METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.

SOX2 downregulation of PML increases HCMV gene expression and growth of glioma cells.

The presence of human cytomegalovirus (HCMV) in glioblastoma (GBM) and improved outcomes of GBM patients receiving therapies targeting the virus have implicated HCMV in GBM progression. However, a unifying mechanism that accounts for the contribution of HCMV to the malignant phenotype of GBM remains incompletely defined. Here we have identified SOX2, a marker of glioma stem cells (GSCs), as a key determinant of HCMV gene expression in gliomas. Our studies demonstrated that SOX2 downregulated promyelocytic leukemia (PML) and Sp100 and consequently facilitated viral gene expression by decreasing the amount of PML nuclear bodies in HCMV-infected glioma cells. Conversely, the expression of PML antagonized the effects of SOX2 on HCMV gene expression. Furthermore, this regulation of SOX2 on HCMV infection was demonstrated in a neurosphere assay of GSCs and in a murine xenograft model utilizing xenografts from patient-derived glioma tissue. In both cases, SOX2 overexpression facilitated the growth of neurospheres and xenografts implanted in immunodeficient mice. Lastly, the expression of SOX2 and HCMV immediate early 1 (IE1) protein could be correlated in tissues from glioma patients, and interestingly, elevated levels of SOX2 and IE1 were predictive of a worse clinical outcome. These studies argue that HCMV gene expression in gliomas is regulated by SOX2 through its regulation of PML expression and that targeting molecules in this SOX2-PML pathway could identify therapies for glioma treatment.

Histone methylation-mediated microRNA-32-5p down-regulation in sensory neurons regulates pain behaviors via targeting Cav3.2 channels.

microRNA (miRNA)­mediated gene regulation has been studied as a therapeutic approach, but its functional regulatory mechanism in neuropathic pain is not well understood. Here, we identify that miRNA-32-5p (miR-32-5p) is a functional RNA in regulating trigeminal-mediated neuropathic pain. High-throughput sequencing and qPCR analysis showed that miR-32-5p was the most down-regulated miRNA in the injured trigeminal ganglion (TG) of rats. Intra-TG injection of miR-32-5p agomir or overexpression of miR-32-5p by lentiviral delivery in neurons of the injured TG attenuated established trigeminal neuropathic pain. miR-32-5p overexpression did not affect acute physiological pain, while miR-32-5p down-regulation in intact rats was sufficient to cause pain-related behaviors. Nerve injury increased the methylated histone occupancy of binding sites for the transcription factor glucocorticoid receptor in the miR-32-5p promoter region. Inhibition of the enzymes that catalyze H3K9me2 and H3K27me3 restored the expression of miR-32-5p and markedly attenuated pain behaviors. Further, miR-32-5p­targeted Cav3.2 T-type Ca2+ channels and decreased miR-32-5p associated with neuropathic pain caused an increase in Cav3.2 protein expression and T-type channel currents. Conversely, miR-32-5p overexpression in injured TG suppressed the increased expression of Cav3.2 and reversed mechanical allodynia. Together, we conclude that histone methylation-mediated miR-32-5p down-regulation in TG neurons regulates trigeminal neuropathic pain by targeting Cav3.2 channels.

Cancer cases attributable to modifiable lifestyle risk factors in Switzerland between 2015 and 2019.

Several modifiable lifestyle risk factors have been linked to higher cancer risk in the literature. Determining the proportion and number of cancer cases attributable to these risk factors is pivotal in informing effective cancer prevention and control plans that have the greatest effect on reducing cancer incidence. We aimed to estimate the proportion and number of incident cancer cases that were attributable to modifiable lifestyle risk factors (ie, tobacco smoking, high alcohol consumption, excess body weight, physical inactivity and unhealthy diet) in Switzerland between 2015 and 2019. The exposure prevalence of selected risk factors was estimated based on the representative national nutrition survey menuCH, the associated relative risks were obtained from systematic literature reviews and the numbers of incident cancer cases were provided by the National Institute for Cancer Epidemiology and Registration. The fractions and numbers of attributable cases were calculated overall, by sex and by the three major language regions of Switzerland. The investigated modifiable risk factors combined were linked to 25.2% of potentially preventable incident cancer cases in Switzerland between 2015 and 2019. The proportion and numbers were slightly larger in males (28.4%, 6945 cases per year) than in females (21.9%, 4493 cases per year), and variations were observed between language regions. Tobacco smoking, excess body weight and high alcohol consumption were the leading contributors to lifestyle-attributable cancer cases. The observed differences in the leading risk factors both within Switzerland and compared to other countries underline the need for regionally and nationally tailored cancer prevention and education strategies.

