Relationships among Sleep Time, Physical Activity Time, Screen Time, and Nutrition Literacy of Adolescents: A Cross-Sectional Study in Chongqing, China.

Background: Unhealthy lifestyles among adolescents are reaching alarming levels and have become a major public health problem. This study aimed to assess the relationship between sleep time, physical activity (PA) time, screen time (ST), and nutritional literacy (NL). Methods: This cross-sectional online study involving adolescents aged 10-18 years was conducted in September 2020 in 239 schools in Chongqing, China. NL was measured using the "Nutrition Literacy Scale for middle school students in Chongqing (CM-NLS)". According to the recommended by the Chinese dietary guidelines (2022), we divided the sleep time of junior high school students into <9 h and ≥9 h, high school students into <8 h and ≥8 h, divided the workdays into weekend PA time < 1 h and ≥1 h, and divided the workdays into weekend ST < 2 h and ≥2 h. The multinomial logistic regression model was used to examine the association. Results: A total of 18,660 adolescents (50.2% males) were included. The proportion of participants that were junior high school students and attended boarding schools was 57.2% and 65.3%, respectively. Compared with senior high school students, junior high school students had a higher level of NL. Whether on workdays or weekends, participants with sleep time ≥ 8/9 h, PA time ≥ 1 h, and ST < 2 h per day had higher levels of NL. On weekdays, participants who met the sleep time ≥ 8 h/9 h (OR = 1.48, 95% CI: 1.36, 1.62) and PA time ≥ 1 h (OR = 1.69, 95% CI: 1.59, 1.81) had higher reporting of NL levels. Conclusions: Sleep time, PA time, and ST were positively correlated with NL among adolescents, especially junior high school students.

Efficient regulation of cadmium accumulation by carboxymethylammonium chloride in rice: Correlation analysis and expression of transporter gene OsGLR3.

The mechanism of carboxymethylammonium chloride (CC) regulating cadmium (Cd) accumulation in rice was studied in field and hydroponic experiments. Field experiments showed that 0.2-1.2 mmol L-1 CC spraying effectively reduced Cd accumulation by 44 %-77 % in early rice grains and 39 %-78 % in late rice grains, significantly increased calcium (Ca) content and amino acids content in grains, as well as alleviated Cd-induced oxidative damage in leaves. Hydroponic experiments further verified the inhibition effect of CC on Cd accumulation. 1.2 mmol L-1 CC made the highest decrease of Cd content in shoots and roots of hydroponic seedlings by 45 % and 53 %, respectively. Exogenous CC significantly increased glutamate (Glu), glycine (Gly) and glutathione (GSH) content, and improved the activities of catalase (CAT) and superoxide dismutase (SOD) by 41-131 % and 11-121 % in shoots of hydroponic seedlings, respectively. Exogenous CC also increased the relative expression of OsGLR3.1-3.5 in the shoots and roots of hydroponic seedlings. The quantum computational chemistry was used to clarify that the Gly radical provided by CC could form various complexes with Cd through carboxyl oxygen atoms. These results showed that exogenous application of CC improved the tolerance to Cd by enhancing the antioxidant capacity; inhibited the absorption, transport and accumulation of Cd in rice by (1) promoting chelation, (2) increasing the GLRs activity through upregulating the content of Glu, Gly, as well as the expression of OsGLR3.1-3.5.

Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model.

BACKGROUND: Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. METHODS: Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. RESULTS: After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. CONCLUSIONS: Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.

CacyBP promotes the development of lung adenocarcinoma by regulating OTUD5.

Lung cancer is the most common and lethal malignancy, with lung adenocarcinoma accounting for approximately 40% of all cases. Despite some progress in understanding the pathogenesis of this disease and developing new therapeutic approaches, the current treatments for lung adenocarcinoma remain ineffective due to factors such as high tumour heterogeneity and drug resistance. Therefore, there is an urgent need to identify novel therapeutic targets. CacyBP can regulate a variety of physiological processes by binding to different proteins, but its function in lung adenocarcinoma is unknown. Here, we show that CacyBP is highly expressed in lung adenocarcinoma tissues, and high CacyBP expression correlates with poorer patient survival. Moreover, overexpression of CacyBP promoted the proliferation, migration and invasion of lung adenocarcinoma cell lines. Further mechanistic studies revealed that CacyBP interacts with the tumour suppressor OTUD5, enhances the ubiquitination and proteasomal degradation of OTUD5, and regulates tumorigenesis via OTUD5. In conclusion, our study reveals a novel mechanism by which CacyBP promotes tumorigenesis by increasing the ubiquitination level and proteasome-dependent degradation of OTUD5, providing a potential target for the treatment of lung adenocarcinoma.

