Population genomics highlights structural variations in local adaptation to saline coastal environments in woolly grape.

Structural variations (SVs) are a feature of plant genomes that has been largely unexplored despite their significant impact on plant phenotypic traits and local adaptation to abiotic and biotic stress. In this study, we employed woolly grape (Vitis retordii), a species native to the tropical and subtropical regions of East Asia with both coastal and inland habitats, as a valuable model for examining the impact of SVs on local adaptation. We assembled a haplotype-resolved chromosomal reference genome for woolly grape, and conducted population genetic analyses based on whole-genome sequencing (WGS) data from coastal and inland populations. The demographic analyses revealed recent bottlenecks in all populations and asymmetric gene flow from the inland to the coastal population. In total, 1,035 genes associated with plant adaptive regulation for salt stress, radiation, and environmental adaptation were detected underlying local selection by SVs and SNPs in the coastal population, of which 37.29% and 65.26% were detected by SVs and SNPs, respectively. Candidate genes such as FSD2, RGA1, and AAP8 associated with salt tolerance were found to be highly differentiated and selected during the process of local adaptation to coastal habitats in SV regions. Our study highlights the importance of SVs in local adaptation; candidate genes related to salt stress and climatic adaptation to tropical and subtropical environments are important genomic resources for future breeding programs of grapevine and its rootstocks.

Self-Powered and Self-Recoverable Multimodal Force Sensors Based on Trap State and Interfacial Electron Transfer.

Multi-dimensional force sensing that combines intensity, location, area and the like could gather a wealth of information from mechanical stimuli. Developing materials with force-induced optical and electrical dual responses would provide unique opportunities to multi-dimensional force sensing, with electrical signals quantifying the force amplitude and the luminescence output providing spatial distribution of force. However, the reliance on external power supply and high-energy excitation source brings significant challenges to the applicability of multi-dimensional force sensors. Here we reported the mechanical energy-driven and sunlight-activated materials with force-induced dual responses, and investigated the underlying mechanisms of self-sustainable force sensing. Theoretical analysis and experimental data unraveled that trap-controlled luminescence and interfacial electron transfer play a major role in force-induced optical and electrical output. These materials were manufactured into pressure sensor with renewable dual-mode output for quantifying and visualization of pressures by electrical and optical output, respectively, without power supply and high-energy irradiation. The quantification of tactile sensation and stimuli localization of mice highlighted the multi-dimensional sensing ability of the sensor. Overall, this self-powered pressure sensor with multimodal output provides more modalities of force sensing, poised to change the way that intelligent devices sense with the world.

Prediction of vascular complications in free flap reconstruction with machine learning.

OBJECTIVE: This study aims to explore the risk factors of vascular complications following free flap reconstruction and to develop a clinical auxiliary assessment tool for predicting vascular complications in patients undergoing free flap reconstruction leveraging machine learning methods. METHODS: We reviewed the medical data of patients who underwent free flap reconstruction at the Affiliated Hospital of Zunyi Medical University retrospectively from January 1, 2019, to December 31, 2021. Statistical analysis was used to screen risk factors. A training data set was generated and augmented using the synthetic minority oversampling technique. Logistic regression, random forest and neural network, models were trained, using this dataset. The performance of these three predictive models was then evaluated and compared using a test set, with four metrics, area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 570 patients who underwent free flap reconstruction were included in this study, 46 of whom developed postoperative vascular complications. Among the models tested, the neural network model exhibited superior performance on the test set, achieving an AUC of 0.828. Multivariate logistic regression analysis identified that preoperative hemoglobin levels, preoperative fibrinogen levels, operation duration, smoking history, the number of anastomoses, and peripheral vascular injury as statistically significant independent risk factors for vascular complications post-free flap reconstruction. The top five predictive factors in the neural network were fibrinogen content, operation duration, donor site, body mass index (BMI), and platelet count. CONCLUSION: Hemoglobin levels, fibrinogen levels, operation duration, smoking history, and anastomotic veins are independent risk factors for vascular complications following free flap reconstruction. These risk factors enhance the ability of machine learning models to predict the occurrence of vascular complications and identify high-risk patients. The neural network model outperformed the logistic regression and random forest models, suggesting its potential to aid clinicians in early identification of high-risk patients thereby mitigating patient suffering and improving prognosis.

NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin.

BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

Association of different milk fat content with coronary artery disease and myocardial infarction risk: A Mendelian randomization study.

BACKGROUND: Numerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk. METHODS: For the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results. RESULTS: After adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261-12.432; P < 0.001; FDR-corrected P < 0.001) and MI (OR = 2.287; 95% CI 1.218-4.300; P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI. CONCLUSION: Our findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.

Accuracy of 3.0T magnetic resonance angiography for the detection of arteriovenous fistula dysfunction in hemodialysis patients requiring interventional therapy: a prospective study.

Background: Color Doppler ultrasonography (CDUS) is feasible to detect arteriovenous fistula (AVF) dysfunction in hemodialysis patients but is not sufficient to map the structure of fistula required for interventions. This study is designed to evaluate the diagnostic accuracy of three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) at 3.0T versus CDUS for AVF dysfunction, by using digital subtraction angiography (DSA) as reference. Methods: This prospective study enrolled 68 consecutive patients with dysfunctional AVF who underwent both CDUS and TOF-MRA at Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The analysis of the dysfunctional AVFs was divided into three regions: the feeding artery, fistula and draining veins. In the whole- and per-regional-based analyses, two observers who were blinded to the clinical and DSA results independently analyzed all CDUS and TOF-MRA datasets. The image quality and stenosis severity of the lesions on TOF-MRA were evaluated. A receiver operating characteristic curve was applied to analyze the detection of AVF dysfunction with TOF-MRA. Results: A total of 204 vessel regions were evaluated. The whole-region-based image quality of TOF-MRA was poorer in patients with a total occlusion (1.8±0.8) than in those with stenosis (2.7±0.6, P<0.001). In the whole-region analyses, TOF-MRA had higher sensitivity [99.1% (94.6-100.0%) vs. 82.9% (74.6-89.0%), P<0.001] and similar specificity [93.1% (85.0-97.1%) vs. 94.3% (86.5-97.9%), P=0.755] than CDUS. The per-region-based analyses showed that TOF-MRA yielded higher sensitivity [fistula region, 98.1% (88.4-99.9%) vs. 80.8% (67.0-89.9%); P=0.004; draining vein region, 100.0% (92.5-100.0%) vs. 85.0% (72.9-2.5%); P=0.003] and similar specificity [fistula region, 88.2% (62.3-97.8%) vs. 88.2% (62.3-97.9%); P>0.99; draining vein region, 100.0% (59.8-100.0%) vs. 87.5% (46.7-99.3%); P>0.99] than CDUS. Sensitivity and specificity of TOF-MRA were comparable to those of CDUS in feeding artery region. Conclusions: TOF-MRA is a feasible and accurate method to display AVF dysfunction in hemodialysis patients, and this method might fulfill the endovascular treatment planning requirements.

Schiff base functionalized dialdehyde starch for enhanced removal of Cu (II): Preparation, performances, DFT calculations.

Dialdehyde starch modified by 2-hydrazinopyridine (HYD-DAS) based on the reaction of dialdehyde starch (DAS) and 2-hydrazinopyridine was synthesized and characterized by FT-IR spectra, element analysis and SEM. HYD-DAS can efficiently adsorb Cu (II) ion to demonstrate visual color changes from yellow to dark brown in aqueous solutions. The influence on HYD-DAS to Cu (II) adsorption including pH value of solution, isotherm, kinetics, thermodynamics and possible mechanism had also been examined. Batch experiments indicate that HYD-DAS's to Cu (II) adsorption reaches equilibrium within 250 min, and its adsorption capacity and rate are 195.75 mg/g and 98.63 %, respectively. Moreover, HYD-DAS to Cu (II) adsorption remains robust and underscoring after five cycles to exhibit good selectivity and reusability. Kinetics studies suggest the absorption process follows a quasi-second-order with isotherms aligning to the Langmuir monolayer model, and thermodynamics reveals that it is a spontaneous endothermic nature of adsorption. Based on the analyses of XPS and DFT calculations, a possible mechanism for HYD-DAS to Cu (II) adsorption is that Cu (II) combined with nitrogen atoms from Schiff base and hydrazine pyridine ring in HYD-DAS.

Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy.

Proteolysis targeting chimeras (PROTACs) have emerged as revolutionary anticancer therapeutics that degrade disease-causing proteins. However, the anticancer performance of PROTACs is often impaired by their insufficient bioavailability, unsatisfactory tumor specificity and ability to induce acquired drug resistance. Herein, we propose a polymer-conjugated PROTAC prodrug platform for the tumor-targeted delivery of the most prevalent von Hippel-Lindau (VHL)- and cereblon (CRBN)-based PROTACs, as well as for the precise codelivery of a degrader and conventional small-molecule drugs. The self-assembling PROTAC prodrug nanoparticles (NPs) can specifically target and be activated inside tumor cells to release the free PROTAC for precise protein degradation. The PROTAC prodrug NPs caused more efficient regression of MDA-MB-231 breast tumors in a mouse model by degrading bromodomain-containing protein 4 (BRD4) or cyclin-dependent kinase 9 (CDK9) with decreased systemic toxicity. In addition, we demonstrated that the PROTAC prodrug NPs can serve as a versatile platform for the codelivery of a PROTAC and chemotherapeutics for enhanced anticancer efficiency and combination benefits. This study paves the way for utilizing tumor-targeted protein degradation for precise anticancer therapy and the effective combination treatment of complex diseases.

Progress on H2B as a multifunctional protein related to pathogens.

Histone H2B is a member of the core histones, which together with other histones form the nucleosome, the basic structural unit of chromosomes. As scientists delve deeper into histones, researchers gradually realize that histone H2B is not only an important part of nucleosomes, but also plays a momentous role in regulating gene transcription, acting as a receptor and antimicrobial action outside the nucleus. There are a variety of epigenetically modified sites in the H2B tail rich in arginine and lysine, which can occur in ubiquitination, phosphorylation, methylation, acetylation, etc. When stimulated by foreign factors such as bacteria, viruses or parasites, histone H2B can act as a receptor for the recognition of these pathogens, and induce an intrinsic immune response to enhance host defense. In addition, the extrachromosomal histone H2B is also an important anti-microorganism agent, which may be the key to the development of antibiotics in the future. This review aims to summarize the interaction between histone H2B and etiological agents and explore the role of H2B in epigenetic modifications, receptors and antimicrobial activity.

Sirt1 Inhibits Atrial Fibrosis by Downregulating the Expression of the Transforming Growth Factor-ß1/Smad Pathway.

Background: Atrial fibrosis is an important factor leading to atrial fibrillation, and the transforming growth factor-ß1/Smad pathway is a key factor in inducing atrial fibrosis. Sirt1 is a member of the histone deacetylase (sirtuin) family, and recent studies have proven its cardioprotective effects. Objectives: This study explored the effect of Sirt1 on atrial fibrosis through the transforming growth factor-ß1/Smad pathway. Methods: We analyzed human right atrial appendage tissues and explored the relationship between Sirt1 and atrial fibrosis at the morphological, functional and molecular levels by Masson trichrome staining, immunofluorescence, real-time quantitative polymerase chain reaction and Western blot analysis. Rat atrial fibroblasts were extracted and treated by the Sirt1 agonist resveratrol, inhibitor sirtinol, and recombinant human transforming growth factor-ß1 protein. The expression levels of related proteins were detected by Western blot, and the effect on the migration of atrial fibroblasts was detected by wound healing assay. Results: We found that the expression of Sirt1 was reduced in the right atrial appendage tissues of patients with atrial fibrillation, and the degree of fibrosis was increased. In atrial fibroblasts, the activation of Sirt1 could inhibit the expression of transforming growth factor-ß1/Smad and reduce the development of fibrosis, while inhibiting Sirt1 reduced its inhibitory effect on the transforming growth factor-ß1/Smad pathway. Conclusions: These findings indicate that Sirt1 inhibits atrial fibrosis by downregulating the expression of the transforming growth factor-ß1/Smad pathway, and provide potential targets for the treatment of atrial fibrillation.

