A metal-poor star with abundances from a pair-instability supernova.

The most massive and shortest-lived stars dominate the chemical evolution of the pre-galactic era. On the basis of numerical simulations, it has long been speculated that the mass of such first-generation stars was up to several hundred solar masses1-4. The very massive first-generation stars with a mass range from 140 to 260 solar masses are predicted to enrich the early interstellar medium through pair-instability supernovae (PISNe)5. Decades of observational efforts, however, have not been able to uniquely identify the imprints of such very massive stars on the most metal-poor stars in the Milky Way6,7. Here we report the chemical composition of a very metal-poor (VMP) star with extremely low sodium and cobalt abundances. The sodium with respect to iron in this star is more than two orders of magnitude lower than that of the Sun. This star exhibits very large abundance variance between the odd- and even-charge-number elements, such as sodium/magnesium and cobalt/nickel. Such peculiar odd-even effect, along with deficiencies of sodium and α elements, are consistent with the prediction of primordial pair-instability supernova (PISN) from stars more massive than 140 solar masses. This provides a clear chemical signature indicating the existence of very massive stars in the early universe.

BRCC3 Regulation of ALK2 in Vascular Smooth Muscle Cells: Implication in Pulmonary Hypertension.

BACKGROUND: An imbalance of antiproliferative BMP (bone morphogenetic protein) signaling and proliferative TGF-ß (transforming growth factor-ß) signaling is implicated in the development of pulmonary arterial hypertension (PAH). The posttranslational modification (eg, phosphorylation and ubiquitination) of TGF-ß family receptors, including BMPR2 (bone morphogenetic protein type 2 receptor)/ALK2 (activin receptor-like kinase-2) and TGF-ßR2/R1, and receptor-regulated Smads significantly affects their activity and thus regulates the target cell fate. BRCC3 modifies the activity and stability of its substrate proteins through K63-dependent deubiquitination. By modulating the posttranslational modifications of the BMP/TGF-ß-PPARγ pathway, BRCC3 may play a role in pulmonary vascular remodeling, hence the pathogenesis of PAH. METHODS: Bioinformatic analyses were used to explore the mechanism by which BRCC3 deubiquitinates ALK2. Cultured pulmonary artery smooth muscle cells (PASMCs), mouse models, and specimens from patients with idiopathic PAH were used to investigate the rebalance between BMP and TGF-ß signaling in regulating ALK2 phosphorylation and ubiquitination in the context of pulmonary hypertension. RESULTS: BRCC3 was significantly downregulated in PASMCs from patients with PAH and animals with experimental pulmonary hypertension. BRCC3, by de-ubiquitinating ALK2 at Lys-472 and Lys-475, activated receptor-regulated Smad1/5/9, which resulted in transcriptional activation of BMP-regulated PPARγ, p53, and Id1. Overexpression of BRCC3 also attenuated TGF-ß signaling by downregulating TGF-ß expression and inhibiting phosphorylation of Smad3. Experiments in vitro indicated that overexpression of BRCC3 or the de-ubiquitin-mimetic ALK2-K472/475R attenuated PASMC proliferation and migration and enhanced PASMC apoptosis. In SM22α-BRCC3-Tg mice, pulmonary hypertension was ameliorated because of activation of the ALK2-Smad1/5-PPARγ axis in PASMCs. In contrast, Brcc3-/- mice showed increased susceptibility of experimental pulmonary hypertension because of inhibition of the ALK2-Smad1/5 signaling. CONCLUSIONS: These results suggest a pivotal role of BRCC3 in sustaining pulmonary vascular homeostasis by maintaining the integrity of the BMP signaling (ie, the ALK2-Smad1/5-PPARγ axis) while suppressing TGF-ß signaling in PASMCs. Such rebalance of BMP/TGF-ß pathways is translationally important for PAH alleviation.

Reduction of Oxidative Stress and Excitotoxicity by Mesenchymal Stem Cell Biomimetic Co-Delivery System for Cerebral Ischemia-Reperfusion Injury Treatment.

