MEMS-actuated terahertz metamaterials driven by phase-transition materials.

The non-ionizing and penetrative characteristics of terahertz (THz) radiation have recently led to its adoption across a variety of applications. To effectively utilize THz radiation, modulators with precise control are imperative. While most recent THz modulators manipulate the amplitude, frequency, or phase of incident THz radiation, considerably less progress has been made toward THz polarization modulation. Conventional methods for polarization control suffer from high driving voltages, restricted modulation depth, and narrow band capabilities, which hinder device performance and broader applications. Consequently, an ideal THz modulator that offers high modulation depth along with ease of processing and operation is required. In this paper, we propose and realize a THz metamaterial comprised of microelectromechanical systems (MEMS) actuated by the phase-transition material vanadium dioxide (VO2). Simulation and experimental results of the three-dimensional metamaterials show that by leveraging the unique phase-transition attributes of VO2, our THz polarization modulator offers notable advancements over existing designs, including broad operation spectrum, high modulation depth, ease of fabrication, ease of operation condition, and continuous modulation capabilities. These enhanced features make the system a viable candidate for a range of THz applications, including telecommunications, imaging, and radar systems.

Mesenchymal stem cell-derived exosomes in cardiovascular and cerebrovascular diseases: From mechanisms to therapy.

Cardiovascular and cerebrovascular diseases (CVDs) remain an intractable problem and have high morbidity and mortality worldwide, as well as substantial health and economic burdens, representing an urgent clinical need. In recent years, the focus of research has shifted from the use of mesenchymal stem cells (MSCs) for transplantation to the use of their secretory exosomes (MSC-exosomes) for the treatment of numerous CVDs, including atherosclerosis, myocardial infarction (MI), heart failure (HF), ischemia/reperfusion (I/R), aneurysm, and stroke. MSCs are pluripotent stem cells with multiple differentiation pathways that exert pleiotropic effects by producing soluble factors, the most effective components of which are exosomes. MSC-exosomes are considered to be an excellent and promising cell-free therapy for CVDs due to their higher circulating stability, improved biocompatibility, reduced toxicity, and immunogenicity. In addition, exosomes play critical roles in repairing CVDs by inhibiting apoptosis, regulating inflammation, ameliorating cardiac remodeling, and promoting angiogenesis. Herein, we describe knowledge about the biological characteristics of MSC-exosomes, investigate the mechanism by which MSC-exosomes mediate therapeutic repair, and summarize recent advances in the efficacy of MSC-exosomes in CVDs, with a view toward future clinical applications.

Selective recognition of Hg2+ ions in aqueous solution by a CdII-based metal-organic framework with good stability and vacant coordination sites.

A novel water-stable CdII-based metal-organic framework, namely {[Cd(BIBT)(TDC)]·2H2O}n (JXUST-28, BIBT = 4,7-bi(1H-imidazol-1-yl)benzo-[2,1,3]thiadiazole and H2TDC = 2,5-thiophenedicarboxylic acid), was synthesized using a mixed-ligand strategy. Structural analysis demonstrates that JXUST-28 exhibits a two-dimensional layer structure with 4-connected sql topology. Intriguingly, JXUST-28 presents good stability in boiling water (at least 5 days), common organic solvents and aqueous solutions with different pH values of 2-12 (more than 24 hours). Furthermore, fluorescence experiments revealed that JXUST-28 could sense Hg2+ ions in aqueous solution via a quenching effect with a detection limit of 0.097 µM. Meanwhile, JXUST-28 can also be regenerated at least 5 times to detect Hg2+ ions. In addition, light-emitting diode lamps, luminescent films, and test papers of JXUST-28 have been successfully developed for practical applications.

Dihydroquercetin Attenuates Silica-Induced Pulmonary Fibrosis by Inhibiting Ferroptosis Signaling Pathway.

