Low H2O2 consumption Fenton-like catalysts for pollutant cleavage based on the construction of a dual reaction center.

High energy consumption has seriously hindered the development of Fenton-like reactions for the removal of refractory organic pollutants in water. To solve this problem, we designed a novel Fenton-like catalyst (Cu-PAN3) by coprecipitation and carbon thermal reduction. The catalyst exhibits excellent Fenton-like catalytic activity and stability for the degradation of various pollutants with low H2O2 consumption. The experimental results indicate that the dual reaction centers (DRCs) are composed of Cu-N-C and Cu-O-C bridges between copper and graphene-like carbon, which form electron-poor/rich centers on the catalyst surface. H2O2 is mainly reduced at electron-rich Cu centers to free radicals for pollutant degradation. Meanwhile, pollutants can be oxidized by donating electrons to the electron-poor C centers of the catalyst, which inhibits the ineffective decomposition of H2O2 at the electron-poor centers. This therefore significantly reduces the consumption of H2O2 and reduces energy consumption.

Mechanism insights into the histopathological changes of polypropylene microplastics induced gut and liver in zebrafish.

Microplastics (MPs), emerging as significant pollutants, have been consistently detected in aquatic environments, with the Yangtze River experiencing a particularly severe level of microplastic pollution, exceeding all other watersheds in China. Polypropylene (PP), the plastic most abundantly found in the middle and lower reaches of the Yangtze River Basin, has less comprehensive research results into its toxic effects. Consequently, the present investigation employed zebrafish as a model organism to delve into the toxicological impacts of polypropylene microplastics (PP-MPs) with a diameter of 5 µm across varying concentrations (300 mg/L and 600 mg/L). Using histopathological, microbiota profiling, and transcriptomic approaches, we systematically evaluated the impact of PP-MPs exposure on the intestine and liver of zebrafish. Histopathological analysis revealed that exposure to PP-MPs resulted in thinner intestinal walls, damaged intestinal mucosa, and hepatic cellular damage. Intestinal microbiota profiling demonstrated that, the richness, uniformity, diversity, and homogeneity of gut microbes significantly increased after the PP-MPs exposure at high concentration. These alterations were accompanied by shifts in the relative abundance of microbiota associated with intestinal pathologies, suggesting a profound impact on the intestinal microbial community structure. Concurrently, hepatic transcriptome analysis and RT-qPCR indicated that the downregulation of pathways and genes associated with cell proliferation regulation and DNA damage repair mechanisms contributed to hepatic cellular damage, ultimately exerting adverse effects on the liver. Correlation analysis between the intestinal microbiota and liver transcriptome profiles further highlighted significant associations between intestinal microbiota and the downregulated hepatic pathways. Collectively, these results provide novel insights into the subacute toxicological mechanisms of PP-MPs in aquatic organisms and highlight the need for further research on the ecological and health risks associated with PP-MPs pollution.

Circ_0005615 enhances multiple myeloma progression through interaction with EIF4A3 to regulate MAP3K4 m6A modification mediated by ALKBH5.

BACKGROUND: Circular RNAs (circRNAs) are associated with development and progression of multiple myeloma (MM). However, the role and mechanism of circ_0005615 in MM have not been elucidated. METHODS: Circ_0005615 was determined by GEO database. quantitative RT-PCR was performed to confirm the expression of circ_0005615 in peripheral blood of MM patients and MM cells. The roles of circ_0005615 in MM were analyzed using CCK8, transwell invasion, cell apoptosis and tumor xenograft experiments. Bioinformatics tools, RIP and RNA pull down assays were conducted to explore the downstream of circ_0005615. Furthermore, the mechanism was investigated by quantitative RT-PCR, western blot, dot blot and meRIP-PCR assays. RESULTS: Circ_0005615 was upregulated in MM. Overexpression of circ_0005615 promoted cell viability and invasion, and suppressed apoptosis in vitro, which were opposite when circ_0005615 was knockdowned. Mechanistically, EIF4A3, a RNA-binding protein (RBP), could directly bind to circ_0005615 and ALKBH5, where ALKBH5 could directly combine with MAP3K4, forming a circ_0005615- EIF4A3-ALKBH5-MAP3K4 module. Furthermore, circ_0005615 overexpression increased m6A methylation of MAP3K4 by inhibiting ALKBH5, leading to decreased MAP3K4. Further functional experiments indicated that ALKBH5 overexpression weakened the promoting roles of circ_0005615 overexpression in MAP3K4 m6A methylation and tumor progression in MM. The above functions and mechanism were also verified in vivo. CONCLUSIONS: Elevated circ_0005615 decreased MAP3K4 mediated by ALKBH5 through interacting with EIF4A3, thereby accelerating MM progression. Circ_0005615 might be a promising biomarker and target of MM.

