MicroRNAs (miRNAs) are post-transcriptional gene suppressors and potential mediators of environmental effects. In addition to human miRNAs, viral miRNAs expressed from latent viral sequences are detectable in human cells.

Asthma caused substantial economic and health care burden and is susceptible to air pollution. Particularly, when it comes to elder asthma patient (older than 65), the phenomenon is more significant. The aim of this study is to investigate the Markov-based acute effects of air pollution on elder asthma hospitalizations, in forms of transition probabilities.

Aluminum-ion batteries (AIBs) have been highlighted as a potential alternative to lithium-ion batteries for large-scale energy storage due to the abundant reserve, light weight, low cost, and good safety of Al. However, the development of AIBs faces challenges due to the usage of AlCl3-based ionic liquid electrolytes, which are expensive, corrosive, and sensitive to humidity. Here, we develop a low-cost, non-corrosive, and air-stable hydrated eutectic electrolyte composed of aluminum perchlorate nonahydrate and methylurea (MU) ligand. Through optimizing the molar ratio to achieve the unique solvation structure, the formed Al(ClO4)3·9H2O/MU hydrated deep eutectic electrolyte (AMHEE) with an average coordination number of 2.4 can facilely realize stable and reversible deposition/stripping of Al. When combining with vanadium oxide nanorods positive electrode, the Al-ion full battery delivers a high discharge capacity of 320 mAh g-1 with good capacity retention. The unique solvation structure with a low desolvation energy of the AMHEE enables Al3+ insertion/extraction during charge/discharge processes, which is evidenced by in situ synchrotron radiation X-ray diffraction. This work opens a new pathway of developing low-cost, safe, environmentally friendly and high-performance electrolytes for practical and sustainable AIBs.

Cyclic dimeric adenosine monophosphate (c-di-AMP) is a ubiquitous second messenger of bacteria involved in diverse physiological processes as well as host immune responses. MSMEG_2630 is a c-di-AMP phosphodiesterase (cnpB) of Mycobacterium smegmatis, which is homologous to Mycobacterium tuberculosis Rv2837c. In this study, cnpB-deleted (ΔcnpB), -complemented (ΔcnpB::C), and -overexpressed (ΔcnpB::O) strains of M. smegmatis were constructed to investigate the role of c-di-AMP in regulating mycobacterial physiology and immunogenicity. This study provides more precise evidence that elevated c-di-AMP level resulted in smaller colonies, shorter bacteria length, impaired growth, and inhibition of potassium transporter in M. smegmatis. This is the first study to report that elevated c-di-AMP level could inhibit biofilm formation and induce porphyrin accumulation in M. smegmatis by regulating associated gene expressions, which may have effects on drug resistance and virulence of mycobacterium. Moreover, the cnpB-deleted strain with an elevated c-di-AMP level could induce enhanced Th1 immune responses after M. tuberculosis infection. Further, the pathological changes and the bacteria burden in ΔcnpB group were comparable with the wild-type M. smegmatis group against M. tuberculosis venous infection in the mouse model. Our findings enhanced the understanding of the physiological role of c-di-AMP in mycobacterium, and M. smegmatis cnpB-deleted strain with elevated c-di-AMP level showed the potential for a vaccine against tuberculosis.

Drug resistance is a major obstacle in cancer treatment and recurrence prevention and leads to poor outcomes in patients suffering from osteosarcoma. Clarification of the mechanism of drug resistance and exploration of effective strategies to overcome this obstacle could lead to clinical benefits for these patients. The expression of far upstream element-binding protein 1 (FUBP1) was found to be markedly elevated in osteosarcoma cell lines and clinical specimens compared with osteoblast cells and normal bone specimens. High expression of FUBP1 was correlated with a more aggressive phenotype and a poor prognosis in osteosarcoma patients. We found that overexpression of FUBP1 confers lobaplatin resistance, whereas the inhibition of FUBP1 sensitizes osteosarcoma cells to lobaplatin-induced cytotoxicity both in vivo and in vitro. Chromatin immunoprecipitation-seq and RNA-seq were performed to explore the potential mechanism. It was revealed that FUBP1 could regulate the transcription of prostaglandin E synthase (PTGES) and subsequently activate the arachidonic acid (AA) metabolic pathway, which leads to resistance to lobaplatin. Our investigation provides evidence that FUBP1 is a potential therapeutic target for osteosarcoma patients. Targeting FUBP1, its downstream target PTGES and the AA metabolic pathway may be promising strategies for sensitizing chemoresistant osteosarcoma cells to lobaplatin.