Silicosis is a fatal occupational lung disease which currently has no effective treatment. Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-inflammatory, anti-oxidant and anti-cancer bioactivity. However, whether DHQ protects against silica-induced lung fibrosis remains unknown. Therefore, we aimed to investigate the effect of DHQ on silica-induced lung fibrosis and the underlying molecular mechanism in vivo and in vitro. Our results demonstrated that DHQ treatment markedly attenuated SiO2-induced inflammation and fibrosis degree of lung tissues in the C57BL/6 mice. Additionally, experiments in vitro also confirmed that conditioned medium from DHQ-treated human bronchial epithelial (HBE) cells significantly decreased expression of fibrosis markers of human fetal lung fibroblast cells (MRC-5), such as α-SMA, collagen1 and fibronectin. Interestingly, HBE cells treated by DHQ showed few morphological features of ferroptosis compared with SiO2-treated cells. Furthermore, DHQ treatment remarkably inhibited ferroptosis in activated HBE cells by decreasing the accumulation of iron and lipid peroxidation products, and increasing levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4), whereas stimulation of ferroptosis by specific inducer erastin deeply impaired anti-fibrosis effect of DHQ in vitro. More importantly, our results showed that DHQ also evidently suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Nevertheless, activation of ferritinophagy by specific inducer rapamycin (Rapa) evidently blocked DHQ-inhibited HBE cells ferritinophagy and anti-fibrosis effect of DHQ. Overall, our research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis, which provided a preliminary theoretical basis for the clinical application of DHQ in the treatment of silicosis.

Mental Disorders Associated with COVID-19 Related Unemployment.

In response to the COVID-19 pandemic, restrictions on economic activities have resulted in a sharp rise of unemployment. The purpose of this research is to explore mental disorders associated with COVID-19 related unemployment using a large, nationally representative dataset, the 2020 COVID-19 Household Pulse Survey. ANOVA with post hoc tests (Tukey HSD) are utilized to reveal the mean difference of mental disorders between various employment status, as well as between reasons of unemployment. Binary logit model is used to investigate the potential effect of different reasons of unemployment on mental disorders. Individuals who were not working during the pandemic due to involuntary reasons had higher probabilities of mental disorders than those who were working and those who voluntarily separated from work. Among respondents who were not working due to COVID-19 related reasons, respondents whose employer went out of business were the most likely to experience mental disorders. Household job uncertainty in the next four weeks positively contributed to mental disorders. Government should consider measures to contain the spread of virous while keeping as many people employed as possible. Government should also consider providing adequate financial and counseling assistance to individuals who are in the greatest need for such support.

A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR-24-3p/CDK4/pRb axis.

Circular RNAs (circRNAs) have been established to be involved in numerous processes in the human genome, but their function in vascular aging remains largely unknown. In this study, we aimed to characterize and analyze the function of a circular intronic RNA, ciPVT1, in endothelial cell senescence. We observed significant downregulation of ciPVT1 in senescent endothelial cells. In proliferating endothelial cells, ciPVT1 knockdown induced a premature senescence-like phenotype, inhibited proliferation, and led to an impairment in angiogenesis. An in vivo angiogenic plug assay revealed that ciPVT1 silencing significantly inhibited endothelial tube formation and decreased hemoglobin content. Conversely, overexpression of ciPVT1 in old endothelial cells delayed senescence, promoted proliferation, and increased angiogenic activity. Mechanistic studies revealed that ciPVT1 can sponge miR-24-3p to upregulate the expression of CDK4, resulting in enhanced Rb phosphorylation. Moreover, enforced expression of ciPVT1 reversed the senescence induction effect of miR-24-3p in endothelial cells. In summary, the present study reveals a pivotal role for ciPVT1 in regulating endothelial cell senescence and may have important implications in the search of strategies to counteract the development of age-associated vascular pathologies.

circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression.

Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. Circular RNAs (circRNAs) are endogenous RNA molecules with covalently closed-loop structures, which have been reported to be abnormally expressed in many human diseases. However, the potential role of circRNAs in endothelial cell senescence and atherosclerosis remains largely unknown. Here, we compared the expression patterns of circRNAs in young and senescent human endothelial cells with RNA sequencing. Among the differentially expressed circRNAs, circGNAQ, a circRNA enriched in vascular endothelium, was significantly downregulated in senescent endothelial cells. circGNAQ silencing triggered endothelial cell senescence, as determined by a rise in senescence-associated ß-galactosidase activity, reduced cell proliferation, and suppressed angiogenesis; circGNAQ overexpression showed the opposite effects. Mechanistic studies revealed that circGNAQ acted as an endogenous miR-146a-5p sponge to increase the expression of its target gene PLK2 by decoying the miR-146a-5p, thereby delaying endothelial cell senescence. In vivo studies showed that circGNAQ overexpression in the endothelium inhibited endothelial cell senescence and atherosclerosis progression. These results suggest that circGNAQ plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that the management of circGNAQ provides a potential therapeutic approach for limiting the progression of atherosclerosis.

