Cryo-EM structures of the plant plastid-encoded RNA polymerase.

Chloroplasts are green plastids in the cytoplasm of eukaryotic algae and plants responsible for photosynthesis. The plastid-encoded RNA polymerase (PEP) plays an essential role during chloroplast biogenesis from proplastids and functions as the predominant RNA polymerase in mature chloroplasts. The PEP-centered transcription apparatus comprises a bacterial-origin PEP core and more than a dozen eukaryotic-origin PEP-associated proteins (PAPs) encoded in the nucleus. Here, we determined the cryo-EM structures of Nicotiana tabacum (tobacco) PEP-PAP apoenzyme and PEP-PAP transcription elongation complexes at near-atomic resolutions. Our data show the PEP core adopts a typical fold as bacterial RNAP. Fifteen PAPs bind at the periphery of the PEP core, facilitate assembling the PEP-PAP supercomplex, protect the complex from oxidation damage, and likely couple gene transcription with RNA processing. Our results report the high-resolution architecture of the chloroplast transcription apparatus and provide the structural basis for the mechanistic and functional study of transcription regulation in chloroplasts.

Functionalized DNA Origami-Enabled Detection of Biomarkers.

Biomarkers are crucial physiological and pathological indicators in the host. Over the years, numerous detection methods have been developed for biomarkers, given their significant potential in various biological and biomedical applications. Among these, the detection system based on functionalized DNA origami has emerged as a promising approach due to its precise control over sensing modules, enabling sensitive, specific, and programmable biomarker detection. We summarize the advancements in biomarker detection using functionalized DNA origami, focusing on strategies for DNA origami functionalization, mechanisms of biomarker recognition, and applications in disease diagnosis and monitoring. These applications are organized into sections based on the type of biomarkers - nucleic acids, proteins, small molecules, and ions - and concludes with a discussion on the advantages and challenges associated with using functionalized DNA origami systems for biomarker detection.

Twin-Field Quantum Key Distribution with Local Frequency Reference.

Twin-field quantum key distribution (TFQKD) overcomes the linear rate-loss limit, which promises a boost of secure key rate over long distance. However, the complexity of eliminating the frequency differences between the independent laser sources hinders its practical application. We analyzed and determined the frequency stability requirements for implementing TFQKD using frequency-stabilized lasers. Based on this analysis, we proposed and demonstrated a simple and practical approach that utilizes the saturated absorption spectroscopy of acetylene as an absolute reference, eliminating the need for fast frequency locking to achieve TFQKD. Adopting the 4-intensity sending-or-not-sending TFQKD protocol, we experimentally demonstrated the TFQKD over 502, 301, and 201 km ultralow-loss optical fiber, respectively. We expect this high-performance scheme will find widespread usage in future intercity and free-space quantum communication networks.

Minor (≤ 10%) Ground-Glass Opacity Component in Clinical Stage I Non-Small Cell Lung Cancer: Associations With Pathologic Characteristics and Clinical Outcomes.

BACKGROUND. The presence of a ground-glass opacity (GGO) component is a favorable prognostic factor in non-small cell lung cancer (NSCLC), although the prognostic impact of a very small GGO component remains poorly investigated. OBJECTIVE. The purpose of this article is to investigate the impact of a minor (≤ 10%) GGO component on the prognosis of clinical stage I NSCLC in comparison with pure-solid nodules. METHODS. This retrospective study included 382 patients (mean age, 60.8 years; 210 men, 172 women) who underwent surgical resection between January 1, 2015, and December 31, 2015, for clinical stage I NSCLC appearing on preoperative chest CT as a nodule with a consolidation-to-tumor ratio (CTR) of 0.9 to 1.0. Two radiologists independently assigned nodules to groups as either minor GGO (CTR, ≥ 0.9 and < 1.0) or pure solid (CTR = 1.0). Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed by Kaplan-Meier curves and compared between groups using log-rank tests. Cox proportional hazards models were used to assess associations with outcomes. RESULTS. The two radiologists agreed for all nodules' classification into the minor-GGO (n = 106) or pure-solid (n = 276) groups. The mean CTR of the minor-GGO group was 0.93 ± 0.02 (SD) (range, 0.90-0.97). Minor-GGO nodules, in comparison with pure-solid nodules, showed greater solid-component diameter (2.68 vs 2.16 cm; p < .001) and total nodule diameter (2.89 vs 2.16 cm; p < .001). The minor-GGO group, in comparison with the pure-solid group, showed lower frequencies of visceral pleural invasion (6.6% vs 17.0%, p = .009) and pathologic lymph node involvement (4.7% vs 20.3%, p < .001), and EGFR mutation (71.6% vs 39.9%; p < .001). The minor-GGO group, in comparison with the pure-solid group, showed better 5-year RFS (83.4% vs 55.0%; p < .001) and higher frequency of better 5-year CSS (92.4% vs 76.4%, p = .004). In multivariable analysis adjusting for patient, imaging, pathologic, and genetic factors, a minor-GGO component was independently associated with a decreased likelihood of recurrence (HR = 0.37, p = .001) but not with the likelihood of CSS. CONCLUSION. Among patients with clinical stage I NSCLC, cancers with a minor-GGO component were associated with a better prognosis versus those with a pure-solid appearance. CLINICAL IMPACT. Radiologists encountering predominantly solid nodules on CT should carefully assess images for even a minor-GGO component given the favorable prognosis.

