The OsZIP2 transporter is involved in root-to-shoot translocation and intervascular transfer of cadmium in rice.

Cadmium (Cd) is a toxic metal that poses serious threats to human health. Rice is a major source of dietary Cd but how rice plants transport Cd to the grain is not fully understood. Here, we characterize the function of the ZIP (ZRT, IRT-like protein) family protein, OsZIP2, in the root-to-shoot translocation of Cd and intervascular transfer of Cd in nodes. OsZIP2 is localized at the plasma membrane and exhibited Cd2+ transport activity when heterologously expressed in yeast. OsZIP2 is strongly expressed in xylem parenchyma cells in roots and in enlarged vascular bundles in nodes. Knockout of OsZIP2 significantly enhanced root-to-shoot translocation of Cd and alleviated the inhibition of root elongation by excess Cd stress; whereas overexpression of OsZIP2 decreased Cd translocation to shoots and resulted in Cd sensitivity. Knockout of OsZIP2 increased Cd allocation to the flag leaf but decreased Cd allocation to the panicle and grain. We further reveal that the variation of OsZIP2 expression level contributes to grain Cd concentration among rice germplasms. Our results demonstrate that OsZIP2 functions in root-to-shoot translocation of Cd in roots and intervascular transfer of Cd in nodes, which can be used for breeding low Cd rice varieties.

Alterations in dynamic regional homogeneity within default mode network in patients with thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is a significant autoimmune eye disease known for causing exophthalmos and substantial optic nerve damage. Prior investigations have solely focused on static functional MRI (fMRI) scans of the brain in TAO patients, neglecting the assessment of temporal variations in local brain activity. This study aimed to characterize alterations in dynamic regional homogeneity (dReHo) in TAO patients and differentiate between TAO patients and healthy controls using support vector machine (SVM) classification. Thirty-two patients with TAO and 32 healthy controls underwent resting-state fMRI scans. We calculated dReHo using sliding-window methods to evaluate changes in regional brain activity and compared these findings between the two groups. Subsequently, we employed SVM, a machine learning algorithm, to investigate the potential use of dReHo maps as diagnostic markers for TAO. Compared to healthy controls, individuals with active TAO demonstrated significantly higher dReHo values in the right angular gyrus, left precuneus, right inferior parietal as well as the left superior parietal gyrus. The SVM model demonstrated an accuracy ranging from 65.62 to 68.75% in distinguishing between TAO patients and healthy controls based on dReHo variability in these identified brain regions, with an area under the curve of 0.70 to 0.76. TAO patients showed increased dReHo in default mode network-related brain regions. The accuracy of classifying TAO patients and healthy controls based on dReHo was notably high. These results offer new insights for investigating the pathogenesis and clinical diagnostic classification of individuals with TAO.

Submucosal Trans-Septal Suturing Technique After a Septal Extension Graft with Porous High-Density Polyethylene: A Technical Report.

BACKGROUND: Porous high-density polyethylene (pHDPE) is an alternative material for a septal extension graft (SEG) in oriental rhinoplasty when autologous cartilage is limited. Although nasal packing (NP) and trans-septal suturing (TSS) techniques are routine procedures to obviate the dead space after septoplasty, they are associated with certain discomforts and complications. OBJECTIVE: To investigate the application of a submucosal trans-septal suturing (STSS) technique after SEG with pHDPE. METHODS: A prospective study was conducted on 60 female participants who underwent SEG with pHDPE. The participants were randomly divided into the NP group and STSS group. The extra surgical duration of NP and STSS, pain, nasal obstruction, and sleeping disturbance as well as postoperative complications were recorded and compared between groups. RESULTS: No significant difference was found between group NP and group STSS in terms of mean age. The mean extra surgical duration of group STSS was significantly longer than group NP. There were significant higher pains of group NP at 24 hours and 48 hours postoperatively, compared with group STSS. The NP group also experienced significantly more nasal obstruction and sleep disturbance within 48h postoperatively compared to the STSS group. There was one infection in each group, minor bleeding in two NP patients, and one STSS patient. There was no major bleeding, hematoma, graft exposure, or septal perforation in both groups. CONCLUSION: Although STSS needs a longer extra surgical duration than NP, it significantly improves the patient's postoperative comfort with a faster return to normal respiration compared to NP. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study.

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

Assessing the causal association between sleep apnea and the human gut microbiome composition: A two-sample Mendelian randomization study.

