Erratum: DNA Extraction and Comparison Between Old and Fresh Necrophilic Fly Samples.

This corrects the article 10.3791/66737.

Hypoxia-induced LAMB2-enriched extracellular vesicles promote peritoneal metastasis in gastric cancer via the ROCK1-CAV1-Rab11 axis.

Peritoneal metastasis is one of the most common risk factors contributing to the poor prognosis of gastric cancer. We previously reported that extracellular vesicles from gastric cancer cells could facilitate peritoneal metastasis. However, their impact on gastric cancer-induced peritoneal metastasis under hypoxic conditions remains unclear. This study aims to elucidate how hypoxia-resistant gastric cancer cell-derived extracellular vesicles affect the peritoneal metastasis of normoxic gastric cancer cells. Proteomic analysis revealed elevated levels of Caveolin1 and Laminin ß2 in hypoxia-resistant gastric cancer cells and their corresponding extracellular vesicles. Importantly, Caveolin1 was found to play a central role in mediating Laminin ß2 sorting into extracellular vesicles derived from hypoxia-resistant gastric cancer cells, and subsequently, extracellular vesicle-associated Laminin ß2 promoted peritoneal metastasis in normoxic gastric cancer cells by activating the AKT pathway. Further investigation confirmed that Caveolin1 activation by Rho-related Coiled-coil kinase 1-mediated phosphorylation of Y14 residue is a key factor facilitating Laminin ß2 sorting into extracellular vesicles. Moreover, Y14 phosphorylated- Caveolin1 enhanced Laminin ß2 sorting by activating Rab11. Finally, our study demonstrated that a combined assessment of plasma extracellular vesicle-associated Caveolin1 and extracellular vesicle-associated Laminin ß2 could provide an accurate predictive tool for peritoneal metastasis occurrence in gastric cancer.

Investigating the impact of STING pathway activation on breast cancer treatment outcomes: development and validation of a prognostic model.

Introduction: Breast cancer (BRCA) is a significant cause of cancer-associated mortality across the globe. Current therapeutic approaches face challenges such as drug resistance and metastasis. Immune signaling is triggered by chromosomal instability (CIN) generates misplaced DNA structures that activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, triggering. Studies have linked STING activation to BRCA treatment. Methods: The bulk RNA-seq data for patients with BRCA were collected from the TCGA-BRCA cohort, GSE20685, and GSE96058 cohorts. STING pathway-related genes (SRGs) were obtained from the Reactome database. Differentially expressed genes were analyzed using the limma package. Immune cell infiltration was analyzed using the IOBR package. Gene Ontology biological processes, Kyoto Encyclopedia of Genes and Genomes pathways, and cancer hallmark pathways were analyzed using the MSigDB database. Prognostic models were prepared using the least absolute shrinkage and selection operator and multiple-factor Cox regression analysis. Single-cell analysis was performed using the Seurat and SCP pipeline. Results: The expression patterns and clinical relevance of SRGs were analyzed in patients with BRCA. Transcriptional differences in the SRGs were observed between normal and tumorous tissues, with global down-regulated STING1 and up-regulated TBK1 in BRCA tissue. Tumor tissues were classified through consensus clustering analysis into two distinct groups, with differences in clinical characteristics and immune infiltration. A prognostic model related to the differences in STING pathway activity-high prognostic stratification potency-was developed and validated. Correlation analysis revealed suppressed overall immune activation in patients with BRCA having higher risk scores. Gemcitabine had a more favorable outcome in the low-risk group. The activity of the prognostic model at the single-cell level was confirmed through single-cell analysis, particularly in CD8 T cells and intratumor natural killer cells. Conclusion: A STING pathway-related prognostic model developed and validated and the model could accurately predict BRCA patient outcomes. These findings have important implications for the personalized treatment and management of patients with BRCA.

