Defense against Paramecium predation via long filament morphology favors the survival of Raphidiopsis raciborskii populations.

Raphidiopsis blooms are notorious for cyanotoxin formation and strong invasiveness, threatening the stability of aquatic ecosystems and human health. The protozoa Paramecium can potentially serve as an organism for controlling Raphidiopsis blooms owing to its grazing effect. However, the grazing ability of Paramecium is largely determined by the size of the prey, and the population of Raphidiopsis consists of filaments of varying lengths and sizes. The selective grazing behavior of Paramecium toward short-length or small-sized filaments in the Raphidiopsis population, as opposed to long filaments, remains unclear. Therefore, in this study, we co-cultured the predator Paramecium sp. with different initial abundances and the prey Raphidiopsis raciborskii to explore this knowledge gap. Our results suggested that: (1) the population of R. raciborskii declined under the selective grazing effect of Paramecium sp. on short filaments, whereas R. raciborskii with long filaments survived; (2) the growth of Paramecium sp. feeding on the same abundance of R. raciborskii was reduced at higher initial abundances, whereas its carrying capacity exhibited an opposite trend; (3) under ingestion by Paramecium sp., the morphology of R. raciborskii developed in the direction of becoming larger, and higher initial abundances of Paramecium sp. intensified this process; (4) increasing initial abundance of Paramecium sp. aggravated the decline of R. raciborskii photosynthetic activity. Therefore, the grazing effect of Paramecium sp. on R. raciborskii mainly affects filaments of short length or small size. Collectively, these results clarify the inter-species interaction between the protozoa Paramecium and filamentous cyanobacteria Raphidiopsis, including population dynamics and morphological and physiological changes in the predator and prey. Such insights into the interactions between Paramecium and R. raciborskii may have implications for the biological control of blooms caused by filamentous cyanobacteria.

Unequal Health Burden from Air Pollution among Minors in Education.

Air pollution exposure has been linked to a variety of adverse health outcomes among minors; yet little is known about the associated health inequity across regions and schools. Here, we assessed the unequal health burden linked to particulate matter exposure among minors of 10,358 schools in China through 12,439,232 individual health records. Our findings highlight the persistent health risks with superlinear concentration-response patterns and following inverted U-shaped risk trends, that each 10 µg/m3 increase in PM2.5 exposure resulted in 4.1% (3.9-4.2%) additional school absenteeism risk. Compared to urban well-built schools, minors in rural poor-built schools experienced significantly higher exposure and slower rate of risk reduction and had over 80.0% less medical resources while bearing 145.2% of the health burden. Disparities in pollution exposure, built environment, and resource allocation are intertwined to shape the health inequity pattern, especially between rural and urban schools. These findings underscore the urgency for persistent efforts aimed at disadvantaged schools to reduce pollution exposure and equitably distribute social resources, ultimately securing an impartial health-centered education for minors.

Stellate ganglion block for visceral pain in elderly patients undergoing video-assisted thoracoscopic lung cancer surgery: a randomized, controlled trial.