Clinical Significance of Monitoring Circulating Free DNA and Plasma Heat Shock Protein 90alpha in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer in China and has an extremely poor prognosis. Circulating free DNA (cfDNA) and plasma heat shock protein 90alpha (Hsp90a) are two novel noninvasive biomarkers for diagnosis and prognostic prediction of several types of cancer. However, to the best of our knowledge, the roles of the two biomarkers in ESCC are still unknown. METHODS: Here, we recruited 93 primary ESCC patients and detected plasma concentrations of the two markers at different time points, including 1-3 days pre-chemotherapy, 1-7 days pre-surgery and 7-14 days post-surgery. Baseline concentrations of the two markers were associated with main characteristics of ESCC patients which were collected at first diagnosis. Correlation between the two markers and traditional serum biomarkers at baseline was also examined. Furthermore, dynamic changes of the cfDNA and Hsp90α concentrations among different time points and the potential clinical significance were assessed. RESULTS: Consequently, there was no significant association between baseline concentrations of the two markers and clinical features. Especially, cfDNA demonstrated stronger correlation with other circulating biomarkers than Hsp90α at baseline level. Importantly, both cfDNA and Hsp90α concentrations were significantly increased after surgery. Kaplan-Meier survival analysis showed that a change in concentration of cfDNA (ΔcfDNA) but not Hsp90α (ΔHSP90ɑ) between pre-surgery and post-surgery had significant effect on the overall survival of surgical patients with ESCC. CONCLUSION: Thus, ΔcfDNA evaluation could be a promising prognostic marker for surgical ESCC patients. Our findings may improve the understanding of the function of cfDNA and Hsp90α in ESCC.

Circular RNAs: Promising Biomarkers for Age-related Diseases.

Aging is a complex biological process closely linked with the occurrence and development of age-related diseases. Despite recent advances in lifestyle management and drug therapy, the late diagnosis of these diseases causes severe complications, usually resulting in death and consequently impacting social economies. Therefore, the identification of reliable biomarkers and the creation of effective treatment alternatives for age-related diseases are needed. Circular RNAs (circRNAs) are a novel class of RNA molecules that form covalently closed loops capable of regulating gene expression at multiple levels. Several studies have reported the emerging functional roles of circRNAs in various conditions, providing new perspectives regarding cellular physiology and disease pathology. Notably, accumulating evidence demonstrates the involvement of circRNAs in the regulation of age-related pathologies, including cardio-cerebrovascular disease, neurodegenerative disease, cancer, diabetes, rheumatoid arthritis, and osteoporosis. Therefore, the association of circRNAs with these age-related pathologies highlights their potential as diagnostic biomarkers and therapeutic targets for better disease management. Here, we review the biogenesis and function of circRNAs, with a special focus on their regulatory roles in aging-related pathologies, as well as discuss their potential as biological biomarkers and therapeutic targets for these diseases.

Plasma-Derived Exosomal Circular RNA hsa_circ_0005540 as a Novel Diagnostic Biomarker for Coronary Artery Disease.

BACKGROUND: Exosomes exist in almost all body fluid and contain diverse biological contents which may be reflective of disease state. Circular RNAs (circRNAs) are stable in structure and have a long half-life in exosomes without degradation, thus making them reliable biomarkers. However, the potential of exosomal circRNAs as biomarkers of coronary artery disease (CAD) remains to be established. Here, we aimed to investigate the expression levels and the potential use of exosomal circRNAs as diagnostic biomarkers for CAD. METHODS: CircRNA expression levels in exosomes obtained from three plasma samples of CAD patients and three paired controls were analyzed using RNA sequencing. Exosomal circRNAs obtained in the profiling phase were then verified in two-center validation cohorts. Finally, the ability of exosomal circRNAs, adjusting for Framingham Heart Study (FHS) risk factors, was determined to discriminate between CAD patients and non-CAD controls. RESULTS: 355 circRNAs were differentially expressed between these two groups: 164 were upregulated, and 191 were downregulated. Here, we selected the potential circRNAs (fold change > 4, P < 0.05) as candidate biomarkers for further validation. Our data showed that only hsa_circ_0005540 was significantly associated with CAD (P < 0.0001). After adjustment for risk factors, hsa_circ_0005540 showed a high discriminatory power for CAD in ROC analyses (AUC = 0.853; 95%confidence interval (CI) = 0.799 - 0.906, P < 0.001). CONCLUSION: Our results suggest that plasma exosomal hsa_circ_0005540 can be used as a promising diagnostic biomarker of CAD.

CircFOXO3 rs12196996, a polymorphism at the gene flanking intron, is associated with circFOXO3 levels and the risk of coronary artery disease.

