 20% causal associations. Computational models that predict causal miRNA-disease associations provide effective guidance in identifying novel interpretations of disease mechanisms and potential therapeutic targets. Although several predictive models for miRNA-disease associations exist, it is still challenging to discriminate causal miRNA-disease associations from non-causal ones. Hence, there is a pressing need to develop an efficient prediction model for causal miRNA-disease association prediction. Results We developed DNI-MDCAP, an improved computational model that incorporated additional miRNA similarity metrics, deep graph embedding learning-based network imputation and semi-supervised learning framework. Through extensive predictive performance evaluation, including tenfold cross-validation and independent test, DNI-MDCAP showed excellent performance in identifying causal miRNA-disease associations, achieving an area under the receiver operating characteristic curve (AUROC) of 0.896 and 0.889, respectively. Regarding the challenge of discriminating causal miRNA-disease associations from non-causal ones, DNI-MDCAP exhibited superior predictive performance compared to existing models MDCAP and LE-MDCAP, reaching an AUROC of 0.870. Wilcoxon test also indicated significantly higher prediction scores for causal associations than for non-causal ones. Finally, the potential causal miRNA-disease associations predicted by DNI-MDCAP, exemplified by diabetic nephropathies and hsa-miR-193a, have been validated by recently published literature, further supporting the reliability of the prediction model. Conclusions DNI-MDCAP is a dedicated tool to specifically distinguish causal miRNA-disease associations with substantially improved accuracy. DNI-MDCAP is freely accessible at http://www.rnanut.net/DNIMDCAP/ .

Abstract Aims Heart failure (HF) and sleep‐disordered breathing (SDB) frequently coexist. We aimed to compare the prognostic value of different nocturnal hypoxic burden metrics in hospitalized HF patients. Methods and results HF patients underwent polygraphy screening for SDB in this prospective cohort. Hypoxic burden metrics assessed using pulse oximetry included time 52.0 min (HR 1.56, 95% CI: 1.21–2.02, P = 0.001) had a greater risk of the composite outcome than those with T90 95%, meanSO2

Background: The pathogenesis of diabetes and its microvascular complications are intimately associated with renin angiotensin system dysregulation. Evidence suggests the angiotensin converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang 1–7)/Mas receptor (MasR) axis regulates metabolic imbalances, inflammatory responses, reduces oxidative stress, and sustains microvascular integrity, thereby strengthening defences against diabetic conditions. This study aims to conduct a comprehensive analysis of the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications over the past two decades, focusing on key contributors, research hotspots, and thematic trends. Methods: This cross-sectional bibliometric analysis of 349 English-language publications was performed using HistCite, VOSviewer, CiteSpace, and Bibliometrix R for visualization and metric analysis. Primary analytical metrics included publication count and keyword trend dynamics. Results: The United States, contributing 105 articles, emerged as the most productive country, with the University of Florida leading institutions with 18 publications. Benter IF was the most prolific author with 14 publications, and Clinical Science was the leading journal with 13 articles. A total of 151 of the 527 author's keywords with two or more occurrences clustered into four major clusters: diabetic microvascular pathogenesis, metabolic systems, type 2 diabetes, and coronavirus infections. Keywords such as “SARS”, “ACE2”, “coronavirus”, “receptor” and “infection” displayed the strongest citation bursts. The thematic evolution in this field expanded from focusing on the renin angiotensin system (2002–2009) to incorporating ACE2 and diabetes metabolism (2010–2016). The latter period (2017–2023) witnessed a significant surge in diabetes research, reflecting the impact of COVID-19 and associated conditions such as diabetic retinopathy and cardiomyopathy. Conclusions: This scientometric study offers a detailed analysis of the ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications, providing valuable insights for future research directions.

Abstract Fish dietary niche is a core focus, and it reflects the diversity of resources, habitats, or environments occupied by a species. However, whether geographic segregation among different populations triggers dietary diversification and concomitant fish niche shift remains unknown. In the present study, we selected the Black Amur bream (Megalobrama terminalis) is a migratory fish species that plays an important role in the material transfer and energy cycling of river ecosystems, inhabiting southern China drainage with multiple geographic populations. Here, we utilized the combined analyses of 18S rDNA high‐throughput sequencing in fish gut contents and fatty acid (FA) in muscle tissues to evaluate potential spatial patterns of habitat and resource use for M. terminalis in three rivers of southern China. Our results showed that prey items of the Xijiang (XR) population (Pearl River) exhibited the highest species diversity and richness among the three geographic populations. Moreover, diet composition of M. terminalis was affected by spatial differences associated with geographic segregation. Analyses of FA biomarkers indicated that the highest levels of C16:0, C18:3n‐3, and C18:2n‐6c were found in Wanquan (WS) population (Wanquan River). The XR population exhibited a distinct FA profile characterized by higher amounts of arachidonic acid (ARA) and docosahexaenoic acid (DHA). The Moyang (MY) population (Moyang River) acted as the linkage between WS and XR populations and consisted of middle levels of saturated FAs (SFAs) and polyunsaturated FAs (PUFAs). The XR population displayed a greater FA niche width compared with WS population. Furthermore, we observed a close positive relationship between the niche width and α‐diversity indices of dietary resources for FA proflies. Our study provides valued information to develop different conservation strategies among different populations and improve fisheries management for M. terminalis and other endemic species in local rivers.