BACKGROUND: Visceral pain occurs commonly following thoracic surgery, but an effective method to relieve visceral pain in thoracic surgery remains controversial. We test the effect of stellate ganglion blocks (SGB) on perioperative visceral pain following video-assisted thoracoscopic surgery (VATS). METHODS: A prospective, randomized, controlled trial enrolled 77 elderly patients undergoing VATS. Patients were randomized to SGB followed by modified intercostal nerve block (Group S, n=37); or modified intercostal nerve block only (Group C, n=40). Remifentanil 0.02-0.2 µg·kg-1·min-1 was titrated to keep pain threshold index values between 40-65 and maintain mean arterial pressure or heart rate values around 20% of baseline values. Patient-controlled intravenous analgesia with sufentanil was used in the postoperative period. The co-primary outcomes were the perioperative cumulative opioid consumption and pain scores on movement at 24 h after surgery. RESULTS: Compared with control group, SGB greatly reduced the intraoperative remifentanil consumption[300.00(235.00-450.00)µg versus 710.00(500.00-915.00)µg; P<0.01], with no difference in cumulative sufentanil consumption to 48h post-surgery. There was a statistically significant difference in pain scores on movement at 24h between groups [4.00(3.00-4.00) versus 4.00(3.25-5.00); P=0.01]. Further exploratory analyses showed significant difference for intra-chest pain on movement at 24h [3.00(2.00-3.00) versus 3.00(2.25-4.00); P=0.01]. No significant difference was observed in nausea/vomiting, time to pass flatus and postoperative length of stay. CONCLUSION: Preoperative stellate ganglion blocks for elderly patients could effectively blunt intraoperative visceral stress and reduce postoperative visceral pain extending 24 h after VATS. This initial finding deserve further investigation.

PPA1 promotes adipogenesis by regulating the stability of C/EBPs.

Adipogenesis significantly contributes to healthy adipose tissue expansion in obesity. Increasing adipocyte number or function to alleviate adipose tissue overload could serve as a therapeutic strategy for both lipodystrophy and obesity-related metabolic syndrome. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate (PPi) and is involved in many biochemical reactions, but its function in adipose tissue has not been studied previously. In this study, we demonstrated that adipose-specific PPA1 knockout (PPA1AKO) mice showed lipodystrophy and spontaneously developed hepatic steatosis and severe insulin resistance under normal chow diet feeding. PPA1 deficiency suppressed the differentiation of primary adipocyte precursors and 3T3-L1 cells. Notably, PPA1 overexpression can restore inhibited adipogenesis in preadipocytes isolated from db/db mice and type 2 diabetes patients. Mechanistic studies have revealed that PPA1 acts as a positive regulator of early adipocyte differentiation by promoting CCAAT/enhancer-binding proteinß and δ (C/EBPß and δ) protein stability. Moreover, the function of PPA1 in adipogenesis is independent of its PPi catalytic activity. Collectively, our in vivo and in vitro findings demonstrated that PPA1 is a novel critical upstream regulator of adipogenesis, controlling adipose tissue development and whole-body metabolic homeostasis.

Effect of Overheating on the Tensile Properties of Nickel-Based Superalloy GH4720Li.

Aero-engines can be exposed to One Engine Inoperative (OEI) conditions during service, and the resulting overheating effect may significantly impact their structural integrity and flight safety. This paper focuses on the influence of overheating on the microstructural evolution and tensile properties of the GH4720Li alloy, a nickel-based polycrystalline superalloy commonly used in turbine disks. Based on the typical OEI operating conditions of a real aero-engine, a series of non-isothermal high-temperature tensile tests involving an OEI stage of 800 °C were conducted. The effects of OEI-induced overheating on the microstructure and tensile properties of the GH4720Li alloy were investigated. The results showed that, after OEI treatment, the primary γ' phase in this alloy was partially dissolved. The GH4720Li superalloy also exhibited numerous microcracks at the grain boundaries, resulting in complex effects on its tensile properties. The alloy's yield strength and ultimate tensile strength were slightly decreased, whereas its ductility decreased considerably. The OEI-induced embrittlement phenomenon was mainly caused by the non-uniform distribution of the tertiary γ' phase within grains. The formation of microcracks nucleated at the interfaces between the primary γ' precipitates and γ matrix phase was another key factor.

Continued Rise in Health Burden from Ambient PM2.5 in India under SSP Scenarios Until 2100 despite Decreasing Concentrations.