A cerebral ischemia-reperfusion injury is ensued by an intricate interplay between various pathological processes including excitotoxicity, oxidative stress, inflammation, and apoptosis. For a long time, drug intervention policies targeting a single signaling pathway have failed to achieve the anticipated clinical efficacy in the intricate and dynamic inflammatory environment of the brain. Moreover, inadequate targeted drug delivery remains a significant challenge in cerebral ischemia-reperfusion injury therapy. In this study, a multifunctional nanoplatform (designated as PB-006@MSC) is developed using ZL006-loaded Prussian blue nanoparticles (PBNPs) camouflaged by a mesenchymal stem cell (MSC) membrane (MSCm). ZL006 is a neuroprotectant. It can be loaded efficiently into the free radical scavenger PBNP through mesoporous adsorption. This can simultaneously modulate multiple targets and pathways. MSCm biomimetics can reduce the nanoparticle immunogenicity, efficiently enhance their homing capability to the cerebral ischemic penumbra, and realize active-targeting therapy for ischemic stroke. In animal experiments, PB-006@MSC integrated reactive oxygen species (ROS) scavenging and neuroprotection. Thereby, it selectively targeted the cerebral ischemic penumbra (about fourfold higher accumulation at 24 h than in the non-targeted group), demonstrated a remarkable therapeutic efficacy in reducing the volume of cerebral infarction (from 37.1% to 2.3%), protected the neurogenic functions, and ameliorated the mortality.

Oxidants Controlled C-H Bond Functionalization of N-Aryltetrahydroisoquinolines: The Construction of the Quaternary Carbon Center and Cleavage of the C-N Bond.

Initiated by triarylamine radical cation salt (TBPA), the direct C-H bond functionalization of α-N-aryltetrahydroisoquinoline esters was smoothly realized, giving a series of α-hydroxylated derivatives with a quaternary carbon center in good yields. Differently, in the presence of tert-butyl nitrite (TBN), the C-N single bond was cleaved to keto esters. The mechanistic study revealed that these reactions were mediated by a similar mechanism, in which the N-nitrosation might provide a driving force to the C-N bond cleavage.

CBr4 as a Mild Oxidant-Enabled Oxidation of a sp3 C-H Bond: A Facile Synthesis of the Persistent Iminium Salts of Tetrahydroisoquinolines.

Using CBr4 as a mild oxidant, the direct C-H bond oxidation of N-aryltetrahydroisoquinolines was achieved, giving a series of the corresponding iminium salts in high yields under metal- and photo-free reaction conditions. This reaction is superior in high yields and good functional group tolerance, and the late-stage derivatization showed that these iminium salts can readily be applied to the synthesis of the functionalized THIQs.

Efficacy of transcutaneous electrical nerve stimulation combined with mirabegron therapy compared with mirabegron monotherapy for overactive bladder: a prospective randomized controlled study.

PURPOSE: The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB). METHODS: In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment. RESULTS: TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation. CONCLUSIONS: The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB. TRIAL REGISTRATION NUMBER: ChiCTR2400080528 (31.01.2024, retrospectively registered).

Single-Electron Reduction of "Push-Pull" C-C Single Bond and Decyanation Using Tertiary Amines as the Organic Electron Donor.

Using commercially available tertiary amines as an organic electron donor (OED), the reduction of "push-pull" C-C single bond and reductive decyanation of tetrahydroisoquinolines were realized. These reactions exhibited higher reaction efficiency and better functional group tolerance compared with those of metallic reductants, and the mechanistic study indicated that a radical intermediate was involved in the reduction of the C-C single bond, which provides a new way to the OED-enabled mild reduction.

Bibliometric analysis of research trends in the relationship between frailty and neoplasms over the past decade.

BACKGROUND: The relationship between frailty and neoplasms has attracted increasing attention from researchers in recent years. This study aims to identify current research hotspots and status in this field through bibliometric and visualization analysis. METHODS: Literature on the relationship between frailty and neoplasms, meeting the inclusion criteria, was collected from the Core Collection. Bibliometric analysis and visualization were performed using WoS, VOSviewer, and CiteSpace. RESULTS: Our study included 7410 documents on frailty and neoplasms, authored by 43,605 researchers from 9478 institutions across 115 countries, and published in 2067 journals. The USA emerged as the most productive and influential country in this field, with 3059 publications and 89,319 citations. The University of Texas MD Anderson Cancer Center and Mayo Clinic were recognized as the most productive institution and the institution with the highest citation count, respectively. The Journal of Geriatric Oncology was the leading publisher. Kirsten K Ness and James L Kirkland were identified as the most productive and most cited authors, respectively. Cluster analysis identified five key areas: body condition and nutrition, quality of life, frailty, mortality and care, and the elderly and frailty. CONCLUSION: The relationship between frailty and neoplasms remains a contentious and frequently discussed topic. Our findings indicate that research primarily focuses on cancer, the elderly, clinical trials, adverse health outcomes, frailty assessment, and nutrition.