Abstract Objective To characterize the phenotype spectrum, diagnosis, and response to growth‐promoting therapy in patients with ACAN variants causing familial short stature. Methods Three families with ACAN variants causing short stature were reported. Similar cases in the literature were summarized, and the genotype and phenotype were analyzed. Results Three novel heterozygous variants, c.757+1G>A, (splicing), c.6229delG, p.(Asp2078Tfs*1), and c.6679C>T, p.(Gln2227*) in the ACAN gene were identified. A total of 314 individuals with heterozygous variants from 105 families and 8 individuals with homozygous variants from 4 families were confirmed to have ACAN variants from literature and our 3 cases. Including our 3 cases, the variants reported comprised 33 frameshift, 39 missense, 23 nonsense, 5 splicing, 4 deletion, and 1 translocation variants. Variation points are scattered throughout the gene, while exons 12, 15, and 10 were most common (25/105, 11/105, and 10/105, respectively). Some identical variants existing in different families could be hot variants, c.532A>T, p.(Asn178Tyr), c.1411C>T, p.(Gln471*), c.1608C>A, p.(Tyr536*), c.2026+1G>A, (splicing), and c.7276G>T, p.(Glu2426*). Short stature, early‐onset osteoarthritis, brachydactyly, midfacial hypoplasia, and early growth cessation were the common phenotypic features. The 48 children who received rhGH (and GnRHa) treatment had a significant height improvement compared with before (−2.18 ± 1.06 SD vs. −2.69 ± 0.95 SD, p

Background This study investigated the association of sex with cardiovascular outcomes in a prospective cohort of patients with heart failure (HF) with obstructive sleep apnea or central sleep apnea. Methods and Results Patients were screened for sleep apnea on admission using multichannel cardiopulmonary monitoring from May 2015 to July 2018. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for worsening HF. Ultimately, 453 patients with HF with obstructive sleep apnea or central sleep apnea were included; 71 (15.7%) and 382 (84.3%) were women and men, respectively. During a median follow‐up of 2.33 years, 248 (54.7%) patients experienced the primary outcome. In the overall population, after adjusting for potential confounders, women had an increased risk of the primary outcome (66.2% versus 52.6%; hazard ratio [HR], 1.47 [95% CI, 1.05–2.04]; P=0.024) and HF rehospitalization (62.0% versus 46.6%; HR, 1.55 [95% CI, 1.10–2.19]; P=0.013) compared with men but a comparable risk of cardiovascular death (21.1% versus 23.3%; HR, 0.78 [95% CI, 0.44–1.37]; P=0.383). Likewise, in patients with HF with obstructive sleep apnea, women had a higher risk of the primary outcome (81.8% versus 46.3%, HR, 2.37 [95% CI, 1.28–4.38]; P=0.006) and HF rehospitalization (81.8% versus 44.7%, HR, 2.46 [95% CI, 1.32–4.56], P=0.004). However, in patients with HF with central sleep apnea, there was no statistically significant difference between women and men. Conclusions In hospitalized patients with HF, female sex was associated with an increased risk of the primary outcome and HF rehospitalization, especially in those with obstructive sleep apnea. Screening for sleep apnea should be emphasized to improve the prognosis. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.

Leaf-mining flies (Diptera: Agromyzidae) are a diverse family of small-bodied insects that feed on living plant tissues as larvae. Various species in this family are considered globally invasive and have caused great agricultural economic losses. In China, economically important vegetable crops have been seriously damaged by these pest insects, especially by species of the genus Liriomyza. However, these species are difficult to differentiate because of their morphological similarities, and the Chinese fauna remains poorly known. To explore the relevant pest species in China and their phylogeny, agromyzid leafminers were collected from 2016 to 2019, and identified based on morphological characteristics and DNA barcodes. In total, 27 species from five genera of Agromyzidae were sampled and identified, including 16 species of Liriomyza. Both mitochondrial and nuclear genes were used to reconstruct their phylogenetic relationships and estimate the divergence time. Highly congruent and well-supported phylogenetic trees were obtained using the Bayesian inference and maximum-likelihood methods. This analysis revealed two main clades in Liriomyza, and clade 2 was inferred to have diverged from clade 1 approximately 27.40 million years ago (95% highest posterior density: 23.03–31.52 million years ago) in the Oligocene. Differences were observed in the distribution patterns and host associations between the Liriomyza clades. Clade 2 species are distributed in cool, high-latitude environments, suggesting that they may have evolved into a cool-adapted lineage.