Forecasting alterations in ambient air pollution and the consequent health implications is crucial for safeguarding public health, advancing environmental sustainability, informing economic decision making, and promoting appropriate policy and regulatory action. However, predicting such changes poses a substantial challenge, requiring accurate data, sophisticated modeling methodologies, and a meticulous evaluation of multiple drivers. In this study, we calculate premature deaths due to ambient fine particulate matter (PM2.5) exposure in India from the 2020s (2016-2020) to the 2100s (2095-2100) under four different socioeconomic and climate scenarios (SSPs) based on four CMIP6 models. PM2.5 concentrations decreased in all SSP scenarios except for SSP3-7.0, with the lowest concentration observed in SSP1-2.6. The results indicate an upward trend in the five-year average number of deaths across all scenarios, ranging from 1.01 million in the 2020s to 4.12-5.44 million in the 2100s. Further analysis revealed that the benefits of reducing PM2.5 concentrations under all scenarios are largely mitigated by population aging and growth. These findings underscore the importance of proactive measures and an integrated approach in India to improve atmospheric quality and reduce vulnerability to aging under changing climate conditions.

Genome-wide evolutionary analysis of TKL_CTR1-DRK-2 gene family and functional characterization reveals that TaCTR1 positively regulates flowering time in wheat.

BACKGROUND: Flowering time has an important effect on regional adaptation and yields for crops. The tyrosine kinase-like (TKL) gene family is widely existed and participates in many biological processes in plants. Furthermore, only few TKLs have been characterized functions in controlling flowering time in wheat. RESULTS: Here, we report that TaCTR1, a tyrosine kinase-like (TKL) gene, regulates flowering time in wheat. Based on identification and evolutionary analysis of TKL_CTR1-DRK-2 subfamily in 15 plants, we proposed an evolutionary model for TaCTR1, suggesting that occurrence of some exon fusion events during evolution. The overexpression of TaCTR1 caused early flowering time in transgenic lines. Transcriptomics analysis enabled identification of mass differential expression genes including plant hormone (ET, ABA, IAA, BR) signaling, flavonoid biosynthesis, phenolamides and antioxidant, and flowering-related genes in TaCTR1 overexpression transgenic lines compared with WT plants. qRT-PCR results showed that the expression levels of ethylene (ET) signal-related genes (ETR, EIN, ERF) and flowering-related genes (FT, PPD1, CO, PRR, PHY) were altered in TaCTR1-overexpressing wheat compared with WT plants. Metabonomics analysis showed that flavonoid contents were altered. CONCLUSIONS: Thus, the results show that TaCTR1 plays a positive role in controlling flowering time by activating various signaling pathways and regulating flowering-related genes, and will provide new insights on the mechanisms of wheat flowering regulation.

Revealing the Nature of Binary-Phase on Structural Stability of Sodium Layered Oxide Cathodes.

The emergence of layered sodium transition metal oxides featuring a multiphase structure presents a promising approach for cathode materials in sodium-ion batteries, showcasing notably improved energy storage capacity. However, the advancement of cathodes with multiphase structures faces obstacles due to the limited understanding of the integrated structural effects. Herein, the integrated structural effects by an in-depth structure-chemistry analysis in the developed layered cathode system NaxCu0.1Co0.1Ni0.25Mn0.4Ti0.15O2 with purposely designed P2/O3 phase integration, are comprehended. The results affirm that integrated phase ratio plays a pivotal role in electrochemical/structural stability, particularly at high voltage and with the incorporation of anionic redox. In contrast to previous reports advocating solely for the enhanced electrochemical performance in biphasic structures, it is demonstrated that an inappropriate composite structure is more destructive than a single-phase design. The in situ X-ray diffraction results, coupled with density functional theory computations further confirm that the biphasic structure with P2:O3 = 4:6 shows suppressed irreversible phase transition at high desodiated states and thus exhibits optimized electrochemical performance. These fundamental discoveries provide clues to the design of high-performance layered oxide cathodes for next-generation SIBs.

Life disturbance and hospital visit experiences among Chinese patients with benign prostatic hyperplasia: a qualitative study.