Pharmacokinetic, bioequivalence, and safety assessments of two brands of 30-mg nifedipine controlled-release formulations in Chinese healthy subjects.

OBJECTIVE: This study aimed to analyze the pharmacokinetic (PK) characteristics, safety, and bioequivalence (BE) of a test (T) preparation of a nifedipine controlled-release tablet and the reference (R) drug (Adalat GTIS) in Chinese study participants in the context of fasting and postprandial states. MATERIALS AND METHODS: An open-label, single-center, randomized, single-dose, two-period study was designed including two separate arms, one with administration under fasting conditions and one with administration under postprandial conditions (high-fat, high-calorie breakfast). After oral administration, the nifedipine concentrations in plasma were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) at regular intervals. Primary PK parameters, including the area under the concentration curve from 0 to infinity (AUC0-∞), the area under the concentration profile from 0 to the last measurable concentration time (AUC0-t), and maximal measured plasma concentration (Cmax) were log-transformed with BE limits of 80 - 125% to evaluate BE. All adverse events (AEs) were wholly supervised. RESULTS: The PK profiles of the T and R formulations were comparable to each other under both fasting and postprandial conditions. The 90% confidence intervals (CIs) of the AUC0-∞, AUC0-t, and Cmax were 92.69 - 106.06%, 93.32 - 107.05%, and 99.53 - 116.71%, respectively, under the fasting state. The 90% CIs of the AUC0-∞, AUC0-t, and Cmax were 105.05 - 117.40%, 105.43 - 117.82%, and 102.66 - 116.30%, respectively, in the postprandial arm. 47 cases of drug-associated AEs were noted in the entire research. CONCLUSION: Under both the fasting and postprandial states, the two nifedipine controlled-release formulations were bioequivalent and safe in healthy Chinese subjects.

Minimally invasive palliative treatment of malignant tracheoesophageal fistula using cardiac septal occluder.

INTRODUCTION: Tracheoesophageal fistula (TEF) especially malignant TEF (mTEF) is an uncommon yet critical medical condition necessitating immediate intervention. This life-threatening condition frequently manifests in critically ill patients who are dependent on prolonged mechanical ventilation and are unsuitable candidates for thoracotomy due to their compromised health status. The Management of these mTEF patients remain a significant challenge.This study aimed to evaluate the safety and efficacy of using a cardiac septal occluder for the closure of mTEF. METHODS: 8 patients with mTEF underwent closure surgery using atrial/ventricular septal defect (ASD/VSD) septal occluders at the Respiratory Department of HuBei Yichang Central People's Hospital from 2021 to 2023. The procedure involved percutaneous placement of the occluder through the fistula to achieve closure. RESULTS: The placement of the cardiac septal occluder was successfully achieved with ease and efficiency in all patients. The study demonstrated that the use of cardiac septal occluder therapy in patients with mTEF can alleviate symptoms, improve quality of life, and enhance survival rates, with no significant complications observed. Furthermore, the study provided comprehensive details on surgical indications, preoperative evaluation and diagnosis, selection of occluder, methods of occlusion, and postoperative care. CONCLUSIONS: The application of cardiac septal occluder in the treatment of mTEF is a safe and effective palliative treatment. This approach may be particularly beneficial for patients with a high risk of complications and mortality associated with traditional surgical interventions.