Abstract Background This study aimed to examine the direct and indirect pathways from childhood socioeconomic status (SES) to the prevalence of edentulism in mid-to-late age Chinese individuals using structural equation modeling (SEM). Methods This study analyzed data from 17,032 mid- to-late age Chinese individuals in the 2014 and 2015 China Health and Retirement Longitudinal Study (CHARLS). Childhood SES was determined based on the parents’ education and occupation, financial situation of the family, primary residence, food availability, and medical convenience. Adulthood SES was established according to educational achievements of the individuals. Edentulism is defined as the loss of all natural teeth. SEM was used to examine the statistical significance of the association between childhood SES and edentulism, mediated by childhood health, adulthood SES, and adult health. Results Childhood SES had significant indirect (β = -0.026, p

Abstract Aim To explore the relationship between the serum sodium level on admission and all‐cause mortality in HF patients. Design A single‐center retrospective cohort study. Methods Patients hospitalized with HF at the Heart Failure Center, Fuwai Hospital, from November 2008 to November 2018 were enrolled. Results A total of 3649 patients were included, and the mean sodium level was 137.19 ± 4.36 mmol/L, with a range from 115.6 to 160.9 mmol/L. During a median follow‐up of 1101 days, mortality occurred in 1413 (38.7%) hospital survivors. After adjustment for age, sex, and other potential confounders, patients with sodium levels

Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing’s syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients’ circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.

Chromodomain helicase DNA-binding protein 1 like (CHD1L) is an oncogene that promotes tumor progression, metastasis, and multidrug resistance. CHD1L expression is indicative of poor outcomes and low survival in cancer patients with various cancer types. Herein, we report a set of CHD1L inhibitors (CHD1Li) discovered from high-throughput screening and evaluated using enzyme inhibition, 3D tumor organoid cytotoxicity and mechanistic assays. The structurally distinct compounds 8-11 emerged as hits with promising bioactivity by targeting CHD1L. CHD1Li were further examined for their stability in human and mouse liver microsomes, which showed compounds 9 and 11 to be the most metabolically stable. Additionally, molecular modeling studies of CHD1Li with the target protein shed light on key pharmacophore features driving CHD1L binding. Taken together, these results expand the chemical space of CHD1Li as a potential targeted therapy for colorectal cancer and other cancers.

Purpose: To examine the use of multimodal data and multi-omics strategies for optic nerve disease screening. Methods: This was a single-center retrospective study. A deep learning model was created from fundus photography and infrared reflectance (IR) images of patients with diabetic optic neuropathy, glaucomatous optic neuropathy, and optic neuritis. Patients who were seen at the Ophthalmology Department of First Affiliated Hospital of Nanchang University in Jiangxi Province from November 2019 to April 2023 were included in this study. The data were analyzed in single and multimodal modes following the traditional omics, Resnet101, and fusion models. The accuracy and area-under-the-curve (AUC) of each model were compared. Results: A total of 312 images fundus and infrared fundus photographs were collected from 156 patients. When multi-modal data was used, the accuracy of the traditional omics mode, Resnet101, and fusion models with the training set were 0.97, 0.98, and 0.99, respectively. The accuracy of the same models with the test sets were 0.72, 0.87, and 0.88, respectively. We compared single- and multi-mode states by applying the data to the different groups in the learning model. In the traditional omics model, the macro-average AUCs of the features extracted from fundus photography, IR images, and multimodal data were 0.94, 0.90, and 0.96, respectively. When the same data were processed in the Resnet101 model, the scores were 0.97 equally. However, when multimodal data was utilized, the macro-average AUCs in the traditional omics, Resnet101, and fusion modesl were 0.96, 0.97, and 0.99, respectively. Conclusion: The deep learning model based on multimodal data and multi-omics strategies can improve the accuracy of screening and diagnosing diabetic optic neuropathy, glaucomatous optic neuropathy, and optic neuritis.

ABSTRACTMalignant pleural effusion (MPE) is a functional ‘cold’ tumor microenvironment in which the antitumor activity of CD8+ T cells and natural killer T (NKT)-like cells is suppressed and the function of regulatory T (Treg) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detected a distinct subset of NKT-like cells expressing FOXP3 in MPE. Through single-cell RNA sequencing (scRNA-seq) analysis, we found that the glycolysis pathway and pyruvate metabolism were highly activated in FOXP3+ NKT-like cells. Similar to Treg cells, FOXP3+ NKT-like cells highly expressed monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase B to uptake and utilize lactate, thereby maintaining their immunosuppressive function and hyperlactylation in MPE. Furthermore, we found that MCT1 small molecule inhibitor 7ACC2 significantly reduced FOXP3 expression and histone lactylation levels in NKT-like cells in vitro. In conclusion, we reveal for the first time the altered phenotypic and metabolic features of FOXP3+ NKT-like cells in human MPE.