BACKGROUND: The impact of lower urinary tract symptoms (LUTS) on the quality of life of patients with benign prostatic hyperplasia (BPH) has been rarely reported. Additionally, the challenges faced by these patients in seeking medical care have often been overlooked. In order to explore the personal struggles caused by LUTS and the difficulties or barriers experienced by Chinese patients with BPH when seeking help, we conducted a qualitative interview study. METHODS: Qualitative interviews were conducted among 46 patients with BPH who were hospitalized in three tertiary hospitals in China from July 2021 to November 2022. Grounded theory was adopted as the methodology for the qualitative study. After obtaining written informed consent from the study participants, semi-structured interviews were conducted according to the question guidelines. The interview process was audio-recorded; subsequently, the recordings were transcribed, coded, and thematically analyzed. RESULTS: The difficulties faced by Chinese patients with BPH were classified into seven main themes: (i) disturbed life, (ii) mental burden, (iii) disease cognition and communication, (iv) delayed treatment, (v) medication status, (vi) hospital visits barriers, and (vii) medical insurance issues. Further, each theme was subdivided into 2-5 sub-themes. CONCLUSIONS: LUTS have a certain effect on the life and spirit of patients with BPH. These patients face different degrees of difficulties in treatment and hospital visits. Therefore, better healthcare systems and additional social support are crucial for improving the current plight of these patients.

Bibliometric analysis and global trends in uterus transplantation.

AIM: The purpose of this study was to characterize publication patterns, academic influence, research trends, and the recent developments in uterus transplantation (UTx) across the globe. METHODS: The Web of Science Core Collection database was searched for documents published from the time the database began to include relevant articles to December 15, 2023. With the use of VOSviewer, Citespace, BICOMB, and Incites, a cross-sectional bibliometric analysis was conducted to extract or calculate the evaluative indexes. Publications were categorized by country, institution, author, journal, highly cited papers, and keywords. The variables were compared in terms of publication and academic influence, which further included citation count, citation impact, Hirsh index, journal impact factor, total link strength, collaboration metrics, and impact relative to the world. RESULTS: A total of 581 papers concerning UTx were initially identified after retrieval, and 425 documents were included. Of the 41 countries participating in relevant studies, the USA and Sweden were in leading positions in terms of publications, citations, and academic influence. The most versatile institution was the University of Gothenburg, which is followed by Baylor University. The most productive scholars and journals were Brännström M. and Fertility and Sterility, respectively. Five groups of cutting-edge keywords were identified: venous drainage, donors and donation, women, fertility preservation, and fertility. Topics about surgery, first live birth, risk, and in vitro fertilization remain hot in this field. CONCLUSIONS: UTx is anticipated to enter a golden era in the coming years. This study provides some guidance concerning the authors involved in promoting UTx research, the current development of UTx, and journals to submit their innovative research. This also helps to reach a comprehensive insight and prospect in the near future. In order to establish recognized standards and benefit more patients who are disturbed by uterine infertility, large-scale and well-designed clinical trials are required.

Microplastics have additive effects on cadmium accumulation and toxicity in Rice flower carp (Procypris merus).