Background: Studies have linked gut microbiota dysbiosis with sleep apnea; however, no causal relationship was found in human subjects. Finding new targets for the pathophysiology of sleep apnea might be made possible by systematically investigating the causal relationship between the human gut microbiota and sleep apnea. Methods: A two-sample Mendelian randomization analysis was conducted. The human gut microbiome composition data, spanning five taxonomic levels, were acquired from a genome-wide association study that included 18,340 participants from 24 cohorts. Genome-wide association study data for sleep apnea were obtained from the Sleep Disorder Knowledge Portal for primary analysis and the FinnGen consortium for meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results: Using inverse-variance weighted analysis, eight microbial taxa were initially found to be substantially linked with the apnea-hypopnea index. Only three microbial taxa remained significant associations with sleep apnea when combined with the FinnGen consortium (the class Bacilli: B = 8.21%, 95% CI = 0.93%-15.49%; p = 0.03; the order Lactobacillales: B = 7.55%, 95% CI = 0.25%-4.85%; p = 0.04; the genus RuminococcaceaeUCG009: B = -21.63%, 95% CI = -41.47% to -1.80%; p = 0.03). Conclusions: Sleep apnea may lead to gut dysbiosis as significant reductions in butyrate-producing bacteria and increases in lactate-producing bacteria. By integrating genomes and metabolism, the evidence that three microbiome species are causally linked to sleep apnea may offer a fresh perspective on the underlying mechanisms of the condition.

Effectiveness of tranexamic acid on chronic subdural hematoma recurrence: a meta-analysis and systematic review.

Objectives: Our objective was to compare the effectiveness of TXA in improving recurrence in patients with chronic subdural hematoma (CSDH). Methods: Eligible randomized controlled trials (RCTs), prospective trials and retrospective cohort studies were searched in PubMed, Cochrane Library, Embase, and CNKI from database inception to December 2023. After the available studies following inclusion and exclusion criteria were screened, the main outcome measures were strictly extracted. Reman v5.4. was used to assess the overall recurrence rate. A random-effects model was used to assess pooled ORs, with the Mantel-Haenszel estimation method applied. Cochran Q (Chi-square) test and I2 statistics were used to assess inter-study heterogeneity. Funnel plots were used to evaluate publication bias. Results: From the 141 articles found during initial citation screening, 9 literatures were ultimately included in our study. Our NMA results illustrated that patients with newly diagnosed Chronic subdural hematoma revealed a significantly improved recurrence rate when patients were treated with Tranexamic acid (OR: 0.33; 95% CI 0.26-0.41; p < 0.00001) compared with standard neurosurgical treatment. There was no significant difference in the incidence rates of thrombosis (OR: 0.84; 95% CI 0.63-1.12; p = 0.23) and mortality (OR: 1.0; 95% CI 0.57-11.76; p = 0.99), Occurrence of myocardial infarction was significantly less frequent in TXA users than in nonusers (OR: 0.18; 95% CI 0.04-0.82; p = 0.03). Conclusion: TXA can effectively improve the recurrence rate of CDSH. It provides a high level of evidence-based medicine for clinical treatment. In addition, multicenter randomized controlled trials, with dose adjustments, are still needed to determine whether TXA intervention improves neurological function or prognosis.

Functional connectivity alterations in the thalamus among patients with bronchial asthma.

