Dopaminylation of endothelial TPI1 suppresses ferroptotic angiocrine signals to promote lung regeneration over fibrosis.

Lungs can undergo facultative regeneration, but handicapped regeneration often leads to fibrosis. How microenvironmental cues coordinate lung regeneration via modulating cell death remains unknown. Here, we reveal that the neurotransmitter dopamine modifies the endothelial niche to suppress ferroptosis, promoting lung regeneration over fibrosis. A chemoproteomic approach shows that dopamine blocks ferroptosis in endothelial cells (ECs) via dopaminylating triosephosphate isomerase 1 (TPI1). Suppressing TPI1 dopaminylation in ECs triggers ferroptotic angiocrine signaling to aberrantly activate fibroblasts, leading to a transition from lung regeneration to fibrosis. Mechanistically, dopaminylation of glutamine (Q) 65 residue in TPI1 directionally enhances TPI1's activity to convert dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (GAP), directing ether phospholipid synthesis to glucose metabolism in regenerating lung ECs. This metabolic shift attenuates lipid peroxidation and blocks ferroptosis. Restoring TPI1 Q65 dopaminylation in an injured endothelial niche overturns ferroptosis to normalize pro-regenerative angiocrine function and alleviate lung fibrosis. Overall, dopaminylation of TPI1 balances lipid/glucose metabolism and suppresses pro-fibrotic ferroptosis in regenerating lungs.

bZIP Transcription Factors: Structure, Modification, Abiotic Stress Responses and Application in Plant Improvement.

Plant growth, yield, and distribution are significantly impacted by abiotic stresses, affecting global ecosystems and forestry practices. However, plants have evolved complex adaptation mechanisms governed by numerous genes and transcription factors (TFs) to manage these stresses. Among these, bZIP (basic leucine zipper) is a crucial regulator orchestrating morphological adaptations. This review aims to elucidate the multifaceted roles of bZIP TFs in plant species. We discuss the morphological changes induced by stress stimuli and the pivotal functions of bZIP TFs in mediating these responses. While several publications have explored the mechanisms of bZIP TFs in response to abiotic stresses, this review delves into the intricate regulatory networks, summarizing alternative splicing and post-translational modifications, signaling networks interacting with bZIP TFs, and genetic engineering of bZIP TFs. By synthesizing current research, this review provides an updated discussion on bZIP interactions with other proteins to regulate stresses such as cold, heat, drought, and salt. Additionally, it offers avenues for future research and applications of bZIP TFs to improve abiotic stress resilience in plants through genetic engineering.

Non-linear association of liver enzymes with cognitive performance in the elderly: A cross-sectional study.

BACKGROUND: Although liver metabolic dysfunction has been found to potentially elevate susceptibility to cognitive impairment and dementia, there is still insufficient evidence to explore the non-linear association of liver enzymes with cognitive performance. Therefore, we aimed to elucidate the non-linear relationship between liver enzymes and cognitive performance. METHODS: In this cross-sectional study, 2764 individuals aged ≥ 60 who participated in the National Health and Nutrition Survey (NHANES) between 2011 and 2014 were included. The primary data comprised liver enzyme levels (alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyl transferase (GGT)), and cognitive performance was the major measured outcome. The associations were analyzed using weighted multivariate logistic regression, subgroup analysis, a generalized additive model, smooth fitting curves, and threshold effects. RESULTS: The results of the fully adjusted model indicated that ALP was negatively associated with the animal fluency test (AFT) score (OR = 1.48, 95% CI: 1.11-1.98), whereas ALT demonstrated a positive association with the consortium to establish a registry for Alzheimer's disease (CERAD) test score (OR = 0.72, 95% CI: 0.53-0.97). Additionally, the AST/ALT ratio was negatively associated with the global cognitive test (OR = 2.39, 95% CI: 1.53-3.73), CERAD (OR = 2.61, 95% CI: 1.77-3.84), and digit symbol substitution test (DSST) scores (OR = 2.51, 95% CI: 1.57-4.02). GGT was also negatively associated with the AFT score (OR = 1.16, 95% CI: 1.01-1.33) in unadjusted model. A non-linear relationship was observed between liver enzymes and the risk of cognitive impairment as assessed by the global cognitive test. Specifically, when ALP > 60 U/L, 0.77 < AST/ALT < 1.76, and 25 < GGT < 94 U/L, higher liver enzyme levels were significantly associated with an elevated cognitive impairment risk, while a lower cognitive impairment risk when ALT level was > 17 U/L. CONCLUSIONS: There is a non-linear relationship between liver enzymes and cognitive performance, indicating that liver enzyme levels should be maintained within a certain level to mitigate the risk of cognitive impairment.