Abstract Objective Previous reports on the epidemiology, influencing factors, and the prognostic value of the components of PR interval in hospitalized heart failure patients were limited. Methods This study retrospectively enrolled 1182 patients hospitalized with heart failure from 2014 to 2017. Multiple linear regression analysis was used to explore the association between the components of PR interval and the baseline parameters. The primary outcome was all-cause death or heart transplantation. Multivariable-adjusted Cox proportional hazard regression models were constructed to explore the predictive value of the components of PR interval for the primary outcome. Results In multiple linear regression analysis, higher height (for every 10 cm increase in height: regression coefficient 4.83, P

Highlights 1. Cycloplegic drugs have effects on the ocular biological parameters of children at different ages. 2. The effects of different types of cycloplegic drugs were almost the same in children within the same age groups. 3. There were significant differences in the effects of different types of cycloplegic drugs on ocular biological parameters in children of different age groups.

The effects of gamma-aminobutyric acid (GABA) on aquatic animals remain to be explored. Here, we conducted GABA addition tests, both in water and in feed, as well as ammonia stress tests using Micropterus salmoides (M. salmoides). The tissue structure and indicators associated with the oxidative state of M. salmoides were evaluated to assess the effects. The results showed that, the levels of alanine aminotransferase, alkaline phosphatase, and total antioxidant capacity in most of the GABA water addition groups were lower than those in the control group at 96 h after the addition of GABA. In the gill of feed addition groups (GL: 30 mg kg−1; GM: 90 mg kg−1; GH: 150 mg kg−1), the contents of glutathione (GSH) in the GH group were significantly higher when compared with their control group (CK group: 0 mg kg−1) at day 12 and day 15. In the following ammonia stress test, the tissue damage of the gill, brain, and kidney were alleviated in the GM and GH groups. The GSH contents of all tissues in all groups decreased gradually with the prolongation of the stress time. Conversely, the malondialdehyde (MDA) and nitric oxide (NO) contents have the opposite trend. The results suggested that GABA addition in water may not be applicable in actual aquaculture. The inclusion of GABA in the feed at concentrations of 90 and 150 mg kg−1 contributed to improving the ammonia resistance of M. salmoides by reducing tissue damage and the inflammatory response, as well as improving the antioxidant status. Moreover, the gill might be the target tissue protected by GABA in M. salmoides under ammonia stress. These results could enrich our basic understanding of the effect of GABA on aquatic animals and help us find possible ways to solve the environmental stress problems in aquaculture.

Objectives: Despite the many reported studies on macrophages in ulcerative colitis (UC), the overall research trends in this field are unclear. This study evaluates the research trends and hotspots regarding macrophages in UC using bibliometric analysis. Methods: A systematic search was conducted in the Web of Science database to identify publications related to macrophages in UC from 2012 to 2021. R package ‘bibliometrix’, VOSviewers, CiteSpace and Microsoft Excel were utilised for the bibliometric analysis. Results: 1074 articles published between 2012 and 2021 were analysed. The number of publications on macrophages in UC showed a consistently increasing trend, with USA and China as the leading contributors to this field. Notably, Georgia State University and Nanjing University contributed significantly to this field. Among the authors, Wang Y had the highest productivity, while Wu X received the most citations. The journal Gut was identified as the most authoritative journal in this field. Co-citation analysis revealed that the exploration of the mechanisms of macrophages in UC through in vivo and in vitro experiments was the primary focus of research. Moreover, the emerging research hotspots included keywords such as ‘macrophage polarization’, ‘gut microbiota’ and ‘NLRP3 inflammasome’. Conclusions: Research on macrophages in UC holds significant value and practical implications. Additionally, China demonstrated prolific output in this field, while the USA had the most influential contributions. Currently, research hotspots are centred around the modulation of gut microbiota to regulate macrophage polarization and macrophage pyroptosis as potential strategies for mitigating UC.