Objective: Bronchial Asthma (BA) is a common chronic respiratory disease worldwide. Earlier research has demonstrated abnormal functional connectivity (FC) in multiple cognition-related cortices in asthma patients. The thalamus (Thal) serves as a relay center for transmitting sensory signals, yet the modifications in the thalamic FC among individuals with asthma remain uncertain. This research employed the resting-state functional connectivity (rsFC) approach to explore alterations in thalamic functional connectivity among individuals with BA. Patients and methods: After excluding participants who did not meet the criteria, this study finally included 31 patients with BA, with a gender distribution of 16 males and 15 females. Subsequently, we recruited 31 healthy control participants (HC) matched for age, gender, and educational background. All participants underwent the Montreal Cognitive Assessment (MoCA) and the Hamilton Depression Rating Scale (HAMD) assessment. Following this, both groups underwent head magnetic resonance imaging scans, and resting-state functional magnetic resonance imaging (rs-fMRI) data was collected. Based on the AAL (Automated Anatomical Labeling) template, the bilateral thalamic regions were used as seed points (ROI) for subsequent rsFC research. Pearson correlation analysis was used to explore the relationship between thalamic functional connectivity and neuropsychological scales in both groups. After controlling for potential confounding factors such as age, gender, intelligence, and emotional level, a two-sample t-test was further used to explore differences in thalamic functional connectivity between the two groups of participants. Result: Compared to the HC group, the BA group demonstrated heightened functional connectivity (FC) between the left thalamus and the left cerebellar posterior lobe (CPL), left postcentral gyrus (PCG), and right superior frontal gyrus (SFG). Concurrently, there was a decrease in FC with both the Lentiform Nucleus (LN) and the left corpus callosum (CC). Performing FC analysis with the right thalamus as the Region of Interest (ROI) revealed an increase in FC between the right thalamus and the right SFG as well as the left CPL. Conversely, a decrease in FC was observed between the right thalamus and the right LN as well as the left CC. Conclusion: In our study, we have verified the presence of aberrant FC patterns in the thalamus of BA patients. When compared to HCs, BA patients exhibit aberrant alterations in FC between the thalamus and various brain areas connected to vision, hearing, emotional regulation, cognitive control, somatic sensations, and wakefulness. This provides further confirmation of the substantial role played by the thalamus in the advancement of BA.

MicroRNA164 Affects Plant Responses to UV Radiation in Perennial Ryegrass.

Increasing the ultraviolet radiation (UV) level, particularly UV-B due to damage to the stratospheric ozone layer by human activities, has huge negative effects on plant and animal metabolism. As a widely grown cool-season forage grass and turfgrass in the world, perennial ryegrass (Lolium perenne) is UV-B-sensitive. To study the effects of miR164, a highly conserved microRNA in plants, on perennial ryegrass under UV stress, both OsmiR164a overexpression (OE164) and target mimicry (MIM164) transgenic perennial ryegrass plants were generated using agrobacterium-mediated transformation, and UV-B treatment (~600 µw cm-2) of 7 days was imposed. Morphological and physiological analysis showed that the miR164 gene affected perennial ryegrass UV tolerance negatively, demonstrated by the more scorching leaves, higher leaf electrolyte leakage, and lower relative water content in OE164 than the WT and MIM164 plants after UV stress. The increased UV sensitivity could be partially due to the reduction in antioxidative capacity and the accumulation of anthocyanins. This study indicated the potential of targeting miR164 and/or its targeted genes for the genetic manipulation of UV responses in forage grasses/turfgrasses; further research to reveal the molecular mechanism underlying how miR164 affects plant UV responses is needed.

Flexible ureteroscopy with a tip-flexible pressure-controlling ureteral access sheath for renal stones in children.

BACKGROUND: To evaluate the safety and efficacy of flexible ureteroscopy using a tip-flexible pressure-controlling ureteral access sheath (TFPC-UAS) for renal stones in children. METHODS: Consecutive patients aged 5-18 years with renal stones of diameter 1-3 cm were enrolled between January 2022 and November 2023 at Ganzhou People's Hospital. The patients were treated with flexible ureteroscopy using the TFPC-UAS. The renal pelvic pressure (RPP) parameters were set as follows: control value at -10 mmHg to 5 mmHg, warning value at 20 mmHg, and limit value at 30 mmHg. The infusion flow rate was set to 100-120 mL/min. A holmium laser (276 µm) was used to fragment the stone at 2.0-2.5 J/pulse with a frequency of 20-30 pulses/s. The cases were analyzed for RPP, operative time, stone-free rate, and complications. RESULTS: A total of 21 consecutive patients were included. Two patients were switched to percutaneous nephrolithotomy owing to sheath placement failure. The RPP was -4.6±2.1 mmHg. The mean operative time was 56.5±17.1 min. The postoperative hospitalization time was 1.5±0.3 days. The stone-free rates at 1 day and 1 month after surgery were 81.0% and 85.7%, respectively. Residual stones in two patients were cleared after extracorporeal shockwave lithotripsy. Three cases of Clavien I complications and one case of Clavien II complications occurred. No major complications (Clavien grade III-V) were observed. CONCLUSIONS: Flexible ureteroscopy with a TFPC-UAS is safe and effective for renal stones in children.

SELENOI Functions as a Key Modulator of Ferroptosis Pathway in Colitis and Colorectal Cancer.