The moderating role of work environment in the relationship between proactive personality and personal growth initiative among nurses: a cross-sectional study.

BACKGROUNDS: Personal growth initiative (PGI) is regarded as a meaningful concept with potential value at both the individual and organizational levels, but little is known about the factors that contribute to nurses' PGI. This study aimed to explore how proactive personality and hospital work environment affect PGI of clinical nurses. METHODS: A cross-sectional study was conducted between September and October 2022 among 4414 nurses from 10 tertiary general hospitals in 10 cities in Sichuan, China, using a two-stage sampling method. Self-reported anonymous online questionnaires, such as sociodemographic information survey, personal growth initiative scale II, the 10-item proactive personality scale, and practice environment scale-nursing work index were used to collect data. Multiple hierarchical regression analyses were performed to examine research hypotheses. RESULTS: Among the control variables in this study, nurses' self-perceptions of general health status and professional title positively predicted PGI (ß = 0.462, 95%CI = 0.272-0.653; ß = 1.078, 95%CI = 0.508-1.648). After adding control variables, both proactive personality (ß = 1.143, 95%CI = 1.096-1.190) and work environment (ß = 3.391, 95%CI = 2.904-3.879) positively predicted PGI. The work environment positively moderated the association between proactive personality and PGI (ß = 0.108, 95%CI = 0.025-0.191). These predictors jointly explained 50.3% of the variance in PGI. CONCLUSIONS: Nurses with a greater tendency to have a typical proactive personality have higher levels of personal growth initiative, and this positive effect will be better highlighted in a healthier work environment. Nursing managers should prioritize the employment of people with proactive personality traits, focus on the development and stimulation of proactive personality traits in nurses, and establish a supportive work environment to maximize the personal growth initiative of nurses.

Echocardiographic evaluation of right heart failure which might be associated with DNA damage response in SU5416-hypoxia induced pulmonary hypertension rat model.

Right heart failure is the leading cause of death in pulmonary hypertension (PH), and echocardiography is a commonly used tool for evaluating the risk hierarchy of PH. However, few studies have explored the dynamic changes in the structural and functional changes of the right heart during the process of PH. Previous studies have found that pulmonary circulation coupling right ventricular adaptation depends on the degree of pressure overload and other factors. In this study, we performed a time-dependent evaluation of right heart functional changes using transthoracic echocardiography in a SU5416 plus hypoxia (SuHx)-induced PH rat model. Rats were examined in 1-, 2-, 4-, and 6-week using right-heart catheterization, cardiac echocardiography, and harvested heart tissue. Our study found that echocardiographic measures of the right ventricle (RV) gradually worsened with the increase of right ventricular systolic pressure, and right heart hypofunction occurred at an earlier stage than pulmonary artery thickening during the development of PH. Furthermore, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2), a marker of myocardial damage, was highly expressed in week 2 of SuHx-induced PH and had higher levels of expression of γ-H2AX at all timepoints, as well as higher levels of DDR-related proteins p-ATM and p53/p-p53 and p21 in week 4 and week 6. Our study demonstrates that the structure and function of the RV begin to deteriorate with DNA damage and cellular senescence during the early stages of PH development.

Size Segregation of Gold Nanoparticles into Bilayer-like Vesicular Assembly.

Size segregation of nanoparticles with different sizes into highly ordered, unique nanostructures is important for their practical applications. Herein, we demonstrate spontaneous self-assembly of the binary mixtures of small and large gold nanoparticles (GNPs; 5/15, 5/20, or 10/20 in diameter) in the presence of a tetra(ethylene glycol)-terminated octafluoro-4,4'-biphenol ligand, namely, TeOFBL, resulting in a size-segregated assembly. The outer single layer of large GNPs forming a gold nanoparticle vesicle (GNV) encapsulated the inner vesicle-like assembly composed of small GNPs, which is referred to as bilayer-like GNV and similar to the molecular bilayer structure of a liposome. The size segregation was driven by the solvophobic feature of the TeOFBLs on the surface of GNPs. A time-course study indicated that size segregation occurred instantaneously during the mixing stage of the self-organization process. The size-segregated precursors quickly fused with each other through the inner-inner and outer-outer layer fashion to form the bilayer-like GNV. This study provides a new approach to creating biomimetic bilayer capsules with different physical properties for potential applications such as surface-enhanced Raman scattering and drug delivery.

Experiences of older people, healthcare providers and caregivers on implementing person-centered care for community-dwelling older people: a systematic review and qualitative meta-synthesis.