A new microalgal negative carbon technology for landfill leachate treatment: Simultaneous removal of nitrogen and phosphorus.

Replete with ammonia nitrogen and organic pollutants, landfill leachate typically undergoes treatment employing expensive and carbon-intensive integrated techniques. We propose a novel microalgae technology for efficient, low-carbon simultaneous treatment of carbon, nitrogen, and phosphorus in landfill leachate (LL). The microbial composition comprises a mixed microalgae culture with Chlorella accounting for 82.58%. After seven days, the process with an N/P ratio of approximately 14:1 removed 98.81% of NH4+-N, 88.62 % of TN, and 99.55% of TP. Notably, the concentrations of NH4+-N and TP met the discharge standards, while the removal rate of NH4+-N was nearly three times higher than previously reported in relevant studies. The microalgae achieved a removal efficiency of 64.27% for Total Organic Carbon (TOC) and 99.26% for Inorganic Carbon (IC) under mixotrophic cultivation, yielding a biomass of 1.18 g/L. The treatment process employed in this study results in a carbon emissions equivalent of -8.25 kgCO2/kgNremoved, representing a reduction of 33.56 kgCO2 compared to the 2AO + MBR process. In addition, shake flask experiments were conducted to evaluate the biodegradability of leachate after microalgae treatment. After microalgae treatment, the TOCB (Biodegradable Total Organic Carbon)/TOC ratio decreased from 56.54% to 27.71%, with no significant improvement in biodegradability. It establishes a fundamental foundation for further applied research in microalgae treatment of leachate.

Characterization, evolution, and abiotic stress responses of leucine-rich repeat receptor-like protein kinases (LRR-RLK) in Liriodendron chinense.

BACKGROUND: Liriodendron chinense is susceptible to extinction due to the increasing severity of abiotic stresses resulting from global climate change, consequently impacting its growth, development, and geographic distribution. However, the L. chinense remains pivotal in both socio-economic and ecological realms. The LRR-RLK (leucine-rich repeat receptor-like protein kinase) genes, constituting a substantial cluster of receptor-like kinases in plants, are crucial for plant growth and stress regulation and are unexplored in the L. chinense. RESULT: 233 LchiLRR-RLK genes were discovered, unevenly distributed across 17 chromosomes and 24 contigs. Among these, 67 pairs of paralogous genes demonstrated gene linkages, facilitating the expansion of the LchiLRR-RLK gene family through tandem (35.82%) and segmental (64.18%) duplications. The synonymous and nonsynonymous ratios showed that the LchiLRR-RLK genes underwent a purifying or stabilizing selection during evolution. Investigations in the conserved domain and protein structures revealed that the LchiLRR-RLKs are highly conserved, carrying conserved protein kinase and leucine-rich repeat-like domians that promote clustering in different groups implicating gene evolutionary conservation. A deeper analysis of LchiLRR-RLK full protein sequences phylogeny showed 13 groups with a common ancestor protein. Interspecies gene collinearity showed more orthologous gene pairs between L. chinense and P. trichocarpa, suggesting various similar biological functions between the two plant species. Analysis of the functional roles of the LchiLRR-RLK genes using the qPCR demonstrated that they are involved in cold, heat, and salt stress regulation, especially, members of subgroups VIII, III, and Xa. CONCLUSION: Conclusively, the LRR-RLK genes are conserved in L. chinense and function to regulate the temperature and salt stresses, and this research provides new insights into understanding LchiLRR-RLK genes and their regulatory effects in abiotic stresses.