Ferroptosis plays important roles both in normal physiology and multiple human diseases. It is well known that selenoprotein named glutathione peroxidase 4 (GPX4) is a crucial regulator for ferroptosis. However, it remains unknown whether other selenoproteins responsible for the regulation of ferroptosis, particularly in gut diseases. In this study, it is observed that Selenoprotein I (Selenoi) prevents ferroptosis by maintaining ether lipids homeostasis. Specific deletion of Selenoi in intestinal epithelial cells induced the occurrence of ferroptosis, leading to impaired intestinal regeneration and compromised colonic tumor growth. Mechanistically, Selenoi deficiency causes a remarkable decrease in ether-linked phosphatidylethanolamine (ePE) and a marked increase in ether-linked phosphatidylcholine (ePC). The imbalance of ePE and ePC results in the upregulation of phospholipase A2, group IIA (Pla2g2a) and group V (Pla2g5), as well as arachidonate-15-lipoxygenase (Alox15), which give rise to excessive lipid peroxidation. Knockdown of PLA2G2A, PLA2G5, or ALOX15 can reverse the ferroptosis phenotypes, suggesting that they are downstream effectors of SELENOI. Strikingly, GPX4 overexpression cannot rescue the ferroptosis phenotypes of SELENOI-knockdown cells, while SELENOI overexpression can partially rescue GPX4-knockdown-induced ferroptosis. It suggests that SELENOI prevents ferroptosis independent of GPX4. Taken together, these findings strongly support the notion that SELENOI functions as a novel suppressor of ferroptosis during colitis and colon tumorigenesis.

Porcine lung tissue slices: a culture model for PRCV infection and innate immune response investigations.

Respiratory coronaviruses (RCoVs) significantly threaten human health, necessitating the development of an ex vivo respiratory culture system for investigating RCoVs infection. Here, we successfully generated a porcine precision-cut lung slices (PCLSs) culture system, containing all resident lung cell types in their natural arrangement. Next, this culture system was inoculated with a porcine respiratory coronavirus (PRCV), exhibiting clinical features akin to humans who were infected by SARS-CoV-2. The results demonstrated that PRCV efficiently infected and replicated within PCLSs, targeting ciliated cells in the bronchioles, terminal bronchioles, respiratory bronchioles, and pulmonary alveoli. Additionally, through RNA-Seq analysis of the innate immune response in PCLSs following PRCV infection, expression levels of interferons, inflammatory cytokines and IFN stimulated genes were significantly upregulated. This ex vivo model may not only offer new insights into PRCV infection in the porcine respiratory tract but also serve as a valuable tool for studying human respiratory CoVs infection.

Peritendinous Submembrane Access Technique for Management of Acute Ruptures of the Achilles Tendon: A Retrospective Study of 249 Cases.

OBJECTIVE: Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re-rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS-PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury. METHODS: This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS-PSAT at our institution and were followed up for 8-48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS), associated with local complications and isokinetic tests. RESULTS: None of the patients had infection, necrosis, or sural nerve injury. Re-rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS-AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05). CONCLUSION: The MIS-PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re-rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.

Understanding the role of boron in plant adaptation to soil salinity.

Soil salinity is a major environmental constraint affecting the sustainability and profitability of agricultural production systems. Salinity stress tolerance has been present in wild crop relatives but then lost, or significantly weakened, during their domestication. Given the genetic and physiological complexity of salinity tolerance traits, agronomical solutions may be a suitable alternative to crop breeding for improved salinity stress tolerance. One of them is optimizing fertilization practices to assist plants in dealing with elevated salt levels in the soil. In this review, we analyse the causal relationship between the availability of boron (an essential metalloid micronutrient) and plant's adaptive responses to salinity stress at the whole-plant, cellular, and molecular levels, and a possibility of using boron for salt stress mitigation. The topics covered include the impact of salinity and the role of boron in cell wall remodelling, plasma membrane integrity, hormonal signalling, and operation of various membrane transporters mediating plant ionic and water homeostasis. Of specific interest is the role of boron in the regulation of H+-ATPase activity whose operation is essential for the control of a broad range of voltage-gated ion channels. The complex relationship between boron availability and expression patterns and the operation of aquaporins is also discussed.

Promoting Cross-Link Reaction of Polymers by the Matrix-Filler Interface Effect: Role of Coupling Agents and Intermediate Linkers.