Native T1-mapping as a predictor of progressive renal function decline in chronic kidney disease patients.

BACKGROUND: To investigate the potential of Native T1-mapping in predicting the prognosis of patients with chronic kidney disease (CKD). METHODS: We enrolled 119 CKD patients as the study subjects and included 20 healthy volunteers as the control group, with follow-up extending until October 2022. Out of these patients, 63 underwent kidney biopsy measurements, and these patients were categorized into high (25-50%), low (< 25%), and no renal interstitial fibrosis (IF) (0%) groups. The study's endpoint event was the initiation of renal replacement therapy, kidney transplantation, or an increase of over 30% in serum creatinine levels. Cox regression analysis determined factors influencing unfavorable kidney outcomes. We employed Kaplan-Meier analysis to contrast kidney survival rates between the high and low T1 groups. Additionally, receiver-operating characteristic (ROC) curve analysis assessed the predictive accuracy of Native T1-mapping for kidney endpoint events. RESULTS: T1 values across varying fibrosis degree groups showed statistical significance (F = 4.772, P < 0.05). Multivariate Cox regression pinpointed 24-h urine protein, cystatin C(CysC), hemoglobin(Hb), and T1 as factors tied to the emergence of kidney endpoint events. Kaplan-Meier survival analysis revealed a markedly higher likelihood of kidney endpoint events in the high T1 group compared to the low T1 value group (P < 0.001). The ROC curves for variables (CysC, T1, Hb) tied to kidney endpoint events demonstrated area under the curves(AUCs) of 0.83 (95%CI: 0.75-0.91) for CysC, 0.77 (95%CI: 0.68-0.86) for T1, and 0.73 (95%CI: 0.63-0.83) for Hb. Combining these variables elevated the AUC to 0.88 (95%CI: 0.81-0.94). CONCLUSION: Native T1-mapping holds promise in facilitating more precise and earlier detection of CKD patients most at risk for end-stage renal disease.

Bone marrow mesenchymal stem cell-derived exosomes promote osteoblast proliferation, migration and inhibit apoptosis by regulating KLF3-AS1/miR-338-3p.

AIM: This study aimed to investigate the effect and mechanism of bone marrow mesenchymal stem cell-derived exosomes on osteoblast function. METHODS: The expression of KLF3-AS1 and miR-338-3p in serum of fracture patients was detected by qRT-PCR. Exosomes from BMSCs were isolated by ultrafast centrifugation. MC3T3-E1 cells were cultured in vitro as experimental cells. Intracellular gene expression was regulated by transfection of si-KLF3-AS1 or miR-338-3p inhibitors. MTT assay, Transwell assay and flow cytometry were used to evaluate cell viability, migration, and apoptosis. The luciferase reporter gene was used to verify the targeting relationship between KLF3-AS1 and miR-338-3p. Bioinformatics analysis was used to identify the basic functions and possible enrichment pathways of miR-338-3p target genes. RESULTS: The expressions of KLF3-AS1 and miR-338-3p in the serum of fracture patients were down-regulated and up-regulated, respectively. The expression of KLF3-AS1 was increased in MC3T3-E1 cells cultured with BMSCs-Exo, while the viability and migration ability of MC3T3-E1 cells were enhanced, and the apoptosis ability was weakened. Further analysis revealed miR-338-3p was the target gene of KLF3-AS1. The expression of miR-338-3p was downregulated in MC3T3-E1 cells cultured with BMSCs-Exo. Inhibition of miR-338-3p in MC3T3-E1 cells enhanced the viability and migration ability of MC3T3-E1 cells when cultured with BMSCs-Exo, while suppressing apoptosis. Bioinformatics analysis demonstrated that the target genes of miR-338-3p were predominantly localized at the axon's initiation site, involved in biological processes such as development and growth regulation, and mainly enriched in MAPK and ErbB signaling pathways. CONCLUSION: In vitro, BMSCs-Exo exhibits the capacity to enhance proliferation and migration while inhibiting apoptosis of MC3T3-E1 cells, potentially achieved through modulation of KLF3-AS1 and miR-338-3p expression in MC3T3-E1 cells.

Role of C/EBP Homologous Protein in Vascular Stenosis After Carotid Artery Injury.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

[Analysis of clinical characteristics and molecular genetics in eighteen patients with 1q21.1 microdeletion syndrome].