Identification of ferroptosis-related key genes associated with immune infiltration in sepsis by bioinformatics analysis and in vivo validation.

OBJECTIVES: Sepsis is a life-threatening infectious disease in which an immune inflammatory response is triggered. The potential effect of ferroptosis-related genes (FRGs) in inflammation of sepsis remained unclear. We focused on identifying and validating core FRGs and their association with immune infiltration in blood from currently all patients with sepsis. METHODS: All current raw data of septic blood were obtained from Gene Expression Omnibus. After removing the batch effect merging into a complete dataset and obtaining Diferentially expressed genes (DEGs). Common cross-talk genes were identified from DEGs and FRGs. WGCNA, GO, KEGG, PPI, GESA, ROC curves, and LASSO regression analysis were performed to indentify and validate key genes based on external septic datasets. Infiltrated immune cells in 2 hub genes (MAPK14 and ACSL4) were conducted using CIBERSORT algorithm and Spearman correlation analysis. Further, the expressions of 2 core FRGs were verified in the LPS-induced ALI and cardiac injury sepsis mice. RESULTS: MAPK14 and ACSL4 were identified, mostly enriched in T cell infiltration through NOD-like receptor signaling pathway according to the high or low 2 hub genes expression. The upregulated 2 ferroptosis-related genes were validated in LPS-induced ALI and cardiac injury mice, accompanied by upregulation of the NLRP3 pathway. CONCLUSION: MAPK14 and ACSL4 could become robustly reliable and promising biomarkers for sepsis by regulating ferroptosis through the NLRP3 pathway, which is mainly associated with T-cell infiltration.

Regulation of nitrite-dependent anaerobic methane oxidation bacteria by available phosphorus and microbial communities in lake sediments of cold and arid regions.

As global anthropogenic nitrogen inputs continue to rise, nitrite-dependent anaerobic methane oxidation (N-DAMO) plays an increasingly significant role in CH4 consumption in lake sediments. However, there is a dearth of knowledge regarding the effects of anthropogenic activities on N-DAMO bacteria in lakes in the cold and arid regions. Sediment samples were collected from five sampling areas in Lake Ulansuhai at varying depth ranges (0-20, 20-40, and 40-60 cm). The ecological characterization and niche differentiation of N-DAMO bacteria were investigated using bioinformatics and molecular biology techniques. Quantitative PCR confirmed the presence of N-DAMO bacteria in Lake Ulansuhai sediments, with 16S rRNA gene abundances ranging from 1.72 × 104 to 5.75 × 105 copies·g-1 dry sediment. The highest abundance was observed at the farmland drainage outlet with high available phosphorus (AP). Anthropogenic disturbances led to a significant increase in the abundance of N-DAMO bacteria, though their diversity remained unaffected. The heterogeneous community of N-DAMO bacteria was affected by interactions among various environmental characteristics, with AP and oxidation-reduction potential identified as the key drivers in this study. The Mantel test indicated that the N-DAMO bacterial abundance was more readily influenced by the presence of the denitrification genes (nirS and nirK). Network analysis revealed that the community structure of N-DAMO bacteria generated numerous links (especially positive links) with microbial taxa involved in carbon and nitrogen cycles, such as methanogens and nitrifying bacteria. In summary, N-DAMO bacteria exhibited sensitivity to both environmental and microbial factors under various human disturbances. This study provides valuable insights into the distribution patterns of N-DAMO bacteria and their roles in nitrogen and carbon cycling within lake ecosystems.

Unveiling the role of ferrous ion in driving microalgae granulation from salt-tolerant strains for mariculture wastewater treatment.

Development of microalgal-bacterial granular sludge (MBGS) from saline-adapted microalgae is a promising approach for efficient mariculture wastewater treatment, whereas the elusive mechanisms governing granulation have impeded its widespread adoption. In this study, spherical and regular MBGS were successfully developed from mixed culture of pure Spirulina platensis and Chlorella sp. GY-H4 at 10 mg/L Fe2+ concentration. The addition of Fe2+ was proven to induce the formation of Fe-precipitates which served as nucleation sites for microbial attachment and granulation initiation. Additionally, Fe2+ increased the prevalence of exopolysaccharide-producing cyanobacteria, i.e. Synechocystis and Leptolyngbya, facilitating microbial cell adhesion. Furthermore, it stimulated the secretion of extracellular proteins (particularly tryptophan and aromatic proteins), which acted as structural backbone for the development of spherical granule form microalgal flocs. Lastly, it fostered the accumulation of exogenous heterotrophic functional genera, resulting in the efficient removal of DOC (98 %), PO43--P (98 %) and NH4+-N (87 %). Nevertheless, inadequate Fe2+ hindered microalgal floc transformation into granules, excessive Fe2+ expanded the anaerobic zone within the granules, almost halved protein content in the TB-EPS, and inhibited the functional genes expression, ultimately leading to an irregular granular morphology and diminished nutrient removal. This research provides valuable insights into the mechanisms by which Fe2+ promotes the granulation of salt-tolerant microalgae, offering guidance for the establishment and stable operation of MBGS systems in mariculture wastewater treatment.