The matrix-filler interface effect plays an important role in determining the structural stability and mechanical properties of polymer composite materials, which remain ambiguous and need to be studied. The network-forming dynamics of poly(3,3-bis (azidomethyl) oxetane-tetrahydrofuran) (PBT) at the ammonium perchlorate (AP) surface was studied by using atomistic molecular dynamics simulation, considering the additives of curing agent toluene diisocyanate (TDI), cross-linker trimethylolpropane (TMP), and coupling agent triethanolamine (TEA). The presence of the AP surface promotes chain cross-link reaction, which is attributed to the increased production of intermediate linkers formed by TDI, TMP, and TEA. The intermediate linker has three reactive sites that can react with PBT main chains to form a cross-linked structure. Owing to the strong interaction with the AP surface, the coupling agent TEA plays a dominant role in forming the intermediate linker. At the early stage of network forming (reaction ratio r < 30%), the AP surface adsorbs TEA, which leads to a maximum contact density to PBT. As r increases to 60%, the density of intermediate linkers near the AP surface reaches a maximum value. Consequently, the chain cross-link reactions between the intermediate linker and PBT main chains are enhanced as r > 60%. This work explains the micromechanism of the promotion of chain cross-link reaction by the interface effect and provides important insights on designing polymer materials with high mechanical properties.

Fabrication of Multiple-Channel Electrochemical Microneedle Electrode Array via Separated Functionalization and Assembly Method.

Real-time monitoring of physiological indicators inside the body is pivotal for contemporary diagnostics and treatments. Implantable electrodes can not only track specific biomarkers but also facilitate therapeutic interventions. By modifying biometric components, implantable electrodes enable in situ metabolite detection in living tissues, notably beneficial in invasive glucose monitoring, which effectively alleviates the self-blood-glucose-managing burden for patients. However, the development of implantable electrochemical electrodes, especially multi-channel sensing devices, still faces challenges: (1) The complexity of direct preparation hinders functionalized or multi-parameter sensing on a small scale. (2) The fine structure of individual electrodes results in low spatial resolution for sensor functionalization. (3) There is limited conductivity due to simple device structures and weakly conductive electrode materials (such as silicon or polymers). To address these challenges, we developed multiple-channel electrochemical microneedle electrode arrays (MCEMEAs) via a separated functionalization and assembly process. Two-dimensional microneedle (2dMN)-based and one-dimensional microneedle (1dMN)-based electrodes were prepared by laser patterning, which were then modified as sensing electrodes by electrochemical deposition and glucose oxidase decoration to achieve separated functionalization and reduce mutual interference. The electrodes were then assembled into 2dMN- and 1dMN-based multi-channel electrochemical arrays (MCEAs), respectively, to avoid damaging functionalized coatings. In vitro and in vivo results demonstrated that the as-prepared MCEAs exhibit excellent transdermal capability, detection sensitivity, selectivity, and reproducibility, which was capable of real-time, in situ glucose concentration monitoring.

Maillard Reaction Inspired Microexplosion toward Fast Synthesis of Two-Dimensional Mesoporous Tin Oxides for Efficient Chemiresistive Gas Sensing.

Two-dimensional (2D) mesoporous transition metal oxides are highly desired in various applications, but their fast and low-cost synthesis remains a great challenge. Herein, a Maillard reaction inspired microexplosion approach is applied to rapidly synthesize ultrathin 2D mesoporous tin oxide (mSnO2). During the microexplosion between granular ammonia nitrate with melanoidin at high temperature, the organic species can be carbonized and expanded rapidly due to the instantaneous release of gases, thus producing ultrathin carbonaceous templates with rich functional groups to effectively anchor SnO2 nanoparticles on the surface. The subsequent removal of carbonaceous templates via calcination in air results in the formation of 2D mSnO2 due to the confinement effect of the templates. Pd nanoparticles are controllably deposited on the surface of 2D mSnO2 via in situ reduction, forming ultrathin 2D Pd/mSnO2 nanocomposites with thicknesses of 6-8 nm. Owing to the unique 2D mesoporous structure with rich oxygen defects and highly exposed metal-metal oxide interfaces, 2D Pd/mSnO2 exhibits excellent sensing performance toward acetone with high sensitivity, a short response time, and good selectivity under low working temperature (100 °C). This fast and convenient microexplosion synthesis strategy opens up the possibility of constructing 2D porous functional materials for various applications including high-performance gas sensors.

