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Purpose: The aim of this study is to investigate the role of the neutrophil to lymphocyte ratio (NLR) in patients diagnosed with the chronic obstructive pulmonary disease-obstructive sleep apnea (COPD-OSA) overlap syndrome and comorbid pulmonary hypertension (PH). Patients and methods: We enrolled a consecutive of stable COPD patients and conducted spirometry measurements, nocturnal polysomnography (PSG), and echocardiography for all participants. Clinical laboratory data were collected. Results: A total of 178 patients with stable COPD were enrolled among whom 33.14% (59/178) were diagnosed with OSA. Of the patients with overlap syndrome, 35.59% (21/59) showed comorbid PH, compared to 34.45% (41/119) in COPD patients without OSA. There was no significant difference in the occurrence of PH between COPD with and without OSA. NLR was significantly higher in patients with overlap syndrome compared to those with either disease alone. The difference in NLR between COPD-OSA patients with and without PH was not significant. Correlation analysis revealed that NLR was associated with age, total sleep time spent with oxygen saturation below 90% (T90), CRP, pulmonary artery systolic pressure (PASP), and minimum peripheral capillary oxygen saturation (SpO2min) in all COPD patients. NLR was identified as an independent factor contributing to OSA in COPD. The median cut-off value for detecting OSA in stable COPD was 2.49. However, NLR was not found to be a predictor for PH in COPD-OSA overlap syndrome. Conclusions: NLR can serve as a predictive marker for comorbid OSA in patients with COPD. NLR is expected to increase its clinical application as a convenient and cost-effective biomarker for COPD-OSA overlap syndrome. [ABSTRACT FROM AUTHOR]

2,6-Di-tert-butyl-4-methylphenol (BHT) is an excellent antioxidant that is easily oxidized to 2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone (BHTOOH). For the safety of BHT production and usage, it is meaningful to study the thermal stability and decomposition properties of BHT and BHTOOH. In this paper, the thermal decomposition properties of BHT and BHTOOH were compared by the mini closed pressure vessel test (MCPVT) and differential scanning calorimetry (DSC). Their kinetics of thermal decomposition were studied using thermogravimetric analysis (TGA). The thermal decomposition products of BHT and BHTOOH were analyzed by gas chromatography-mass spectrometry (GC–MS). The results show that there was no significant change in temperature pressure when BHT was warmed up under a nitrogen atmosphere, indicating that BHT was stable within 400 K. The thermal decomposition reaction of BHTOOH was rapid with an initial reaction temperature of 375.2 K. The initial exothermic temperature (Ti) and heat release (QDSC) of DSC were 384.9 K and 865.0 J g−1, respectively. The apparent activation energies (Ea) for the thermal decomposition reactions of BHT and BHTOOH calculated by the Kissinger method were 151.8 kJ mol−1 and 66.07 kJ mol−1, respectively. The main decomposition products of BHT were isobutene and 2-tert-butyl-4-methylphenol. The thermal decomposition products of BHTOOH included BHT, 2,6-di-tert-butyl-4-ethylphenol, 3,5-di-tert-butyl-4-hydroxybenzaldehyde, 4,4′-(1,2-ethanediyl) bis [2,6-bis (1,1-dimethylethyl) phenol, etc. Based on the thermal decomposition behavior and products, the reaction pathway has been described. These results indicate that BHT is a potential thermal hazard during production, storage and application. For the safety of the chemical industry, the oxidation of BHT should be avoided. [ABSTRACT FROM AUTHOR]

Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or β (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.Interim data from a clinical trial of mRNA-3927—an mRNA therapeutic for propionic acidaemia—provide early indications of the safety and efficacy of the treatment, and suggest that this approach might be applicable to other rare diseases. [ABSTRACT FROM AUTHOR]

This paper verifies the low Mach number limit of the non-isentropic compressible magnetohydrodynamic (MHD) equations with or without the magnetic diffusion in a three-dimensional bounded domain when the temperature variation is large but finite. The uniform estimates of strong solutions are established in a short time interval independent of the Mach number, provided that the slip boundary condition for the velocity and the Neumann boundary condition for the temperature are imposed and the initial data is well-prepared. [ABSTRACT FROM AUTHOR]