Dual Engine Boosts Organic Photoelectrochemical Transistor for Enhanced Modulation and Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.

Single-nucleus RNA transcriptome profiling reveals murine adipose tissue endothelial cell proliferation gene networks involved in obesity development.

Endothelial cells play an important role in the metabolism of adipose tissue (AT). This study aimed to analyze the changes that adipose tissue in AT endothelial cells undergo during the development of obesity, using single-nucleus RNA sequence (snRNA-seq). Mouse paraepididymal AT cells were subjected to snRNA-seq with the 10X Genomics platform. The cell types were then clustered using t-distributed stochastic neighbor embedding and unbiased computational informatics analyses. Protein-protein interactions network was established using the STRING database and visualized using Cytoscape. The dataset was subjected to differential gene enrichment analysis. In total, 21,333 cells acquired from 24 mouse paraepididymal AT samples were analyzed using snRNA-seq. This study identified 18 distinct clusters and annotated macrophages, fibroblasts, epithelial cells, T cells, endothelial cells, stem cells, neutrophil cells, and neutrophil cell types based on representative markers. Cluster 12 was defined as endothelial cells. The proportion of endothelial cells decreased with the development of obesity. Inflammatory factors, such as Vegfa and Prdm16 were upregulated in the medium obesity group but downregulated in the obesity group. Genes, such as Prox1, Erg, Flt4, Kdr, Flt1, and Pecam1 promoted the proliferation of AT endothelial cells and maintained the internal environment of AT. This study established a reference model and general framework for studying the mechanisms, biomarkers, and therapeutic targets of endothelial cell dysfunction-related diseases at the single-cell level.

Multilevel Screening Strategy to Identify the Hydrophobic Organic Components of Ambient PM2.5 Associated with Hepatocellular Steatosis.

Hepatic steatosis is the first step in a series of events that drives hepatic disease and has been considerably associated with exposure to fine particulate matter (PM2.5). Although the chemical constituents of particles matter in the negative health effects, the specific components of PM2.5 that trigger hepatic steatosis remain unclear. New strategies prioritizing the identification of the key components with the highest potential to cause adverse effects among the numerous components of PM2.5 are needed. Herein, we established a high-resolution mass spectrometry (MS) data set comprising the hydrophobic organic components corresponding to 67 PM2.5 samples in total from Taiyuan and Guangzhou, two representative cities in North and South China, respectively. The lipid accumulation bioeffect profiles of the above samples were also obtained. Considerable hepatocyte lipid accumulation was observed in most PM2.5 extracts. Subsequently, 40 of 695 components were initially screened through machine learning-assisted data filtering based on an integrated bioassay with MS data. Next, nine compounds were further selected as candidates contributing to hepatocellular steatosis based on absorption, distribution, metabolism, and excretion evaluation and molecular dockingin silico. Finally, seven components were confirmed in vitro. This study provided a multilevel screening strategy for key active components in PM2.5 and provided insight into the hydrophobic PM2.5 components that induce hepatocellular steatosis.

Supramolecular prodrug of SN38 based on endogenous albumin and SN38 prodrug modified with semaglutide side chain to improve the tumor distribution.