Effect of Raloxifene Treatment on Apolipoproteins and Lipoprotein(a) Concentrations in Postmenopausal Women: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIM: Although various randomized controlled trials (RCTs) have evaluated the effect of raloxifene on apolipoproteins and lipoprotein(a) concentrations in postmenopausal women, the results have been inconsistent and inconclusive. Therefore, we conducted this meta-analysis of RCTs to investigate the effect of raloxifene administration on apolipoproteins and lipoprotein(a) [Lp(a)] concentrations in postmenopausal women. METHODS: Two independent researchers systematically searched the scientific literature (including PubMed/Medline, Scopus, Web of Science, and EMBASE) for English-language randomized controlled trials (RCTs) published up to June 2024. We included RCTs reporting the impact of raloxifene on apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and Lp(a) levels in postmenopausal women. The primary outcome of interest was change in Lp(a), and the secondary outcomes were changes in ApoA-I and ApoB. FINDINGS: The present meta-analysis incorporated 12 publications with 14 RCT arms. The comprehensive outcomes derived from the random-effects model revealed a statistically significant increase in ApoA-I (WMD: 6.06 mg/dL, 95% CI: 4.38, 7.75, P < 0.001) and decrease in ApoB concentrations (WMD: -8.48 mg/dL, 95% CI: -10.60, -6.36, P < 0.001) and Lp(a) (WMD: -3.02 mg/dL, 95% CI: -4.83, -1.21, P < 0.001) following the administration of raloxifene in postmenopausal women. In the subgroup analyses, the increase in ApoA-I and the decrease in ApoB and Lp(a) levels were greater in RCTs with a mean participant age of ≥60 years and a duration of ≤12 weeks. IMPLICATIONS: The current meta-analysis of RCTs demonstrates that treatment with raloxifene reduces ApoB and Lp(a) levels while increasing ApoA-I levels in postmenopausal women. Since these effects on lipid components are associated with a reduced risk of cardiovascular disease (CVD), raloxifene could be a suitable therapy for postmenopausal women who are at an increased risk of CVD and have other medical indications for raloxifene administration.

Morphological and phylogenetic analyses reveal two new Alternaria species (Pleosporales, Pleosporaceae) in Alternaria section from Cucurbitaceae plants in China.

Alternaria species are commonly found as saprophytes, endophytes and plant pathogens. During a survey of small-spored Alternaria in China, two new species were discovered from Cucurbitaceae plants collected in Hubei and Sichuan provinces. This study identified two new species of Alternaria using seven genes (ITS, GAPDH, TEF1, RPB2, Alt a 1, EndoPG, and OPA10-2) for phylogenetic analyses and morphological characteristics. The two new species A.jingzhouensis and A.momordicae were described and illustrated. Alternariajingzhouensis sp. nov., associated with Citrulluslanatus, is characterized by producing muriform, ellipsoidal, flask-shaped, rostrate, and beaked conidia. It differs from A.koreana, A.ovoidea, and A.baoshanensis by bearing conidia in a simple conidiogenous locus with occasionally longer beaks in a chain, and from A.momordicae sp. nov. by having shorter beaks. Alternariamomordicae sp. nov. from Momordicacharantia was distinct from A.koreana, A.ovoidea, and A.baoshanensis by producing muriform, long ellipsoid or ovoid to obclavate, sometimes inverted club-shaped conidia on a single conidiogenous locus with a wider body and longer beak in a chain, and distinct from A.jingzhouensis sp. nov. by a longer beak conidia. These two species were clearly distinguished from other species in the section Alternaria based on DNA based phylogeny and morphological characteristics. The morphological features were discussed and compared to relevant species in the present paper.

Multi-Objective Optimization of Laser Cleaning Quality of Q390 Steel Rust Layer Based on Response Surface Methodology and NSGA-II Algorithm.