Role of polyphenols in remodeling the host gut microbiota in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The pathophysiology of PCOS is complex. Recent studies have reported that apart from hyperandrogenism, insulin resistance, systemic chronic inflammation, and ovarian dysfunction, gut microbiota dysbiosis is also involved in PCOS development and may aggravate inflammation and metabolic dysfunction, forming a vicious cycle. As naturally occurring plant secondary metabolites, polyphenols have been demonstrated to have anticancer, antibacterial, vasodilator, and analgesic properties, mechanistically creating putative bioactive, low-molecular-weight metabolites in the human gut. Here, we summarize the role of gut microbiota dysbiosis in the development of PCOS and demonstrate the ability of different polyphenols - including anthocyanin, catechins, and resveratrol - to regulate gut microbes and alleviate chronic inflammation, thus providing new insights that may assist in the development of novel therapeutic strategies to treat women with PCOS.

IDI1 inhibits the cGAS-Sting signaling pathway in hepatocellular carcinoma.

Metabolic reprogramming is one of the prominent features that distinguishes tumor cells from normal cells. The role of metabolic abnormalities in regulating innate immunity is poorly understood. In this study, we found that IDI1 is significantly upregulated in liver cancer. IDI1 has no significant effect on the growth or invasion of liver cancer cells but significantly promotes liver cancer development in mice. Through molecular mechanism studies, we found that IDI1 interacts with the important regulator of innate immunity cGAS and recruits the E3 ligase TRIM41 to promote cGAS ubiquitination and degradation, inhibiting the cGAS-Sting signaling pathway. IDI1 inhibits the phosphorylation of TBK1 and the downstream factor IRF3 as well as the expression of CCL5 and CXCL10. In summary, this study revealed the important role of the metabolic enzyme IDI1 in the regulation of innate immunity, suggesting that it may be a potential target for liver cancer treatment.

Arsenic exposure and pulmonary function decline: Potential mediating role of TRAIL in chronic obstructive pulmonary disease patients.

BACKGROUND: Environmental arsenic (As) exposure is strongly related to the progression of chronic obstructive pulmonary disease (COPD). Pulmonary epithelial cells apoptosis is implicated in the pathophysiological mechanisms of COPD. However, the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), one biomarker of apoptosis, remains unclear in As-mediated pulmonary function alternations in COPD patients. METHODS: This study included 239 COPD patients. The serum level of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was measured by enzyme-linked immunosorbent assay (ELISA). The blood As level was determined through inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Blood As levels exhibited a negative and dose-dependent correlation with pulmonary function. Per unit elevation of blood arsenic concentrations was related to reductions of 0.339 L in FEV1, 0.311 L in FVC, 1.171% in FEV1/FVC%, and 7.999% in FEV1% in COPD subjects. Additionally, a positive dose-response correlation of blood As with serum TRAIL was found in COPD subjects. Additionally, the level of serum TRAIL was negatively linked to lung function. Elevated TRAIL significantly mediated As-induced decreases of 11.05%, 13.35%, and 31.78% in FVC, FEV1, and FEV1%, respectively among the COPD patients. CONCLUSION: Blood As level is positively correlated with pulmonary function decline and serum TRAIL increase in individuals with COPD. Our findings suggest that elevated TRAIL levels may serve as a mediating mechanism through which As contributes to declining lung function in COPD patients.

UB-612 pan-SARS-CoV-2 T cell immunity-promoting vaccine protects against COVID-19 moderate-severe disease.

UB-612 pan-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine targets the monomeric Spike S1-receptor binding domain (RBD) subunit protein along with five sequence-conserved T cell epitopes found on Spike S2 and non-Spike M and N proteins. UB-612 vaccination safely induces potent, broad, and long-lasting immunity against SARS-CoV-2. A phase-2 trial-extended observational study during the Omicron BA.2-/BA.5-dominated outbreak was conducted to investigate UB-612's protective effect against COVID-19 hospitalization and intensive care unit (ICU) admission (H-ICU). Additionally, memory viral-neutralizing titer and T cell immunity behind disease protection were explored. No cases of H-ICU were reported beyond 14 months post-second dose or beyond 10 months post-booster (third dose). The positive outcome correlates with strong cytotoxic CD8 T cell immunity, in line with the results of an ongoing phase-3 heterologous booster trial showing that UB-612 can enhance anti-BA.5 seroconversion rate and viral-neutralizing titer for mRNA, adeno-vectored, and virus-inactivated vaccine platforms. The UB-612 multitope vaccine may serve as an effective primer and booster for those at risk of SARS-CoV-2 infection.