IntroductionChildhood eating behaviors and temperament may have important implication for constructing the pathways from maternal feeding practices to childhood overweight and obesity (OW/OB). Examining multiple feeding styles simultaneously to childhood OW/OB is critical through the mediators of early childhood temperament and eating behaviors.MethodsThis cross-sectional study recruited mothers mainly responsible for child care from two hospitals and two healthcare centers in eastern China. Sociodemographic characteristics, and data from the Infant Feeding Style Questionnaire (IFSQ), the short form of Children Behavior Questionnaire [Revised (IBQ-RSF)], and the Child Eating Behavior Questionnaire for toddler (CEBQ-T) were collected. Weight and recumbent length were measured to calculate the age- and sex-specific body mass index (BMI) z-scores (BMIz). The structural equation modeling (SEM) approach was used to examine direct and indirect pathways from five maternal feeding styles to childhood OW/OB through temperament and eating behaviors.ResultsA total of 486 children were recruited, 73 (15.02%) children were OW/OB; the age of the children was 14.55 (SD = 5.14) months, and the age of the mothers was 29.90 (SD = 3.63) years. The responsive feeding exerted significant direct (β = −0.098), indirect (β = −0.136) and total (β = −0.234) effects on childhood OW/OB. Restrictive feeding had significant direct (β = 0.222), indirect (β = 0.102) and total (β = 0.324) effects on childhood OW/OB. Indulgent feeding had significant direct (β = 0.220), indirect (β = 0.063), and total (β = 0.283) effects on childhood OW/OB. Pressuring feeding had significant direct (β = −0.116), indirect (β = −0.096) and total (β = −0.212) effects on childhood OW/OB.DiscussionThere was a direct effect of feeding practices on childhood OW/OB; feeding practices indirectly predicted childhood OW/OB through temperament and eating behaviors in children aged 6–23 months. This study could help governments agencies, policymakers, and healthcare workers to establish optimal intervention programs targeting feeding practices through childhood eating behaviors and temperament to prevent childhood OW/OB.

Ferroptosis, an established form of programmed cell death discovered in 2012, is characterized by an imbalance in iron metabolism, lipid metabolism, and antioxidant metabolism. Activated CD8 + T cells can trigger ferroptosis in tumor cells by releasing interferon-γ, which initiates the ferroptosis program. Despite the remarkable progress made in treating various tumors with immunotherapy, such as anti-PD1/PDL1, there are still significant challenges to overcome, including limited treatment options and drug resistance. In this review, we exam the potential biological significance of the ferroptosis phenotype using bioinformatics and review the latest advancements in understanding the mechanism of ferroptosis-mediated anti-tumor immunotherapy. Furthermore, we revisit the host immune system, immune microenvironment, ferroptotic defense system, metabolic reprogramming, and key genes that regulate the occurrence and resistance of ferroptosis of tumor cell. Additionally, several immune-combined ferroptosis treatment strategies were put forward to improve immunotherapy efficacy and to provide new insights into reversing anti-tumor immune drug resistance.

Variation in hydrological connectivity (HC) between rivers and lakes gives rise to periodic large water level fluctuation (WLF) in river-connected lakes (RCL). However, how WLF shapes the material cycling and concomitant trophodynamics of RCL remain unclear. Here we evaluated the resource availability, relative contributions of autochthonous and allochthonous carbon sources (by Bayesian mixing models) and trophic structure (using δ13C and δ15N) of Lake Poyang, the largest freshwater lake in China, during different hydrological periods. Terrestrial C3 plants in the aquatic/terrestrial transition zones (ATTZ) were the main supporter of aquatic consumers all year round. Compared with historical data, the contributions of autochthonous production to aquatic food webs were low. This is primarily ascribed to the influences of hydrological regimes in that the operation of Three Gorges Dam and HC changed the rhythm of WLF in Lake Poyang, restricting the production of aquatic vegetation and epiphytic algae. Most common fish species indicated higher trophic positions (TPs) during the dry than wet season, but only eleven of thirty-six common species showed a statistically significant increase (p

Abstract Background Prader–Willi syndrome (PWS) is a rare and multisystemic genetic disorder that is characterized by severe hypotonia, hyperphagia, short stature, and global developmental delay. Although early recombinant human growth hormone (rhGH) treatment has been proven to rescue some symptoms and bring additional benefits to PWS patients, studies in patients under 2 years old are scarce. Thus, this study aims to investigate the effectiveness and safety of rhGH treatment for young children. Methods A total of 96 genetically confirmed Chinese PWS infants or toddlers (47 males) followed between 2013 and 2022 were retrospectively analyzed. Sixty-five infants (early treatment group) started rhGH treatment during their first year, and 31 toddlers (later treatment group) started at the age of 1–2 years. Auxological parameters, carbohydrate metabolism parameters, thyroid function, liver function, insulin-like growth factor-1 (IGF-1), and radiographs were acquired before the initiation of the treatment and every 3–6 months thereafter. Height/length, weight, and weight for height were expressed as standard deviation scores (SDSs) according to WHO child growth standards. Results The mean SDS of length/height in the early treatment group was significantly higher than that in the later treatment group throughout the observation period (all P

