Potential therapeutic applications of circular RNA in acute kidney injury.

Acute kidney injury (AKI) is a common clinical syndrome characterized by a rapid deterioration in renal function, manifested by a significant increase in creatinine and a sharp decrease in urine output. The incidence of morbidity and mortality associated with AKI is on the rise, with most patients progressing to chronic kidney disease or end-stage renal disease. Treatment options for patients with AKI remain limited. Circular RNA (circRNA) is a wide and diverse class of non-coding RNAs that are present in a variety of organisms and are involved in gene expression regulation. Studies have shown that circRNA acts as a competing RNA, is involved in disease occurrence and development, and has potential as a disease diagnostic and prognostic marker. CircRNA is involved in the regulation of important biological processes, including apoptosis, oxidative stress, and inflammation. This study reviews the current status and progress of circRNA research in the context of AKI.

FGCD: a database of fungal gene clusters related to secondary metabolism.

Fungal secondary metabolites are not necessary for growth, but they are important for fungal metabolism and ecology because they provide selective advantages for competition, survival and interactions with the environment. These various metabolites are widely used as medicinal precursors and insecticides. Secondary metabolism genes are commonly arranged in clusters along chromosomes, which allow for the coordinate control of complete pathways. In this study, we created the Fungal Gene Cluster Database to store, retrieve, and visualize secondary metabolite gene cluster information across fungal species. The database was created by merging data from RNA sequencing, Basic Local Alignment Search Tool, genome browser, enrichment analysis and the R Shiny web framework to visualize and query putative gene clusters. This database facilitated the rapid and thorough examination of significant gene clusters across fungal species by detecting, defining and graphically displaying the architecture, organization and expression patterns of secondary metabolite gene clusters. In general, this genomic resource makes use of the tremendous chemical variety of the products of these ecologically and biotechnologically significant gene clusters to our further understanding of fungal secondary metabolism. Database URL: https://www.hebaubioinformatics.cn/FungalGeneCluster/.

The mmu_circ_003062, hsa_circ_0075663/miR-490-3p/CACNA1H axis mediates apoptosis in renal tubular cells in association with endoplasmic reticulum stress following ischemic acute kidney injury.

BACKGROUND: While recent studies have suggested a potential involvement of circRNAs in acute kidney injury (AKI) after ischemia, mmu_circ_003062 role is undetermined. METHODS: The levels of mmu_circ_003062, miR-490-3p, CACNA1H, GRP78, CHOP and hsa_circ_0075663 were detected by Relative qPCR in Boston University mouse proximal tubule (BUMPT) cells, mouse kidneys, and human renal tubular epithelial (HK-2) cells. Moreover, the levels of hsa_circ_0075663 in serum and urine of patients with AKI following cardiopulmonary resuscitation (CPR) were detected by absolute quantitative PCR. Western blot was used to detect the relative expression of the protein. The function and regulatory mechanism of mmu_circ_003062 and hsa_circ_0075663 were investigated through a series of in vitro and in vivo experiments, including bioinformatic prediction, luciferase reporter assays, FISH, FCM, TUNEL staining, and H&E staining. RESULTS: It was found that mmu_circ_003062, hsa_circ_0075663 mediated apoptosis after ischemia/reperfusion (I/R) by interaction with miR-490-3p to enhance CACNA1H expression, thereby leading to the upregulation of endoplasmic reticulum stress (ERS)-relevant proteins GRP78 and CHOP. Ultimately, mmu_circ_003062 downregulation significantly ameliorated ischemic AKI by modulating the miR-490-3p/CACNA1H/GRP78 and CHOP pathway. Furthermore, the plasma and urinary levels of hsa_circ_0075663 in patients with AKI following CPR were significantly higher than non-AKI patients, exhibited a strongly correlation with serum creatinine. CONCLUSION: The involvement of mmu_circ_003062, hsa_circ_0075663/miR-490-3p/CACNA1H/GRP78 and CHOP axis is significant in the development of ischemic AKI. Moreover, hsa_circ_0075663 has potential as an early diagnostic biomarker.