CircFOXO3 plays an important role in the pathogenesis of coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) at circRNA flanking introns may change its back-splicing and influence circRNA formation. Here, we aimed to investigate the influence of the polymorphisms at the circFOXO3 flanking introns on individual susceptibility to CAD. A total of 1185 individuals were included in the case-control study. In a multivariate logistic regression analysis, we determined that the rs12196996 G variant was significantly associated with increased CAD risk (OR = 1.36, P = 0.014). A similar trend of the association was observed in the recessive model (OR = 2.57, P = 0.003). Stratified analysis revealed a more significant association with CAD risk among younger subjects and non-smokers. Consistent with these results, the haplotype rs12196996G-rs9398171C containing rs12196996G allele was also associated with increased CAD risk (OR = 1.31, P = 0.013). Further investigation revealed that the rs12196996 GG genotype was associated with decreased circFOXO3 expression, but not linear FOXO3 levels. Taken together, our data provide the first evidence that the rs12196996 polymorphism at the circFOXO3 gene flanking intron is associated with CAD risk in the Chinese Han population, which is probably due to influence circFOXO3 levels.

Selective Conversion of 5-Hydroxymethylfuraldehyde Using Cp*Ir Catalysts in Aqueous Formate Buffer Solution.

The highly selective hydrogenation/hydrolytic ring-opening reaction of 5-hydroxymethylfuraldehyde (5-HMF) was catalyzed by homogeneous Cp*Ir(III) half-sandwich complexes to produce 1-hydroxy-2,5-hexanedione (HHD). Adjustment of pH was found to regulate the distribution of products and reaction selectivity, and full conversion of 5-HMF to HHD with 99 % selectivity was achieved at pH 2.5. A mechanistic study revealed that the hydrolysis/ring-opening reaction of 2,5-bis-(hydroxymethyl)furan is the important intermediate reaction step. In addition, an isolated yield of 85 % for HHD was obtained in a 10 g-scale experiment, and the reaction with fructose as the starting material also led to a 98 % GC yield (71.9 % to fructose) of HHD owing to the excellent tolerance of the catalyst under acidic conditions.

Blood transfusion does not affect survival of gastric cancer patients.

BACKGROUND: To initially assess the impact of perioperative blood transfusions (PBTs) on overall survival of patients underwent curative resection of Ⅰ-Ⅲ TNM stage gastric cancer (GC) using the propensity scoring method. METHODS: The medical records of 1150 GC patients who underwent curative resection in the Tianjin Cancer Hospital between 2003 and 2008 were retrospectively analyzed. Both transfusion and nontransfusion patients were assessed the prognostic differences after surgery using the propensity score analysis. RESULTS: A total of 299 GC patients (26.0%) were administrated the PBT. With the unadjusted analysis, patients with PBT presented older age, more operative blood loss, lower hemoglobin, lower albumin level, and higher risk of the advanced disease. The 5-y survival rate for patients with PBT was 31.0%, which was significantly lower than that (47.9%) of patients without PBT (P < 0.05). However, we demonstrated that there was not any statistical 5-y survival rate difference of between patients with PBT and patients without PBT with the propensity score analysis (31.0% versus 31.3%, P > 0.05). In addition, we also found that PBT was not significantly associated with the increasing risk of mortality (hazard ratio, 1.054; P = 0.628). CONCLUSIONS: PBT could not give rise to the worse prognoses of GC patients.

Alkanes from Bioderived Furans by using Metal Triflates and Palladium-Catalyzed Hydrodeoxygenation of Cyclic Ethers.

Using a metal triflate and Pd/C as catalysts, alkanes were prepared from bioderived furans in a one-pot hydrodeoxygenation (HDO) process. During the reaction, the metal triflate plays a crucial role in the ring-opening HDO of furan compounds. The entire reaction process has goes through two major phases: at low temperatures, saturation of the exocyclic double bond and furan ring are catalyzed by Pd/C; at high temperatures, the HDO of saturated furan compounds is catalyzed by the metal triflate. The reaction mechanism was verified by analyzing the changes of the intermediates during the reaction. In addition, different metal triflates, solvents, and catalyst recycling were also investigated.

Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for examination of methylated status of protocadherin10 (PCDH10) promoter to predict the prognosis of gastric cancer.