BACKGROUND: Person-centered care (PCC) is a critical approach to improving the quality of care for community-dwelling older people. Old-age care services could be provided according to older peoples' choices, needs, and preferences. The purpose of this study was to synthesize research evidence on the experiences of older people, healthcare providers, and caregivers with PCC and to identify the enablers and barriers to implementing PCC for community-dwelling older people. METHODS: A meta-synthesis of qualitative research design was adopted. Data searches were performed using CINAHL (EBSCOhost), PubMed (OvidSP), Embase (Ovid), Cochrane Database, and PsycINFO (Ovid) in published articles and were reviewed from the earliest date to February 2023. The Qualitative Method Appraisal Tool was used to conduct a quality appraisal on selected articles. Data were extracted based on the capacity, opportunity, and motivation-behavior model (COM-B model), and the findings were synthesized using the meta-aggregative approach. RESULTS: Twelve included articles were analyzed to identify 122 findings that were organized into 11 categories and combined into three synthesized findings-capacities of older people, healthcare providers, and caregivers; opportunities in the implementation of PCC; motivation in implementing PCC. Capacities consisted of a lack of person-centered knowledge and skills, negative attitudes toward shared decision-making, and a lack of formal training to enhance capabilities among HCPs. Opportunities included a lack of coordination in resource allocation, strengthening multidisciplinary teamwork, establishing a desirable environment, and time constraints. Motivation in implementing PCC included encouraging self-reflection and regulation, respecting the autonomy of older people, lack of clear reward and empowerment mechanisms, and being resilient and optimistic. CONCLUSIONS: The findings of this research provide a reference for implementing successful PCC in the community. The researchers identified barriers and facilitators of implementing PCC, facilitating through stakeholder's person-centered knowledge and skills being valued and respecting the autonomy of older people. Establishing a positive environment and strengthening multidisciplinary team members also promotes the implementation of PCC. However, additional studies are required to explore the influencing factors and address the barriers.

Factors associated with the perceived need for assistance from voluntary services in home-based older adults in Chinese urban areas: a cross-sectional study.

BACKGROUND: With China's rapidly aging population, meeting the diverse care needs of senior citizens is becoming more challenging. Although voluntary social services have numerous advantages and are popular among older adults, there is little information on the need for assistance from volunteer-based social services, particularly those with a medical background, and influencing factors among urban home-based older adults. This study aimed to assess the need for assistance from voluntary services and related factors among urban home-based older adults in China. METHODS: A cross-sectional study was conducted in 2022 on communities in four cities in China. The 27-item Home-Based Older Adults Assistance Need Scale was used to measure the assistance needs of 498 participants aged 60 and above. Multiple linear regression models were conducted to identify salient variables associated with the need for assistance from voluntary services. RESULTS: The mean score of the need for assistance from voluntary services was 88.60 ± 24.37. The mean scores of the items examining four dimensions, namely, health maintenance, visiting communication, social intercourse, and daily life, were 3.64 ± 1.08, 3.49 ± 1.04, 3.33 ± 1.08, and 2.78 ± 1.08, respectively. The level of depression, willingness to assist older adults, attaching importance to health preservation, ability to self-comfort, desire to accept assistance from others, and the presence of more children or none at all were all positively correlated with the perceived need for assistance from voluntary services. In contrast, social care obtained from visiting medical institutions was negatively correlated. These seven factors explained 28.5% of the total variance. CONCLUSIONS: Urban home-based older adults in China were found to have significant requirements for assistance from volunteer services, and several complex factors were associated with more significant assistance needs. These findings may encourage the extremely limited numbers of social volunteers, particularly those with a medical background, to identify priorities in providing assistance services to the large numbers of urban home-based older adults and thus improve service delivery.

Carbon reduction behavior of waste power battery recycling enterprises considering learning effects.