DNA methylation has been found to regulate microRNAs (miRNAs) expression, but the prognostic value of miRNA-related DNA methylation aberration remained largely elusive in cancers including glioblastomas (GBMs). This study aimed to investigate the clinical and biological feature of miRNA methylation in GBMs of non-glioma-CpG island methylator phenotype (non-G-CIMP).

Our previous studies have demonstrated that human parvovirus B19 (B19V) is involved in the pathogenesis of thymic hyperplasia-associated myasthenia gravis (MG). However, more cases need to be assessed to further elucidate the relationship between this virus and thymoma-associated MG.

Myocardial ischemia-reperfusion (MI/R) injury is a common and serious complication following reperfusion treatment for myocardial infarction (MI). Increasing evidence has verified the crucial role of circular RNAs (circRNAs) in the MI/R injury processes. The objective of this study was to investigate the effects and potential regulatory mechanisms of circHMGA2 on MI/R injury. Hypoxia/reoxygenation (H/R) models were established using human cardiac myocytes (HCMs) and mice models were induced by MI/R. The level of circHMGA2 was detected by RT-qPCR. Myocardial function was evaluated by the hemodynamic parameters, the activity of serum myocardial enzymes, HE staining and TUNEL assays. Cell proliferation was measured by CCK-8 assay. The ferrous ion (Fe2+) level was determined with an iron assay kit. Ferroptosis- and pyroptosis-related proteins were determined using western blotting. The levels of oxidative stress and inflammatory factors were analyzed using DCFH-DA staining or ELISA assays. CircHMGA2 was upregulated in H/R-induced HCMs and myocardial tissues of MI/R mice. In vitro, circHMGA2 knockdown attenuated the proliferation inhibition, restrained the ferroptosis and pyroptosis in H/R-induced HCMs. This regulatory mechanism may be associated with the suppression of NLRP3 pathway. In vivo, circHMGA2 depletion attenuated myocardial tissue damage of MI/R mice through inhibiting the oxidative stress and pyroptosis. Taken together, CircHMGA2 enhanced MI/R injury via promoting ferroptosis and pyroptosis, providing new insights into the treatment of MI/R injury.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains the most common cause of death from a single infectious disease. More safe and effective vaccines are necessary for preventing the prevalence of TB. In this study, a subunit vaccine of ESAT-6 formulated with c-di-AMP (ESAT-6:c-di-AMP) promoted mucosal and systemic immune responses in spleen and lung. ESAT-6:c-di-AMP inhibited the differentiations of CD8+ T cells as well as macrophages, but promoted the differentiations of ILCs in lung. The co-stimulation also enhanced inflammatory cytokines production in MH-S cells. It was first revealed that ESAT-6 and c-di-AMP regulated autophagy of macrophages in different stages, which together resulted in the inhibition of Mtb growth in macrophages during early infection. After Mtb infection, the level of ESAT-6-specific immune responses induced by ESAT-6:c-di-AMP dropped sharply. Finally, inoculation of ESAT-6:c-di-AMP led to significant reduction of bacterial burdens in lungs and spleens of immunized mice. Our results demonstrated that subunit vaccine ESAT-6:c-di-AMP could elicit innate and adaptive immune responses which provided protection against Mtb challenge, and c-di-AMP as a mucosal adjuvant could enhance immunogenicity of antigen, especially for innate immunity, which might be used for new mucosal vaccine against TB.

Rosmarinic acid (RosA), a natural poly-phenolic compound isolated from a variety of Labiatae herbs, has been reported to have a range of biological effects.

Airborne particulate matter (PM) is causing more and more serious air pollution and threatening the public health. However, existing air filter technologies with the easy-to-block manner can rarely meet the requirements of high-performance PM filters. Here we propose a conceptually new type of inertial impaction filters for rapidly high-efficiency PM removal. Under the airflow velocity of 8.0 m/s, the real inertial impaction filters show high PM removal efficiencies of up to 97.77 ± 1.53% and 99.47 ± 0.45% for PM2.5 and PM10, respectively. Compared with the traditional air filters reported previously, the inertia impaction filters exhibit extremely low pressure drop of 5-10 Pa and high quality factor (QF) values of 0.380 Pa-1 and 0.524 Pa-1 for PM2.5 and PM10, respectively. These greatly improved QF values are achieved through a series of inertial separation processes. The feature dimension of filtration channel is dozens of times larger than PM average size, which greatly decreases airflow resistance. Particularly, this inertial structure can be made of various types of materials, which shows great potential for low-cost fabrication of large-area devices. As a stand-alone device or incorporated with the existing PM air filter, this inertial impaction filter will bring great benefits to the public health.