A model for predicting return of spontaneous circulation and neurological outcomes in adults after in-hospital cardiac arrest: development and evaluation.

Introduction: In-hospital CA (IHCA) is associated with rates of high incidence, low return of spontaneous circulation (ROSC), low survival to discharge, and poor neurological outcomes. We aimed to construct and evaluate prediction models for non-return of spontaneous circulation (non-ROSC) and poor neurological outcomes 12 months after ROSC (PNO-12). Methods: We retrospectively analyzed baseline and clinical data from patients experiencing cardiac arrest (CA) in a big academic hospital of Jilin University in China. Patients experiencing CA between September 1, 2019 and December 31, 2020 were categorized into the ROSC and non-ROSC groups. Patients maintaining ROSC >20 min were divided into the good and PNO-12 subgroups. Results: Univariate and multivariate logistic regression identified independent factors associated with non-ROSC and PNO-12. Two nomogram prediction models were constructed and evaluated. Of 2,129 patients with IHCA, 851 were included in the study. Multivariate logistic regression analysis revealed that male sex, age >80 years, CPR duration >23 min, and total dose of adrenaline >3 mg were significant risk factors for non-ROSC. Before CA, combined arrhythmia, initial defibrillation rhythm, and advanced airway management (mainly as endotracheal intubation) also influenced outcomes. The area under the receiver operating characteristic curve in the prediction model was 0.904 (C-index: 0.901). Respiratory failure, shock, CA in the monitoring area, advanced airway management, and noradrenaline administration were independent risk factors for PNO-12. The AUC was 0.912 (C-index: 0.918). Conclusions: Prediction models based on IHCA data could be helpful to reduce mortality rates and improve prognosis.

Meta-analysis of the effects of inert gases on cerebral ischemia-reperfusion injury.

Recently, noble gas has become a hot spot within the medical field like respiratory organ cerebral anemia, acute urinary organ injury and transplantation. However, the shield performance in cerebral ischemia-reperfusion injury (CIRI) has not reached an accord. This study aims to evaluate existing evidence through meta-analysis to determine the effects of inert gases on the level of blood glucose, partial pressure of oxygen, and lactate levels in CIRI. We searched relevant articles within the following both Chinese and English databases: PubMed, Web of science, Embase, CNKI, Cochrane Library and Scopus. The search was conducted from the time of database establishment to the end of May 2023, and two researchers independently entered the data into Revman 5.3 and Stata 15.1. There were total 14 articles were enclosed within the search. The results showed that the amount of partial pressure of blood oxygen in the noble gas cluster was beyond that in the medicine gas cluster (P < 0.05), and the inert gas group had lower lactate acid and blood glucose levels than the medical gas group. The partial pressure of oxygen (SMD = 1.51, 95% CI 0.10 ~ 0.91 P = 0.04), the blood glucose level (SMD = - 0.59, 95% CI - 0.92 ~ - 0.27 P = 0.0004) and the lactic acid level (SMD = - 0.42, 95% CI - 0.80 ~ - 0.03 P = 0.03) (P < 0.05). These results are evaluated as medium-quality evidence. Inert gas can effectively regulate blood glucose level, partial pressure of oxygen and lactate level, and this regulatory function mainly plays a protective role in the small animal ischemia-reperfusion injury model. This finding provides an assessment and evidence of the effectiveness of inert gases for clinical practice, and provides the possibility for the application of noble gases in the treatment of CIRI. However, more operations are still needed before designing clinical trials, such as the analysis of the inhalation time, inhalation dose and efficacy of different inert gases, and the effective comparison of the effects in large-scale animal experiments.

Hemoglobin as a prognostic marker for neurological outcomes in post-cardiac arrest patients: a meta-analysis.