To improve the laser cleaning surface quality of rust layers in Q390 steel, a method of determining the optimal cleaning parameters is proposed that is based on response surface methodology and the second-generation non-dominated sorting genetic algorithm (NSGA-II). It involves constructing a mathematical model of the input variables (laser power, cleaning speed, scanning speed, and repetition frequency) and the objective values (surface oxygen content, rust layer removal rate, and surface roughness). The effects of the laser cleaning process parameters on the cleaning surface quality were analyzed in our study, and accordingly, NSGA-II was used to determine the optimal process parameters. The results indicate that the optimal process parameters are as follows: a laser power of 44.99 W, cleaning speed of 174.01 mm/min, scanning speed of 3852.03 mm/s, and repetition frequency of 116 kHz. With these parameters, the surface corrosion is effectively removed, revealing a distinct metal luster and meeting the standard for surface treatment before welding.

Two novel species and a new host record of Alternaria (Pleosporales, Pleosporaceae) from sunflower (Compositae) in Myanmar.

Sunflower (Helianthusannuus L.) is a widely cultivated, fast-growing crop known for its seeds and oil, with substantial ecological and economic importance globally. However, it faces challenges from leaf diseases caused by Alternaria species, which threaten its yield. Three small-spored Alternaria species were isolated from leaf spot and blight symptoms on sunflower in Myanmar. All the species were determined based on morphological characterization and a multi-locus phylogenetic assessment of seven genes, including the internal transcribed spacer of rDNA region (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RNA polymerase second largest subunit (RPB2), translation elongation factor 1-α (TEF1), Alternaria major allergen gene (Alt a 1), endopolygalacturonase gene (EndoPG), and an anonymous gene region (OPA10-2). The results introduced two new Alternaria species, A.myanmarensis sp. nov. and A.yamethinensis sp. nov., and a known species of A.burnsii, firstly reported from sunflower.

Diagnostic, predictive and prognostic molecular biomarkers in clear cell renal cell carcinoma: A retrospective study.

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of kidney cancer. Many patients are diagnosed at advanced stages, making early detection crucial. Unfortunately, there are currently no noninvasive tests for ccRCC, emphasizing the need for new biomarkers. Additionally, ccRCC often develops resistance to treatments like radiotherapy and chemotherapy. Identifying biomarkers that predict treatment outcomes is vital for personalized care. The integration of artificial intelligence (AI), multi-omics analysis, and computational biology holds promise in bolstering detection precision and resilience, opening avenues for future investigations. The amalgamation of radiogenomics and biomaterial-basedimmunomodulation signifies a revolutionary breakthrough in diagnostic medicine. This review summarizes existing literature and highlights emerging biomarkers that enhance diagnostic, predictive, and prognostic capabilities for ccRCC, setting the stage for future clinical research.

DNA Extraction and Comparison between Old and Fresh Necrophilic Fly Samples.

A total of five samples of Chrysomya megacephala samples - three fresh samples, one sample stored in alcohol for 2 years, and one sample stored in dry sealed storage for 2 years protected from light only - were selected to investigate whether a blood DNA extraction kit could extract DNA from necrophilous flies and to determine whether alcohol could prolong the preservation of necrophilous flies' DNA. First, the blood DNA extraction kit was used to extract DNA from their thorax tissues. Then, the DNA purity and concentration were examined using a microplate reader and a fluorometer. Finally, PCR amplification and electrophoresis of the extracted DNA were done with necrophilic fly-specific primers located in the mitochondrial CO I gene sequence. The results showed that the DNA purity of all samples was greater than 2.0. The DNA concentration was observed to be of the following order: fresh samples > alcohol-preserved old samples > untreated, old samples. All samples had specific electrophoretic bands after PCR amplification. In conclusion, a blood DNA extraction kit can be used to extract DNA from necrophilic flies successfully, and the DNA concentration of fresh fly samples is greater than that of old fly samples. The flies can be stored in alcohol for a long time.

Na3[Al2B6P4O22(OH)3](H2O)6 and Na3[Al2BP2O11](H2O)0.5: Two Remarkable Complex Aluminum Borophosphates.