Procypris merus, a local fish species found in Guangxi, China is often exposed to both microplastics (MPs) and Cd. However, it remains unclear how these two pollutants affect P. merus. Therefore, we investigated the effects of MPs on Cd accumulation in P. merus. To this end, P. merus was separately exposed to Cd and MPs (500 µg/L) or their combination for 14 days. We found that MPs enhanced Cd accumulation in liver and gills of P. merus. Further, both the single-contaminant (MP and Cd) and combined treatments resulted in lesions in these two tissues, with more severe damage associated with the combined treatment. Even though the effect of MP on the antioxidant defense system of P. merus was limited, the Cd-only and combined treatments considerably affected the antioxidant parameters of P. merus, with the combined treatment showing a stronger effect. GO and KEGG analyses revealed that the differentially expressed genes (DEGs; TNF-related apoptosis-inducing ligand receptor, trail-r) in the Cd-only treatment group were enriched for immune-related GO terms and cell growth and death related pathways, indicating that Cd toxicity affected immune defense in P. merus. The MP-only treatment downregulated DEGs (acyl-CoA synthetase long chain family member 1a, acsl1a) related to lipid metabolism, possibly leading to lipid accumulation in the liver. The combined treatment also upregulated DEGs (aspartate aminotransferase 1, ast 1) associated with immune-related GO terms and amino acid metabolism pathways, suggesting that it affected immune function in P. merus, thereby negatively impacting its health. Results indicated that MPs have additive effects on Cd accumulation and toxicity in rice flower carp. Consequently, MPs ingested by P. merus can promote Cd accumulation, more adverse effects on the health may occur after combined exposure, which can eventually reach humans through the food chain and pose potential risks to human health.

The dairy-derived peptide Miltin exerts anti-obesity effects by increasing adipocyte thermogenesis.

Growing research has highlighted that the consumption of dairy products improves the metabolic health in obese individuals by functioning as regulatory modulators. However, the molecular basis of this effect remains largely unknown. Herein, we report a dairy-derived peptide, which we named Miltin, that activates the thermogenesis of brown adipocytes and increases white adipocyte browning. Previously, Miltin was merely identified for its antioxidant capacity, although it is commonly present in different dairy products. In this study, we revealed the effect of Miltin in modulating adipose thermogenesis and further explored its potential in treating obesity through in vivo and in vitro strategies. The administration of Miltin in mice fed with a high-fat diet resulted in enhanced thermogenesis, improved glucose homeostasis, and reduced body mass and lipid accumulation, indicating the anti-obesity effect of Miltin. Genomic analysis revealed that Miltin modulates thermogenesis by inducing the activation of the MAPK signaling pathway by preferentially interacting with GADD45γ to promote its stability. Together, our findings indicate that Miltin's role in initiating the thermogenesis of adipocytes makes it a potential anti-obesity therapy for future development.

Microfluidic chip as a promising evaluation method in assisted reproduction: A systematic review.

The aim of assisted reproductive technology (ART) is to select the high-quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However, functional evaluation is hindered by intra- and inter-operator variability. Microfluidic chips emerge as the one of the most powerful tools to analyze biological samples for reduced size, precise control, and flexible extension. Herein, a systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and IEEE Xplore databases until March 2023. We displayed and prospected all detection strategies based on microfluidics in the ART field. After full-text screening, 71 studies were identified as eligible for inclusion. The percentages of human and mouse studies equaled with 31.5%. The prominent country in terms of publication number was the USA (n = 13). Polydimethylsiloxane (n = 49) and soft lithography (n = 28) were the most commonly used material and fabrication method, respectively. All articles were classified into three types: sperm (n = 38), oocytes (n = 20), and embryos (n = 13). The assessment contents included motility, counting, mechanics, permeability, impedance, secretion, oxygen consumption, and metabolism. Collectively, the microfluidic chip technology facilitates more efficient, accurate, and objective evaluation in ART. It can even be combined with artificial intelligence to assist the daily activities of embryologists. More well-designed clinical studies and affordable integrated microfluidic chips are needed to validate the safety, efficacy, and reproducibility. Trial registration: The protocol was registered in the Open Science Frame REGISTRIES (identification: osf.io/6rv4a).

Association between perioperative self-reported sleep disturbances and delirium risk in elderly patients following total joint arthroplasty: a cohort study.