Association of blood cadmium concentration with chronic obstructive pulmonary disease progression: a prospective cohort study.

BACKGROUND: Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation. METHODS: Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records. RESULTS: Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration. CONCLUSION: Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression.

CircFN1 promotes acute myeloid leukemia cell proliferation and invasion but refrains apoptosis via miR-1294/ARHGEF10L axis.

Previous studies have proved circFN1 is highly expressed in acute myeloid leukemia (AML) patients and AML cell lines. This study aims to investigate the impact of circFN1 on AML and its mechanism. Via real-time quantitative PCR to detect circFN1, miR-1294, ARHGEF10L expressions in clinical plasma samples and AML cell lines, AML cells were cultured in vitro and transfected with si-circFN1, pcDNA3.1-circFN1, and si-ARHGEF10L, respectively, or co-transfected pcDNA3.1-circFN1 + miR-1294 mimic and pcDNA3.1-circFN1 + si-ARHGEF10L. Using dual luciferase reporter experiment to detect the relationship between circFN1 and miR-1294, as well as miR-1294 and ARHGEF10L. CCK-8 was used to detect cell proliferation, Transwell to cell invasion, TUNEL staining and flow cytometry to detect cell apoptosis, RT-qPCR to circFN1 RNA, miR-1294, and ARHGEF10L expression levels in HL-60 cells, and western blot to ARHGEF10L protein expression level in HL-60 cells. We found highly expressed circFN1 and ARHGEF10L, as well as low-expressed miR-1294 in AML patients and AML cell lines. In contrast to si-NC group, si-circFN1 group could signally inhibit HL-60 cell proliferation and migration, but promote cell apoptosis; compared with mimic NC group, miR-1294 mimic group could visually inhibit HL-60 cell proliferation and migration, but promote cell apoptosis. miR-1294 was the target of circFN1, and ARHGEF10L was the target of miR-1294. Over-expressing miR-1294 or silencing ARHGEF10L could signally inhibit circFN1 promoting HL-60 cell proliferation and migration and repressing cell apoptosis. circFN1 promotes proliferation and invasion of AML cell and represses cell apoptosis via regulating miR-1294/ARHGEF10L axis, which provides new insight for molecular targeted-treatment for AML.

Longitudinal associations between serum IL-34 with severity and prognosis in community-acquired pneumonia patients.

BACKGROUND: Interleukin-34 (IL-34) is a hematopoietic cytokine and a ligand of colony-stimulating factor 1 receptor (CSF-1R). Numerous studies have demonstrated that IL-34 is involved in several inflammatory diseases. Nevertheless, the role of IL-34 is obscure in community-acquired pneumonia (CAP) patients. This research aimed to assess the associations of serum IL-34 with severity and prognosis in CAP patients through a longitudinal study. METHODS: CAP patients and healthy volunteers were recruited. Peripheral blood samples were collected. Serum IL-34 and inflammatory cytokines were tested by enzyme linked immunosorbent assay (ELISA). Demographic characteristics and clinical information were acquired through electronic medical records. RESULTS: Serum IL-34 was elevated in CAP patients compared with healthy volunteers. The content of serum IL-34 was gradually upregulated with increased CAP severity scores. Mixed logistic and linear regression models suggested that serum IL-34 elevation was associated with increased PSI and SMART-COP scores. Correlative analysis found that serum IL-34 was positively correlated with inflammatory cytokines among CAP patients. A longitudinal study indicated that higher serum IL-34 at admission elevated the risks of mechanical ventilation and death during hospitalization. Serum IL-34 had a higher predictive capacity for death than CAP severity scores. CONCLUSION: There are prominently positive dose-response associations between serum IL-34 at admission with the severity and poor prognosis, suggesting that IL-34 is implicated in the occurrence and development of CAP. Serum IL-34 may serve as a biomarker to forecast disease progression and poor prognosis in CAP patients.

Silencing lncRNA-DARS-AS1 suppresses nonsmall cell lung cancer progression by stimulating miR-302a-3p to inhibit ACAT1 expression.