PGD2/DP1 axis promotes liver regeneration by secreting Wnt2 in Kupffer cells in mice.

BACKGROUND AND AIMS: The liver possesses a remarkable regenerative capacity in response to injuries or viral infections. Various growth factors and cytokines are involved in regulating liver regeneration. Prostaglandin (PG) D2, a pro-resolution lipid mediator, is the most abundant hepatic prostanoid. However, the role of PGD2 in the injury-induced liver regeneration remains unclear. APPROACH AND RESULTS: Two-thirds partial hepatectomy (70% PH), massive hepatectomy (85% resection), and carbon tetrachloride-induced chronic injury were performed in mice to study the mechanisms of live regeneration. Hepatic PGD2 production was elevated in mice after PH. Global deletion of D prostanoid receptor (DP) 1, but not DP2, slowed PH-induced liver regeneration in mice, as evidenced by lower liver weight to body weight ratio, less Ki67+ hepatocyte proliferation, and G2/M phase hepatocytes. Additionally, DP1 deficiency specifically in resident Kupffer cells (KCs), and not in endothelial cells or hepatic stellate cells, retarded liver regeneration in mice post-PH. Conversely, the overexpression of exogenous DP1 in KCs accelerated liver regeneration in mice. Mechanistically, DP1 activation promoted Wnt2 transcription in a PKA/CREB-dependent manner in resident KCs and mediated hepatocyte proliferation through Frizzled8/ß-catenin signaling. Adeno-associated virus vector serotype 8 (AAV8)-mediated Frizzled8 knockdown in hepatocytes attenuated accelerated liver regeneration in KC-DP1 transgenic mice post-PH. Treatment with the DP1 receptor agonist BW245C promotes PH-induced liver regeneration in mice. CONCLUSIONS: DP1 activation mediates crosstalk between KCs and hepatocytes through Wnt2, and facilitates liver regeneration. Hence, DP1 may serve as a novel therapeutic target in acute and chronic liver diseases.

Knowledge and attitude toward postoperative antithrombotic management and prevention in patients with coronary revascularization: a cross-sectional study.

Background: This study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization. Methods: This cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire. Results: This study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0-26) and 43.68 ± 6.01 (range: 21-50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000-5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2-3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2-3 months (OR = 3.342, P = 0.033) were independently associated with attitude. Conclusion: CAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

Sequential high-recovery nanofiltration and electrochemical degradation for the treatment of pharmaceutical wastewater.

The presence of antibiotics in aquatic ecosystems poses a significant concern for public health and aquatic life, owing to their contribution to the proliferation of antibiotic-resistant bacteria. Effective wastewater treatment strategies are needed to ensure that discharges from pharmaceutical manufacturing facilities are adequately controlled. Here we propose the sequential use of nanofiltration (NF) for concentrating a real pharmaceutical effluent derived from azithromycin production, followed by electrochemical oxidation for thorough removal of pharmaceutical compounds. The NF membrane demonstrated its capability to concentrate wastewater at a high recovery value of 95 % and 99.7 ± 0.2 % rejection to azithromycin. The subsequent electrochemical oxidation process completely degraded azithromycin in the concentrate within 30 min and reduced total organic carbon by 95 % in 180 min. Such integrated treatment approach minimized the electrochemically-treated volume through a low-energy membrane approach and enhanced mass transfer towards the electrodes, therefore driving the process toward zero-liquid-discharge objectives. Overall, our integrated approach holds promises for cost-effective and sustainable removal of trace pharmaceutical compounds and other organics in pharmaceutical wastewater.

Solid-Emission-Tunable Squaraine with Thermal-Promoted Aggregate-State Transitions for Fast Thermal History Sensing.