The aim of this study was to investigate the relationship between serum level of hemoglobin and neurological outcomes following cardiac arrest. Relevant studies were identified by searching electronic databases including PubMed, Web of Science, Cochrane Library, and Embase from June 2012 through April 2023. Articles were rigorously reviewed for their study inclusion and exclusion criteria. Pooled effect date was determined using the standardized mean difference (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa Scale was used to evaluate study quality. Subgroup analyses were conducted to determine confounding factors affecting patient outcomes. Study heterogeneity, sensitivity, and publication bias were also determined.This meta-analysis included 11 studies involving 2519 patients. Our results suggest that high serum level of hemoglobin may improve neurological prognosis(SMD = 0.60, 95%CI = 0.49-0.71, I2 = 10.85). The findings of this study indicate that serum level of hemoglobin may be associated with better neurological prognosis, perhaps an appropriate increase in serum haemoglobin levels can improve the neurological prognosis of patients in cardiac arrest.

Contribution and therapeutic value of mitophagy in cerebral ischemia-reperfusion injury after cardiac arrest.

Cardiopulmonary resuscitation and related life support technologies have improved substantially in recent years; however, mortality and disability rates from cardiac arrest (CA) remain high and are closely associated with the high incidence of cerebral ischemia-reperfusion injury (CIRI), which is explained by a "double-hit" model (i.e., resulting from both ischemia and reperfusion). Mitochondria are important power plants in the cell and participate in various biochemical processes, such as cell differentiation and signaling in eukaryotes. Various mitochondrial processes, including energy metabolism, calcium homeostasis, free radical production, and apoptosis, are involved in several important stages of the progression and development of CIRI. Mitophagy is a key mechanism of the endogenous removal of damaged mitochondria to maintain organelle function and is a critical target for CIRI treatment after CA. Mitophagy also plays an essential role in attenuating ischemia-reperfusion in other organs, particularly during post-cardiac arrest myocardial dysfunction. Regulation of mitophagy may influence necroptosis (a programmed cell death pathway), which is the main endpoint of organ ischemia-reperfusion injury. In this review, we summarize the main signaling pathways related to mitophagy and their associated regulatory proteins. New therapeutic methods and drugs targeting mitophagy in ischemia-reperfusion animal models are also discussed. In-depth studies of the mechanisms underlying the regulation of mitophagy will enhance our understanding of the damage and repair processes in CIRI after CA, thereby contributing to the development of new therapeutic strategies.

Harnessing the therapeutic potential of mesenchymal stem cell-derived exosomes in cardiac arrest: Current advances and future perspectives.

BACKGROUND: Cardiac arrest (CA), characterized by sudden onset and high mortality rates, is one of the leading causes of death globally, with a survival rate of approximately 6-24%. Studies suggest that the restoration of spontaneous circulation (ROSC) hardly improved the mortality rate and prognosis of patients diagnosed with CA, largely due to ischemia-reperfusion injury. MAIN BODY: Mesenchymal stem cells (MSCs) exhibit self-renewal and strong potential for multilineage differentiation. Their effects are largely mediated by extracellular vesicles (EVs). Exosomes are the most extensively studied subgroup of EVs. EVs mainly mediate intercellular communication by transferring vesicular proteins, lipids, nucleic acids, and other substances to regulate multiple processes, such as cytokine production, cell proliferation, apoptosis, and metabolism. Thus, exosomes exhibit significant potential for therapeutic application in wound repair, tissue reconstruction, inflammatory reaction, and ischemic diseases. CONCLUSION: Based on similar pathological mechanisms underlying post-cardiac arrest syndrome involving various tissues and organs in many diseases, the review summarizes the therapeutic effects of MSC-derived exosomes and explores the prospects for their application in the treatment of CA.

Identification and expression analysis of maize NF-YA subunit genes.