Abstract Aims Heart failure (HF) remains a major public health problem with increasing prevalence in China. This study evaluated the clinical performance and quality measures for HF management to identify gaps in the standardization of care for patients hospitalized for HF in China. Methods and results Following the results of China‐HF stage I (2012–2015), the second stage of the China‐HF was launched in 2017. Among 113 hospitals with ≥100 cases, the China‐HF Stage II assessed the quality of care measures for HF and compared results with previous data in China and the US‐based Get with The Guidelines‐Heart Failure (GWTG‐HF) registries. In total, 34 938 patients hospitalized with HF were enrolled from January 2017 to October 2020. Echocardiographic left ventricular function and natriuretic peptide test were performed in 93.7% and 93.0% of the cases, respectively. Adherence to standardized guidelines in China‐HF stage II was higher than that in the China‐HF stage I, but generally lower than GWTG‐HF registry with 78.2% of eligible patients was prescribed oral diuretics, 78.7% renin‐angiotensin‐system inhibitors, and 82.2% beta‐blockers. Implantable cardioverter‐defibrillators and cardiac resynchronization devices were implanted in 3.9% and 14.6%, respectively. In contrast, the proportion of eligible patients discharged with spironolactone (87.8%) was higher than GWTG‐HF. The median length of hospitalization was 9 (6, 12) days, and 938 (2.8%) patients died or withdrew from treatment during hospitalization. Conclusions Despite significant improvements in the use of guideline‐recommended testing and therapy, there remain major gaps in quality of care for patients hospitalized for HF in China that are generally larger than gaps observed in the United States.

Abstract The effects of cycloplegia on ocular biological parameters in children have been extensively studied, but few studies have compared these parameters between different refractive states, ages, and sexes. Therefore, the purpose of this study was to investigate the changes in ocular biometry before and after cycloplegia in different groups based on dioptre, age and sex. We examined a total of 2049 participants in this cross-sectional study. A comprehensive eye examination was conducted before cycloplegia. Cycloplegia was implemented with the application of atropine or tropicamide. Ocular biological parameters were evaluated after cycloplegia, including axial length (AL), mean keratometry (K), flat keratometry (K1), steep keratometry (K2), central corneal thickness (CCT), anterior chamber depth (ACD) and white-to-white (WTW) distance. All the participants were categorized based on dioptre, age and sex. Statistical analysis was performed with paired t tests and Wilcoxon signed-rank tests. Regarding dioptre, AL was found to be increased significantly in the Fs, Ast and FA (p 0.05). Regarding sex, AL and WTW were found to decrease significantly among males and increase significantly among females (p

AIM: To observe the efficacy of different dosage regimens of ranibizumab in the treatment of choroid neovascularization secondary to pathological myopia(PM-CNV), and to explore the related factors affecting retreatment.METHODS: The medical records of 42 patients(43 eyes)diagnosed with PM-CNV in our hospital from January 2015 to January 2020 and treated with intravitreal injection of ranibizumab were retrospectively analyzed. According to different dosage regimens, they were divided into group A(3+PRN, 22 cases with 22 eyes)and group B(1+PRN, 20 cases with 21 eyes). Followed up for 12mo, the changes of best corrected visual acuity(BCVA), central macular thickness(CMT)and choroidal neovascularization(CNV)were observed and compared between the two groups. The times of intravitreal injection, retreatment rate and recurrence rate after initial treatment were compared between the two groups, and the related factors affecting retreatment were analyzed.RESULTS: At 1,3,6 and 12mo, the BCVA(LogMAR), CMT and CNV thickness in the two groups were significantly improved compared with those before treatment(P300μm and baseline CNV area >1.0mm2 were all related factors affecting retreatment.CONCLUSION: Intravitreal injection of ranibizumab 1+PRN and 3+PRN can both effectively improve the visual prognosis and anatomical structure of PM-CNV patients, but the 1+PRN treatment has less injection times than the 3+PRN treatment, which reduces the risk and cost of treatment.

Abstract Aims The prognostic significance of D‐dimer in hospitalized heart failure (HF) patients is incompletely characterized. We aimed to assess the association of D‐dimer levels on admission with adverse events at follow‐up in patients hospitalized with HF across all ejection fraction (EF) phenotypes. Methods and results Consecutive patients hospitalized from December 2006 to December 2017 for HF with D‐dimer and EF values available (n = 1795) were enrolled. Associations between D‐dimer and all‐cause death were examined at 1‐year follow‐up. Median age was 57 years, 73.4% were male, and the majority (72.1%) were in New York Heart Association Classes III–IV. EF was reduced in 53.3% (HFrEF), mildly reduced in 16.3% (HFmrEF), and preserved in 30.4% (HFpEF). Median (interquartile range) D‐dimer on admission was 0.56 (0.27–1.295) μg/mL FEU (fibrinogen‐equivalent unit) in the whole cohort, 0.64 (0.28–1.48) μg/mL FEU in HFrEF, 0.50 (0.27–1.03) μg/mL FEU in HFmrEF, and 0.495 (0.25–1.10) μg/mL FEU in HFpEF (P = 0.001). At 1‐year follow‐up, higher D‐dimer (D‐dimer ≥0.56 μg/mL FEU) independently predicted all‐cause death in total cohort [hazard ratio (HR) 1.55; 95% confidence interval (CI), 1.15–2.1], in HFrEF (HR, 1.49; P = 0.039), and in HFpEF (HR, 2.06; P = 0.033). However, no relationship was found for HFrEF or HFmrEF when D‐dimer was treated as quartiles. In sensitivity analysis, quantitatively similar but more pronounced association between D‐dimer and all‐cause death was observed in total cohort and HFpEF cohort. Conclusions In hospitalized HF patients, higher D‐dimer concentration was a significant and independent predictor of 1‐year all‐cause mortality. Across all HF phenotypes, this effect was most evident in HFpEF patients.