Effects of different dietary fiber supplement strategies on incidence of acute gastrointestinal injury in ICU patients: A prospective observational study.

OBJECTIVE: This study aimed to explore the effects of dietary fiber (DF) supplement strategies on the incidence of acute gastrointestinal injury (AGI) in critically ill patients. DESIGN: A prospective observational study. SETTING: The study was conducted in the First Affiliated Hospital of Soochow University from April 2021 to March 2023. METHODS: Using a five-day dietary log counted the amount of DF supplement. The best fitting trajectories of DF supplement were determined based on the latent class trajectory modelling (LCTM). The data of AGI were evaluated on the day 5 (D5) and day 7 (D7) after intensive care unit admission. RESULTS: A total of 179 patients were included in the study. The LCTM yielded a four-trajectories of models, named; Sustained Low - Group, Slowly Rising - Group, Early Supplement & Slowly Rising - Group and Rapidly Rising - Group, respectively. The incidences of AGI on D5 and D7 were 51.4 % and 40.0 %, respectively. There was an increased risk in the grade of AGI in the Sustained Low - Group compared with the Rapidly Rising - Group on D5 [odds ratio (OR), 4.8; 95 % confidence interval (CI), 1.9-12.1] and D7 (OR, 12.0; 95 % CI, 3.9-37.0); and an increased risk in the Slowly Rising - Group on D5 (OR, 3.6; 95 % CI, 1.3-9.9). CONCLUSION: The supplement of DF in critically ill patients may be insufficient and the incidence of AGI is high. Sustained low and slow rising DF supplement may be associated with an increased risk in the AGI. IMPLICATIONS FOR CLINICAL PRACTICE: The clinical staff could focus on the supplementation of not only the three macronutrients, but also DF in critically ill patients.

GPR41 deficiency aggravates type 1 diabetes in streptozotocin-treated mice by promoting dendritic cell maturation.

Disturbances in intestinal immune homeostasis predispose susceptible individuals to type 1 diabetes (T1D). G-protein-coupled receptor 41 (GPR41) is a receptor for short-chain fatty acids (SCFAs) mainly produced by gut microbiota, which plays key roles in maintaining intestinal homeostasis. In this study, we investigated the role of GPR41 in the progression of T1D. In non-obese diabetic (NOD) mice, we found that aberrant reduction of GPR41 expression in the pancreas and colons was associated with the development of T1D. GPR41-deficient (Gpr41-/-) mice displayed significantly exacerbated streptozotocin (STZ)-induced T1D compared to wild-type mice. Furthermore, Gpr41-/- mice showed enhanced gut immune dysregulation and increased migration of gut-primed IFN-γ+ T cells to the pancreas. In bone marrow-derived dendritic cells from Gpr41-/- mice, the expression of suppressor of cytokine signaling 3 (SOCS) was significantly inhibited, while the phosphorylation of STAT3 was significantly increased, thus promoting dendritic cell (DC) maturation. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (BMDC) from Gpr41-/- mice accelerated T1D in irradiated NOD mice. We conclude that GPR41 is essential for maintaining intestinal and pancreatic immune homeostasis and acts as a negative regulator of DC maturation in T1D. GPR41 may be a potential therapeutic target for T1D.

"Always online": How and when task interdependence and dispositional workplace anxiety affect workplace telepressure after hours.

Information and communication technology (ICT) provides employees with convenience in communication. However, it also creates a preoccupation with and urges to respond quickly to work-related ICT messages during nonworking time, which is defined as workplace telepressure after hours (WTA). Drawing on the job demand-resource model, conservation of resource theory, and workplace anxiety theory, this study explores how and when task interdependence and dispositional workplace anxiety affect WTA and how individuals cope with WTA. A total of 269 full-time workers from an online survey panel completed questionnaires at three time-points. We found that both task interdependence and dispositional workplace anxiety are positively related to WTA. The perception of pay-for-responsiveness moderates the relationship between task interdependence and WTA, such that the relationship is significant only for employees with a strong perception of pay-for-responsiveness. Others' approval contingency of self-worth moderates the relationship between dispositional workplace anxiety and WTA, and the relationship is significant only for employees with high degrees of others' approval contingency of self-worth. Finally, WTA arising from external work requirements or the internal pursuit of achieving work goals prompts employees to generate responsiveness coping strategies. Overall, these findings suggest that task interdependence and dispositional workplace anxiety are important factors affecting employees' WTA and highlight the importance of being responsive to WTA.