Perioperative sleep disturbance may increase delirium risk. However, the role of perioperative sleep disturbance in delirium following total joint arthroplasty remains unclear. This prospective cohort study aimed to observe the delirium risk in patients with sleep disturbances. After excluding pre-existing sleep disturbances, older patients scheduled for total joint arthroplasty from July 17, 2022, to January 12, 2023, were recruited. Preoperative sleep disturbance or postoperative sleep disturbance was defined as a Chinese version of the Richards-Campbell Sleep Questionnaire (RCSQ) score of <50 during hospitalisation. A cut-off score of 25 was used to classify the severity of sleep disturbance. The primary outcome was the incidence of postoperative delirium. In all, 11.6% of cohort patients (34/294) developed delirium. After multivariate analysis, a preoperative Day 1 RCSQ score of ≤25 (odds ratio [OR] 3.62, 95% confidence interval [CI] 1.19-10.92; p = 0.02), occurrence of sleep disturbances (OR 2.76, 95% CI 1.19-6.38; p = 0.02) and RCSQ score of ≤25(OR 2.91, 95% CI 1.33-6.37; p = 0.007) postoperatively were strong independent predictors of delirium. After sensitivity analysis for daily delirium, a postoperative Day 1 RCSQ score of ≤25 (OR 9.27, 95% CI 2.72-36.15; p < 0.001) was associated with a greater risk of delirium on postoperative Day 1, with a reasonable discriminative area under the curve of 0.730. We concluded that postoperative but not preoperative sleep disturbances may be an independent factor for delirium risk. Sleep disturbance on the first night after surgery was a good predictor of subsequent delirium, no matter the nature of self-reported sleep disturbance.

Whole-course application of dexmedetomidine as an adjuvant to spinal-epidural anesthesia for cesarean section: A randomized, controlled trial.

Background: Dexmedetomidine is known to prolong the analgesic duration of spinal anesthesia, but it can be challenging to achieve further extension without opioids. Therefore, this study aimed to investigate a novel analgesic strategy using dexmedetomidine as an adjuvant to spinal-epidural anesthesia for elective cesarean surgery. Methods: The study was a randomized, double-blind, controlled trial conducted at a single center. Sixty parturients who underwent elective cesarean were randomly assigned to either group C or group D. Group D received an intrathecal injection of 12.5 mg ropivacaine and 5 µg dexmedetomidine followed by continuous epidural patient-controlled analgesia (PCA) infusion with a total volume of 100 ml, containing 0.2 % ropivacaine and 0.5 µg/kg dexmedetomidine. Group C received an intrathecal injection of 12.5 mg ropivacaine with an equivalent saline placebo followed by a similar PCA infusion, containing 0.2 % ropivacaine and an equivalent saline placebo. Results: The primary outcome was visual analog scale score on movement at 24 h after surgery. The results showed that the rest and motion pain scores in group D were significantly lower than those in group C at 6 h, 12 h, and 24 h after surgery (P < 0.05), with the differences at 24 h were 5.0 (5.0, 5.0)in group D versus 5.0 (5.0, 6.0) in group C (P = 0.04). Additionally, the time to the first PCA in group D was significantly longer than that in group C (P < 0.05), as well as the time of sensory and motor recovery. Conclusions: Whole-course application of dexmedetomidine as an adjuvant to spinal-epidural anesthesia could effectively extend the analgesic duration of ropivacaine to 24 h following elective cesarean surgery.

The combined detection of hematological indicators is used for the differential diagnosis of colorectal cancer and benign-colorectal lesions.