Long noncoding RNAs (LncRNAs) have been gaining attention as potential therapeutic targets for lung cancer. In this study, we investigated the expression and biological behavior of lncRNA DARS-AS1, its predicted interacting partner miR-302a-3p, and ACAT1 in nonsmall cell lung cancer (NSCLC). The transcript level of DARS-AS1, miR-302a-3p, and ACAT1 was analyzed using qRT-PCR. Endogenous expression of ACAT1 and the expression of-and changes in-AKT/ERK pathway-related proteins were determined using western blotting. MTS, Transwell, and apoptosis experiments were used to investigate the behavior of cells. The subcellular localization of DARS-AS1 was verified using FISH, and its binding site was verified using dual-luciferase reporter experiments. The binding of DARS-AS1 to miR-302a-3p was verified using RNA co-immunoprecipitation. In vivo experiments were performed using a xenograft model to determine the effect of DARS-AS1 knockout on ACAT1 and NSCLC. lncRNA DARS-AS1 was upregulated in NSCLC cell lines and tissues and the expression of lncRNA DARS-AS1 was negatively correlated with survival of patients with NSCLC. Knockdown of DARS-AS1 inhibited the malignant behaviors of NSCLC via upregulating miR-302a-3p. miR-302a-3p induced suppression of malignancy through regulating oncogene ACAT1. This study demonstrates that the DARS-AS1-miR-302a-3p-ACAT1 pathway plays a key role in NSCLC.

Deteriorated sleep quality and associate factors in patients with type 2 diabetes mellitus complicated with diabetic peripheral neuropathy.

Objectives: To understand the sleep quality and its influencing factors in patients with type 2 diabetes mellitus (T2DM) who suffered diabetic peripheral neuropathy (DPN), and provide evidence for clinicians to carry out comprehensive intervention measures to improve the sleep quality of patients. Methods: Patients who were admitted to the Endocrinology Department of Affiliated Hospital of Zunyi Medical University were recruited from May to December 2022, and the investigation were conducted by face-to-face interview. The questionnaires included PSQI questionnaire and influencing factors, such as lifestyle and health status. Results: Among the 193 patients, 40.4% of the patients never took physical examination, 56.5% of the patients had duration of illness greater than 5 years, 61.7% of the patients had had an operation, 10.4% of the patients had bad dietary status, and 55.4% of the patients had physical pain. In addition, the PSQI general score was 8.34 ± 3.98, the occurrence rate of poor sleep quality (PSQI ≥ 8) was 54.4%, and the results showed that sleep quality of the physical pain group was worse than the no pain group. Moreover, the results of multivariate analysis revealed that the factors affecting sleep quality were lower frequency of exercise, bad dietary status, lower frequency of physical examination, longer duration of illness, and smoking, and the OR and 95% CI were [1.40, 1.04∼1.89], [3.42, 1.86∼6.29], [1.49, 1.01∼2.20], [1.78, 1.09∼2.92], [2.38, 1.17∼4.88], respectively. Conclusion: Patients with DPN have higher risk of poor sleep quality. Moreover, there were many risk factors associated with poor sleep quality, clinicians and health policymakers should timely detect and effectively intervene in these factors to improve the sleep quality, which is important to enhance the quality of life of T2DM patients complicated with DPN.

Experimental study on the effects of different exposure conditions and contrast agent concentrations on spectral computed tomography virtual non-contrast images.

Background: The early diagnosis of thrombosis and fat embolism is important for subsequent treatment regimens. Spectral computed tomography (CT) virtual non-contrast (VNC) scanning can not only accurately diagnose thrombosis and medium fat embolism but can also reduce the radiation dose and scanning time. However, there is a relative paucity of studies on what contrast concentration and exposure conditions are best for the quality of VNC images. To address this issue, this study aimed to investigate the effects of different exposure conditions and contrast concentrations on the quality of VNC images of low-density substances in spectral CT. Methods: Four solution groups [i.e., groups A (15 mgI/mL), B (10 mgI/mL), C (5 mgI/mL), and D (the control group)] were matched with normal saline and contrast agent groups. Four groups of solution, duck blood clots, and fat were injected into four sections of the pig large intestine, respectively. CT scans with different exposure amounts were performed under the condition of 120 KV. Comparing the true non-contrast (TNC) image based on solution D group with the VNC images of the other three solution groups. The differences in the CT values, standard deviation (SD) values, and contrast noise ratio (CNR) values of the duck blood and fat under different iodine concentrations and exposures were compared. The image quality was evaluated using a three-point method and the Kappa consistency test was performed. The consistency of the tissue CT values in the TNC and VNC images was analyzed by drawing Bland-Altman scatter plots. Results: The CT values of the duck blood in the VNC20mAs and VNCC groups were lower than those in the TNC groups (P<0.05). Under different exposures and contrast agent concentrations, the CT value of the fat in the VNC group was higher than that in the TNC group (P<0.05). The SD values of the duck blood and fat in three groups (i.e., groups A, B, and C) were lower than those in the TNC group (P<0.05). The CNR value of the duck blood in the VNC20mAs group was lower than that in the TNC group (Z=-2.10, P=0.04), and the CNR values of the duck blood and fat in the VNC group were higher than those in the TNC groups in the remaining different exposure and concentration groups (P<0.05). The CT values of the lesions in the two groups were consistent, and there were no statistically significant differences between the subjective scores of the TNC and VNC images (z=-1.34, P=0.18); the subjective evaluations of the two physicians had good consistency (K=0.80). Conclusions: Under the conditions of higher contrast agent concentrations and proper exposure conditions, the VNC images were better able to restore the CT values of the blood clots, reduce the SD values of the blood clots and fat. In addition, and improve the CNR values of the blood clots and fat. In addition, the quality of the two images was similar.