Two remarkable aluminum borophosphates (AlBPOs), namely, Na3[Al2B6P4O22(OH)3](H2O)6 (denoted as ABPO1) and Na3[Al2BP2O11](H2O)0.5 (denoted as ABPO2), have been designed and prepared by low-temperature flux syntheses. The exceptional open framework structure of ABPO1 is formed by a unique microanionic network [Al2B6P4O22(OH)3]n3-, which contains three types of 8-, 12-, and 16-membered ring (MR) tunnels. Interestingly, these tunnels are featured by a type of super-nanocage as large as ∼1.753 nm × 1.753 nm × 1.753 nm, which is the first example of AlBPOs containing extra-large cages. Importantly, it was found that Na+ can be partially exchanged by K+, Sr2+, Cd2+, and Ni2+, which means that it is a potential ionic exchanger for removing radionuclides and toxic cations. The structure of ABPO2 features a unique 2D anionic AlBPO layer composed of corner-sharing AlO6 octahedra and AlO4, BO4, and PO4 tetrahedra. To the best of our knowledge, this is the first example of both AlO6 octahedra and AlO4 tetrahedra being contained in the structure. 9-MRs can be observed along the b-axis. Herein, the syntheses and topological structures of ABPO1 and ABPO2 as well as elemental analysis, thermal stability, infrared spectroscopy, UV-vis diffuse reflectance, structural properties, and ionic exchange properties are also discussed.

Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies.

Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy.

A Stochastic Model Based on Optimal Satellite Subset Selection Strategy for Smartphone Pseudorange Relative Positioning.

In order to overcome the limitations of traditional stochastic models for smartphones, we introduce a double-difference code pseudorange residual (DDPR)-dependent stochastic model based on an optimal satellite subset, with the goal of mitigating the constraints imposed by the quality of GNSS observations in smartphones on the accuracy and reliability of phone-based GNSS positioning. In our methodology, the satellite selection process involved considering the integrated carrier-to-noise density ratio (C/N0) index of both the reference station and the smartphone, enabling us to construct a satellite subset characterized by superior observation quality. Furthermore, by leveraging the optimal subset of satellites and incorporating the C/N0-dependent stochastic model, we could determine the approximate location of the terminal through pseudorange differential positioning. Subsequently, we estimated the DDPRs for all satellites and utilized these values as prior information to build a stochastic model of the observations. Our findings indicate that in occluded environments, the DDPR-dependent stochastic model significantly enhances positioning accuracy for both the Huawei Mate40 and P40 terminals compared to the C/N0-dependent model. Numerically, the improvements in the north (N), east (E), and up (U) directions were approximately 30%, 32%, and 34% for the Mate40, and 26%, 33%, and 24% for the P40 terminal. This suggests that the proposed DDPR-dependent stochastic model effectively identifies and mitigates large gross error signals caused by multipath and non-line-of-sight (NLOS) signals, thereby assigning lower weights to these problematic observations and ultimately enhancing positioning accuracy. Moreover, the weighting method involves minimal computations and is straightforward to implement, making it particularly suitable for GNSS positioning applications on smartphones in complex urban environments.

Association between white blood cells and ultra-early hematoma growth in patients with spontaneous intracerebral hemorrhage.

Background: Ultra-early inflammatory reaction after spontaneous intracerebral hemorrhage (sICH) plays an important role in the coagulation process and is closely related to early hematoma expansion. However, the relationship between ultra-early hematoma growth (uHG) and ultra-early inflammatory reaction remains unknown. Objective: To evaluate the association between ultra-early inflammatory indicators and uHG in patients with sICH. Methods: We retrospectively included 225 patients with acute sICH who were divided into the uHG ≤4.7 ml/h group and the uHG >4.7 ml/h group, respectively. The uHG was defined as hematoma volume (milliliter) at the primary computed tomography (CT) scan divided by time (hour) from onset to the performance of primary CT within 6 h after onset. The white blood cells (WBC), blood hypersensitive C-reactive protein, National Institutes of Health Stroke Scale (NIHSS) score and other related baseline data were collected and compared between the two groups. The multivariate regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the independent risk factors for uHG >4.7 ml/h. Results: NIHSS score and WBC were independent risk factors for uHG in patients with acute sICH (OR 1.188, 95% CI: 1.111-1.271, p < 0.001; OR 1.151, 95% CI: 1.018-1.300, p = 0.024; respectively). The area under curve of ROC for WBC and NIHSS score was 0.658 and 0.754, respectively (all p < 0.001), while the WBC combined with NIHSS score was 0.773 (p < 0.001). Conclusion: WBC count within 6h after onset might be an independent risk factor for the increase of uHG in patients with sICH.