Background Although immune checkpoint blockade (ICB) therapy has shown remarkable benefits in cancers, a subset of patients with cancer exhibits unresponsiveness or develop acquired resistance due to the existence of abundant immunosuppressive cells. Tumor-associated macrophages (TAMs), as the dominant immunosuppressive population, impede the antitumor immune response; however, the underlying mechanisms have not been fully elucidated yet.Methods Single-cell RNA sequencing analysis was performed to portray macrophage landscape and revealed the underlying mechanism of component 1q (C1q)+ TAMs. Malignant pleural effusion (MPE) of human and mouse was used to explore the phenotypes and functions of C1q+ TAMs.Results C1q+ TAMs highly expressed multiple inhibitory molecules and their high infiltration was significantly correlated with poor prognosis. C1q+ TAMs promote MPE immunosuppression through impairing the antitumor effects of CD8+ T cells. Mechanistically, C1q+ TAMs enhance fatty acid binding protein 5 (FABP5)-mediated fatty acid metabolism, which activate transcription factor peroxisome proliferator-activated receptor-gamma, increasing the gene expression of inhibitory molecules. A high-fat diet increases the expression of inhibitory molecules in C1q+ TAMs and the immunosuppression of MPE microenvironment, whereas a low-fat diet ameliorates these effects. Moreover, FABP5 inhibition represses the expression of inhibitory molecules in TAMs and tumor progression, while enhancing the efficacy of ICB therapy in MPE and lung cancer.Conclusions C1q+ TAMs impede antitumor effects of CD8+ T cells promoting MPE immunosuppression. Targeting C1q+ TAMs effectively alleviates the immunosuppression and enhances the efficacy of ICB therapy. C1q+ TAMs subset has great potential to be a therapeutic target for cancer immunotherapy.

In aquatic animals, the gut microbiota has a significant function in host health and is impacted by the environmental microbiota. To conveniently monitor, assess and predict aquatic animals’ health, a general and effective microbiota health index (microHI) would be helpful, and the correlation between the aquatic environmental microHI and wildlife gut microHI could be expected. Here, we proposed a general microHI based on the microbial phenotypes of mobile element content, potential pathogenicity and oxidative stress tolerance, and then tested the reliability of the fish gut microHI and its correlation with the environmental microHI in the middle Yangtze River. The results showed that there were positive correlations among the abundance ratios of microbes with the microbial phenotypes of mobile element content, potential pathogenicity and oxidative stress tolerance, suggesting that defining the microHI using the average abundance ratios of microbes without these microbial phenotypes is suitable. Fish gut samples with a lower microHI were more likely to have been obtained from specimens with a disordered microbiota (always means unhealthy host), indicating that the gut microHI has the potential to be used to evaluate the health status of aquatic animals. In the middle Yangtze River, the aquatic environmental microHI had hundred-kilometers-scale high spatial heterogeneity but month-scale low temporal heterogeneity from June to September 2020, and in the section with a low aquatic environmental microHI, the fish gut samples were more likely to have relatively low gut microHIs, indicating that the environmental microHI has the potential to be used to predict the health status of aquatic animals at the community level. The current work initially showed the possibility of using environmental microHI to predict aquatic animals’ health although it was not very exact and precise. We encourage more researches to assess the quantitative relationship between the aquatic environmental microHI and aquatic animal gut microHI.

The transverse mode instability (TMI) is a thermal-optical effect, inducing a sudden deterioration of beam quality and average power. This non-linear effect will greatly limit the power scaling of fiber lasers. We demonstrate a direct pump modulation to mitigate TMI in a 30 μm-core-diameter all-fiber laser oscillator. It only relies on function generator and pump drivers without the need of feedback control units. The groups of pump LDs and pump drivers and the phase difference between the channels of function generator have a great impact on the beam stability. Compared with the TMI threshold 180 W in continuous wave (CW) mode, the maximum average output power of a stabilized beam is increased up to 310 W via a multi-parameter-based direct pump modulation.