Association between computed tomography-quantified respiratory muscles and chronic obstructive pulmonary disease: a retrospective study.

BACKGROUND: This study examined the association between chest muscles and chronic obstructive pulmonary disease (COPD) and the relationship between chest muscle areas and acute exacerbations of COPD (AECOPD). METHODS: There were 168 subjects in the non-COPD group and 101 patients in the COPD group. The respiratory and accessory respiratory muscle areas were obtained using 3D Slicer software to analysis the imaging of  computed tomography (CT). Univariate and multivariate Poisson regressions were used to analyze the number of AECOPD cases during the preceding year. The cutoff value was obtained using a receiver operating characteristic (ROC) curve. RESULTS: We scanned 6342 subjects records, 269 of which were included in this study. We then measured the following muscle areas (non-COPD group vs. COPD group): pectoralis major (19.06 ± 5.36 cm2 vs. 13.25 ± 3.71 cm2, P < 0.001), pectoralis minor (6.81 ± 2.03 cm2 vs. 5.95 ± 1.81 cm2, P = 0.001), diaphragmatic dome (1.39 ± 0.97 cm2 vs. 0.85 ± 0.72 cm2, P = 0.011), musculus serratus anterior (28.03 ± 14.95 cm2 vs.16.76 ± 12.69 cm2, P < 0.001), intercostal muscle (12.36 ± 6.64 cm2 vs. 7.15 ± 5.6 cm2, P < 0.001), pectoralis subcutaneous fat (25.91 ± 13.23 cm2 vs. 18.79 ± 10.81 cm2, P < 0.001), paravertebral muscle (14.8 ± 4.35 cm2 vs. 13.33 ± 4.27 cm2, P = 0.007), and paravertebral subcutaneous fat (12.57 ± 5.09 cm2 vs. 10.14 ± 6.94 cm2, P = 0.001). The areas under the ROC curve for the pectoralis major, intercostal, and the musculus serratus anterior muscle areas were 81.56%, 73.28%, and 71.56%, respectively. Pectoralis major area was negatively associated with the number of AECOPD during the preceding year after adjustment (relative risk, 0.936; 95% confidence interval, 0.879-0.996; P = 0.037). CONCLUSION: The pectoralis major muscle area was negative associated with COPD. Moreover, there was a negative correlation between the number of AECOPD during the preceding year and the pectoralis major area.

The CoNUT score predicts the length of hospital stay and the risk of long CoVID / La puntuación CONUT predice la duración de la estancia hospitalaria y el riesgo de COVID persistente

Objective: the Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status of patients. We aimed toinvestigate the value of CONUT score on predicting length of hospital stay (LOS) and the risk of long COVID in patients with COVID-19.Methods: a total of 151 patients with COVID-19 were enrolled for analysis. Patients were followed up for two years from three months after theonset of SARS-CoV-2 infection. CONUT score was calculated on admission. The correlation between CONUT score and LOS were assessed bySpearman’s rank correlation coefficient and multivariate linear analysis. The association between different CONUT grade and long COVID wasevaluated by Kaplan-Meier survival curves with log-rank test and Cox proportional hazard models.Results: Spearman’s rank correlation coefficient showed that CONUT scores were positively correlated with LOS (r = 0.469, p < 0.001). Multivari-ate linear analysis showed that CONUT score is the only independent determinant of LOS (B 2.055, 95 % CI: 1.067-3.043, p < 0.001). A total of 53(35.10 %) patients with long COVID were identified. Kaplan-Meier cumulative survival curves and Cox proportional hazards analyses showed thatthe incidence of long COVID in patients with a higher CONUT score was significantly higher than in patients with lower CONUT score (p < 0.001).Conclusions: higher CONUT score predicts longer LOS and the risk of long COVID in patients with COVID-19. The CONUT score might be usefulfor risk stratification in COVID-19 patients and help to develop new nutritional treatment strategies for long COVID.(AU)