Organic Electrode Materials for Energy Storage and Conversion: Mechanism, Characteristics, and Applications.

ConspectusLithium ion batteries (LIBs) with inorganic intercalation compounds as electrode active materials have become an indispensable part of human life. However, the rapid increase in their annual production raises concerns about limited mineral reserves and related environmental issues. Therefore, organic electrode materials (OEMs) for rechargeable batteries have once again come into the focus of researchers because of their design flexibility, sustainability, and environmental compatibility. Compared with conventional inorganic cathode materials for Li ion batteries, OEMs possess some unique characteristics including flexible molecular structure, weak intermolecular interaction, being highly soluble in electrolytes, and moderate electrochemical potentials. These unique characteristics make OEMs suitable for applications in multivalent ion batteries, low-temperature batteries, redox flow batteries, and decoupled water electrolysis. Specifically, the flexible molecular structure and weak intermolecular interaction of OEMs make multivalent ions easily accessible to the redox sites of OEMs and facilitate the desolvation process on the redox site, thus improving the low-temperature performance, while the highly soluble nature enables OEMs as redox couples for aqueous redox flow batteries. Finally, the moderate electrochemical potential and reversible proton storage and release of OEMs make them suitable as redox mediators for water electrolysis. Over the past ten years, although various new OEMs have been developed for Li-organic batteries, Na-organic batteries, Zn-organic batteries, and other battery systems, batteries with OEMs still face many challenges, such as poor cycle stability, inferior energy density, and limited rate capability. Therefore, previous reviews of OEMs mainly focused on organic molecular design for organic batteries or strategies to improve the electrochemical performance of OEMs. A comprehensive review to explore the characteristics of OEMs and establish the correlation between these characteristics and their specific application in energy storage and conversion is still lacking.In this Account, we initially provide an overview of the sustainability and environmental friendliness of OEMs for energy storage and conversion. Subsequently, we summarize the charge storage mechanisms of the different types of OEMs. Thereafter, we explore the characteristics of OEMs in comparison with conventional inorganic intercalation compounds including their structural flexibility, high solubility in the electrolyte, and appropriate electrochemical potential in order to establish the correlations between their characteristics and potential applications. Unlike previous reviews that mainly introduce the electrochemical performance progress of different organic batteries, this Account specifically focuses on some exceptional applications of OEMs corresponding to the characteristics of organic electrode materials in energy storage and conversion, as previously published by our groups. These applications include monovalent ion batteries, multivalent ion batteries, low-temperature batteries, redox flow batteries with soluble OEMs, and decoupled water electrolysis employing organic electrodes as redox mediators. We hope that this Account will make an invaluable contribution to the development of organic electrode materials for next-generation batteries and help to unlock a world of potential energy storage applications.

DNA-PKcs/AKT1 inhibits epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis by inducing ubiquitination and degradation of Twist1.

INTRODUCTION: Radiation-induced pulmonary fibrosis (RIPF) is a chronic, progressive, irreversible lung interstitial disease that develops after radiotherapy. Although several previous studies have focused on the mechanism of epithelial-mesenchymal transition (EMT) in lung epithelial cells, the essential factors involved in this process remain poorly understood. The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) exhibits strong repair capacity when cells undergo radiation-induced damage; whether DNA-PKcs regulates EMT during RIPF remains unclear. OBJECTIVES: To investigate the role and molecular mechanism of DNA-PKcs in RIPF and provide an important theoretical basis for utilising DNA-PKcs-targeted drugs for preventing RIPF. METHODS: DNA-PKcs knockout (DPK-/-) mice were generated via the Cas9/sgRNA technique and subjected to whole chest ionizing radiation (IR) at a 20 Gy dose. Before whole chest IR, the mice were intragastrically administered the DNA-PKcs-targeted drug VND3207. Lung tissues were collected at 1 and 5 months after IR. RESULTS: The expression of DNA-PKcs is low in pulmonary fibrosis (PF) patients. DNA-PKcs deficiency significantly exacerbated RIPF by promoting EMT in lung epithelial cells. Mechanistically, DNA-PKcs deletion by shRNA or inhibitor NU7441 maintained the protein stability of Twist1. Furthermore, AKT1 mediated the interaction between DNA-PKcs and Twist1. High Twist1 expression and EMT-associated changes caused by DNA-PKcs deletion were blocked by insulin-like growth factor-1 (IGF-1), an AKT1 agonist. The radioprotective drug VND3207 prevented IR-induced EMT and alleviated RIPF in mice by stimulating the kinase activity of DNA-PKcs. CONCLUSION: Our study clarified the critical role and mechanism of DNA-PKcs in RIPF and showed that it could be a potential target for preventing RIPF.