First Report of Tobacco Leaf Tip Blight Caused by Alternaria gossypina in China.

Tobacco (Nicotiana tabacum L.) belongs to the family Solanaceae, an economically significant crop (Zhou et al. 2023). Twelve samples with leaf spots were collected in Keti Village, Changshun County, Zunyi City, Guizhou province, China in 2022. Twenty-five percent of the samples had dry lesions near the leaf tip which resulted leaf tip blight after development. Fungi were isolated by a previous method (Wei et al. 2022). Six Alternaria strains were obtained and preserved in the Fungal Herbarium of Yangtze University (YZU), Jingzhou, Hubei, China. Among them, one strain YZU 221477 showed distinct cultural characteristics out of five A. alternata strains, which was again determined by growing on potato dextrose agar (PDA) at 25°C for 7 days in dark to evaluate. The colonies (60 mm in diameter) were white cottony in the center surrounded by vinaceous purple. To examine the morphology, mycelia were inoculated onto potato carrot agar (PCA) at 22°C, following an 8 h light/16 h dark photoperiod (Simmons 2007). Conidia were obclavate or ovoid, normally 3-5 conidial units per chain, 20-38 × 10-16.5 µm, 3 to 5 transverse septa, beakless or a short beak (4-30 µm). The observation results were consistent with those of A. gossypina (Zhang 2003). Total genomic DNA was extracted using the CTAB method and seven gene regions including internal transcribed spacer of rDNA (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), translation elongation factor 1 alpha (TEF1), RNA polymerase second largest subunit (RPB2), Alternaria major allergen gene (Alt a 1), endopolygalacturonase (EndoPG) and an anonymous gene region (OPA10-2) were amplified with ITS5/ITS4, gpd1/gpd2, EF1-728F/EF1-986R, RPB2-5F/RPB2-7cR, Alt-for/Alt-rev, PG3/PG2b and OPA10-2L/OPA10-2R primers, respectively. All sequences were deposited in GenBank (ITS: OR710806; GAPDH: PP057862; TEF1: PP158601; RPB2: PP057863; Alt a 1: PP057865; EndoPG: PP057861; OPA10-2: PP057864). Combining with relevant sequences retrieved from the NCBI database were used for the phylogenetic analysis. Maximum Likelihood (ML) tree was constructed with RAxML v.7.2.8 employing GTRCAT model using 1000 bootstrap (BS) replicates to assess statistical support. The results indicated that the present strain grouped with A. gossypina (type strain of CBS 104.32) supported with 73% bootstrap values, also having a support of 0.83 Bayesian posterior probabilities values. Based on morphology and molecular evidence, the strain YZU 221477 is identified as Alternaria gossypina. Pathogenicity was examined to fulfill Koch's postulates. Mycelial plugs (6 mm diameter) of the present strain and A. alternata cultivated on PDA were taken from the margin and inoculated onto viable tobacco leaves (Cultivar: Yunyan 87, n=3) growing forty days, while controls were inoculated with sterile PDA. The assay was conducted three times. The plants were maintained at 25°C with humidity levels over 85% in a greenhouse. Leaves were evaluated after 7 days, necrotic spots encircled by yellow halos were on both inoculums, except controls. Pathogen re-isolation confirmed that it was the same as inoculated fungus based on morphology. A. gossypina was firstly found on cotton (Hopkins 1931), late reported to induce disease on Minneola, Nopalea, Hibiscus, Citrus, Solanum and Ageratina. To our knowledge, this is the first report of A. gossypina causing tobacco leaf tip blight in China, and it also provides a basis for controlling of tobacco leaf tip blight.