Objetivo: la escala de valoración del estado nutricional CONUT es una herramienta objetiva ampliamente utilizada para evaluar el estado nutricionalde los pacientes. Nuestro objetivo fue investigar el valor de la puntuación CONUT para predecir la duración de la estancia hospitalaria (LOS) y elriesgo de COVID persistente en pacientes con COVID-19.Métodos: se inscribieron para el análisis un total de 151 pacientes con COVID-19. Los pacientes se sometieron a un seguimiento de dos añosa partir de los tres meses posteriores al inicio de la infección por SARS-CoV-2. La puntuación CONUT se calculó al ingreso. La correlación entrela puntuación CONUT y la LOS se evaluó mediante el coeficiente de correlación de rangos de Spearman y el análisis lineal multivariante. Laasociación entre diferentes grados CONUT y COVID persistente se evaluó mediante curvas de supervivencia de Kaplan-Meier con prueba derango logarítmico y modelos de riesgo proporcional de Cox.Resultados: el coeficiente de correlación de rango de Spearman mostró que las puntuaciones CONUT se correlacionaron positivamente con LOS(r = 0,469, p <0,001). El análisis lineal multivariante mostró que la puntuación CONUT es el único determinante independiente de LOS (B 2,055,IC 95 %: 1,067-3,043, p < 0,001). Se identificaron un total de 53 (35,10 %) pacientes con COVID persistente. Las curvas de supervivenciaacumulada de Kaplan-Meier y los análisis de riesgos proporcionales de Cox mostraron que la incidencia de COVID persistente en pacientes conuna puntuación CONUT más alta fue significativamente mayor que en pacientes con una puntuación CONUT más baja (p < 0,001).Conclusiones: una puntuación CONUT más alta predice una LOS más larga y el riesgo de COVID persistente en pacientes con COVID-19. Lapuntuación CONUT podría ser útil para la estratificación de riesgo en pacientes con COVID-19 y ayudar a desarrollar nuevas estrategias detratamiento nutricional para COVID persistente.(AU)

Cooperation with dynamic asymmetric evaluation in complex networks from a risk perspective.

The choice of strategy exposes individuals to the risk of betrayal. This induces individuals' irrational tendencies in strategy selection, which further influences the emergence of cooperative behavior. However, the underlying mechanisms connecting risk perception and the emergence of cooperation are still not fully understood. To address this, the classic evolutionary game model on complex networks is extended. We depict the interaction between strategy imitation and payoff evaluation from two perspectives: dynamic adjustment and irrational assessment. Specifically, the probability distortion involved in the dynamic selection of imitative reference points, as well as the asymmetric psychological utility associated with reference point dependence, is emphasized. Monte Carlo simulations demonstrate that individual irrational cognition induced by the risk of strategy selection can promote the emergence of cooperative behavior. Among them, the risk sensitivity within psychological utility has the most significant moderating effect. Moreover, the promoting effect of strong heterogeneity and high clustering in the network topology on cooperation under risk scenarios has been clarified. Additionally, the influence of initial states on the emergence of cooperation follows a step-like pattern. This research offers valuable insights for further exploring the cooperation mechanisms among irrational agents, even in scenarios involving the regulation of group cooperation behavior in risky situations.

The CONUT score predicts the length of hospital stay and the risk of long COVID.

Introduction: Objective: the Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status of patients. We aimed to investigate the value of CONUT score on predicting length of hospital stay (LOS) and the risk of long COVID in patients with COVID-19. Methods: a total of 151 patients with COVID-19 were enrolled for analysis. Patients were followed up for two years from three months after the onset of SARS-CoV-2 infection. CONUT score was calculated on admission. The correlation between CONUT score and LOS were assessed by Spearman's rank correlation coefficient and multivariate linear analysis. The association between different CONUT grade and long COVID was evaluated by Kaplan-Meier survival curves with log-rank test and Cox proportional hazard models. Results: Spearman's rank correlation coefficient showed that CONUT scores were positively correlated with LOS (r = 0.469, p < 0.001). Multivariate linear analysis showed that CONUT score is the only independent determinant of LOS (B 2.055, 95 % CI: 1.067-3.043, p < 0.001). A total of 53 (35.10 %) patients with long COVID were identified. Kaplan-Meier cumulative survival curves and Cox proportional hazards analyses showed that the incidence of long COVID in patients with a higher CONUT score was significantly higher than in patients with lower CONUT score (p < 0.001). Conclusions: higher CONUT score predicts longer LOS and the risk of long COVID in patients with COVID-19. The CONUT score might be useful for risk stratification in COVID-19 patients and help to develop new nutritional treatment strategies for long COVID.