OBJECTIVE: This article aims to investigate the clinical value of hemoglobin/red cell distribution width ratio (Hb/RDW), C-reactive protein/albumin ratio (CAR) and plateletcrit (PCT) combined with carcinoembryonic antigen (CEA) in colorectal cancer (CRC) auxiliary diagnosis. METHODS: We retrospectively analyzed in 718 subjects (212 with CRC, 209 with benign colorectal lesions (BCL), 111 with other cancers, and 186 healthy controls). RESULTS: The CAR, PCT, and CEA in the CRC group were higher than those in the BCL, other cancers, and the healthy control group. However, Hb/RDW in the CRC group was lower than the other three groups. Moreover, there were significant differences in Hb/RDW and CEA among different T-N-M stages (all P< 0.05). Multivariate logistic regression showed that low level of Hb/RDW and high level of CAR, CEA, PCT were risk factors for CRC, and are correlated with CRC stage. Additionally, the area under the receiver operating characteristic curve (AUC) of Hb/RDW+CEA (AUC: 0.735), CAR+CEA (AUC: 0.748), PCT+CEA (AUC: 0.807) was larger than that of Hb/RDW (AUC: 0.503), CAR (AUC: 0.614), or PCT (AUC: 0.713) alone (all P< 0.001) in distinguishing CRC from BCL. CONCLUSIONS: Hb/RDW, CAR, PCT, and CEA are independent risk factors for CRC. Hb/RDW, CAR, and PCT combined with CEA have significant value for auxiliary differential diagnosis of CRC and BCL.

Leukocyte Telomere Length and the Risk of Prostate Cancer and Benign Prostatic Hyperplasia: Insights From UK Biobank and Mendelian Randomization Study.

BACKGROUND: Previous observational studies have been controversial regarding the association of leukocyte telomere length (LTL) with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: First, we conducted an observational study utilizing UK Biobank data. The correlation between LTL and the risk of PCa and BPH was evaluated via multivariate-adjusted logistic regression. Then, we conducted a 2-sample Mendelian randomization to examine causal links between LTL (472 174 individuals) and PCa as well as BPH. To verify the reliability of the primary analysis, we conducted a second analysis and sensitivity analyses. RESULTS: In the UK Biobank study, individuals in the longer quartiles of LTL were observed to have a higher risk of PCa (1.155-fold to 1.349-fold, all p < .001) and BPH (1.119-fold to 1.212-fold, all p < .001) compared to those in the lowest quartile in multivariate-adjusted logistic regression. We observed that genetically predicted longer LTL resulted in a 1.427-fold risk of PCa (odds ratio [OR] = 1.427, 95% confidence interval [CI] = 1.197-1.702, p < .001) and 1.539-fold risk of BPH (OR = 1.539, 95% CI = 1.387-1.707, p < .001) in the primary analysis. In the second analysis, the results also indicated that longer LTL increased the genetic liability to both PCa (OR = 1.338, 95% CI = 1.189-1.507, p < .001) and BPH (OR = 1.006, 95% CI = 1.003-1.008, p < .001). Sensitivity analyses also supported the reliability of the results. CONCLUSIONS: Our study provides convincing evidence supporting that longer LTL increases the risk of PCa and BPH in European individuals. Large-scale studies are needed to elucidate the potential mechanisms of LTL in PCa and BPH occurrence.

ß-Cell miRNA-503-5p Induced by Hypomethylation and Inflammation Promotes Insulin Resistance and ß-Cell Decompensation.

Chronic inflammation promotes pancreatic ß-cell decompensation to insulin resistance because of local accumulation of supraphysiologic interleukin 1ß (IL-1ß) levels. However, the underlying molecular mechanisms remain elusive. We show that miR-503-5p is exclusively upregulated in islets from humans with type 2 diabetes and diabetic rodents because of its promoter hypomethylation and increased local IL-1ß levels. ß-Cell-specific miR-503 transgenic mice display mild or severe diabetes in a time- and expression-dependent manner. By contrast, deletion of the miR-503 cluster protects mice from high-fat diet-induced insulin resistance and glucose intolerance. Mechanistically, miR-503-5p represses c-Jun N-terminal kinase-interacting protein 2 (JIP2) translation to activate mitogen-activated protein kinase signaling cascades, thus inhibiting glucose-stimulated insulin secretion (GSIS) and compensatory ß-cell proliferation. In addition, ß-cell miR-503-5p is packaged in nanovesicles to dampen insulin signaling transduction in liver and adipose tissues by targeting insulin receptors. Notably, specifically blocking the miR-503 cluster in ß-cells effectively remits aging-associated diabetes through recovery of GSIS capacity and insulin sensitivity. Our findings demonstrate that ß-cell miR-503-5p is required for the development of insulin resistance and ß-cell decompensation, providing a potential therapeutic target against diabetes. ARTICLE HIGHLIGHTS: Promoter hypomethylation during natural aging permits miR-503-5p overexpression in islets under inflammation conditions, conserving from rodents to humans. Impaired ß-cells release nanovesicular miR-503-5p to accumulate in liver and adipose tissue, leading to their insulin resistance via the miR-503-5p/insulin receptor/phosphorylated AKT axis. Accumulated miR-503-5p in ß-cells impairs glucose-stimulated insulin secretion via the JIP2-coordinated mitogen-activated protein kinase signaling cascades. Specific blockage of ß-cell miR-503-5p improves ß-cell function and glucose tolerance in aging mice.