Determining thermal history is crucial in many industrial processes, but reliable and sensitive organic thermal history indicators are currently absent. Herein, we report on the development of a squaraine-based fluorescent molecule, DPEA-SQ, for the detection of thermal exposure histories up to 436 K. DPEA-SQ forms multiple single crystals (DPEA-SQ-I, DPEA-SQ-II, and DPEA-SQ-III) with different conformations and aggregate-state packing modes, contributing to their different fluorescence wavelengths, lifetimes, and efficiencies. Interestingly, DPEA-SQ-I and DPEA-SQ-III undergo aggregate-state structural transitions to form the thermodynamically more stable DPEA-SQ-II, which are accompanied by changes in their fluorescence. By taking advantage of similar aggregate-state structural transformations during heating, a high-temperature thermal exposure history of up to 436 K is recorded and reflected by their fluorescence. To demonstrate the potential practical applications of DPEA-SQ, a DPEA-SQ-Powder/PDMS film is prepared and coated on an electric circuit board, which enables real-time monitoring of localized overheating by the naked eye. Additionally, the fluorescence peaks of DPEA-SQ-Powder and DPEA-SQ-Powder/PDMS films remain unchanged after storage at 373 K for 52 days, demonstrating high aggregate-state stability. The fast and reliable responses of this system make it an excellent candidate for the detection of overtemperature traces in electronic components and circuit diagnosis.

A close-up of regulatory networks and signaling pathways of MKK5 in biotic and abiotic stresses.

Mitogen-activated protein Kinase Kinase 5 (MKK5) is a central hub in the complex phosphorylation chain reaction of the Mitogen-activated protein kinases (MAPK) cascade, regulating plant responses to biotic and abiotic stresses. This review manuscript aims to provide a comprehensive analysis of the regulatory mechanism of the MKK5 involved in stress adaptation. This review will delve into the intricate post-transcriptional and post-translational modifications of the MKK5, discussing how they affect its expression, activity, and subcellular localization in response to stress signals. We also discuss the integration of the MKK5 into complex signaling pathways, orchestrating plant immunity against pathogens and its modulating role in regulating abiotic stresses, such as: drought, cold, heat, and salinity, through the phytohormonal signaling pathways. Furthermore, we highlight potential applications of the MKK5 for engineering stress-resilient crops and provide future perspectives that may pave the way for future studies. This review manuscript aims to provide valuable insights into the mechanisms underlying MKK5 regulation, bridge the gap from numerous previous findings, and offer a firm base in the knowledge of MKK5, its regulating roles, and its involvement in environmental stress regulation.

Synergistic effect on simultaneous treatment of Cr(VI) and chloramphenicol using a non-thermal plasma technology.

Toxic organic and heavy metal contaminants commonly exist in industrial waste stream(s) and treatment is of great challenge. In this study, a dielectric barrier discharge (DBD) non-thermal plasma technology was employed for the simultaneous treatment of two important contaminants, chloramphenicol (CAP) and Cr(VI) in an aqueous solution through redox transformations. More than 70% of CAP and 20% of TOC were degraded in 60 min, while Cr(VI) was completely removed in 10 min. The hydroxyl radicals were the main active species for the degradation. Meanwhile, the consumption of hydroxyl radicals was beneficial to the reduction of Cr(VI). The synergistic effect was investigated between CAP degradation and Cr(VI) reduction. The reduction of Cr(VI) would be enhanced in the presence of CAP with a low concentration and could be inhibited under a high concentration, because part of hydroxyl radicals could be consumed by the low-concentration CAP and the obtained intermediates with a higher kinetic rate. However, CAP with a high concentration could react with such reductive species as eaq- and •H, which could compete with Cr(VI) and inhibit the reduction. In addition, the presence of Cr(VI) enhanced the degradation and mineralization of CAP; the study of obtained intermediates indicated that the presence of Cr(VI) changed the degradation path of CAP as Cr(VI) would react with reductive species, enhance the generation of hydroxyl radicals, and cause more hydroxylation reactions. Moreover, the mechanism for the simultaneous redox transformations of CAP and Cr(VI) was illustrated. This study indicates that the DBD non-thermal plasma technology can be one of better solutions for simultaneous elimination of heavy metal and organic contaminants in aquatic environments.