Introducción: Objetivo: la escala de valoración del estado nutricional CONUT es una herramienta objetiva ampliamente utilizada para evaluar el estado nutricional de los pacientes. Nuestro objetivo fue investigar el valor de la puntuación CONUT para predecir la duración de la estancia hospitalaria (LOS) y el riesgo de COVID persistente en pacientes con COVID-19. Métodos: se inscribieron para el análisis un total de 151 pacientes con COVID-19. Los pacientes se sometieron a un seguimiento de dos años a partir de los tres meses posteriores al inicio de la infección por SARS-CoV-2. La puntuación CONUT se calculó al ingreso. La correlación entre la puntuación CONUT y la LOS se evaluó mediante el coeficiente de correlación de rangos de Spearman y el análisis lineal multivariante. La asociación entre diferentes grados CONUT y COVID persistente se evaluó mediante curvas de supervivencia de Kaplan-Meier con prueba de rango logarítmico y modelos de riesgo proporcional de Cox. Resultados: el coeficiente de correlación de rango de Spearman mostró que las puntuaciones CONUT se correlacionaron positivamente con LOS (r = 0,469, p <0,001). El análisis lineal multivariante mostró que la puntuación CONUT es el único determinante independiente de LOS (B 2,055, IC 95 %: 1,067-3,043, p < 0,001). Se identificaron un total de 53 (35,10 %) pacientes con COVID persistente. Las curvas de supervivencia acumulada de Kaplan-Meier y los análisis de riesgos proporcionales de Cox mostraron que la incidencia de COVID persistente en pacientes con una puntuación CONUT más alta fue significativamente mayor que en pacientes con una puntuación CONUT más baja (p < 0,001). Conclusiones: una puntuación CONUT más alta predice una LOS más larga y el riesgo de COVID persistente en pacientes con COVID-19. La puntuación CONUT podría ser útil para la estratificación de riesgo en pacientes con COVID-19 y ayudar a desarrollar nuevas estrategias de tratamiento nutricional para COVID persistente.

Elevated plasma pyruvate kinase M2 concentrations are associated with the clinical severity and prognosis of coronary artery disease.

Introduction: Pyruvate kinase M2 (PKM2) was involved in the pathophysiology of atherosclerosis and coronary artery disease (CAD). We tested whether plasma PKM2 concentrations were correlated with clinical severity and major adverse cardiovascular events (MACEs) in CAD patients. Materials and methods: A total of 2443 CAD patients and 238 controls were enrolled. The follow-up time was two years. Plasma PKM2 concentrations were detected by enzyme-linked immunosorbent assay (ELISA) kits (Cloud-Clone, Wuhan, China) using SpectraMax i3x Multi-Mode Microplate Reader (Molecular Devices, San Jose, USA). The predictors of acute coronary syndrome (ACS) were assessed by logistic regression analysis. The association between PKM2 concentration in different quartiles and MACEs was evaluated by Kaplan-Meier (KM) curves with log-rank test and Cox proportional hazard models. The predictive value of PKM2 and a cluster of conventional risk factors was determined by Receiver operating characteristic (ROC) curves. The net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) were utilized to evaluate the enhancement in risk prediction when PKM2 was added to a predictive model containing a cluster of conventional risk factors. Results: In CAD patients, PKM2 concentration was the independent predictor of ACS (P < 0.001). Kaplan-Meier cumulative survival curves and Cox proportional hazards analyses revealed that patients with a higher PKM2 concentration had higher incidence of MACEs compared to those with a lower PKM2 concentration (P < 0.001). The addition of PKM2 to a cluster of conventional risk factors significantly increased its prognostic value of MACEs. Conclusion: Baseline plasma PKM2 concentrations predict the clinical severity and prognosis of CAD.

Unveiling the mechanisms of Fe(III)-loaded chitosan composite (CTS-Fe) in enhancing anaerobic digestion of waste activated sludge.

Anaerobic digestion (AD) of waste activated sludge (WAS) is usually limited by the low generation efficiency of methane. Fe(III)-loaded chitosan composite (CTS-Fe) have been reported to effectively enhanced the digestion of WAS, but its role in promoting anaerobic sludge digestion remains unclear. In present study, the effects of CTS-Fe on the hydrolysis and methanogenesis stages of WAS anaerobic digestion were investigated. The addition of CTS-Fe increased methane production potential by 8%-23% under the tested conditions with the addition of 5-20 g/L CTS-Fe. Besides, the results demonstrate that the addition of CTS-Fe could effectively promote the hydrolysis of WAS, evidenced by lower protein or polysaccharides concentration, higher soluble organic carbon in rector adding CTS-Fe, as well as the increased activity of extracellular hydrolase with higher CTS-Fe concentration. Meanwhile, the enrichment of Clostridia abundance (iron-reducing bacteria (IRBs)) was observed in CTS-Fe adding reactor (8.9%-13.8%), which was higher than that in the control reactor (7.9%). The observation further suggesting the acceleration of hydrolysis through dissimilatory iron reduction (DIR) process, thus providing abundant substrates for methanogenesis. However, the presence of CTS-Fe was inhibited the acetoclastic and hydrogenotrophic methanogenesis process, which could be ascribed to the Fe(III) act as electron acceptor coupled to methane for anaerobic oxidation. Furthermore, coenzyme F420 activity in the CTS-Fe added reactor was 34.9% lower than in the blank, also abundance of microorganisms involved in hydrogenotrophic methanogenesis was decreased. Results from this study could provide theoretical support for the practical applications of CTS-Fe.