To improve the biodistribution of the drug in the tumor, a supramolecular prodrug of SN38 was fabricated in situ between endogenous albumin and SN38 prodrug modified with semaglutide side chain. Firstly, SN38 was conjugated with semaglutide side chain and octadecanedioic acid via glycine linkers to obtain SI-Gly-SN38 and OA-Gly-SN38 prodrugs, respectively. Both SI-Gly-SN38 and OA-Gly-SN38 exhibited excellent stability in PBS for over 24 h. Due to the strong binding affinity of the semaglutide side chain with albumin, the plasma half-life of SI-Gly-SN38 was 2.7 times higher than that of OA-Gly-SN38. Furthermore, with addition of HSA, the fluorescence intensity of SI-Gly-SN38 was 4 times higher than that of OA-Gly-SN38, confirming its strong binding capability with HSA. MTT assay showed that the cytotoxicity of SI-Gly-SN38 and OA-Gly-SN38 was higher than that of Irinotecan. Even incubated with HSA, the SI-Gly-SN38 and OA-Gly-SN38 still maintained high cytotoxicity, indicating minimal influence of HSA on their cytotoxicity. In vivo pharmacokinetic studies demonstrated that the circulation half-life of SI-Gly-SN38 was twice that of OA-Gly-SN38. SI-Gly-SN38 exhibited significantly reduced accumulation in the lungs, being only 0.23 times that of OA-Gly-SN38. The release of free SN38 in the lungs from SI-Gly-SN38 was only 0.4 times that from OA-Gly-SN38 and Irinotecan. The SI-Gly-SN38 showed the highest accumulation in tumors. The tumor inhibition rate of SI-Gly-SN38 was 6.42% higher than that of OA-Gly-SN38, and 8.67% higher than that of Irinotecan, respectively. These results indicate that the supramolecular prodrug delivery system can be constructed between SI-Gly-SN38 and endogenous albumin, which improves drug biodistribution in vivo, enhances tumor accumulation, and plays a crucial role in tumor growth inhibition.

Factors associated with the level of self-management in elderly patients with chronic diseases: a pathway analysis.

BACKGROUND: To analyze the effects and pathways of factors such as psychological capital, family functioning, and sources of meaning in life on the level of self-management in elderly patients with chronic diseases and to provide a basis for the development of relevant nursing interventions in the future. METHODS: Convenience sampling was used to select elderly patients with chronic diseases who underwent medical checkups and consultations at three community hospitals in Jinzhou city from March 2023 to October 2023, and the self-designed General Information Questionnaire (GIS), Psychological Capital of the Elderly Scale (PCE), Family Functioning Index Questionnaire (APGAR), Sources of Meaning of Life Scale for Older Adults(SMSE), and Self-Management Behavior of Chronic Patients Scale (SMCS) were used. SPSS 26.0 was used for data entry, one-way analysis, Pearson correlation analysis, and multiple linear regression were used to analyze the data, and Amos 17.0 was used to construct the structural equation model. RESULTS: A total of 355 elderly patients with chronic diseases were included, and their self-management score was 74.75 ± 12.93, which was moderate. The results of the influencing factor analysis showed that the influencing factors of the self-management level of elderly chronic disease patients were age, years of illness, psychological capital, family functioning, and sources of meaning in life (p < 0.05). Path analysis revealed that sources of meaning in life were a partial mediator of the relationship between psychological capital and self-management, with an effect value of 0.166 (95% CI: 0.042,0.391), accounting for 37.6% of the total effect; life meaning was a partial mediator of family functioning and self-management level, with an effect value of 0.231 (95% CI: 0.040,0.452), accounting for 54.0% of the total effect. accounting for 54.0% of the total effect. CONCLUSION: The self-management of elderly patients with chronic diseases is intermediate. Healthcare professionals should actively implement holistic healthcare management measures from the family aspect to help patients understand the meaning of life and improve the level of patients' psychological capital to improve the self-management level of elderly patients with chronic diseases.

TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination.