NF-YAs encode subunits of the nuclear factor-Y (NF-Y) gene family. NF-YAs represent a kind of conservative transcription factor in plants and are involved in plant growth and development, as well as resistance to biotic and abiotic stress. In this study, 16 maize (Zea mays) NF-YA subunit genes were identified using bioinformatics methods, and they were divided into three categories by a phylogenetic analysis. A conserved domain analysis showed that most contained a CCAAT-binding transcription factor (CBFB) _NF-YA domain. Maize NF-YA subunit genes showed very obvious tissue expression characteristics. The expression level of the NF-YA subunit genes significantly changed under different abiotic stresses, including Fusarium graminearum infection and salicylic acid (SA) or jasmonic acid (JA) treatments. After inoculation with Setosphaeria turcica and Cochliobolus heterostrophus, the lesion areas of nfya01 and nfya06 were significantly larger than that of B73, indicating that ZmNFYA01 and ZmNFYA06 positively regulated maize disease resistance. ZmNFYA01 and ZmNFYA06 may regulated maize disease resistance by affecting the transcription levels of ZmPRs. Thus, NF-YA subunit genes played important roles in promoting maize growth and development and resistance to stress. The results laid a foundation for clarifying the functions and regulatory mechanisms of NF-YA subunit genes in maize.

Maize stalk rot caused by Fusarium graminearum alters soil microbial composition and is directly inhibited by Bacillus siamensis isolated from rhizosphere soil.

Maize stalk rot caused by Fusarium graminearum can reduce the yield of maize and efficiency of mechanized harvesting. Besides, deoxynivalenol and zearalenone toxins produced by F. graminearum can also affect domestic animals and human health. As chemical fungicides are expensive and exert negative effects on the environment, the use of biological control agents has become attractive in recent years. In the present study, we collected rhizosphere soil with severe stalk rot disease (ZDD), the rhizosphere soil with disease-free near by the ZDD (ZDH), and measured rhizosphere microbial diversity and microbial taxonomic composition by amplicon sequencing targeting either bacteria or fungi. The results showed that Fusarium stalk rot caused by the Fusarium species among which F. graminearum is frequent and can reduce the abundance and alpha diversity of rhizosphere microbial community, and shift the beta diversity of microorganisms. Furthermore, a bacterial strain, Bacillus siamensis GL-02, isolated from ZDD, was found to significantly affect growth of F. graminearum. In vitro and in vivo assays demonstrated that B. siamensis GL-02 had good capability to inhibit F. graminearum. These results revealed that B. siamensis GL-02 could be a potential biocontrol agent for the control of maize stalk rot.

Global analysis of lysine 2-hydroxyisobutyrylation during Fusarium graminearum infection in maize.

Proteins post-translational modification (PTMs) is necessary in the whole life process of organisms. Among them, lysine 2-hydroxyisobutyrylation (Khib) plays an important role in protein synthesis, transcriptional regulation, and cell metabolism. Khib is a newly identified PTM in several plant species. However, the function of Khib in maize was unclear. In this study, western blotting results showed that Khib modification level increased significantly after Fusarium graminearum infection, and 2,066 Khib modified sites on 728 proteins were identified in maize, among which 24 Khib sites occurred on core histones. Subcellular localization results showed that these Khib modified proteins were localized in cytoplasm, chloroplast, and nucleus. Then, comparative proteomic analysis of the defense response to F. graminearum infection showed that Khib modification participated in plant resistance to pathogen infection by regulating glycolysis, TCA cycle, protein synthesis, peroxisome, and secondary metabolic processes, such as benzoxazinoid biosynthesis, phenylpropanoid biosynthesis, jasmonic acid synthesis, and tyrosine and tryptophan biosynthesis. In addition, we also demonstrated that lysine 2-hydroxyisobutyrylation sites on histones were involved in the gene expression of pathogenesis-related proteins. Our results provide a new perspective for the study of plant disease resistance, and had directive significance of maize disease resistance for molecular breeding.

TOP1α fine-tunes TOR-PLT2 to maintain root tip homeostasis in response to sugars.