The metabolism of nonstructural carbohydrates, lipids, and energy in two Cycas species with differential tolerance to unexpected freezing stress.

Introduction: With the climate warming, the occurrence of freezing events is projected to increase in late spring and early autumn in the Northern Hemisphere. Observation of morphological traits showed that Cycas panzhihuaensis was more tolerant to unexpected freezing stress than C. bifida. Energy balance is crucial for plant tolerance to stress. Here, we aimed to determine whether the different responses of the two species to the unpredicted freezing stress were associated with the metabolism of energy and related substances. Methods: The effects of unexpected freezing temperatures on C. panzhihuaensis and C. bifida were studied by measuring chlorophyll fluorescence parameters, energy charge and the profile of nonstructural carbohydrates (NSC) and lipids. Results: C. panzhihuaensis exhibited higher stability of photosynthetic machinery than C. bifida under unpredicted freezing events. Significant interaction between species and treatments were observed in the energy charge, the level of NSC and its most components and the amount of most lipid categories and lipid classes. The decrease of soluble sugar and the increase of neutral glycerolipids at the early freezing stage, the accumulation of membrane glycerolipids at the late freezing stage and the continuous decrease of energy charge during the freezing period were the characteristics of C. panzhihuaensis responding to unexpected freezing stress. The degradation of membrane glycerolipids and the continuous decrease of soluble sugar during the freezing period and the accumulation of neutral glycerolipids and energy charge at the late freezing stage represented the characteristics of C. bifida responses. Discussion: The different freezing sensitivity between C. panzhihuaensis and C. bifida might be associated with the differential patterns of the metabolism of energy, NSC and lipids. C. panzhihuaensis possesses the potential to be introduced to the areas of higher latitudes and altitudes.

The secreted peptide BATSP1 promotes thermogenesis in adipocytes.

Although brown adipose tissue (BAT) has historically been viewed as a major site for energy dissipation through thermogenesis, its endocrine function has been increasingly recognized. However, the circulating factors in BAT that play a key role in controlling systemic energy homeostasis remain largely unexplored. Here, we performed a peptidomic analysis to profile the extracellular peptides released from human brown adipocytes upon exposure to thermogenic stimuli. Specifically, we identified a secreted peptide that modulates adipocyte thermogenesis in a cell-autonomous manner, and we named it BATSP1. BATSP1 promoted BAT thermogenesis and induced browning of white adipose tissue in vivo, leading to increased energy expenditure under cold stress. BATSP1 treatment in mice prevented high-fat diet-induced obesity and improved glucose tolerance and insulin resistance. Mechanistically, BATSP1 facilitated the nucleocytoplasmic shuttling of forkhead transcription factor 1 (FOXO1) and released its transcriptional inhibition of uncoupling protein 1 (UCP1). Overall, we provide a comprehensive analysis of the human brown adipocyte extracellular peptidome following acute forskolin (FSK) stimulation and identify BATSP1 as a novel regulator of thermogenesis that may offer a potential approach for obesity treatment.