OBJECTIVE: To explore the clinical characteristics of 1q21.1 microdeletion by using single nucleotide polymorphism microarrays (SNP array). METHODS: Eighteen cases of 1q21.1 microdeletion syndrome diagnosed at the Longgang District Maternal and Child Health Care Hospital of Shenzhen City from June 2017 to December 2022 were selected as the study subjects. Clinical data of the patients were collected. Results of chromosomal karyotyping and SNP assay were retrospectively analyzed. RESULTS: Among the 18 cases with 1q21.1 microdeletions, 13 had a deletion between BP3 and BP4, 4 had a deletion between BP1/BP2 and BP4, whilst 1 had a proximal 1q21.1 deletion (between BP2 and BP3) involving the Thrombocytopenia-absent radius (TAR) region. The deletions had spanned from 360 kb to 3.9 Mb, which encompassed the GJA5, GJA8, CHD1L, RBM8AB and other morbid genes. In three families, the proband child has inherited the same 1q21.1 microdeletion from their parents, whose clinical phenotype was normal or slightly abnormal. The clinical phenotypes of 1q21.1 microdeletion had included cognitive or behavioral deficits in 9 cases (9/18, 50.0%), growth retardation in 8 cases (8/18, 44.4%), craniofacial deformities in 7 cases (7/18, 38.8%), cardiovascular malformations in 5 cases (5/18, 27.8%), and microcephaly in 3 cases (3/18, 16.7%). CONCLUSION: 1q21.1 microdeletion syndrome has incomplete penetrance and varied expression such as intellectual impairment, growth and development delay, and microcephaly, with a wide range of non-specific phenotypes.

Triphasic Hydroxysilylation of Alkenes by Mechanically Piezoelectric Catalysis.

The 1,2-hydroxysilylation of alkenes is crucial for synthesizing organosilicon compounds which are key intermediates in material science, pharmaceuticals, and organic synthesis. The development of strategies employing hydrogen atom transfer pathways is currently hindered by the existence of various competing reactions. Herein, we reported a novel mechanochemical strategy for the triphasic 1,2-hydroxysilylation of alkenes through a single-electron-transfer pathway. Our approach not only circumvents competitive reactions to enable the first-ever 1,2-hydroxysilylation of unactivated alkenes but also pioneers the research in mechanic force-induced triphasic reactions under ambient conditions. This gentle method offers excellent compatibility with various functional groups, operates under simple and solvent-free conditions, ensures rapid reaction time. Preliminary mechanistic investigations suggest that silylboronate can be transformed to a silicon radical by highly polarized Li2TiO3 particles and oxygen under ball-milling condition.

The Bayesian Regularized Quantile Varying Coefficient Model.

The quantile varying coefficient (VC) model can flexibly capture dynamical patterns of regression coefficients. In addition, due to the quantile check loss function, it is robust against outliers and heavy-tailed distributions of the response variable, and can provide a more comprehensive picture of modeling via exploring the conditional quantiles of the response variable. Although extensive studies have been conducted to examine variable selection for the high-dimensional quantile varying coefficient models, the Bayesian analysis has been rarely developed. The Bayesian regularized quantile varying coefficient model has been proposed to incorporate robustness against data heterogeneity while accommodating the non-linear interactions between the effect modifier and predictors. Selecting important varying coefficients can be achieved through Bayesian variable selection. Incorporating the multivariate spike-and-slab priors further improves performance by inducing exact sparsity. The Gibbs sampler has been derived to conduct efficient posterior inference of the sparse Bayesian quantile VC model through Markov chain Monte Carlo (MCMC). The merit of the proposed model in selection and estimation accuracy over the alternatives has been systematically investigated in simulation under specific quantile levels and multiple heavy-tailed model errors. In the case study, the proposed model leads to identification of biologically sensible markers in a non-linear gene-environment interaction study using the NHS data.

Efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials.