Reversal of pulmonary veno-occlusive disease phenotypes by inhibition of the integrated stress response.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension arising from EIF2AK4 gene mutations or mitomycin C (MMC) administration. The lack of effective PVOD therapies is compounded by a limited understanding of the mechanisms driving the vascular remodeling in PVOD. We show that the administration of MMC in rats mediates the activation of protein kinase R (PKR) and the integrated stress response (ISR), which lead to the release of the endothelial adhesion molecule VE-Cadherin in the complex with Rad51 to the circulation, disruption of endothelial barrier, and vascular remodeling. Pharmacological inhibition of PKR or ISR attenuates the depletion of VE-Cadherin, elevation of vascular permeability, and vascular remodeling instigated by MMC, suggesting potential clinical intervention for PVOD. Finally, the severity of PVOD phenotypes was increased by a heterozygous BMPR2 mutation that truncates the carboxyl tail of BMPR2, underscoring the role of deregulated BMP signal in the development of PVOD.

Influence of Smoking Habits on the Efficacy of EGFR-TKI Therapy in Patients with Advanced NSCLC: A Systematic Review and Meta-Analysis.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered as the first-line treatment for advanced EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to analyze the efficacy of EGFR-TKIs treatment in patients with advanced NSCLC of different smoking habits. Methods: We conducted a search for meta-analyses and systematic reviews on the PubMed, MEDLINE, Embase, and the Cochrane Library to address this knowledge gap. Patients were divided into 2 groups: (1) experimental group: treated with EGFR-TKIs or EGFR-TKIs combined with chemotherapy, immunotherapy, antiangiogenesis, radiotherapy and (2) control group: treated with chemotherapy. Progressive-free survival (PFS) and total survival (OS) were adopted for evaluating the efficacy of EGFR-TKIs between experimental group and control group. Results: Eleven studies including 6760 patients were included in the meta-analysis. The results showed that smoking (including previous and current smoking) significantly reduces the PFS and OS in comparison to non-smoking group in the treatment of NSCLC with EGFR-TKIs. In addition, EGFR-TKIs combined with anti-vascular endothelial growth factor therapy can reduce the risk of disease progression in smokers. Conclusions: Our study indicated that smoking significantly reduced the PFS and OS in comparison to non-smoking group in the treatment of NSCLC with EGFR-TKIs.

Experimental and Modeling Study on the Ignition Kinetics of Nitromethane behind Reflected Shock Waves.

Nitromethane (NM) is the simplest nitroalkane fuel and has demonstrated potential usage as propellant and fuel additive. Thus, understanding the combustion characteristics and chemistry of NM is critical to the development of hierarchical detailed kinetic models of nitro-containing energetic materials. Herein, to further investigate the ignition kinetics of NM and supplement the experimental database for kinetic mechanism development, an experimental and kinetic modeling analysis of the ignition delay times (IDTs) of NM behind reflected shock waves at high fuel concentrations is reported against previous studies. Specifically, the IDTs of NM are measured via a high-pressure shock tube within the temperature from 900 to 1150 K at pressures of 5 and 10 bar and equivalence ratios of 0.5, 1.0, and 2.0. Brute-force sensitivity analysis and chemical explosive mode analysis in combination with reaction path analysis are employed to reveal the fundamental ignition kinetics of NM. Finally, a skeletal mechanism for NM is derived via the combination of directed relation graph-based methods, which demonstrates good prediction accuracy of NM ignition and flame speeds. The present work should be valuable for understanding the combustion chemistry of NM and the development of the fundamental reaction mechanism of nitroalkane fuels.