In this study, a method of stabilizing the output beam of a large-mode-area fiber amplifier operating above the mode instability threshold is demonstrated. A mode control system based on the photonic lantern is used to excite dynamic mode beatings as the seeding stage of a 42/250 µm Yb-doped fiber amplifier. We propose a theoretical explanation for the validity of this method: provided that the mode interference patterns generated by input mode beatings are antisymmetric to those in the main amplifier caused by thermally induced non-linear effects, the refractive index grating will not be formed to indicate the onset of mode instability. Experimentally, significant mode stability and beam quality improvement have been achieved in this system at power levels of up to nearly four times the mode instabilities threshold.

Background Machine‐learning‐based prediction models (MLBPMs) have shown satisfactory performance in predicting clinical outcomes in patients with heart failure with reduced and preserved ejection fraction. However, their usefulness has yet to be fully elucidated in patients with heart failure with mildly reduced ejection fraction. This pilot study aims to evaluate the prediction performance of MLBPMs in a heart failure with mildly reduced ejection fraction cohort with long‐term follow‐up data. Methods and Results A total of 424 patients with heart failure with mildly reduced ejection fraction were enrolled in our study. The primary outcome was all‐cause mortality. Two feature selection strategies were introduced for MLBPM development. The “All‐in” (67 features) strategy was based on feature correlation, multicollinearity, and clinical significance. The other strategy was the CoxBoost algorithm with 10‐fold cross‐validation (17 features), which was based on the selection result of the “All‐in” strategy. Six MLBPMs with 5‐fold cross‐validation based on the “All‐in” and the CoxBoost algorithm with 10‐fold cross‐validation strategy were developed by the eXtreme Gradient Boosting, random forest, and support vector machine algorithms. The logistic regression model with 14 benchmark predictors was used as a reference model. During a median follow‐up of 1008 (750, 1937) days, 121 patients met the primary outcome. Overall, MLBPMs outperformed the logistic model. The “All‐in” eXtreme Gradient Boosting model had the best performance, with an accuracy of 85.4% and a precision of 70.3%. The area under the receiver‐operating characteristic curve was 0.916 (95% CI, 0.887–0.945). The Brier score was 0.12. Conclusions The MLBPMs could significantly improve outcome prediction in patients with heart failure with mildly reduced ejection fraction, which would further optimize the management of these patients.

Despite the emerging prevalence of left ventricular (LV) thrombus in dilated cardiomyopathy (DCM), clinical characteristics, management, and disease prognosis are poorly studied. We aim to assess the efficacy/safety profile of direct oral anticoagulants (DOACs) compared to warfarin by evaluating thrombus evolution, risk for stroke and systemic embolism (SSE), heart failure (HF) rehospitalization, all-cause mortality, and major adverse cardiovascular events (MACEs), and determine the impact of thrombus evolution on adverse events. We performed a historical cohort study of patients with a primary diagnosis of DCM and LV thrombus. Relationships between anticoagulants and thrombus resolution were analyzed with the Kaplan-Meier method and Cox regression. Associations between longitudinal thrombus evolution and adverse event hazard were measured with joint modeling. Among 122 patients included, 58.0% were prescribed warfarin, and 42.0% DOACs. Complete thrombus resolution at 90-day-after-index and 180-day-after-index was observed in 93 and 111 patients, with no difference in cumulative resolution between DOACs and warfarin. During a median follow-up of 12.5 months, MACE, all-cause death, SSE, and HF rehospitalization occurred in 42.6%, 27.9%, 4.1%, and 13.9% of patients, comparable in warfarin and DOACs groups. Thrombus persistence was associated with a higher risk of HF rehospitalization. Thrombus progression was associated with poor prognosis, with per unit increment in square-root-transformed thrombus-area resulting in a 1.0691-fold increase in MACE risk and a 1.0546-fold increase in death risk. This study suggests that in DCM patients with LV thrombus, DOACs were comparable to warfarin in thrombus resolution and safety profile. Thrombus persistence or progression was associated with an increased risk of HF rehospitalization, MACE, and mortality.

The prediction of the water film depth (WFD) on the road surface can help with road skid resistance research and reduce the risk associated with driving on rainy days. At present, there are many empirical and analytical models based on drainage length, slope, rainfall intensity and other parameters. Considering the influence of road surface runoff and starting from the Reynolds number formula of road surface water flow, a new road surface WFD calculation formula that considers the movement state of laminar water flow is derived. The results show that the changing trends of various parameters in the prediction model (drainage length, rainfall intensity, road slope) affecting WFD are consistent with those of the existing model. It is also found that the initial water film depth, initial speed of rainwater, and rainfall angle have little impact on WFD. The predicted value of the model has a suitable matching degree compared with the classical empirical model, which provides a new approach to the prediction of road water film depth.