Background: As the development of novel anti-angiogenic drugs and the continuous evolution of guideline recommendations, the efficacy and safety of anti-angiogenic agents in ovarian cancer (OC) remains unclear. Consequently, a meta-analysis was carried out to assess the efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for OC. Methods: An exhaustive literature review was performed across multiple databases, including PubMed, Embase, Web of Science, and Cochrane, encompassing all relevant randomized controlled trials (RCTs) up until 6 April 2024. The evaluation of efficacy outcomes incorporated progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Safety was assessed through the occurrence of any grade adverse events (AEs) and grade ≥3 AEs. Synthesis of the data involved the calculation of hazard ratios (HRs), relative risks (RRs), and their corresponding 95% confidence intervals (CIs) and prediction intervals (PIs). Trial sequential analysis was executed employing TSA v0.9.5.10 Beta software, STATA 12.0, and R software 4.3.1. Results: In this meta-analysis, 35 RCTs were included, encompassing 16,199 subjects in total. The overall analysis indicated that anti-angiogenic drug combination therapy significantly improved PFS (HR [95% CI] = 0.678 [0.606-0.759], 95% PI: 0.415-1.108), OS (HR [95% CI] = 0.917 [0.870-0.966], 95% PI: 0.851-0.984), and ORR (RR [95% CI] = 1.441 [1.287-1.614], 95% PI: 1.032-2.014), but also increased the incidence of grade ≥3 AEs (RR [95% CI] = 1.137 [1.099-1.177], 95% PI: 1.011-1.252). The analysis did not corroborate any benefit of anti-angiogenic monotherapy over placebo concerning PFS (HR [95% CI] = 0.956 [0.709-1.288], 95% PI: 0.345-2.645) and OS (HR [95% CI] = 1.039 [0.921-1.173], 95% PI: 0.824-1.331). However, it was observed that monotherapy with anti-angiogenic drugs did increase the incidence of any grade AEs (RR [95% CI] = 1.072 [1.036-1.109], 95% PI: 0.709-1.592). Conclusion: Our study confirmed the PFS, OS, and ORR benefits of anti-angiogenic drug combination therapy for OC patients. The efficacy results of anti-angiogenic monotherapy necessitates further evaluation as more RCTs become available. Clinicians should be vigilant of AEs when administering anti-angiogenic agents in a clinical setting.

Score Dynamics: Scaling Molecular Dynamics with Picoseconds Time Steps via Conditional Diffusion Model.

We propose score dynamics (SD), a general framework for learning accelerated evolution operators with large timesteps from molecular dynamics (MD) simulations. SD is centered around scores or derivatives of the transition log-probability with respect to the dynamical degrees of freedom. The latter play the same role as force fields in MD but are used in denoising diffusion probability models to generate discrete transitions of the dynamical variables in an SD time step, which can be orders of magnitude larger than a typical MD time step. In this work, we construct graph neural network-based SD models of realistic molecular systems that are evolved with 10 ps timesteps. We demonstrate the efficacy of SD with case studies of the alanine dipeptide and short alkanes in aqueous solution. Both equilibrium predictions derived from the stationary distributions of the conditional probability and kinetic predictions for the transition rates and transition paths are in good agreement with MD. Our current SD implementation is about 2 orders of magnitude faster than the MD counterpart for the systems studied in this work. Open challenges and possible future remedies to improve SD are also discussed.

The effect of gonadotropin-releasing hormone analog treatment on the endocrine system in central precocious puberty patients: a meta-analysis.

OBJECTIVES: Gonadotropin-releasing hormone (GnRHa) is the first choice for the treatment of patients with central precocious puberty (CPP). However, the effects of GnRHa on the endocrine system of CPP patients, including insulin sensitivity, lipid level, thyroid function, bone mineral density (BMD), and testosterone (T) level, are currently contradictory. Therefore, the long-term safety of GnRHa therapy remains controversial. CONTENT: A systematic literature search was performed using PubMed, Embase, Cochrane Library, and CNKI databases. The changes in HOMA-IR, TG, LDL-C, HDL-C, TSH, FT3, FT4, T, and BMD in CPP patients before and after GnRHa treatment were compared by meta-analysis. As the heterogeneity between studies, we estimated standard deviation mean differences (SMDs) and 95 % confidence intervals (CIs) using a random-effects model. Egger's test was used to assess publication bias. SUMMARY: A total of 22 studies were included in our meta-analysis. Compared with before GnRHa treatment, there were no statistically significant differences in endocrine indicators including HOMA-IR, TG, LDL-C, HDL-C, TSH, FT4, FT3, T, and BMD of CPP patients treated with GnRHa. OUTLOOK: Treatment with GnRHa for central precocious puberty will not increase the adverse effect on the endocrine system.