Peri-implant epithelial sealing is the first line of defense against external pathogens or stimuli; hence, an essential process to prevent peri-implantitis. Laminin 332 (LN332) is the main component of the internal basal lamina and participates in peri-implant epithelial sealing by forming hemidesmosomes (HDs) with integrin α6β4. In this work, poly (D, L-lactide) (PDLLA)-LN332 composite coating was successfully constructed by a method similar to layer-by-layer assembly, displaying staged LN332 release for as long as 28 days. The PDLLA-LN332 composite coating can activate the intracellular PI3K-Akt pathway via binding to cellular integrin α6β4, which can promote adhesion, migration and proliferation of HaCaT cells and further enhance the expression of keratinocyte HD-related molecules, including integrin α6β4, LN332 and plectin. Furthermore, the PDLLA-LN332 composite coating can promote the adhesion, spreading and proliferation of gingival mesenchymal stem cells and accelerate their epithelial differentiation. Therefore, the PDLLA-LN332 composite coating can enhance implant soft tissue sealing, warranting further in vivo study.

Chromatin-modifying enzymes, especially protein arginine methyltransferases (PRMTs), have been identified as candidate targets for cancer. Cellular or animal-based evidence has suggested an association between coactivator-linked arginine methyltransferase 1 (CARM1) and cancer progression. However, the relationship between CARM1 and patient prognosis and immune infiltration in pancancer patients is unknown. On the basis of the GEO and TCGA databases, we first investigated the possible oncogenic functions of CARM1 in thirty-three tumor types. CARM1 expression was elevated in many types of tumors. In addition, there was a significant association between CARM1 expression and the survival rate of tumor patients. Uterine corpus endometrial carcinoma (UCES) samples had the highest CARM1 mutation frequency of all cancer types. In head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC), CARM1 expression was associated with the level of CD8+ T cell infiltration, and cancer-associated fibroblast infiltration was also observed in other tumors including kidney renal papillary cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). CARM1 was involved in immune modulation and played an important role in the tumor microenvironment (TME). Furthermore, activities associated with RNA transport and its metabolism were included in the possible mechanisms of CARM1. Herein, our first pancancer research explores the oncogenic role of CARM1 in various tumors. CARM1 is associated with immune infiltrates and can be employed as a predictive biomarker in pancancer.

Ozone has become a major air pollutant in recent years, which leading to a variety of lung diseases. This study aimed to explore the mechanisms of pyroptosis and related signaling pathways in ozone-induced lung injury.

Treatment for neuropathic pain as a refractory disease remains unsatisfactory and represents a significant clinical challenge. A highly effective drug is thus urgently needed for neuropathic pain treatment. Dihydromyricetin (DMY) is a flavonoid with a wide range of biological activities. The purpose of this research is to explore the effects of DMY on neuropathic pain and the underlying mechanism of its effect.