Expression of the E3 ligase TRIM21 is increased in a broad spectrum of cancers; however, the functionally relevant molecular pathway targeted by TRIM21 overexpression remains largely unknown. Here, we show that TRIM21 directly interacts with and ubiquitinates CLASPIN, a mediator for ATR-dependent CHK1 activation. TRIM21-mediated K63-linked ubiquitination of CLASPIN counteracts the K6-linked ubiquitination of CLASPIN which is essential for its interaction with TIPIN and subsequent chromatin loading. We further show that overexpression of TRIM21, but not a TRIM21 catalytically inactive mutant, compromises CHK1 activation, leading to replication fork instability and tumorigenesis. Our findings demonstrate that TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination, providing a potential target for cancer therapy.

An inducible CRISPRi circuit for tunable dynamic regulation of gene expression in Saccharopolyspora erythraea.

Actinomyces are gram-positive bacteria known for their valuable secondary metabolites. Redirecting metabolic flux towards desired products in actinomycetes requires precise and dynamic regulation of gene expression. In this study, we integrated the CRISPR interference (CRISPRi) system with a cumate-inducible promoter to develop an inducible gene downregulation method in Saccharopolyspora erythraea, a prominent erythromycin-producing actinobacterium. The functionality of the cumate-inducible promoter was validated using the gusA gene as a reporter, and the successful inducible expression of the dCas9 gene was confirmed. The developed inducible CRISPRi strategy was then employed to downregulate the expression of target genes rppA in the wild-type strain NRRL2338 and sucC in the high erythromycin-producing strain E3. Through dynamic control of sucC expression, a significant enhancement in erythromycin production was achieved in strain E3. This study demonstrated the effectiveness of an inducible gene downregulation approach using CRISPRi and a cumate-inducible promoter, providing valuable insights for optimizing natural product production in actinomyces.

YOLOv8-MU: An Improved YOLOv8 Underwater Detector Based on a Large Kernel Block and a Multi-Branch Reparameterization Module.

Underwater visual detection technology is crucial for marine exploration and monitoring. Given the growing demand for accurate underwater target recognition, this study introduces an innovative architecture, YOLOv8-MU, which significantly enhances the detection accuracy. This model incorporates the large kernel block (LarK block) from UniRepLKNet to optimize the backbone network, achieving a broader receptive field without increasing the model's depth. Additionally, the integration of C2fSTR, which combines the Swin transformer with the C2f module, and the SPPFCSPC_EMA module, which blends Cross-Stage Partial Fast Spatial Pyramid Pooling (SPPFCSPC) with attention mechanisms, notably improves the detection accuracy and robustness for various biological targets. A fusion block from DAMO-YOLO further enhances the multi-scale feature extraction capabilities in the model's neck. Moreover, the adoption of the MPDIoU loss function, designed around the vertex distance, effectively addresses the challenges of localization accuracy and boundary clarity in underwater organism detection. The experimental results on the URPC2019 dataset indicate that YOLOv8-MU achieves an mAP@0.5 of 78.4%, showing an improvement of 4.0% over the original YOLOv8 model. Additionally, on the URPC2020 dataset, it achieves 80.9%, and, on the Aquarium dataset, it reaches 75.5%, surpassing other models, including YOLOv5 and YOLOv8n, thus confirming the wide applicability and generalization capabilities of our proposed improved model architecture. Furthermore, an evaluation on the improved URPC2019 dataset demonstrates leading performance (SOTA), with an mAP@0.5 of 88.1%, further verifying its superiority on this dataset. These results highlight the model's broad applicability and generalization capabilities across various underwater datasets.

Development and validation of a risk prediction model for mild cognitive impairment in elderly patients with type 2 diabetes mellitus.

BACKGROUND: The prevalence of mild cognitive impairment (MCI) is steadily increasing among elderly people with type 2 diabetes (T2DM). This study aimed to create and validate a predictive model based on a nomogram. METHODS: This cross-sectional study collected sociodemographic characteristics, T2DM-related factors, depression, and levels of social support from 530 older adults with T2DM. We used LASSO regression and multifactorial logistic regression to determine the predictors of the model. The performance of the nomogram was evaluated using calibration curves, receiver operating characteristics (ROC), and decision curve analysis (DCA). RESULTS: The nomogram comprised age, smoking, physical activity, social support, depression, living alone, and glycosylated hemoglobin. The AUC for the training and validation sets were 0.914 and 0.859. The DCA showed good clinical applicability. CONCLUSIONS: This predictive nomogram has satisfactory accuracy and discrimination. Therefore, the nomogram can be intuitively and easily used to detect MCI in elderly adults with T2DM.