Aldo-keto reductase-7A2 protects against atorvastatin-induced hepatotoxicity via Nrf2 activation.

Atorvastatin (ATO), as a cholesterol-lowering drug, was the world's best-selling drug in the early 2000s. However, ATO overdose-induced liver or muscle injury is a threat to many patients, which restricts its application. Previous studies suggest that ATO overdose is accompanied with ROS accumulation and increased lipid peroxidation, which are the leading causes of ATO-induced liver damage. This study is, therefore, carried out to investigate the roles of anti-oxidant pathways and enzymes in protection against ATO-induced hepatotoxicity. Here we show that in ATO-challenged HepG2 cells, the expression levels of transcription factor NFE2L2/Nrf2 (nuclear factor erythroid 2 p45-related factor 2) are significantly upregulated. When Nrf2 is pharmacologically inhibited or genetically inactivated, ATO-induced cytotoxicity is significantly aggravated. Aldo-keto reductase-7A (AKR7A) enzymes, transcriptionally regulated by Nrf2, are important for bioactivation and biodetoxification. Here, we reveal that in response to ATO exposure, mRNA levels of human AKR7A2 are significantly upregulated in HepG2 cells. Furthermore, knockdown of AKR7A2 exacerbates ATO-induced hepatotoxicity, suggesting that AKR7A2 is essential for cellular adaptive response to ATO-induced cell damage. In addition, overexpression of AKR7A2 in HepG2 cells can significantly mitigate ATO-induced cytotoxicity and this process is Nrf2-dependent. Taken together, these findings indicate that Nrf2-mediated AKR7A2 is responsive to high concentrations of ATO and contributes to protection against ATO-induced hepatotoxicity, making it a good candidate for mitigating ATO-induced side effects.

The relationship between inflammatory cytokines and in-hospital complications of acute pancreatitis.

OBJECTIVE: Acute necrotic collection (ANC), acute peripancreatic fluid collection (APFC), pleural effusion, and ascites are common early complications of acute pancreatitis. This study aimed to investigate the relationship between 12 serum cytokines and the early complications and severity of acute pancreatitis (AP). METHODS: We retrospectively analyzed the clinical data of 307 patients with AP, and divided them into severe group and mild-to-moderate group according to the revised Atlanta classification. Propensity score matching was used to control for confounding factors. Binary logistic regression analysis was used to explore the relationship between cytokine levels and early complications of AP. RESULTS: Serum levels of interleukin (IL)-1ß, IL-5, IL-6, IL-8, IL-10, IL-17, and tumor necrosis factor-α were significantly higher in the severe acute pancreatitis (SAP) group than in the non-SAP group (p < .05). After adjusting for confounding factors, the upper quartiles of IL-6, IL-8, and IL-10 were associated with an increased risk of ANC compared with those in the lowest quartile (IL-6: quartile 3, odds ratio [OR] = 3.99, 95% confidence interval [CI] = 1.95-8.16; IL-8: quartile 4, OR = 2.47, 95% CI = 1.27-4.84; IL-10: quartile 2, OR = 2.22, 95% CI = 1.09-4.56). APFC was associated with high serum levels of IL-6 (quartile 3, OR = 1.32, 95% CI = 1.02-1.72), pleural effusions were associated with high serum levels of IL-1ß, IL-6, IL-8, and IL-10 (IL-1ß: quartile 4, OR = 2.36, 95% CI = 1.21-4.58; IL-6: quartile 3, OR = 4.67, 95% CI = 2.27-9.61; IL-8: quartile 3, OR = 2.95, 95% CI = 1.51-5.79; IL-10: quartile 4, OR = 3.20, 95% CI = 1.61-6.36), and high serum levels of IL-6 and IL-10 were associated with an increased risk of ascites (IL-6: quartile 3, OR = 3.01, 95% CI = 1.42-6.37; IL-10: quartile 3, OR = 2.57, 95% CI = 1.23-5.37). CONCLUSION: Serum cytokine levels, including IL-1ß, IL-6, IL-8, and IL-10 may be associated with the occurrence of early complications of AP. In daily clinical practice, IL-6 may be the most worthwhile cytokine to be detected.

Deciphering the Enigma of Intramyocardial Hemorrhage Following Reperfusion Therapy in Acute ST-Segment Elevation Myocardial Infarction: A Comprehensive Exploration from Mechanisms to Therapeutic Strategies.