Although the harmful effects of arsenic exposure on the cardiovascular system have received great attention, there is still no effective treatment. Vascular endothelial dysfunction (VED) is the initial step of cardiovascular diseases, where pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function. Here, we explored the protective role of PEDF in VED induced by arsenic, and its underlying molecular mechanism, designing an in vivo rat model of arsenic exposure recovery and in vitro endothelial EA. hy926 cell-based assays. The edema of aortic endothelial cells in rats significantly improved during recovery from arsenite exposure compared with rats exposed to 10 and 50 mg/L arsenite continuously. In addition, serum levels of nitric oxide (NO), von Willebrand factor, and nitric oxide synthase (inducible and total activities) in rats, which were greatly affected by arsenite exposure, returned to levels similar to those in the control group after recovery with distilled water. The recovery from arsenite exposure was associated with increased levels of PEDF; decreased protein levels of Fas, FasL, P53, and phospho-p38; and inhibited apoptosis in aortic endothelial cells in vivo. Recombinant human PEDF treatment (100 nM) prevented the toxic effects of arsenite (50 μM) on endothelial cells in vitro by increasing NO content, decreasing reactive oxygen species (ROS) levels, and inhibiting apoptosis, as well as increasing cell viability and decreasing levels of P53 and phospho-p38. Our findings suggest that PEDF protects endothelial cells from arsenic-induced VED by increasing NO release and inhibiting apoptosis, where P53 and p38MAPK are its main targets.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. More than 25 ALS-related genes have been identified, accounting for approximately 10% of sporadic ALS (SALS) and two-thirds of familial ALS (FALS) cases. Several recent studies showed that genetic factors might have a larger contribution to young-onset ALS than to ALS cases overall. However, the genetic profile of young-onset ALS patients is not yet fully understood. Here, we investigated a cohort of 27 young-onset ALS patients (onset age < 45 years) through whole-exome sequencing (WES). Genetic analysis identified pathogenic variants of FUS (25.9%), SOD1 (22.2%), TARDBP (3.7%), and VCP (3.7%) in 27 young-onset ALS patients. Of 12 identified types of mutations, c.1528A > C in FUS and c.266G > A in VCP were novel. All of the cases in this study reflect a monogenic origin with an autosomal dominant mode of inheritance. Notably, a novel de novo missense mutation, c.1528A > C (p.K510Q), in FUS was identified in a 29-year-old ALS patient. Expression of the K510Q mutant FUS resulted in cytoplasmic mislocalization of FUS in cultured cells and induced neural toxicity in a fly model. This study provides further evidence of the genetic profile of young-onset ALS patients from China and expands the mutational spectrum of the FUS gene, with one new K510Q mutation identified.

Cereal fiber is reported to be associated with obesity and metabolic diseases. However, whether cereal fiber improves leptin resistance and sensitivity remains unclear.

Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal and distal limb muscle involvement. Trinucleotide repeat expansions in LRP12 or GIPC1 were recently reported to be associated with OPDM. However, a significant portion of OPDM patients have unknown genetic causes. In this study, long-read whole-genome sequencing and repeat-primed PCR were performed and we identified GGC repeat expansions in the NOTCH2NLC gene in 16.7% (4/24) of a cohort of Chinese OPDM patients, designated as OPDM type 3 (OPDM3). Methylation analysis indicated that methylation levels of the NOTCH2NLC gene were unaltered in OPDM3 patients, but increased significantly in asymptomatic carriers. Quantitative real-time PCR analysis indicated that NOTCH2NLC mRNA levels were increased in muscle but not in blood of OPDM3 patients. Immunofluorescence on OPDM muscle samples and expressing mutant NOTCH2NLC with (GGC)69 repeat expansions in HEK293 cells indicated that mutant NOTCH2NLC-polyglycine protein might be a major component of intranuclear inclusions, and contribute to toxicity in cultured cells. In addition, two RNA-binding proteins, hnRNP A/B and MBNL1, were both co-localized with p62 in intranuclear inclusions in OPDM muscle samples. These results indicated that a toxic protein gain-of-function mechanism and RNA gain-of-function mechanism may both play a vital role in the pathogenic processes of OPDM3. This study extended the spectrum of NOTCH2NLC repeat expansion-related diseases to a predominant myopathy phenotype presenting as OPDM, and provided evidence for possible pathogenesis of these diseases.

Specific recognition of circulating tumor cells (CTCs) is of great significance for cancer diagnosis and personalized therapy. The antibodies and aptamer are commonly used for recognition of CTCs, but they often suffer from low stability and high cost. Therefore, chemically stable and low-cost artificial recognition elements are still highly demanded. Herein, we prepared nano artificial antibody based on molecular imprinting and applied for fluorescence recognition of CTCs. Surface imprinting was employed to construct a transferrin (TRA)-imprinted layer on the surface of rhodamine doped silica nanoparticles. Take advantage of the specific interaction between TRA and TRA receptor (overexpressed on cancer cells), the as-prepared TRA-imprinted artificial antibody was allowed for specific targeting cancer cells mediated by TRA. And the average recognition efficiency of the artificial antibody for the cancer cells was 88% through flow cytometry. Finally, the nano artificial antibody was successfully applied to specific identify mimetic CTCs, under the same conditions, the recognition ability of artificial antibody for CTCs was 8 times higher than the white blood cells.