First report of leaf blight caused by Stemphylium lycopersici on Salvia splendens in China.

Salvia splendens is a popular ornamental plant in China with extensive potentials, including value in traditional Chinese medicine and in environmental restoration function (Li et al. 2008). In September 2019, leaf blight disease was observed on road side plants of S. splendens in Bayi park, Nanchang city, Jiangxi province, China. The typical symptoms appeared as irregular necrotic spots or leaf blight, accompanied by extensive scorch necrosis or ultimately defoliation. Small segments cut from diseased leaves were surface sterilized in a 2% sodium hypochlorite solution for 2 min and rinsed three times with sterile distilled water. Then, the samples were placed on potato dextrose agar (PDA) plates incubated at 25°C in darkness. Pure cultures were obtained by the hyphal tip method. Morphologically, all 11 colonies were identical to each other on PDA. Two strains, YZU 191468 and YZU 191481, were selected for further study and deposited in the Fungal Herbarium of Yangtze University (YZU), Jingzhou, Hubei, China. The 7-day-old colonies were circular, 53 to 56 mm in diameter, and consisted of white mycelium with a buff margin, and were cinnamon colored in the center of the reverse side. To examine conidial morphology, the mycelium was transferred onto potato carrot agar (PCA) and incubated at 23°C with a period of 8 h light/16 h dark for 7 days. Conidia were normally solitary or two in a chain, ellipsoid or long ellipsoid, beakless, 10 to 23×30 to 60 µm in size (n=50). Based on morphology, the isolates were consistent with Stemphylium lycopersici (Yamamoto 1960). To confirm the identification, genomic DNA was extracted from both isolates and used to amplify the internal transcribed spacer rDNA region (ITS), glyceraldehydes-3-phosphate dehydrogenase (GAPDH) and calmodulin (CAL) genes with primer pairs ITS5/ITS4, gpd1/gpd2, and CALDF1/CALDR2, respectively (Woudenberg et al. 2017). Sequences were deposited in GenBank with accession numbers OP564983 and OP564984 (ITS), OP892529 and OP892530 (GAPDH), OP584970 and OP584971 (CAL). A neighbor-joining tree was constructed with Mega 7.0 based on the combined dataset with 1,000 bootstrap replicates. The resulting phylogenetic tree showed that the strains from S. splendens clustered with S. lycopersici (CBS 122639 and CBS 124980) supported with 100% bootstrap values. The molecular analyses confirmed that the species causing leaf blight symptoms was S. lycopersici. To test pathogenicity, healthy leaves of S. splendens were surface sterilized and inoculated by mycelium blocks (6 mm in diameter) and spore suspension (1×106 spore/mL) of representative strains YZU 191468 and YZU 191481, respectively. Controls were inoculated with blocks of PDA and sterile water. Each strain was inoculated on three leaves of a plant. One clean plant was used as control. The test was replicated three times. After inoculation, the plants were covered with plastic bags and incubated in a greenhouse (25℃, 80 % relative humidity, 8 h light/16 h dark). After 5 days, the inoculated leaves exhibited dark brown spots with white mycelium, followed by withering of necrotic tissues. There were no symptoms observed on the controls. The fungal isolates inoculated leaves had the same morphological characteristics as the strains used for inoculation. S. lycopersici has been found on eggplant and Zinnia elegans in China (He et al. 2019; Yang et al. 2017). To the best of our knowledge, this is the first report of S. lycopersici causing leaf blight on S. splendens in China. This finding offers a new reference for the management and control of S. splendens leaf diseases in China.