Shikonin suppresses rheumatoid arthritis by inducing apoptosis and autophagy via modulation of the AMPK/mTOR/ULK-1 signaling pathway.

BACKGROUND: The overproliferation of fibroblast-like synoviocytes (FLS) contributes to synovial hyperplasia, a pivotal pathological feature of rheumatoid arthritis (RA). Shikonin (SKN), the active compound from Lithospermum erythrorhizon, exerts anti-RA effects by diverse means. However, further research is needed to confirm SKN's in vitro and in vivo anti-proliferative functions and reveal the underlying specific molecular mechanisms. PURPOSE: This study revealed SKN's anti-proliferative effects by inducing both apoptosis and autophagic cell death in RA FLS and adjuvant-induced arthritis (AIA) rat synovium, with involvement of regulating the AMPK/mTOR/ULK-1 pathway. METHODS: SKN's influences on RA FLS were assessed for proliferation, apoptosis, and autophagy with immunofluorescence staining (Ki67, LC3B, P62), EdU incorporation assay, staining assays of Hoechst, Annexin V-FITC/PI, and JC-1, transmission electron microscopy, mCherry-GFP-LC3B puncta assay, and western blot. In AIA rats, SKN's anti-arthritic effects were assessed, and its impacts on synovial proliferation, apoptosis, and autophagy were studied using Ki67 immunohistochemistry, TUNEL, and western blot. The involvement of AMPK/mTOR/ULK-1 pathway was examined via western blot. RESULTS: SKN suppressed RA FLS proliferation with reduced cell viability and decreased Ki67-positive and EdU-positive cells. SKN promoted RA FLS apoptosis, as evidenced by apoptotic nuclear fragmentation, increased Annexin V-FITC/PI-stained cells, reduced mitochondrial potential, elevated Bax/Bcl-2 ratio, and increased cleaved-caspase 3 and cleaved-PARP protein levels. SKN also enhanced RA FLS autophagy, featuring increased LC3B, reduced P62, autophagosome formation, and activated autophagic flux. Autophagy inhibition by 3-MA attenuated SKN's anti-proliferative roles, implying that SKN-induced autophagy contributes to cell death. In vivo, SKN mitigated the severity of rat AIA while also reducing Ki67 expression, inducing apoptosis, and enhancing autophagy within AIA rat synovium. Mechanistically, SKN modulated the AMPK/mTOR/ULK-1 pathway in RA FLS and AIA rat synovium, as shown by elevated P-AMPK and P-ULK-1 expression and decreased P-mTOR expression. This regulation was supported by the reversal of SKN's in vitro and in vivo effects upon co-administration with the AMPK inhibitor compound C. CONCLUSION: SKN exerted in vitro and in vivo anti-proliferative properties by inducing apoptosis and autophagic cell death via modulating the AMPK/mTOR/ULK-1 pathway. Our study revealed novel molecular mechanisms underlying SKN's anti-RA effects.

Association between the ROX index and mortality in patients with acute hypoxemic respiratory failure: a retrospective cohort study.

BACKGROUND: Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. METHOD: Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. RESULT: A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794-0.928] P < 0.001). When the ROX index is above 8.28, no significant association was found between the ROX index and 28-day mortality. In contrast to the Q1 group, the mortality rates in the Q2, Q3, and Q4 groups had a substantial reduction (Q1 vs. Q2: HR, 0.749 [0.590-0.950] P = 0.017; Q3: HR, 0.711 [0.558-0.906] P = 0.006; Q4: HR, 0.641 [0.495-0.830] P < 0.001). CONCLUSION: The ROX index serves as a valuable predictor of mortality risk in adult patients with AHRF, and that a lower ROX index is substantially associated with an increase in mortality.

High ambient temperature may increase the risk of anemia in pregnancy: Identifying susceptible exposure windows.