Prognostic value of geriatric nutritional risk index in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Malnutrition increases the risk of poor prognosis in patients with cardiovascular disease, and our current research was designed to assess the predictive performance of the Geriatric Nutrition Risk Index (GNRI) for the occurrence of poor prognosis after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (SCAD) and to explore possible thresholds for nutritional intervention. METHODS: This study retrospectively enrolled newly diagnosed SCAD patients treated with elective PCI from 2014 to 2017 at Shinonoi General Hospital, with all-cause death as the main follow-up endpoint. Cox regression analysis and restricted cubic spline (RCS) regression analysis were used to explore the association of GNRI with all-cause death risk and its shape. Receiver operating characteristic curve (ROC) analysis and piecewise linear regression analysis were used to evaluate the predictive performance of GNRI level at admission on all-cause death in SCAD patients after PCI and to explore possible nutritional intervention threshold points. RESULTS: The incidence of all-cause death was 40.47/1000 person-years after a mean follow-up of 2.18 years for 204 subjects. Kaplan-Meier curves revealed that subjects at risk of malnutrition had a higher all-cause death risk. In multivariate Cox regression analysis, each unit increase in GNRI reduced the all-cause death risk by 14% (HR 0.86, 95% CI 0.77, 0.95), and subjects in the GNRI > 98 group had a significantly lower risk of death compared to those in the GNRI < 98 group (HR 0.04, 95% CI 0.00, 0.89). ROC analysis showed that the baseline GNRI had a very high predictive performance for all-cause death (AUC = 0.8844), and the predictive threshold was 98.62; additionally, in the RCS regression analysis and piecewise linear regression analysis we found that the threshold point for the GNRI-related all-cause death risk was 98.28 and the risk will be significantly reduced when the subjects' baseline GNRI was greater than 98.28. CONCLUSIONS: GNRI level at admission was an independent predictor of all-cause death in SCAD patients after PCI, and GNRI equal to 98.28 may be a useful threshold for nutritional intervention in SCAD patients treated with PCI.

Ovarian PERK/NRF2/CX43/StAR/progesterone pathway activation mediates female reproductive dysfunction induced by cold exposure.

Ambient air temperature is a key factor affecting human health. Female reproductive disorders are representative health risk events under low temperature. However, the mechanism involving in cold-induced female reproductive disorders remains largely unknown. Female mice were intermittently exposed to cold conditions (4 °C) to address the health risk of low temperature on female reproductive system. Primary granulosa cells (GCs) were prepared and cultured under low temperature (35 °C) or exposed to ß3-adrenoreceptor agonist, isoproterenol, to mimic the condition of cold exposure. Western-blot, RT-PCR, co-IP, ELISA, pharmacological inhibition or siRNA-mediated knockdown of target gene were performed to investigate the possible role of hormones, gap conjunction proteins, and ER stress sensor protein in regulating female reproductive disorders under cold exposure. Cold exposure induced estrous cycle disorder and follicular dysplasia in female mice, accompanying with abnormal upregulation of progesterone and its synthetic rate-limiting enzyme, StAR, in the ovarian granulosa cells. Under the same conditions, an increase in connexin 43 (CX43) expressions in the GCs was also observed, which contributed to elevated progesterone levels in the ovary. Moreover, ER stress sensor protein, PERK, was activated in the ovarian GCs after cold exposure, leading to the upregulation of downstream NRF2-dependent CX43 transcription and aberrant increase in progesterone synthesis. Most importantly, blocking PERK expression in vivo significantly inhibited NRF2/CX43/StAR/progesterone pathway activation in the ovary and efficiently rescued the prolongation of estrous cycle and the increase in follicular atresia of the female mice induced by cold stress. We have elucidated the mechanism of ovarian PERK/NRF2/CX43/StAR/progesterone pathway activation in mediating female reproductive disorder under cold exposure. Targeting PERK might be helpful for maintaining female reproductive health under cold conditions.