Bidirectional Confined Redox Catalysis Manipulated Quasi-Solid Iodine Conversion for Shuttle-Free Solid-State Zn-I2 Battery.

Electrochemically reversible conversion of I2/I- redox couple in a controllable iodine speciation manner is the eternal target for practical metal-iodine batteries. This contribution demonstrates an advanced polyiodide-free Zn-I2 battery achieved by the bidirectional confined redox catalysis-directed quasi-solid iodine conversion. A core-shell structured iodine cathode is fabricated by integrating multiporous Prussian blue nanocubes as a catalytic mediator, and the polypyrrole sheath afforded a confinement environment that favored the iodine redox. The zincate Znx+1FeIII/II[Fe(CN)6]y has substantially faster zinc-ion intercalation kinetics and overlapping kinetic voltage profiles compared with the I2/ZnI2 redox, and behave as a redox mediator that catalyze reduction of polyiodides via chemical redox reactions during battery discharging and an exemplary reaction is Zn(I3)2+2Znx+1FeII[Fe(CN)6]y=3ZnI2+2ZnxFeIII[Fe(CN)6]y,ΔG=-19.3 kJ mol-1). During the following recharging process, the electrodeposited ZnI2 can be facially activated by iron redox hotspots, and the ZnxFe[FeIII/II(CN)6]y served as a cation-transfer mediator and spontaneously catalyze polyiodides oxidation (Zn(I3)2+2ZnxFe[FeIII(CN)6]y=3I2+2Znx+1Fe[FeII(CN)6]y,ΔG = -7.72 kJ mol-1), manipulating the reversible one-step conversion of ZnI2 back to I2. Accordingly, a flexible solid-state battery employing the designed cathode can deliver an energy density of 215 Wh kgiodine -1.

Systematic identification of reference genes for qRT-PCR of Ardisia kteniophylla A. DC under different experimental conditions and for anthocyanin-related genes studies.

Ardisia kteniophylla A. DC, widely known as folk medicinal herb and ornamental plant, has been extensively investigated due to its unique leaf color, anti-cancer and other pharmacological activities. The quantitative real-time PCR (qRT-PCR) was an excellent tool for the analysis of gene expression with its high sensitivity and quantitative properties. Normalizing gene expression with stable reference genes was essential for qRT-PCR accuracy. In addition, no studies have yet been performed on the selection, verification and stability of internal reference genes suitable for A. kteniophylla, which has greatly hindered the biomolecular researches of this species. In this study, 29 candidate genes were successfully screened according to stable expression patterns of large-scale RNA seq data that from a variety of tissues and the roots of different growth stages in A. kteniophylla. The candidates were then further determined via qRT-PCR in various experimental samples, including MeJA, ABA, SA, NaCl, CuSO4, AgNO3, MnSO4, CoCl2, drought, low temperature, heat, waterlogging, wounding and oxidative stress. To assess the stability of the candidates, five commonly used strategies were employed: delta-CT, geNorm, BestKeeper, NormFinder, and the comprehensive tool RefFinder. In summary, UBC2 and UBA1 were found to be effective in accurately normalizing target gene expression in A. kteniophella regardless of experimental conditions, while PP2A-2 had the lowest stability. Additionally, to verify the reliability of the recommended reference genes under different colored leaf samples, we examined the expression patterns of six genes associated with anthocyanin synthesis and regulation. Our findings suggested that PAP1 and ANS3 may be involved in leaf color change in A. kteniphella. This study successfully identified the ideal reference gene for qRT-PCR analysis in A. kteniphella, providing a foundation for future research on gene function, particularly in the biosynthesis of anthocyanins.