The carbon reduction behavior of waste power battery recycling (WPBR) enterprises is essential for promoting resource conservation and environmental protection. Introducing the learning effects of carbon reduction research and development (R&D) investment, this study constructs an evolutionary game model between local governments and WPBR enterprises to study the behavior choice of carbon reduction. The paper explores the evolutionary process and factors affecting carbon reduction behavior choices of WPBR enterprises from internal R&D motivation and external regulation perspectives. The critical results reveal that the existence of learning effects significantly reduces the probability of environmental regulation by local governments while effectively increasing the probability of WPBR enterprises implementing carbon reduction. The learning rate index positively correlates with the likelihood of enterprises implementing carbon emissions reduction. In addition, carbon reduction subsidies considerably maintain considerably negative relation with the probability of enterprise carbon reduction behavior. The following conclusions are drawn: (1) The learning effect of carbon reduction R&D investment is the intrinsic driving force for WPBR enterprises' carbon reduction behavior, which can promote enterprises to proactively implement carbon reduction under fewer constraints of government environmental regulation; (2) Pollution fines and carbon trade prices in environmental regulation can promote enterprises carbon reduction, while carbon reduction subsidies inhibit their reduction behavior; (3) There exists an evolutionarily stable strategy between government-enterprise game only under the dynamic mechanism. The research provides insights for decision-making on enterprises' carbon reduction R&D investment and local government environmental regulation policy under carbon reduction targets.

Nitrogen addition stimulates N2O emissions via changes in denitrification community composition in a subtropical nitrogen-rich forest.

Microbially driven nitrification and denitrification play important roles in regulating soil N availability and N2O emissions. However, how the composition of nitrifying and denitrifying prokaryotic communities respond to long-term N additions and regulate soil N2O emissions in subtropical forests remains unclear. Seven years of field experiment which included three N treatments (+0, +50, +150 kg N ha-1 yr-1; CK, LN, HN) was conducted in a subtropical forest. Soil available nutrients, N2O emissions, net N mineralization, denitrification potential and enzyme activities, and the composition and diversity of nitrifying and denitrifying communities were measured. Soil N2O emissions from the LN and HN treatments increased by 42.37% and 243.32%, respectively, as compared to the CK. Nitrogen addition significantly inhibited nitrification (N mineralization) and significantly increased denitrification potentials and enzymes. Nitrification and denitrification abundances (except nirK) were significantly lower in the HN, than CK treatment and were not significantly correlated with N2O emissions. Nitrogen addition significantly increased nirK abundance while maintaining the positive effects of denitrification and N2O emissions to N deposition, challenging the conventional wisdom that long-term N addition reduces N2O emissions by inhibiting microbial growth. Structural equation modeling showed that the composition, diversity, and abundance of nirS- and nirK-type denitrifying prokaryotic communities had direct effects on N2O emissions. Mechanistic investigations have revealed that denitrifier keystone taxa transitioned from N2O-reducing (complete denitrification) to N2O-producing (incomplete denitrification) with increasing N addition, increasing structural complexity and diversity of the denitrifier co-occurrence network. These results significantly advance current understanding of the relationship between denitrifying community composition and N2O emissions, and highlight the importance of incorporating denitrifying community dynamics and soil environmental factors together in models to accurately predict key ecosystem processes under global change.

An Imine-Based Porous 3D Covalent Organic Polymer as a New Sorbent for the Solid-Phase Extraction of Amphenicols from Water Sample.

In this paper, an imine-based porous 3D covalent organic polymer (COP) was synthesized via solvothermal condensation. The structure of the 3D COP was fully characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and powder X-ray diffractometry, thermogravimetric analysis, and Brunauer-Emmer-Teller (BET) nitrogen adsorption. This porous 3D COP was used as a new sorbent for the solid-phase extraction (SPE) of amphenicol drugs, including chloramphenicol (CAP), thiamphenicol (TAP), and florfenicol (FF) in aqueous solution. Factors were investigated for their effects on the SPE efficiency, including the types and volume of eluent, washing speed, pH, and salinity of water. Under the optimized conditions, this method gave a wide linear range (0.1-200 ng/mL) with a high correlation coefficient value (R2 > 0.99), low limits of detection (LODs, 0.01-0.03 ng/mL), and low limits of quantification (LOQs, 0.04-0.10 ng/mL). The recoveries ranged from 83.98% to 110.7% with RSDs ≤ 7.02%. The good enrichment performance for this porous 3D COP might contribute to the hydrophobic and π-π interactions, the size-matching effect, hydrogen bonding, and the good chemical stability of 3D COP. This 3D COP-SPE method provides a promising approach to selectively extract trace amounts of CAP, TAP, and FF in environmental water samples in ng quantities.

LncPTSR Triggers Vascular Remodeling in Pulmonary Hypertension by Regulating [Ca2+]i in Pulmonary Arterial Smooth Muscle Cells.