OBJECTIVE: To elucidate the clinical significance of the methylated status of CpG site count of PCDH10 promoter in the survival prediction in gastric cancer (GC). METHODS: In the previous study, we demonstrated that the methylated CpG site count was significantly associated with the overall survival (OS) of GC patients by using the bisulfite genomic sequencing (BGS) with no less than five clones per sample. It was so complex and expensive for patients to undergo the BGS clones. In this study, we detected the different CpG site counts (hypermethylated and hypomethylated) of PCDH10 DNA promoter in GC samples of 471 patients by directly bisulfite genomic sequencing (D-BGS) without any clone. Furthermore, we evaluated the relationships between the methylated status of PCDH10 promoter and OS. RESULTS: Two hundred and fifty-seven of 471 (54.6%) GC patients were identified to present with PCDH10 promoter methylation by D-BGS. Patients who presented with 5 or more methylated CpG site counts of PCDH10 promoter had significantly poorer prognosis than patients who with less than 5 methylated CpG site counts of PCDH10 promoter (p= 0.039). With the multivariate survival analysis, we demonstrated that T stage, N stage and the hypermethylated CpG site counts of PCDH10 DNA promoter were the independent predictors of OS of GC patients. In addition, the hypermethylated CpG site counts of PCDH10 DNA promoter had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other two independent predictors of the OS, indicating the hypermethylated CpG site counts of PCDH10 DNA promoter as the best prognostic predictor of GC. CONCLUSIONS: Our present findings suggested that the hypermethylated CpG site counts of PCDH10 DNA promoter for evaluating the prognosis of GC was reasonable by using the D-BGS.

Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for examination of methylated status of E3 ubiquitin ligase RNF180 DNA promoter to predict the survival of gastric cancer.

BACKGROUND: E3 ubiquitin ligase Ring finger protein 180 (RNF180) has been identified as a novel tumor suppressor in gastric cancer and the methylated CpG site count of RNF180 DNA promoter can predict the prognosis for gastric cancer patients. OBJECTIVE: In the previous study, we demonstrated that methylated CpG site count of RNF180 DNA promoter was significantly associated with the survival of patients with gastric cancer using the bisulfite genomic sequencing (BGS) in the gastric cancer tissue with five clones per sample. It was so complicate for each patient underwent the BGS detection with clones. It is important to explore a simple, rapid and accurate method to detect methylated CpG site count to predicting the prognosis for gastric cancer patients. METHODS: At present study, we detected hypermethylated and hypomethylated CpG site count of RNF180 DNA promoter in samples of 480 gastric cancer patients by direct bisulfite sequencing. RESULTS: We found that patients who possessed seven or less hypermethylated CpG sites of RNF180 DNA promoter had much better survival (p= 0.008), which was similar to our previous research results by using the BGS with clones. With the multivariate survival analysis, we found that T stage, N stage and hypermethylated CpG site count of RNF180 DNA promoter were the independent predictors of prognosis for gastric cancer patients. CONCLUSIONS: hypermethylated CpG site count of RNF180 DNA promoter for evaluating the prognosis of gastric cancer was reasonable by using the direct bisulfite sequencing.

[Advantage of D2+ lymph node dissection for distal advanced gastric cancer].

OBJECTIVE: To evaluate the value of D2+ lymph node dissection for patients with distal advanced gastric cancer. METHODS: Clinicopathological data of 305 cases with distal advanced gastric cancer receiving D2+(n=68) or D2(n=237) lymph node dissection in the Tianjin Cancer Hospital from January 2003 to December 2007 were analyzed retrospectively. The overall 5-year survival rate between the 2 groups. RESULTS: The median survival was 36 months and the 5-year overall survival rate was 40.3% in all patients. The 5-year overall survival rates in the D2+ and D2 groups were 50.4% and 37.4% respectively, and the difference was statistically significant(P=0.049). In multivariate prognostic analysis however, the extent of lymph node dissection was not identified as an independent prognostic factor(P=0.174). Subgroup analysis showed that 5-year survival rate of D2+ group was significantly higher as compared to D2 group for the following subgroups: maximum diameter of tumor larger than 4 cm(43.9% vs. 27.0%), Borrmann type III(-IIII((55.5% vs. 30.1%), poorly differentiated and undifferentiated tumor (49.8% vs. 37.0%), T4 stage (47.8% vs. 31.0%), N2 stage (53.3% vs. 13.9%), N3 stage (20.0% vs. 9.6%) and positive No.6 lymph nodes (33.1% vs. 16.0%). CONCLUSION: Compared with D2 lymph node dissection, D2+ lymph node dissection may benefit some patients with large, poorly differentiated, or late-stage tumor.