The mechanistic basis of sodium exclusion in Puccinellia tenuiflora under conditions of salinity and potassium deprivation.

Soil salinity is a significant threat to global agriculture. Understanding salt exclusion mechanisms in halophyte species may be instrumental in improving salt tolerance in crops. Puccinellia tenuiflora is a typical salt-excluding halophytic grass often found in potassium-deprived saline soils. Our previous work showed that P. tenuiflora possesses stronger selectivity for K+ than for Na+ ; however, the mechanistic basis of this phenomenon remained elusive. Here, P. tenuiflora PutHKT1;5 was cloned and the functions of PutHKT1;5 and PutSOS1 were characterized using heterologous expression systems. Yeast assays showed that PutHKT1;5 possessed Na+ transporting capacity and was highly selective for Na+ over K+ . PutSOS1 was located at the plasma membrane and operated as a Na+ /K+ exchanger, with much stronger Na+ extrusion capacity than its homolog from Arabidopsis. PutHKT2;1 mediated high-affinity K+ and Na+ uptake and its expression levels were upregulated by mild salinity and K+ deprivation. Salinity-induced changes of root PutHKT1;5 and PutHKT1;4 transcript levels matched the expression pattern of root PutSOS1, which was consistent with root Na+ efflux. The transcript levels of root PutHKT2;1 and PutAKT1 were downregulated by salinity. Taken together, these findings demonstrate that the functional activity of PutHKT1;5 and PutSOS1 in P. tenuiflora roots is fine-tuned under saline conditions as well as by operation of other ion transporters/channel (PutHKT1;4, PutHKT2;1, and PutAKT1). This leads to the coordination of radial Na+ and K+ transport processes, their loading to the xylem, or Na+ retrieval and extrusion under conditions of mild salinity and/or K+ deprivation.

Trifolirhizin inhibits proliferation, migration and invasion in nasopharyngeal carcinoma cells via PI3K/Akt signaling pathway suppression.

Nasopharyngeal carcinoma (NPC) is a highly recurrent and metastatic malignant tumor affecting a large number of individuals in southern China. Traditional Chinese herbal medicine has been found to be a rich source of natural compounds with mild therapeutic effects and minimal side effects, making them increasingly popular for treating various diseases. Trifolirhizin, a natural flavonoid derived from leguminous plants, has gained significant attention for its therapeutic potential. In this study, we confirmed that trifolirhizin could effectively inhibit the proliferation, migration and invasion of nasopharyngeal carcinoma 6-10B and HK1 cells. Furthermore, our findings demonstrated that trifolirhizin achieves this by suppressing the PI3K/Akt signaling pathway. The findings of the present study provides a valuable perspective on the potential therapeutic applications of trifolirhizin for the treatment of nasopharyngeal carcinoma.

A cysteine-rich secretory protein involves in phytohormone melatonin mediated plant resistance to CGMMV.

BACKGROUND: Melatonin is considered to be a polyfunctional master regulator in animals and higher plants. Exogenous melatonin inhibits plant infection by multiple diseases; however, the role of melatonin in Cucumber green mottle mosaic virus (CGMMV) infection remains unknown. RESULTS: In this study, we demonstrated that exogenous melatonin treatment can effectively control CGMMV infection. The greatest control effect was achieved by 3 days of root irrigation at a melatonin concentration of 50 µM. Exogenous melatonin showed preventive and therapeutic effects against CGMMV infection at early stage in tobacco and cucumber. We utilized RNA sequencing technology to compare the expression profiles of mock-inoculated, CGMMV-infected, and melatonin+CGMMV-infected tobacco leaves. Defense-related gene CRISP1 was specifically upregulated in response to melatonin, but not to salicylic acid (SA). Silencing CRISP1 enhanced the preventive effects of melatonin on CGMMV infection, but had no effect on CGMMV infection. We also found exogenous melatonin has preventive effects against another Tobamovirus, Pepper mild mottle virus (PMMoV) infection. CONCLUSIONS: Together, these results indicate that exogenous melatonin controls two Tobamovirus infections and inhibition of CRISP1 enhanced melatonin control effects against CGMMV infection, which may lead to the development of a novel melatonin treatment for Tobamovirus control.

