Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165.

BACKGROUND: Aberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored. OBJECTIVES: We aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation. METHODS: We constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge. RESULTS: HDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10fl/fl-LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI. CONCLUSION: These results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI.

Artesunate inhibits vasculogenic mimicry in choroidal melanoma through HIF-1 α/ VEGF/PDGF pathway.

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

Analysis of Diagnostic Efficacy of the International Ovarian Tumor Analysis ADNEX Model and the ACR O-RADS US (Ovarian-Adnexal Reporting and Data System) for Benign and Malignant Ovarian Tumors: A Retrospective Study in a Tumor Center in Northeast China.

This study is to analyze and compare the diagnostic efficacy of the ADNEX model and O-RADS in Northeast China for benign and malignant ovarian-adnexal tumors. From July 2020 to February 2022, ultrasound images of 312 ovarian-adnexal masses included in the study were analyzed retrospectively, and the properties of these masses were identified using the ADNEX model and O-RADS. The diagnostic efficiency of the ADNEX model and O-RADS was analyzed using a ROC curve, and the capacities of the two models in differentiating benign and malignant ovarian masses at the optimum cutoff value were compared, as well as the consistency of their diagnosis results was evaluated. The study included 312 ovarian-adnexal masses, including 145 malignant masses and 167 benign masses from 287 patients with an average age of (46.8 ± 11.3) years. The AUC of the ADNEX model was 0.974, and the optimum cutoff value was the risk value > 24.2%, with the corresponding sensitivity and specificity being 97.93 and 86.83, respectively. The AUC of the O-RADS was 0.956, and the optimum cutoff value was > O-RADS 3, with the corresponding sensitivity and specificity being 97.24 and 85.03, respectively. The AUCs of the two models were 0.924 and 0.911 at the optimum cutoff values, with no statistical differences between them (P = 0.284). Consistency analysis: the kappa values of the two models for the determination and pathological results of masses were 0.840 and 0.815, respectively, and that for the diagnostic outcomes was 0.910. Both the ADNEX model and O-RADS had good diagnostic performance in people from Northeast China. Their diagnostic capabilities were similar, and diagnostic results were highly consistent at the optimum cutoff values.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Rft1 catalyzes lipid-linked oligosaccharide translocation across the ER membrane.

The eukaryotic asparagine (N)-linked glycan is pre-assembled as a fourteen-sugar oligosaccharide on a lipid carrier in the endoplasmic reticulum (ER). Seven sugars are first added to dolichol pyrophosphate (PP-Dol) on the cytoplasmic face of the ER, generating Man5GlcNAc2-PP-Dol (M5GN2-PP-Dol). M5GN2-PP-Dol is then flipped across the bilayer into the lumen by an ER translocator. Genetic studies identified Rft1 as the M5GN2-PP-Dol flippase in vivo but are at odds with biochemical data suggesting Rft1 is dispensable for flipping in vitro. Thus, the question of whether Rft1 plays a direct or an indirect role during M5GN2-PP-Dol translocation has been controversial for over two decades. We describe a completely reconstituted in vitro assay for M5GN2-PP-Dol translocation and demonstrate that purified Rft1 catalyzes the translocation of M5GN2-PP-Dol across the lipid bilayer. These data, combined with in vitro results demonstrating substrate selectivity and rft1∆ phenotypes, confirm the molecular identity of Rft1 as the M5GN2-PP-Dol ER flippase.

Intravascular Ultrasound vs Angiography-Guided Drug-Coated Balloon Angioplasty: The ULTIMATE â ¢ Trial.

BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).

Excess multi-cause mortality linked to influenza virus infection in China, 2012-2021: a population-based study.

Objectives: The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations. Methods: Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death. Results: There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year. Conclusion: Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.

A full-length glycoprotein mRNA vaccine confers complete protection against severe fever with thrombocytopenia syndrome virus, with broad-spectrum protective effects against bandaviruses.

Highly pathogenic viruses from family Phenuiviridae, which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes. IMPORTANCE: Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.