Introduction: Brain metastasis (BM) is an aggressive complication with an extremely poor prognosis in patients with small-cell lung cancer (SCLC). A well-constructed prognostic model could help in providing timely survival consultation or optimizing treatments. Methods: We analyzed clinical data from SCLC patients between 2000 and 2018 based on the Surveillance, Epidemiology, and End Results (SEER) database. We identified significant prognostic factors and integrated them using a multivariable Cox regression approach. Internal validation of the model was performed through a bootstrap resampling procedure. Model performance was evaluated based on the area under the curve (AUC) and calibration curve. Results: A total of 2,454 SCLC patients' clinical data was collected from the database. It was determined that seven clinical parameters were associated with prognosis in SCLC patients with BM. A satisfactory level of discrimination was achieved by the predictive model, with 6-, 12-, and 18-month AUC values of 0.726, 0.707, and 0.737 in the training cohort; and 0.759, 0.742, and 0.744 in the validation cohort. As measured by survival rate probabilities, the calibration curve agreed well with actual observations. Furthermore, prognostic scores were found to significantly alter the survival curves of different risk groups. We then deployed the prognostic model onto a website server so that users can access it easily. Conclusions: In this study, a nomogram and a web-based predictor were developed to predict overall survival in SCLC patients with BM. It may assist physicians in making informed clinical decisions and determining the best treatment plan for each patient. [ABSTRACT FROM AUTHOR]

Obesity is characterized by chronic low-grade inflammation, which is driven by macrophage infiltration in adipose tissue and leads to elevated cytokines such as interleukin-1β (IL-1β) in the circulation and tissues. Previous studies demonstrate that SENP3, a redox-sensitive SUMO2/3-specific protease, is strongly implicated in the development and progression of cancer and cardiovascular diseases. However, the role of SENP3 in obesity-associated inflammation remains largely unknown. To better understand the effects of SENP3 on adipose tissue macrophage (ATM) activation and function within the context of obesity, we generated mice with myeloid-specific deletion of SENP3 (Senp3flox/flox;Lyz2-Cre mice). We found that the expression of SENP3 is dramatically increased in ATMs during high-fat diet (HFD)-induced obesity in mice. Senp3flox/flox;Lyz2-Cre mice show lower body weight gain and reduced adiposity and adipocyte size after challenged with HFD and during aging. Myeloid-specific SENP3 deletion attenuates macrophage infiltration in adipose tissue and reduces serum levels of inflammatory factors during diet and age-induced obesity. Furthermore, we found that SENP3 knockout markedly inhibits cytokine release from macrophage after lipopolysaccharide and palmitic acid treatment in vitro. Mechanistically, in cultured peritoneal macrophages, SENP3 protein level is enhanced by IL-1β, in parallel with the upregulation of Yes-associated protein 1 (YAP1). Moreover, we demonstrated that SENP3 modulates de-SUMO modification of YAP1 and SENP3 deletion abolishes the upregulation of YAP1 induced by IL-1β. Most importantly, SENP3 deficiency reduces YAP1 protein level in adipose tissue during obesity. Our results highlight the important role of SENP3 in ATM inflammation and diet and age-induced obesity. [ABSTRACT FROM AUTHOR]