Development of Regular Hydrophobic Silica Aerogel Microspheres for Efficient Oil Adsorption.

The objective of this research was to develop new hydrophobic silica aerogel microspheres (HSAMs) with water glass and hexmethyldisilazane for oil adsorption. The effects of the hexmethyldisilazane concentration and drying method on the structure and organic liquid adsorption capacity were investigated. The hexmethyldisilazane concentration of the modification solution did not influence the microstructure and pore structure in a noteworthy manner, which depended more on the drying method. Vacuum drying led to more volume shrinkage of the silica gel microsphere (SGM) than supercritical CO2 drying, thus resulting in a larger apparent density, lower pore volume, narrower pore size distribution, and more compact network. Owing to the large pore volume and pore size, the HSAMs synthesized via supercritical CO2 drying had a larger organic liquid adsorption capacity. The adsorption capacities of the HSAMs with pore volumes of 4.04-6.44 cm3/g for colza oil, vacuum pump oil, and hexane are up to 18.3, 18.9, and 11.8 g/g, respectively, higher than for their state-of-the-art counterparts. The new sorbent preparation method is facile, cost-effective, safe, and ecofriendly, and the resulting HSAMs are exceptional in capacity, stability, and regenerability.

Polar Nitrated Aromatic Compounds in Urban Fine Particulate Matter: A Focus on Formation via an Aqueous-Phase Radical Mechanism.

Polar nitrated aromatic compounds (pNACs) are key ambient brown carbon chromophores; however, their formation mechanisms, especially in the aqueous phase, remain unclear. We developed an advanced technique for pNACs and measured 1764 compounds in atmospheric fine particulate matter sampled in urban Beijing, China. Molecular formulas were derived for 433 compounds, of which 17 were confirmed using reference standards. Potential novel species with up to four aromatic rings and a maximum of five functional groups were found. Higher concentrations were detected in the heating season, with a median of 82.6 ng m-3 for Σ17pNACs. Non-negative matrix factorization analysis indicated that primary emissions particularly coal combustion were dominant in the heating season. While in the non-heating season, aqueous-phase nitration could generate abundant pNACs with the carboxyl group, which was confirmed by their significant association with the aerosol liquid water content. Aqueous-phase formation of 3- and 5-nitrosalicylic acids instead of their isomer of 4-hydroxy-3-nitrobenzoic acid suggests the existence of an intermediate where the intramolecular hydrogen bond favors kinetics-controlled NO2• nitration. This study provides not only a promising technique for the pNAC measurement but also evidence for their atmospheric aqueous-phase formation, facilitating further evaluation of pNACs' climatic effects.

Analysis of Prognostic Risk Factors of Sepsis Patients With Myocardial Injury: Six-month Survival Outcome.