Cardiovascular safety of febuxostat versus allopurinol among the Asian patients with or without gout: A systematic review and meta-analysis.

The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.

AMPK/MTOR/TP53 Signaling Pathway Regulation by Calcitonin Gene-Related Peptide Reduces Oxygen-Induced Lung Damage in Neonatal Rats through Autophagy Promotion.

Our previous studies indicated that calcitonin gene-related peptide (CGRP) alleviates hyperoxia-induced lung injury and suggested the possible involvement of autophagy in this process. Herein, we aimed to further explore the potential involvement of tumor protein p53 (TP53) and autophagy in the mode of action of CGRP against hyperoxia-induced lung injury in vitro and in vivo. The study conducted tests on type II alveolar epithelial cells (AECII) and rats that were subjected to hyperoxia treatment or combined treatment of hyperoxia with CGRP, CGRP inhibitor, rapamycin (an autophagy agonist), 3-methyladenine (3-MA, an autophagy inhibitor), TP53 silencing/inhibitor (pifithrin-α), or expression vector/activator (PRIMA-1 (2,2-bis(hydroxymethyl)-3-quinuclidinone)) and their corresponding controls. We found that oxidative stress, apoptosis, and autophagy were all increased by hyperoxia treatment in vitro. However, treating AECII cells with CGRP reversed hyperoxia-induced oxidative stress and apoptosis but further promoted autophagy. In addition, the combined treatment with rapamycin or TP53 silencing with CGRP promoted the effect of CGRP, while contrary results were obtained with combined therapy with 3-MA or TP53 overexpression. In vivo, the number of hyperoxia-induced autophagosomes was promoted in the lung tissue of neonatal rats. Furthermore, hyperoxia increased the expression levels of AMP-activated protein kinase (AMPK) alpha 1 (also known as protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1)) but inhibited TP53 and mechanistic target of rapamycin (MTOR); these expression trends were regulated by CGRP treatment. In conclusion, we showed that CGRP can attenuate hyperoxia-induced lung injury in neonatal rats by enhancing autophagy and regulating the TP53/AMPK/MTOR crosstalk axis.

Effectiveness of S100 calcium-binding protein A12 combined with modified early warning score in the clinical diagnosis of adult community-acquired pneumonia.

Background: Recent studies have found that S100 serum calcium-binding protein A12 (S100A12) has important significance in the expression of acute infectious diseases, and has high clinical application value in the differential diagnosis, prognosis and other aspects of acute infectious diseases. The accuracy of modified early warning score (MEWS) in evaluating the disease risk level of critically ill patients is comparable to Acute Physiology and Chronic Health Evaluation (APACHE II). Methods: Based on MEWS, 108 adult community-acquired pneumonia (CAP) patients were divided into the low-risk, intermediate-risk, and high-risk groups. The differences in invasive mechanical ventilation rate and mortality rate among each group were compared, and the differences of S100A12 in different levels of MEWS scores were compared through one-way analysis of variance. According to the prognosis after 30 days, the patients were divided into the death group and the survival group. Univariate and multivariate logistic regression analyses were used to study the influencing and independent factors of 30-day death in CAP patients. The sensitivity and specificity of S100A12, procalcitonin (PCT), and MEWS scores in predicting the 30-day death in CAP patients were evaluated using the receiver operating characteristic (ROC) curve, as well as the area under each indicator curve. Results: The serum S100A12 concentration increased with the increase in the MEWS stratification, and the mechanical ventilation and mortality rates also increased significantly. Univariate and multivariate analyses were used to explore the factors influencing mortality in adult CAP patients after 30 days. The receiver-operating characteristics curve was used to analyze the sensitivity, specificity, and area under the curves of serum S100A12, PCT, and MEWS in predicting mortality in CAP patients after 30 days. Conclusions: The serum S100A12, PCT, and MEWS can effectively predict the mortality risk in adult CAP patients after 30 days. Serum S100A12 combined with MEWS has a high clinical application value in evaluating the severity and prognosis of adult CAP.