Direct Regeneration of Spent Lithium-Ion Battery Cathodes: From Theoretical Study to Production Practice.

Direct regeneration method has been widely concerned by researchers in the field of battery recycling because of its advantages of in situ regeneration, short process and less pollutant emission. In this review, we firstly analyze the primary causes for the failure of three representative battery cathodes (lithium iron phosphate, layered lithium transition metal oxide and lithium cobalt oxide), targeting at illustrating their underlying regeneration mechanism and applicability. Efficient stripping of material from the collector to obtain pure cathode material has become a first challenge in recycling, for which we report several pretreatment methods currently available for subsequent regeneration processes. We review and discuss emphatically the research progress of five direct regeneration methods, including solid-state sintering, hydrothermal, eutectic molten salt, electrochemical and chemical lithiation methods. Finally, the application of direct regeneration technology in production practice is introduced, the problems exposed at the early stage of the industrialization of direct regeneration technology are revealed, and the prospect of future large-scale commercial production is proposed. It is hoped that this review will give readers a comprehensive and basic understanding of direct regeneration methods for used lithium-ion batteries and promote the industrial application of direct regeneration technology.

Processing of angiocrine alarmin IL-1α in endothelial cells promotes lung and liver fibrosis.

BACKGROUND: Fibrosis results from excessive scar formation after tissue injury. Injured cells release alarmins such as interleukin 1 (IL-1) α and ß as primary mediators initiating tissue repair. However, how alarmins from different cell types differentially regulate fibrosis remains to be explored. METHODS: Here, we used tissue specific knockout strategy to illustrate a unique contribution of endothelial cell-derived IL-1α to lung and liver fibrosis. The two fibrotic animal model triggered by bleomycin and CCl4 were used to study the effects of endothelial paracrine/angiocrine IL-1α in fibrotic progression. Human umbilical vein endothelial cells (HUVEC) were performed to explore the production of angiocrine IL-1α at both transcriptional and post-transcriptional levels in vitro. RESULTS: We found that endothelial paracrine/angiocrine IL-1α primarily promotes lung and liver fibrosis during the early phase of organ repair. By contrast, myeloid cell-specific ablation of IL-1α in mice resulted in little influence on fibrosis, suggesting the specific pro-fibrotic role of IL-1α from endothelial cell but not macrophage. In vitro study revealed a coordinated regulation of IL-1α production in human primary endothelial cells at both transcriptional and post-transcriptional levels. Specifically, the transcription of IL-1α is regulated by RIPK1, and after caspase-8 (CASP8) cleaves the precursor form of IL-1α, its secretion is triggered by ion channel Pannexin 1 upon CASP8 cleavage. CONCLUSIONS: Endothelial cell-produced IL-1α plays a unique role in promoting organ fibrosis. Furthermore, the release of this angiocrine alarmin relies on a unique molecular mechanism involving RIPK1, CASP8, and ion channel Pannexin 1.

Newly graphene/polypyrrole (rGO/PPy) modified carbon felt as bio-cathode in bio-electrochemical systems (BESs) achieving complete denitrification.

Nitrate reduction in bio-electrochemical systems (BESs) has attracted wide attention due to its low sludge yields and cost-efficiency advantages. However, the high resistance of traditional electrodes is considered to limit the denitrification performance of BESs. Herein, a new graphene/polypyrrole (rGO/PPy) modified electrode is fabricated via one-step electrodeposition and used as cathode in BES for improving nitrate removal from wastewater. The formation and morphological results support the successful formation of rGO/PPy nanohybrids and confirm the part covalent bonding of Py into GO honeycomb lattices to form a three-dimensional cross-linked spatial structure. The electrochemical tests indicate that the rGO/PPy electrode outperforms the unmodified electrode due to the 3.9-fold increase in electrochemical active surface area and 6.9-fold decrease in the charge transfer resistance (Rct). Batch denitrification activity tests demonstrate that the BES equipped with modified rGO/PPy biocathode could not only achieve the full denitrification efficiency of 100% with energy recovery (15.9 × 10-2 ± 0.14 A/m2), but also favor microbial attach and growth with improved biocompatible surface. This work provides a feasible electrochemical route to fabricate and design a high-performance bioelectrode to enhance denitrification in BESs.