The Correlation of Centromere Protein Q with Diagnosis and Prognosis in Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear. Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro. Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity. Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.

Targeting a mTOR/autophagy axis: a double-edged sword of rapamycin in spontaneous miscarriage.

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

[Melatonin alleviates autophagy in cortical neurons of neonatal rats with hypoxic- ischemic brain damage via the PI3K/AKT pathway]. / è¤ªé»‘ç´ é€šè¿‡PI3K/AKTé€šè·¯å‡è½»ç¼ºæ°§ç¼ºè¡€æ€§è„‘æŸä¼¤æ–°ç”Ÿå¤§é¼ å¤§è„‘çš®å±‚ç¥žç»ç»†èƒžè‡ªå™¬çš„ç ”ç©¶.

OBJECTIVES: To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the PI3K/AKT signaling pathway, aiming to provide a basis for the clinical application of melatonin. METHODS: Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group, an HIBD group, and a melatonin group (n=9 each). The neonatal rat HIBD model was established using the classic Rice-Vannucci method. Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining. Autophagy-related protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunofluorescence staining and Western blot analysis. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression levels were measured by immunohistochemistry and Western blot. The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis. RESULTS: Twenty-four hours post-modeling, neurons in the sham operation group displayed normal size and orderly arrangement. In contrast, neurons in the HIBD group showed swelling and disorderly arrangement, while those in the melatonin group had relatively normal morphology and more orderly arrangement. Nissl bodies were normal in the sham operation group but distorted in the HIBD group; however, they remained relatively intact in the melatonin group. The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group, but was reduced in the melatonin group compared to the HIBD group (P<0.05). The number of p-PI3K+ and p-AKT+ cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group (P<0.05). LC3 and Beclin-1 protein expression levels were higher, and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group (P<0.05); however, in the melatonin group, LC3 and Beclin-1 levels decreased, and p-PI3K and p-AKT increased compared to the HIBD group (P<0.05). The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+ and p-AKT+ cells between the two groups (P<0.05). CONCLUSIONS: Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD, thereby alleviating HIBD. This mechanism is associated with the PI3K/AKT pathway.

EVA1A reverses lenvatinib resistance in hepatocellular carcinoma through regulating PI3K/AKT/p53 signaling axis.

Lenvatinib is a commonly used first-line drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited due to the drug resistance. EVA1A was a newly identified tumor suppressor, nevertheless, the impact of EVA1A on resistance to lenvatinib treatment in HCC and the potential molecular mechanisms remain unknown. In this study, the expression of EVA1A in HCC lenvatinib-resistant cells is decreased and its low expression was associated with a poor prognosis of HCC. Overexpression of EVA1A reversed lenvatinib resistance in vitro and in vivo, as demonstrated by its ability to promote cell apoptosis and inhibit cell proliferation, invasion, migration, EMT, and tumor growth. Silencing EVA1A in lenvatinib-sensitive parental HCC cells exerted the opposite effect and induced resistance to lenvatinib. Mechanistically, upregulated EVA1A inhibited the PI3K/AKT/MDM2 signaling pathway, resulting in a reduced interaction between MDM2 and p53, thereby stabilizing p53 and enhancing its antitumor activity. In addition, upregulated EVA1A suppressed the PI3K/AKT/mTOR signaling pathway and promoted autophagy, leading to the degradation of mutant p53 and attenuating its oncogenic impact. On the contrary, loss of EVA1A activated the PI3K/AKT/MDM2 signaling pathway and inhibited autophagy, promoting p53 proteasomal degradation and mutant p53 accumulation respectively. These findings establish a crucial role of EVA1A loss in driving lenvatinib resistance involving a mechanism of modulating PI3K/AKT/p53 signaling axis and suggest that upregulating EVA1A is a promising therapeutic strategy for alleviating resistance to lenvatinib, thereby improving the efficacy of HCC treatment.

Burnout among Chinese live streamers: Prevalence and correlates.