Context: Sepsis is a systemic, comprehensive inflammatory response that can induce serious complications for patients. No uniform definition and diagnostic criteria exist internationally for sepsis related to myocardial injury. Studying factors affecting prognosis for sepsis patients with myocardial injury can be helpful in providing a theoretical basis for clinical diagnosis and treatment. Objective: The study intended to explore the predictors of the short-term prognosis for septic patients with myocardial injury and to provide a theoretical basis for improving that prognosis. Design: The research team performed a retrospective study. Setting: The study took place at the Renmin Hospital at Hubei University of Medicine in Shiyan, Hubei, China. Participants: Participants were 138 patients with sepsis and myocardial injury at the hospital between January 2018 and February 2021. Groups: The research team divided participants into a survival group with 114 patients and a mortality group with 24 patients, based on their survival status at six months after being in the hospital. Outcome Measures: The research team collected and analyzed the following data: (1) demographic and clinical characteristics, such as age, gender, underlying disease, and disease severity; (2) echocardiographic indicators, including left ventricular ejection fraction (LVEF), stroke volume (SV), left ventricular end systolic dimension (LVESD), and left ventricular end diastolic dimension (LVEDD); and (3) myocardial injury markers and inflammatory factors, including white blood cell (WBC) count and levels of cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase (CK), C-reactive protein (CRP), and procalcitonin (PCT). Results: The six-month mortality rate for patients with sepsis with myocardial injury was 17.39%. Compared to the survival group at participants' initial visits to the hospital, the mortality group had a significantly greater age (P = .046), sepsis severity (P < .001), heart rate (P < .001), APACHE II score (P < .001), SOFA score (P < .001), and use of vasoactive drugs (P = .002), and its length of hospital stay was significantly shorter (P < .001). The mortality group's LVEF was significantly lower than that of the survival group (P < .001). The mortality group's levels of WBC, cTnI, NT-proBNP, CK, CRP, and PCT were significantly higher than those in survival group (all P < .001). The univariate analysis found that an age>64 years (P < .001), a high APACHE II score (P < .001), an elevated cTnI (P = .017), an elevated NT-proBNP (P = .029), an elevated CK (P < .001), an elevated CRP (P = .031), and an elevated PCT (P < .001) were risk factors for a poor prognosis for patients. Multifactor logistic regression analysis showed that the risk factors for death were an age > 64 years (P < .001), a high APACHE II score (P < .001), and elevated levels of cTnI (P = .013), NT-proBNP (P < .001), CK (P < .001), CRP (P < .001), and PCT (P = .009). Conclusion: In summary, risk factors for poor prognosis in septic patients with myocardial injury included age>64 years, high APACHE II, elevated cTnI, elevated NT-proBNP, elevated CK, elevated CRP, and elevated PCT.

Treatment outcomes of regenerative endodontic procedures in nonvital mature permanent teeth: a retrospective study.

OBJECTIVES: This retrospective study was undertaken to clinically and radiographically evaluate the long-term outcomes of regenerative endodontic procedures (REPs) for nonvital mature permanent teeth, to analyze predictors influencing treatment outcomes. METHODS: Nonvital mature permanent teeth treated by REPs with a minimum follow-up period of 6 months were included from 2015 to 2017. Treatment outcomes were categorized as success and failure. The periapical status and lesion healing were assessed in terms of the periapical index (PAI) and the percentage changes in periapical radiolucency (PARL) area. The clinical and radiographic outcomes of REPs were assessed by Mann-Whitney test at different follow-up period. Kaplan-Meier curves and Univariate Cox regression analysis were conducted to assess the success and identify potential predictors affecting outcomes, respectively. RESULTS: A total of 37 mature teeth with an average follow-up of 4.3 years satisfied the criteria, and 89.2% of the teeth had a successful outcome. Significant differences in PAI scores were found between each period with respect to the baseline (p < .05). Among different periods, there was a significant difference between intervals of 3-6 months and 7-12 months (p = .039) and no significant difference between each interval of more than 12 months (p > .05). Eighty-seven percent of teeth with preoperative PARL presented completely healed. REPs significantly decreased the PARL area at the interval of 7-12 months compared to 3-6 months (p = .025), with no significant difference between each interval of more than 12 months (p > .05). No significant predictor was found for the success of outcome (p > .05). Thirteen teeth (35.1%) regained pulp sensibility, and 40.5% of the teeth exhibited intracanal calcification. CONCLUSIONS: Within the limitations of this study, REPs provided a high long-term success rate and promoted the resolution of PARL as a biologically-based alternative treatment option for nonvital mature teeth. CLINICAL RELEVANCE: REPs provide a high long-term success rate and promoted healing of apical periodontitis comparable with reported outcomes for root canal therapy of mature teeth.