Irisin alleviates hyperoxia-induced bronchopulmonary dysplasia through activation of Nrf2/HO-1 pathway.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common pulmonary injury among premature infants, which is often caused by hyperoxia exposure. Irisin is a novel hormone-like myokine derived mainly from skeletal muscles as well as adipose tissues. Many studies have indicated that Irisin exert a variety of properties against hyperoxia-induced inflammation and oxidative stress (OS). We aimed to evaluate the effects of irisin on hyperoxia-induced lung injury explore the underlying mechanisms. METHODS: BPD model was established after exposing newborn mouse to 85% oxygen. BPD mouse received continuous intraperitoneal injection of irisin at a dose of 25 µg/kg/day. Lung tissues were collected for histological examination at 7 and 14 days after birth. The alveolarization and alveolar vascularization of each animal was assessed. Levels of oxidative stress indicators, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues were detected at 14 days after birth. RESULTS: Hyperoxia exposure induced a markedly alveolar simplification and a disrupted alveolar angiogenesis, which was ameliorated by irisin treatment. The hyperoxia-induced increase in these oxidative stress indicators was significantly reversed by irisin treatment. The Nrf2/HO-1 pathway is inducted in the hyperoxia-induced BPD mouse model, which is further activated by irisin treatment. CONCLUSION: Our results demonstrated the beneficial effects of irisin in reducing the OS, enhancing alveolarization, and promoting vascular development through activation of Nrf2/HO-1 axis in a hyperoxia-induced experimental model of BPD.

Distribution and Drug Resistance of Bacterial Infection in Hospitalized Patients at the Respiratory Department before and after the COVID-19 Pandemic in Guangzhou, China.

Since COVID-19 might have a lasting impact on global public health, it is crucial to analyze its effect on drug-resistant bacterial infections in the respiratory system for the prevention and control of hospital infections. This work aimed to investigate the impact of the COVID-19 outbreak on the clinical distribution and antibiotic resistance of bacterial infection among hospitalized patients in the respiratory unit in order to establish strategies to control antibiotic-resistant infections. Electronic clinical data registry records from 2018 to 2022 were retrospectively analyzed. A total of 36,829 clinical specimens, including sputum, bronchoalveolar lavage fluid, blood, and urine, were collected from 16,073 patients admitted to the Guangzhou First People's Hospital from January 2018 to December 2022. Among them, 2209 samples were culture-positive. The bacterial isolation rates of different types of samples showed a similar trend from 2019 to 2022, with an increase in 2020 and 2022 and a decrease in 2021. Different bacterial species were separated from different types of samples. The most reported pathogens were identified in sputum samples. Gram-positive isolates were prevalent in urine samples, while Gram-negative bacilli were the predominant pathogenic bacteria isolated from respiratory tract and blood samples. Pseudomonas aeruginosa (P. aeruginosa), Acinetobacter baumannii (A. baumannii) complex, and Klebsiella pneumoniae (K. pneumoniae) were the most abundant Gram-negative bacteria in sputum samples, of which A. baumannii complex had the highest resistance to all tested antibiotics except colistin. Notably, there has been a substantial prevalence of carbapenem-resistant P. aeruginosa, A. baumannii, and K. pneumoniae in the past five years. This alarming situation calls for greater attention and precaution with prescribed antibiotics to limit the generation and spread of new multidrug-resistant bacteria and improve therapeutic management.

Effects of deterministic assembly of communities caused by global warming on coexistence patterns and ecosystem functions.

Seasonal rhythms in biological and ecological dynamics are fundamental in regulating the structuring of microbial communities. Evaluating the seasonal rhythms of microorganisms in response to climate change could provide information on their variability and stability over longer timescales (>20-year). However, information on temporal variability in microorganism responses to medium- and long-term global warming is limited. In this study, we aimed to elucidate the temporal dynamics of microbial communities in response to global warming; to this end, we integrated data on the maintenance of species diversity, community composition, temporal turnover rates (v), and community assembly process in two typical ecosystems (meadows and shrub habitat) on the Qinghai-Tibet Plateau. Our results showed that 21 years of global warming would increase the importance of the deterministic process for microorganisms in both ecosystems across all seasons (R2 of grassland (GL) control: 0.524, R2 of GL warming: 0.467; R2 of shrubland (SL) control: 0.556, R2 of SL warming: 0.543), reducing species diversity and altering community composition. Due to environmental filtration pressure from 21 years of warming, the low turnover rate (v of warming: -3.13/-2.00, v of control: -2.44/-1.48) of soil microorganisms reduces the resistance and resilience of ecological communities, which could lead to higher community similarity and more clustered taxonomic assemblages occurring across years. Changes to temperature might increase selection pressure on specialist taxa, which directly causes dominant species (v of warming: -1.63, v of control: -2.49) primarily comprising these taxa to be more strongly impacted by changing temperature than conditionally (v of warming: -1.47, v of control: -1.75) or always rare taxa (v of warming: -0.57, v of control: -1.33). Evaluation of the seasonal rhythms of microorganisms in response to global warming revealed that the variability and stability of different microbial communities in different habitats had dissimilar biological and ecological performances when challenged with an external disturbance. The balance of competition and cooperation, because of environmental selection, also influenced ecosystem function in complex terrestrial ecosystems. Overall, our study enriches the limited information on the temporal variability in microorganism responses to 21 years of global warming, and provides a scientific basis for evaluating the impact of climate warming on the temporal stability of soil ecosystems.