Plant development is highly dependent on energy levels. TARGET OF RAPAMYCIN (TOR) activates the proximal root meristem to promote root development in response to photosynthesis-derived sugars during photomorphogenesis in Arabidopsis thaliana. However, the mechanisms of how root tip homeostasis is maintained to ensure proper root cap structure and gravitropism are unknown. PLETHORA (PLT) transcription factors are pivotal for the root apical meristem (RAM) identity by forming gradients, but how PLT gradients are established and maintained, and their roles in COL development are not well known. We demonstrate that endogenous sucrose induces TOPOISOMERASE1α (TOP1α) expression during the skotomorphogenesis-to-photomorphogenesis transition. TOP1α fine-tunes TOR expression in the root tip columella. TOR maintains columella stem cell identity correlating with reduced quiescent centre cell division in a WUSCHEL RELATED HOMEOBOX5-independent manner. Meanwhile, TOR promotes PLT2 expression and phosphorylates and stabilizes PLT2 to maintain its gradient consistent with TOR expression pattern. PLT2 controls cell division and amyloplast formation to regulate columella development and gravitropism. This elaborate mechanism helps maintain root tip homeostasis and gravitropism in response to energy changes during root development.

BTB and TAZ domain protein BT4 positively regulates the resistance to Botrytis cinerea in Arabidopsis.

BT4 gene was identified to play an important role in Arabidopsis resistance to pst DC3000 in preliminary studies. However, the specific function and molecular mechanism of BT4 gene in regulation of Arabidopsis resistance to Botrytis cinerea had not been described to date. In this study, we found that the expression of BT4 was induced by wounding and B. cinerea inoculation in Arabidopsis. After inoculated with B. cinerea, T-DNA insertion mutants of the BT4 gene, bt4, showed significant susceptibility symptoms, whereas no significant symptoms were found in wild-type (WT), the complemented transgenic plants (CE), and the overexpression transgenic plants (OE). After inoculated with B. cinerea, the expression levels of JAR1 and PDF1.2 genes in bt4 mutant were induced; however, the expression levels of these genes in bt4 mutant were significantly lower than those in the WT, CE, and OE. These results indicated that the BT4 positively regulate the expression of genes in JA/ET signaling pathways. Therefore, the BT4 may be involved in the regulation of JA/ET signaling pathways to affect Arabidopsis resistance to B. cinerea.

Comparative Proteomic Analysis of the Defense Response to Gibberella Stalk Rot in Maize and Reveals That ZmWRKY83 Is Involved in Plant Disease Resistance.

Fusarium graminearum is the causal agent of Gibberella stalk rot in maize stem, resulting in maize lodging, yield, quality, and mechanical harvesting capacity. To date, little is known about the maize stem defense mechanism in response to the invasion of F. graminearum. This study represents a global proteomic approach to document the infection by F. graminearum. A total of 1,894 differentially expressed proteins (DEPs) were identified in maize stem with F. graminearum inoculation. Functional categorization analysis indicated that proteins involved in plant-pathogen interaction were inducible at the early stages of infection. We also found that the expression of proteins involved in phenylpropanoid, flavonoid, and terpenoid biosynthesis were upregulated in response to F. graminearum infection, which may reflect that these secondary metabolism pathways were important in the protection against the fungal attack in maize stem. In continuously upregulated proteins after F. graminearum infection, we identified a WRKY transcription factor, ZmWRKY83, which could improve the resistance to plant pathogens. Together, the results show that the defense response of corn stalks against F. graminearum infection was multifaceted, involving the induction of proteins from various immune-related pathways, which had a directive significance for molecular genetic breeding of maize disease-resistant varieties.

Prognostic nomogram for the severity of acute organophosphate insecticide self-poisoning: a retrospective observational cohort study.