Acute ST-segment elevation myocardial infarction (STEMI) is a formidable challenge in cardiovascular medicine, demanding advanced reperfusion strategies such as emergency percutaneous coronary intervention. While successful revascularization is pivotal, the persistent "no-reflow" phenomenon remains a clinical hurdle, often intertwined with microvascular dysfunction. Within this intricate scenario, the emergence of intramyocardial hemorrhage (IMH) has garnered attention as a significant contributor. This review offers a detailed exploration of the multifaceted relationship between IMH and the "no-reflow" phenomenon, delving into the mechanisms governing IMH occurrence, state-of-the-art diagnostic modalities, predictive factors, clinical implications, and the evolving landscape of preventive and therapeutic strategies. The nuanced examination aims to deepen our comprehension of IMH, providing a foundation for the identification of innovative therapeutic avenues and enhanced clinical outcomes for STEMI patients.

Non-linear trends using the generalized additive models in physical and technical performances of the Chinese Super League players.

This study aimed to investigate the non-linear evolution of position-specific physical and technical performance indicators across different tactical formations in the Chinese Super League (CSL) from the 2015 to the 2021 seasons. Match data were collected from 800 games played in six common formations (3-5-2, 4-3-3, 4-2-3-1, 4-4-2, 3-4-3, and 4-1-4-1). Players were classified into five positions: central defenders (CD; match observations = 2,219), fullbacks (FB; match observations = 2,060), central midfielders (CM; match observations = 2,786), wide midfielders (WM; match observations = 1,587), and forwards (FW; match observations = 1,680). Generalized additive models (GAMs) were constructed to analyze the nonlinear evolution trends in position-specific physical and technical performance across seasons and formations. The results showed that the total distance covered by CDs in the 3-5-2 formation showed a non-linear upward trend from the 2015 to 2021 seasons (R2 = 0.3, p = 0.006); FBs in the 3-4-3, 4-1-4-1, and 3-5-2 formations exhibited non-linear upward trends in number of sprints and sprint distance from the 2015 to 2021 seasons (R2 = 0.189-0.448; P < 0.03, respectively); the high-speed running of FWs in the 4-2-3-1 formation displayed a non-linear decline trend from the 2015 to 2021 seasons (R2 = 0.477; P < 0.001); CMs in the 4-2-3-1 formation demonstrated a non-linear increasing trend in the ball retention percentage (R2 = 0.369; p = 0.001); WMs in the 4-4-2 formation showed a non-linear decreasing trend in ball retention percentage and passes from the 2015 to 2021 seasons (R2 = 0.259-0.29; P = 0.006, respectively). These findings revealed non-linear evolutionary trends in physical and technical performances across positions and formations, providing an in-depth understanding of the changing match demands placed on players during matches. This enables the optimization of training and tactics by developing targeted strategies tailored to meet the specific requirements of different formations and playing positions.

Characteristics of radioactive aerosols during the pre-decommission phase of the experimental shielding reactor.

The decommissioning of nuclear reactors is a global concern, in part because of the generation of radioactive aerosols that can lead to internal radiation exposure. At present, radioactive aerosols generated during nuclear decommissioning have not been actively studied, and data collected from the actual decommissioning are limited. This paper presents a study of radioactive aerosols generated during the pre-decommission phase of an experimental shielding reactor. Among all the on-site operations, cutting resulted in the highest levels of radioactivity. Plasma arc cutting, in particular, had a maximum gross α and ß radioactivity over 0.10 and 0.14 Bq/m3, respectively. Assumed AMAD (activity median aerodynamic diameter) values are employed to assess the impact of particle size on the internal exposure dose resulting from the inhalation of 137Cs aerosols. This assessment is based on the Human Respiratory Tract Model of International Commission on Radiological Protection. When cutting stainless steel by plasma arc, the internal exposure dose caused by 137Cs aerosols with an AMAD of 0.1 µm is estimated to be nearly four times as that of aerosols with an AMAD of 10 µm. Results show that the internal exposure dose is highly dependent on the AMAD, implying the importance of measuring size-related parameters of radioactive aerosols in the future nuclear decommissioning. This study has revealed some characteristics of radioactive aerosols released in decommissioning operations, which can serve as a valuable reference for controlling and removing aerosols during the decommissioning of nuclear facilities.