Coupling Iron Sludge Addition and Intermittent Aeration for Achieving Simultaneous Methanogenesis, Feammox, and Denitrification in a Single Reactor Treating Fish Sludge.

An integrated anaerobic digestion system for the simultaneous removal of carbon and nitrogen from fish sludge was developed by coupling iron sludge supplementation with intermittent aeration. In terms of nitrogen removal, Fe(III) in iron sludge could trigger Feammox reactions and intermittent aeration could drive the Fe(II)/Fe(III) cycle to sustain continuous ammonia removal. Mass balance analysis suggested that nitrate was the main product of Feammox, which was subsequently removed through heterotrophic denitrification. In terms of carbon removal, the Fe(III)-induced dissimilatory iron reduction (DIR) process significantly promoted fish sludge hydrolysis and provided more simple organics for methanogens and denitrifiers, but aeration showed a negative impact on methanogenesis. To promote nitrogen removal and avoid serious methanogenesis inhibition, different aeration intensities were studied. Results showed that compared with the control without aeration or iron sludge addition, aeration for 5 min every 3 days (150 mL/min) contributed to a 29.0% lower NH4+-N concentration and a 12.1% lower total chemical oxygen demand level on day 28, and the decline in methane yield was acceptable (only 13.5% lower). Simultaneous methanogenesis, Feammox, and denitrification in a single reactor treating fish sludge were achieved, which provides a simple and low-cost strategy for the treatment of organic wastewater.

Sodium pyruvate exerts protective effects against cigarette smoke extract-induced ferroptosis in alveolar and bronchial epithelial cells through the GPX4/Nrf2 axis.

BACKGROUND: Ferroptosis in alveolar and bronchial epithelial cells is one of the main mechanisms underlying the development of chronic obstructive pulmonary disease (COPD). Sodium pyruvate (NaPyr) is a natural antioxidant in the body, exhibiting anti-inflammatory and antioxidant activities. NaPyr has been used in a Phase II clinical trial as a novel therapy for COPD; however, the mechanism underlying NaPyr-mediated therapeutic benefits in COPD is not well understood. OBJECTIVE: We aimed to assess the protective effects of NaPyr and elucidate its potential mechanism in cigarette smoke extract (CSE)-induced ferroptosis.To minic the inflammatory response and ferroptosis triggered by cigarette smoke in COPD in an invitro cell based system, we expose a human bronchial epithelial cells to CSE. METHODS: To minic the inflammatory response and ferroptosis triggered by cigarette smoke in COPD in an invitro cell based system, the A549 (human lung carcinoma epithelial cells) and BEAS-2B (bronchial epithelial cells) cell lines were cultured, followed by treatment with CSE. To measure cellular viability and iron levels, we determined the levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), mitochondrial superoxide (MitoSOX), membrane potential (MMP), and inflammatory factors (tumor necrosis factor [TNF] and interleukin [IL]-8), and examined CSE-induced pulmonary inflammation and ferroptosis. To clarify the molecular mechanisms of NaPyr in COPD therapy, we performed western blotting and real-time PCR (qPCR) to determine the expression of glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (Nrf2), and cyclooxygenase 2 (COX2). RESULTS: We found that NaPyr effectively mitigated CSE-induced apoptosis and improved apoptosis induced by erastin, a ferroptosis inducer. NaPyr significantly decreased iron and MDA levels and increased GSH levels in CSE-induced cells. Furthermore, NaPyr suppressed ferroptosis characteristics, such as decreased levels of ROS, MitoSOX, and MMP. NaPyr significantly increases the expression levels of GPX4 and Nrf2, indicating that activation of the GPX4/Nrf2 axis could inhibit ferroptosis in alveolar and bronchial epithelial cells. More importantly, NaPyr inhibited the secretion of downstream inflammatory factors, including TNF and IL-8, by decreasing COX2 expression levels to suppress CSE-induced inflammation. CONCLUSION: Accordingly, NaPyr could mitigate CSE-induced ferroptosis in alveolar and bronchial epithelial cells by activating the GPX4/Nrf2 axis and decreasing COX2 expression levels. In addition, NaPyr reduced the secretion of inflammatory factors (TNF and IL-8), affording a novel therapeutic candidate for COPD.