Nesfatin-1 alleviates hyperoxia-induced bronchopulmonary dysplasia (BPD) via the nuclear factor-κB (NF-κB) p65 signaling pathway.

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in newborns, which severely influences the health of infants and lacks effective clinical treatment strategies. The pathogenesis of BPD is correlated to enhanced inflammation and activated oxidative stress (OS). The application of antioxidants and anti-inflammatory treatment could be hot spots for BPD treatment. Nesfatin-1, a peptide with a suppressive property against inflammation, was tested herein for its potential therapeutic value in BPD. Neonatal SD rats were stimulated with hyperoxia, followed by being intraperitoneally administered with 20 µg/kg/day Nesfatin-1 for 2 weeks. Decreased RAC value in lung tissues, increased wet weight/dry weight (W/D) pulmonary ratio and bronchoalveolar lavage fluid (BALF) proteins, elevated cytokine release in BALF, increased malondialdehyde (MDA) content, and declined superoxide dismutase (SOD) activity were observed in BPD rats, all of which were sharply mitigated by Nesfatin-1. Rat epithelial type II cells (AECIIs) were handled with hyperoxia, and then cultured with 1 and 10 nM Nesfatin-1. Reduced cell viability, elevated lactate dehydrogenase production, elevated cytokine secretion, elevated MDA content, and decreased SOD activity were observed in hyperoxia-handled AECIIs, all of which were markedly alleviated by Nesfatin-1. Furthermore, activated nuclear factor-κB (NF-κB) signaling observed in both BPD rats and hyperoxia-handled AECIIs were notably repressed by Nesfatin-1. Collectively, Nesfatin-1 alleviated hyperoxia-triggered BPD by repressing inflammation and OS via the NF-κB signaling pathway.

Acid rain reduced soil carbon emissions and increased the temperature sensitivity of soil respiration: A comprehensive meta-analysis.

Soil respiration the second-largest carbon flux in terrestrial ecosystems, has been extensively studied across a wide range of biomes. Surprisingly, no consensus exist on how acid rain (AR) impacts the spatiotemporal pattern of soil respiration. Therefore, we conducted a meta-analysis using 318 soil respiration and 263 soil respiration temperature sensitivity (Q10) data points obtained from 48 studies to assess the impact of AR on soil respiration components and their Q10. The results showed that AR reduced soil total respiration (Rt) and soil autotrophic respiration (Ra) by 7.41 % and 20.75 %, respectively. As the H+ input increased, the response rates of Ra to AR (RR-Ra) and soil heterotrophic respiration (Rh) to AR (RR-Rh) decreased and increased, respectively. With increased AR duration, the RR-Ra increased, whereas the RR-Rh did not change. AR increased the Q10 of Rt (Rt-Q10) and Rh (Rh-Q10) by 1.92 % and 9.47 %, respectively, and decreased the Q10 of Ra (Ra-Q10) by 2.77 %. Increased mean annual temperature, mean annual precipitation, and initial soil organic carbon increased the response rate of Ra-Q10 to AR (RR-Ra-Q10) and decreased the response rate of Rh-Q10 to AR (RR-Rh-Q10). However, as the AR frequency and initial soil pH increased, both RR-Ra-Q10 and RR-Rh-Q10 also increased. In summary, AR decreased Rt but increased Q10, likely due to soil acidification (soil pH decreased by 7.84 %), reducing plant root biomass (decreased by 5.67 %) and soil microbial biomass (decreased by 5.67 %), changing microbial communities (increased fungi to bacteria ratio of 15.91 %), and regulated by climate, vegetation, soil and AR regimes. To the best of our knowledge, this is the first study to reveal the large-scale, varied response patterns of soil respiration components and their Q10 to AR. It highlights the importance of applying the reductionism theory in soil respiration research to enhance our understanding of soil carbon cycling processes with in the context of global climate change.