BACKGROUND: The prevalence of burnout among live streamers remains largely unknown. This study aims to investigate the prevalence and factors associated with burnout among Chinese live streamers. METHODS: A cross-sectional study recruited 343 full-time live streamers from 3 companies in Changsha city. Socio-demographic and occupational characteristics were collected using self-designed items. Job stress was assessed using the Job Content Questionnaire (JCQ-22), while supervisor and coworker support were evaluated using the last 8 items of the JCQ-22. Burnout was assessed using the 17-item Chinese version of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). RESULTS: Our findings revealed that 30.6% of live streamers experienced burnout. Lower levels of education (OR = 2.65 and 3.37, p = 0,005 and 0.003), higher monthly income (OR = 10.56 and 11.25, both p = 0.003), being an entertainment-oriented streamer (OR = 2.13, p = 0.028), continuous walking during live streams (OR = 2.81, p = 0.006), significant drop in follower count (OR = 2.65, P = 0.006), live streaming during the daytime (OR = 3.75, p = 0.001), and higher support from supervisors and coworkers (OR = 3.66, p = 0.001) were positively associated with burnout. However, the effects of education and drop in followers on burnout were not significant in the multivariate logistic models (p = 0.321 and 0.988). CONCLUSIONS: Burnout among Chinese live streamers is associated with income, being an entertainment streamer, engaging in continuous walking during live streams, conducting live streams during the daytime, and experiencing excessive support from supervisors and coworkers.

IL-33 in patients with periodontitis and chronic obstructive pulmonary disease.

OBJECTIVE: A link between periodontitis and chronic obstructive pulmonary disease (COPD) has been identified, and interleukin-33 (IL-33) may play an important role in the common inflammatory mechanisms of these diseases. This study analyzed the associations of the serum IL-33 level with the occurrence and severity of periodontitis and COPD. METHODS: A total of 161 participants were divided into four groups: healthy volunteers, periodontitis patients, COPD patients, and patients with both COPD and periodontitis. Associations between serum IL-33 levels were measured by enzyme-linked immunosorbent assay, and clinical factors as well as the risks and severity of periodontitis and COPD were analyzed. RESULTS: Serum IL-33 levels were lower in all patient groups than in healthy controls. A trend toward lower IL-33 levels was observed among patients with both diseases compared with patients with either disease alone. The serum IL-33 level was also inversely associated with the severity of periodontitis and COPD. The serum IL-33 level was negatively associated with risks of periodontitis and COPD, indicating that IL-33 is likely involved in the pathophysiologic mechanism of the relationship between COPD and periodontitis. CONCLUSION: This study advances our understanding of the association between COPD and periodontitis and provides new bases for COPD prevention and treatment.

Probing the interfacial structure of aqueous surfactants through helium atom evaporation.

Dissolved helium atoms evaporate from liquids in super-Maxwellian speed distributions because their interactions are too weak to enforce full thermal equilibration at the surface as they are "squeezed" out of solution. The excess speeds of these He atoms reflect their final interactions with solvent and solute molecules at the surfaces of water and other liquids. We extend this observation by monitoring He atom evaporation from salty water solutions coated with surfactants. These surface-active molecules span neutral, anionic, and cationic amphiphiles: butanol, 3-methyl-1-butanol, pentanol, pentanoic acid, pentanoate, tetrabutylammonium, benzyltrimethylammonium, hexyltrimethylammonium, and dodecyltrimethylammonium, each characterized by surface tension measurements. The helium energy distributions, recorded in vacuum using a salty water microjet, reveal a sharp distinction between neutral and ionic surfactant films. Helium atoms evaporate through neutral surfactant monolayers in speed distributions that are similar to a pure hydrocarbon, reflecting the common alkyl chains of both. In contrast, He atoms appear to evaporate through ionic surfactant layers in distributions that are closer to pure salty water. We speculate that the ionic surfactants distribute themselves more loosely and deeply through the top layers of the aqueous solution than do neutral surfactants, with gaps between the surfactants that may be filled with salty water. This difference is supported by prior molecular dynamics simulations and ion scattering measurements of surfactant solutions.