Arsenic exposure and lung function decline in chronic obstructive pulmonary disease patients: The mediating influence of systematic inflammation and oxidative stress.

Lung tissue is one of the target sites of arsenic (As). The goal of this investigation was to assess the associations of blood As concentration with pulmonary function indicators in patients with chronic obstructive pulmonary disease (COPD), as well as the roles of systemic inflammation and oxidative stress in this relationship. All 791 COPD patients were selected. Blood As concentration, and tumour necrosis factor-α (TNF-α) and 8-iso-prostaglandin-F2α (8-iso-PGF2α) were detected in the serum of COPD cases. Blood As was robustly related to pulmonary function parameters in an inverse dose-dependent manner. Multivariate linear regression analyses verified that a 1-unit increase of blood As was linked to declines of 0.263 L in FVC, 0.288 L in FEV1, 3.454 in FEV1/FVC%, and 0.538 in predicted FEV1%, respectively. The potential for pulmonary function decline gradually increased across the elevated tertiles of blood As. Nonsmokers were susceptible to As-induced pulmonary function reduction. Blood As was positively linked to the levels of TNF-α and 8-iso-PGF2α. Increased TNF-α and 8-iso-PGF2α partially mediated As-induced the reductions in FEV1 and FVC among COPD patients. As exposure is intensely linked to pulmonary function reduction. Systematic inflammation and oxidative stress partially mediate such associations in COPD patients.

Advances of mesenchymal stem cells and their derived extracellular vesicles as a promising therapy for acute respiratory distress syndrome: from bench to clinic.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by diffuse alveolar damage. The period prevalence of ARDS was 10.4% of ICU admissions in 50 countries. Although great progress has been made in supportive care, the hospital mortality rate of severe ARDS is still up to 46.1%. Moreover, up to now, there is no effective pharmacotherapy for ARDS and most clinical trials focusing on consistently effective drugs have met disappointing results. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have spawned intense interest of a wide range of researchers and clinicians due to their robust anti-inflammatory, anti-apoptotic and tissue regeneration properties. A growing body of evidence from preclinical studies confirmed the promising therapeutic potential of MSCs and their EVs in the treatment of ARDS. Based on the inspiring experimental results, clinical trials have been designed to evaluate safety and efficacy of MSCs and their EVs in ARDS patients. Moreover, trials exploring their optimal time window and regimen of drug administration are ongoing. Therefore, this review aims to present an overview of the characteristics of mesenchymal stem cells and their derived EVs, therapeutic mechanisms for ARDS and research progress that has been made over the past 5 years.

PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway.

At present, non-small cell lung cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan-Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2'-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.

Protective effects of yeast extract against alcohol-induced liver injury in rats.

Oxidative stress, inflammatory response, and gut-liver axis dysbiosis have been suggested as the primarily involved in the pathogenesis of alcoholic liver injury. Previous research established that yeast extract (YE) has antioxidant, immune-boosting or microbiota-regulating properties. However, there is currently lack of information regarding the efficacy of YE on alcoholic liver injury. This study seeks to obtain data that will help to address this research gap using a Wistar male rat experimental model. Histologic and biochemical analysis results showed that the groups treated with both low-dose yeast extract (YEL) and high-dose yeast extract (YEH) had lower degrees of alcohol-induced liver injury. The abundance of Peptococcus and Ruminococcus reduced in the low-dose yeast extract (YEL) group, while that of Peptococcus, Romboutsia, Parasutterella, and Faecalibaculum reduced in the high-dose (YEH) group. Furthermore, Spearman analysis showed that the gut microbes were significantly associated with several liver-related indicators. For the analysis of differential metabolites and enriched pathways in the YEL group, the abundance of lysophosphatidylcholine (16:0/0:0) significantly increased, and then the levels of histamine, adenosine and 5' -adenine nucleotide were remarkedly elevated in the YEH group. These findings suggest that both high and low doses of YE can have different protective effects on liver injury in alcoholic liver disease (ALD) rats, in addition to improving gut microbiota disorder. Besides, high-dose YE has been found to be more effective than low-dose YE in metabolic regulation, as well as in dealing with oxidative stress and inflammatory responses.