Replication-competent oncolytic adenovirus (TOA2) gene therapy is a recently introduced anti-tumor treatment regimen with superior results. The biodistribution studies of virus vector-based medicine seem more cautious and have been given much attention recently in terms of its quality and safety in preclinical trials. The current study determined the biodistribution and safety of a replication-competent adenovirus in different organs to predict its toxicity threshold. The present study has used TOA2, while biodistribution analysis was performed in human lung carcinoma A549-induced tumor-bearing nude mice model. Intratumoral injection was applied onto tumor-bearing mice with the adenovirus (3×1010 VP per mouse). Mice were sacrificed at the end of the experiment and the organs were dissected. Biodistribution analysis was done with complete hexon gene detection in each organ using quantitative real-time polymerase chain reaction (qRT-PCR). The biodistribution and concentration profiles showed that the TOA2 is well distributed in the entire tumor tissue. After dose 3 at day 11, the concentration of the virus has increased in the tumor tissue from 2240.54 (± 01.69) copies/100 ng genome to 13,120.28 (± 88.21) copies/100 ng genome on the 18th day, which eventually approached 336.45 (± 23.41) copies/100ng genome on the day 36. On the contrary, the concentration of the same decreased in the order of the liver, kidney, spleen, lung, and heart over time but no distributional traces in gonads. But the concentration found decreased dramatically in blood and other organs, while at the end of the experiment no detectable distribution was seen besides tumor tissue. The study confirms that adenovirus-based tumor therapy using conditionally replicating competent oncolytic TOA2 exhibited great efficiency with no toxicity at all. [ABSTRACT FROM AUTHOR]

This article, published in the Chemistry of Natural Compounds journal, explores the use of the OSMAC strategy to enhance the diversity and yield of bioactive compounds from the endophytic fungus Xylaria sp. GDG-102. The fungus was cultivated in a rice medium with monosodium glutamate, resulting in the isolation of nine compounds with antibacterial properties against various bacteria. The article also presents crystal data for one of the compounds, (αR)-3-chloro-α,4-dihydroxybenzeneacetamide, for the first time. The text provides detailed information about the chemical properties of these compounds, including their molecular formulas, physical characteristics, and nuclear magnetic resonance (NMR) spectra. The research received support from the National Natural Science Foundation of China and the Guangxi Natural Science Foundation of China. [Extracted from the article]

Accurately identifying and differentiating the types of injuries in decomposed corpses is a major challenge in forensic identification. Forensic investigations involving decomposed cadavers pose challenges in determining the cause of death. Traditional methods often lack conclusive evidence. However, the implementation of advanced analytical techniques, such as comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOF/MS), shows promise in overcoming these limitations, but the potential in this area remains limited. Therefore, this study aims to bridge this gap by exploring the potential of GC × GC-TOF/MS in the analysis of volatile organic compounds (VOCs) changes within decaying ante- and post-mortem injuries.The research emphasizes the forensic significance of VOCs changes in decomposed cadavers. We used GC × GC-TOF/MS analysis to identify the specific volatile compounds in putrefied corpse tissue samples from mice. The GC × GC-TOF/MS analysis results showed that under winter conditions, PC1 explained 57.16% of the variance, and PC2 explained 25.23% of the variance; while under summer conditions, PC1 explained 71.89% of the variance, and PC2 explained 24.49% of the variance. This demonstrates the potential of GC × GC-TOF/MS in identifying specific VOCs present in tissue samples that can serve as potential biomarkers for distinguishing between antemortem and postmortem injury. GC × GC-TOF/MS analysis revealed distinct VOC patterns in both conditions. Comprehensive use of GC × GC-TOF/MS analysis enhances accuracy in identifying and characterizing ante- and post-mortem injuries in decomposed cadavers. This study can significantly contribute to the field of forensic medicine and improve the accuracy of forensic investigations. [ABSTRACT FROM AUTHOR]

This article explores the development and challenges of forensic medicine in Africa, comparing it to developed countries. It addresses limited resources, funding, and a shortage of trained professionals. The growth of forensic investigation capabilities and the challenges of funding and technology access are discussed. Training and education have improved, but disparities remain. Partnerships with developed countries and international organizations are crucial to bridge the gap. A comprehensive legal framework is important, but disparities exist among African countries. Harmonizing forensic laws would enhance cooperation. The role of forensic medicine in the criminal justice system is examined, emphasizing the need to build trust in forensic evidence. International collaboration and capacity building are key to advancing forensic medicine in Africa. Investments in infrastructure, funding, training, and legal frameworks are required. By leveraging partnerships, Africa can develop its forensic medicine capabilities for a fair and effective criminal justice system. [ABSTRACT FROM AUTHOR]