Pulmonary hypertension (PH) is characterized by vascular remodeling and sustained increase in right ventricular systolic pressure. The molecular mechanisms behind PH development remain unclear. Here, a long noncoding RNA (lncRNA) attenuated by platelet-derived growth factor BB (PDGF-BB) was identified, and its functional roles were investigated in vitro and in vivo. Using RNA-sequencing data and rapid amplification of cDNA ends, an lncRNA neighboring the locus of ATPase plasma membrane Ca2+ transporting 4 (PMCA4) was identified and named lncPTSR. It is a highly conserved nuclear lncRNA and was downregulated in pulmonary arterial smooth muscle cells (PASMCs) with PDGF-BB stimulation or hypoxia induction. Gene interruption or overexpression assays revealed that lncPTSR negatively regulates rat PASMC proliferation, apoptosis, and migration. LncPTSR interruption in Sprague Dawley rats using adeno-associated virus type 9-mediated shRNA resulted in a significant increase in right ventricular systolic pressure and vascular remodeling in normoxic condition. LncPTSR knockdown also suppressed PMCA4 expression and attenuated the intracellular Ca2 + efflux of PASMCs in vitro and in vivo. Further studies suggest a complex crosstalk between lncPTSR and mitogen-activated protein kinase pathway: inhibition of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase abolishes the PDGF-BB-mediated lncPTSR downregulation, and lncPTSR plays a feedback regulation for mitogen-activated protein kinase-signaling molecules. The present study suggests that lncPTSR participates in pulmonary artery remodeling via modulating the expression of PMCA4 and intracellular Ca2 + homeostasis downstream of PDGF-BB-driven mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling. These results suggest that lncPTSR may be a promising therapeutic target in PH treatment.

Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus.

Metformin is the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intraislet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic ß-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic ß-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic ß-cells and subsequent insulin secretion in T2DM.

AtMYB31 is a wax regulator associated with reproductive development in Arabidopsis.

KEY MESSAGE: AtMYB31, a R2R3-MYB transcription factor that modulates wax biosynthesis in reproductive tissues, is involved in seed development in Arabidopsis. R2R3-MYB transcription factors play important roles in plant development; yet, the exact role of each of them remains to be resolved. Here we report that the Arabidopsis AtMYB31 is required for wax biosynthesis in epidermis of reproductive tissues, and is involved in seed development. AtMYB31 was ubiquitously expressed in both vegetative and reproductive tissues with higher expression levels in siliques and seeds, while AtMYB31 was localized to the nucleus and cytoplasm. Loss of function of AtMYB31 reduced wax accumulation in the epidermis of silique and flower tissues, disrupted seed coat epidermal wall development and mucilage production, altered seed proanthocyanidin and polyester content. AtMYB31 could direct activate expressions of several wax biosynthetic target genes. Altogether, AtMYB31, a R2R3-MYB transcription factor, regulates seed development in Arabidopsis.

Prediction and prognosis of adverse maternal and foetal/neonatal outcomes in pulmonary hypertension: an observational study and nomogram construction.

BACKGROUND: Pregnant women with pulmonary hypertension (PH) have higher mortality rates and poor foetal/neonatal outcomes. Tools to assess these risk factors are not well established. METHODS: Predictive and prognostic nomograms were constructed using data from a "Development" cohort of 420 pregnant patients with PH, recorded between January 2009 and December 2018. Logistic regression analysis established models to predict the probability of adverse maternal and foetal/neonatal events and overall survival by Cox analysis. An independent "Validation" cohort comprised data of 273 consecutive patients assessed from January 2019 until May 2022. Nomogram performance was evaluated internally and implemented with online software to increase the ease of use. RESULTS: Type I respiratory failure, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide [Formula: see text] 1400 ng/L, arrhythmia, and eclampsia with pre-existing hypertension were independent risk factors for maternal mortality or heart failure. Type I respiratory failure, arrhythmia, general anaesthesia for caesarean section, New York Heart Association functional class, and N-terminal pro-brain natriuretic peptide [Formula: see text] 1400 ng/L were independent predictors of pulmonary hypertension survival during pregnancy. For foetal/neonatal adverse clinical events, type I respiratory failure, arrhythmia, general anaesthesia for caesarean section, parity, platelet count, fibrinogen, and left ventricular systolic diameter were important predictors. Nomogram application for the Development and Validation cohorts showed good discrimination and calibration; decision curve analysis demonstrated their clinical utility. CONCLUSIONS: The nomogram and its online software can be used to analyse individual mortality, heart failure risk, overall survival prediction, and adverse foetal/neonatal clinical events, which may be useful to facilitate early intervention and better survival rates.