Mapping the intellectual structure and emerging trends for the application of nanomaterials in gastric cancer: A bibliometric study.

BACKGROUND: Recent reviews have outlined the main nanomaterials used in relation to gastrointestinal tumors and described the basic properties of these materials. However, the research hotspots and trends in the application of nanomaterials in gastric cancer (GC) remain obscure. AIM: To demonstrate the knowledge structure and evolutionary trends of research into the application of nanomaterials in GC. METHODS: Publications related to the application of nanomaterials in GC were retrieved from the Web of Science Core Collection for this systematic review and bibliometric study. VOSviewer and CiteSpace were used for bibliometric and visualization analyses. RESULTS: From 2000 to 2022, the application of nanomaterials in GC developed rapidly. The keyword co-occurrence analysis showed that the related research topics were divided into three clusters: (1) The application of nanomaterials in GC treatment; (2) The application and toxicity of nanomaterials in GC diagnosis; and (3) The effects of nanomaterials on the biological behavior of GC cells. Complexes, silver nanoparticles, and green synthesis are the latest high-frequency keywords that represent promising future research directions. CONCLUSION: The application of nanomaterials in GC diagnosis and treatment and the mechanisms of their effects on GC cells have been major themes in this field over the past 23 years.

Microwave biosensor for the detection of growth inhibition of human liver cancer cells at different concentrations of chemotherapeutic drug.

Cytotoxicity assays are crucial for assessing the efficacy of drugs in killing cancer cells and determining their potential therapeutic value. Measurement of the effect of drug concentration, which is an influence factor on cytotoxicity, is of great importance. This paper proposes a cytotoxicity assay using microwave sensors in an end-point approach based on the detection of the number of live cells for the first time. In contrast to optical methods like fluorescent labeling, this research uses a resonator-type microwave biosensor to evaluate the effects of drug concentrations on cytotoxicity by monitoring electrical parameter changes due to varying cell densities. Initially, the feasibility of treating cells with ultrapure water for cell counting by a microwave biosensor is confirmed. Subsequently, inhibition curves generated by both the CCK-8 method and the new microwave biosensor for various drug concentrations were compared and found to be congruent. This agreement supports the potential of microwave-based methods to quantify cell growth inhibition by drug concentrations.

Glioma-derived exosome Lncrna Agap2-As1 promotes glioma proliferation and metastasis by mediating Tgf-ß1 secretion of myeloid-derived suppressor cells.

Background: Glioma (GBM) is the most prevalent malignancy worldwide with high morbidity and mortality. Exosome-mediated transfer of long noncoding RNA (lncRNA) has been reported to be associated with human cancers, containing GBM. Meanwhile, myeloid-derived suppressor cells (MDSCs) play a vital role in mediating the immunosuppressive environments in GBM. Objectives: This study is designed to explore the role and mechanism of exosomal (Exo) lncRNA AGAP2-AS1 on the MDSC pathway in GBM. Methods: AGAP2-AS1, microRNA-486-3p (miR-486-3p), and Transforming growth factor beta-1 (TGF-ß1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, and invasion were detected by 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and Transwell assays. E-cadherin, Vimentin, CD9, CD81, and TGF-ß1 protein levels were examined using Western blot. Exosomes were detected by a transmission electron microscope (TEM). Binding between miR-486-3p and AGAP2-AS1 or TGF-ß1 was predicted by LncBase or TargetScan and then verified using a dual-luciferase reporter assay. Results: AGAP2-AS1 was highly expressed in GBM tissues and cells. Functionally, AGAP2-AS1 absence or TGF-ß1 knockdown repressed tumor cell growth and metastasis. Furthermore, Exo-AGAP2-AS1 from GBM cells regulated TGF-ß1 expression via sponging miR-486-3p in MDSCs. Exo-AGAP2-AS1 upregulation facilitated GBM cell growth and metastasis via the MDSC pathway. Conclusion: Exo-AGAP2-AS1 boosted GBM cell development partly by regulating the MDSC pathway, hinting at a promising therapeutic target for GBM treatment.

Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy.

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.