Anemia in pregnancy (AIP) is associated with multiple severe maternal and perinatal adverse outcomes. However, there is a lack of evidence on the association between environmental factors and AIP. Aim to explore the association between ambient temperature and the risk of AIP, and identify susceptible exposure windows, we conducted a matched case-control study from 2013 to 2016 in Xi'an, China, which included 710 women with AIP and 1420 women without AIP. The conditional logistic regression model was used to evaluate the association between ambient temperature and AIP at different gestational weeks and gestational months. The association between extreme temperature and AIP was evaluated using the distributed lag nonlinear model (DLNM). We conducted stratified analyses of age, parity, and season of conception, and estimated the interaction between ambient temperature and air pollutants on AIP. Ambient temperature was significantly positively associated with the risk of AIP, and the susceptible exposure windows were 2-25 gestational weeks and 1-6 gestational months, respectively. The strongest effect was observed in the week 8 and month 2, for each 1 °C increase in weekly and monthly mean temperature, the odds ratio (OR) for AIP was 1.038 (95 % confidence interval (CI): 1.022, 1.055) and 1.040 (95 % CI: 1.020, 1.060), respectively. Extreme heat may increase the risk of AIP. Stratified analyses showed that there was no significant difference among different age, parity, and season of conception groups. No significant interaction effect of ambient temperature with air pollution on AIP was found. In summary, high ambient temperature may increase the risk of AIP, and the first and second trimesters may be susceptible exposure windows. Understanding the effect of temperature on pregnant women will be beneficial to reduce the occurrence of AIP.

Efficacy and safety of oral and vaginal administration of misoprostol for induction of labor in high-risk obese pregnant women with hypertension or diabetes mellitus.

OBJECTIVE: This study aims to compare the safety and efficacy of misoprostol administered orally and vaginally in obese pregnant women at term with either gestational hypertension or diabetes. METHODS: A total of 264 pregnant women were enrolled and categorized into two groups based on their primary condition: hypertension (134 cases) or diabetes mellitus (130 cases) and were further divided into subgroups for misoprostol administration: orally (Oral group) or vaginally (Vaginal group). The primary outcomes measured were changes in the Bishop score following treatment, induction of labor (IOL) success rates, requirement for oxytocin augmentation, duration of labor, mode of delivery, and cesarean section rates. RESULTS: Significant enhancements in Bishop scores, decreased cesarean section rates and increased success rates of IOL were noted in both administration groups. The incidence of vaginal delivery within 24 h was significantly higher in the Vaginal group compared to the Oral group. Adverse effects, including nausea, uterine overcontraction, hyperfrequency of uterine contraction and uterine hyperstimulation without fetal heart rate deceleration, were significantly more prevalent in the Vaginal group than in the Oral group. CONCLUSION: Misoprostol administration, both orally and vaginally, proves effective for labor induction in obese pregnant women with hypertension or diabetes. However, the oral route presents a lower risk of adverse maternal and neonatal outcomes, suggesting its preference for safer labor induction in this demographic.

An Enzymatic Carbon-Carbon Bond Cleavage and Aldol Reaction Cascade Converts an Angular Scaffold into the Linear Tetracyclic Core of Ochraceopones.

Meroterpenoids of the ochraceopones family featuring a linear tetracyclic scaffold exhibit exceptional antiviral and anti-inflammatory activities. The biosynthetic pathway and chemical logic to generate this linear tetracycle, however, remain unknown. In this study, we identified and characterized all biosynthetic enzymes to afford ochraceopones and elucidated the complete biosynthetic pathway. We demonstrated that the linear tetracyclic scaffold of ochraceopones was derived from an angular tetracyclic precursor. A multifunctional cytochrome P450 OchH was validated to catalyze the free-radical-initiated carbon-carbon bond cleavage of the angular tetracycle. Then, a new carbon-carbon bond was verified to be constructed using a new aldolase OchL, which catalyzes an intramolecular aldol reaction to form the linear tetracycle. This carbon-carbon bond fragmentation and aldol reaction cascade features an unprecedented strategy for converting a common angular tetracycle to a distinctive linear tetracyclic scaffold in meroterpenoid biosynthesis.