Unraveling the CLCC1 interactome: Impact of the Asp25Glu variant and its interaction with SigmaR1 at the Mitochondrial-Associated ER Membrane (MAM).

The endoplasmic reticulum (ER) plays an indispensable role in cellular processes, including maintenance of calcium homeostasis, and protein folding, synthesized and processing. Disruptions in these processes leading to ER stress and the accumulation of misfolded proteins can instigate the unfolded protein response (UPR), culminating in either restoration of balanced proteostasis or apoptosis. A key player in this intricate balance is CLCC1, an ER-resident chloride channel, whose essential role extends to retinal development, regulation of ER stress, and UPR. The importance of CLCC1 is further underscored by its interaction with proteins localized to mitochondria-associated endoplasmic reticulum membranes (MAMs), where it participates in UPR induction by MAM proteins. In previous research, we identified a p.(Asp25Glu) pathogenic CLCC1 variant associated with retinitis pigmentosa (RP) (CLCC1 hg38 NC_000001.11; NM_001048210.3, c.75C > A; UniprotKB Q96S66). In attempt to decipher the impact of this variant function, we leveraged liquid chromatography-mass spectrometry (LC-MS) to identify likely CLCC1-interacting proteins. We discovered that the CLCC1 interactome is substantially composed of proteins that localize to ER compartments and that the Asp25Glu variant results in noticeable loss and gain of specific protein interactors. Intriguingly, the analysis suggests that the CLCC1Asp25Glu mutant protein exhibits a propensity for increased interactions with cytoplasmic proteins compared to its wild-type counterpart. To corroborate our LC-MS data, we further scrutinized two novel CLCC1 interactors, Calnexin and SigmaR1, chaperone proteins that localize to the ER and MAMs. Through microscopy, we demonstrate that CLCC1 co-localizes with both proteins, thereby validating our initial findings. Moreover, our results reveal that CLCC1 co-localizes with SigmaR1 not merely at the ER, but also at MAMs. These findings reinforce the notion of CLCC1 interacting with MAM proteins at the ER-mitochondria interface, setting the stage for further exploration into how these interactions impact ER or mitochondria function and lead to retinal degenerative disease when impaired.

Risk factors of different mortality periods in older patients with end-stage renal disease undergoing urgent-start peritoneal dialysis: a retrospective observational study.

BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.

Whole-body water mass and kidney function: a Mendelian randomization study.

Background: The morbidity and mortality of chronic kidney disease (CKD) are increasing worldwide, making it a serious public health problem. Although a potential correlation between body water content and CKD progression has been suggested, the presence of a causal association remains uncertain. This study aimed to determine the causal effect of body water content on kidney function. Methods: Genome-wide association study summary data sourced from UK Biobank were used to evaluate single-nucleotide polymorphisms (SNPs) associated with whole-body water mass (BWM). The summary statistics pertaining to kidney function were extracted from the CKDGen consortium. The primary kidney function outcome measures included estimated glomerular filtration rate (eGFR), albuminuria, CKD stages 3-5, and rapid progression to CKD (CKDi25). Two-sample Mendelian randomization (MR) analysis estimated a potential causal relationship between the BWM and kidney function. The inverse variance weighted MR method was used as the primary analysis, accompanied by several sensitive MR analyses. Results: The increase of BWM exhibited a correlation with a reduction in eGFR (ß = -0.02; P = 6.95 × 10-16). Excluding 13 SNPs responsible for pleiotropy (P = 0.05), the increase of BWM was also associated with the decrease of the ratio of urinary albumin to creatinine (ß = -0.16; P = 5.91 × 10-36). For each standard deviation increase in BWM, the risk of CKD stages 3-5 increases by 32% (OR, 1.32; 95% CI, 1.19-1.47; P = 1.43 × 10-7), and the risk of CKDi25 increases by 22% (OR, 1.22; 95% CI, 1.07-1.38; P = 0.002). Conclusion: The increase of BWM is associated with impaired kidney function. Proactively managing body water content is of great significance in preventing the progression of CKD.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosis.