OBJECTIVE: To develop a convenient nomogram for the bedside evaluation of patients with acute organophosphorus poisoning (AOPP). DESIGN: This was a retrospective study. SETTING: Two independent hospitals in northern China, the First Hospital of Jilin University and the Lequn Hospital of the First Hospital of Jilin University. PARTICIPANTS: A total of 1657 consecutive patients admitted for the deliberate oral intake of AOPP within 24 hours from exposure and aged >18 years were enrolled between 1 January 2013 and 31 December 2018. The exclusion criteria were: normal range of plasma cholinesterase, exposure to any other type of poisonous drug(s), severe chronic comorbidities including symptomatic heart failure (New York Heart Association III or IV) or any other kidney, liver and pulmonary diseases. Eight hundred and thirty-four patients were included. PRIMARY OUTCOME MEASURE: The existence of severely poisoned cases, defined as patients with any of the following complications: cardiac arrest, respiratory failure requiring ventilator support, hypotension or in-hospital death. RESULTS: 440 patients from one hospital were included in the study to develop a nomogram of severe AOPP, whereas 394 patients from the other hospital were used for the validation. Associated risk factors were identified by multivariate logistic regression. The nomogram was validated by the area under the receiver operating characteristic curve (AUC). A nomogram was developed with age, white cells, albumin, cholinesterase, blood pH and lactic acid levels. The AUC was 0.875 (95% CI 0.837 to 0.913) and 0.855 (95% CI 0.81 to 0.9) in the derivation and validation cohorts, respectively. The calibration plot for the probability of severe AOPP showed an optimal agreement between the prediction by nomogram and actual observation in both derivation and validation cohorts. CONCLUSION: A convenient severity evaluation nomogram for patients with AOPP was developed, which could be used by physicians in making clinical decisions and predicting patients' prognosis.

Clinical correlates of hypotension in patients with acute organophosphorus poisoning.

BACKGROUND: The aim of the present study is to describe the clinical correlates of hypotension and its associated outcomes in patients with acute organophosphorus poisoning (AOPP). METHODS: In this retrospective cohort study, we analyzed data pertaining to 871 patients with AOPP who were treated at two hospitals. Data from hypotensive and non-hypotensive patients were compared to identify clinical correlates of hypotension. We also evaluated the association between clinical parameters (including hypotension) and in-hospital mortality. RESULTS: The incidence of hypotension in AOPP patients was 16.4%. Hypotensive patients showed significantly higher in-hospital mortality (1.1% vs. 39.9%, P<0.001). Advanced age (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.08-1.44), history of diabetes (OR 2.65, 95% CI 1.14-5.96), and increased white blood cell count (OR 1.06, 95% CI 1.03-1.09), plasma cholinesterase (OR 0.91, 95% CI 0.84-0.94), plasma albumin (OR 0.88, 95% CI 0.85-0.92), serum amylase (OR 1.01, 95% CI 1.01-1.02), and blood pH (OR 0.64, 95% CI 0.54-0.75) were significantly associated with hypotension. After adjusting for potential confounders, hypotension was associated with increased in-hospital mortality (hazard ratio 8.77-37.06, depending on the controlled variables). CONCLUSIONS: Hypotension is a common complication of AOPP and is associated with increased in-hospital mortality. Advanced age, history of diabetes, and changes in laboratory parameters were associated with hypotension in AOPP patients.

Direct label-free methods for identification of target proteins in agrochemicals.

Green agrochemicals are important guarantee for food production and security, and target protein identification is the most important basis for development of novel agrochemicals. Affinity chromatography methods for immobilization of agrochemicals have been widely used to identify and confirm new targets. However, this method often requires modification of the active molecules which can affect or damage its biological activity, and biomacromolecules, particularly most natural products, are hard to be modified either. In order to overcome the shortcomings of molecular modification, label-free technology has been developed based on evaluating responses to thermal or proteolytic treatments. Combined with the chemical biology technology and molecular biology technology, it has been used in the development of drugs and agrochemicals. Herein, common methods of label-free technology for identification of direct target of agrochemicals are reviewed, including the principle, advantages, limitations and applications in the research of agrochemicals in the last decade. And the methods for validation of candidate targets obtained by the label-free methods are also reviewed, which are important to obtain the accurate and reliable targets. Combined application of these methods will greatly reduce the experimental costs and shorten the period for the new target identification and validation by improving its accuracy, which will provide a systematic solution for new ecological agrochemicals research and development.