OBJECTIVE: Serum globulin is associated with inflammatory or immune disorders. However, it has not been established whether it is associated with myasthenia gravis (MG). We investigated the association between globulin with relapse and prognosis in children with MG. METHODS: A cohort of 148 MG cases and 150 healthy children were retrospectively enrolled from January 2015 to December 2021. Multivariate logistic and Cox regression models were used to analyze the treatment outcomes and recurrence of case group, exploring the influence of globulin. RESULTS: Compared with the control group, globulin levels in the MG group were slightly increased (t = 7.244, p < 0.001). After a mean follow-up of 2.25 ± 1.05 years, 35 cases relapsed, with a relapse rate of 23.65%. Logistic regression analysis showed that globulin levels at admission [adjusted odds ratio (OR) = 1.233, 95% confidence interval (CI) 1.028-1.472, p = 0.018] were independent risk factors for relapse. Cox regression analysis confirmed that globulin levels at admission affects relapse-free time [adjusted hazard ratio (HR) = 0.552, 95% CI 0.357-0.852, p = 0.007]. Receiver operating characteristic curve determined 25.10 as the optimal cutoff value for globulin. Cox regression showed that high globulin levels (>25.10) at admission (adjusted HR = 0.607, 95% CI 0.383-0.961, p = 0.033) were independent risk factors for poor therapeutic outcomes at follow-up. Ordinal logistic regression showed that globulin affects the treatment plan (OR = 1.445, 95% CI 1.223-1.847, p = 0.014). CONCLUSIONS: Elevated globulin levels in children with MG on admission predicts a high relapse rate and poor long-term therapeutic efficacies.

Serum globulin in children with myasthenia gravis: predicting relapse and prognosisFirst, the globulin in the MG children was higher than in the healthy controls, and there was some correlation between the globulin and the level of systemic inflammation.Second, globulin has been associated with relapse of MG in children. The higher the globulin, the higher the relapse rate and the shorter the time to prevent a relapse.Third, both initial and final globulin were related to the effect of MG in children, and the higher the long-term effect, the worse the long-term effect. It also influenced the change in treatment plan.

CRISPR/Cas genome editing in plants: mechanisms, applications, and overcoming bottlenecks.

The CRISPR/Cas systems have emerged as transformative tools for precisely manipulating plant genomes and enhancement. It has provided unparalleled applications from modifying the plant genomes to resistant enhancement. This review manuscript summarises the mechanism, application, and current challenges in the CRISPR/Cas genome editing technology. It addresses the molecular mechanisms of different Cas genes, elucidating their applications in various plants through crop improvement, disease resistance, and trait improvement. The advent of the CRISPR/Cas systems has enabled researchers to precisely modify plant genomes through gene knockouts, knock-ins, and gene expression modulation. Despite these successes, the CRISPR/Cas technology faces challenges, including off-target effects, Cas toxicity, and efficiency. In this manuscript, we also discuss these challenges and outline ongoing strategies employed to overcome these challenges, including the development of novel CRISPR/Cas variants with improved specificity and specific delivery methods for different plant species. The manuscript will conclude by addressing the future perspectives of the CRISPR/Cas technology in plants. Although this review manuscript is not conclusive, it aims to provide immense insights into the current state and future potential of CRISPR/Cas in sustainable and secure plant production.