Risk factors for fasting blood glucose control in middle-aged and elderly type 2 diabetes patients.

This study aimed to investigate and analyze the medication use, fasting blood glucose control, and associated risk factors among residents with type 2 diabetes at the grassroots level in Xinjiang Production and Construction Corps. A multi-stage cluster sampling method was employed to conduct a questionnaire survey among residents aged 45 and above in battalions (communities) as the smallest unit. The medication use was recorded, and fasting blood glucose control was considered as the dependent variable. Logistic regression analysis was performed to identify the risk factors influencing fasting blood glucose control among different population characteristics. A total of 2316 participants were included in the study, of which 1072 were male (45.12%), 1418 were aged 65 and above (61.23%), 2031 were Han Chinese (87.69%), and 1551 were from the surrounding areas of Urumqi (66.97%). The main medications used among the top three classes were metformin, insulin, and α-glucosidase inhibitors. The treatment rate for type 2 diabetes was 71.80%, and the fasting blood glucose control rate was 27.98%. Multivariate analysis identified living outside the Urumqi surrounding area, age 65 and above, body mass index ≥ 24, abnormal blood lipids, and untreated hypertension as independent risk factors for poor fasting blood glucose control, while treatment was a protective factor for achieving blood glucose control. The treatment rate and fasting blood glucose control rate among grassroots residents with type 2 diabetes in Xinjiang Production and Construction Corps need improvement. Efforts should be made to enhance patient medication adherence and health management awareness through education. Targeted interventions should be implemented for high-risk populations with identified risk factors to reduce or delay the occurrence of diabetes and its complications, ultimately aiming to reduce mortality rates and improve quality of life.

Viral myocarditis: from molecular mechanisms to therapeutic prospects.

Myocarditis is characterized as local or diffuse inflammatory lesions in the myocardium, primarily caused by viruses and other infections. It is a common cause of sudden cardiac death and dilated cardiomyopathy. In recent years, the global prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the widespread vaccination have coincided with a notable increase in the number of reported cases of myocarditis. In light of the potential threat that myocarditis poses to global public health, numerous studies have sought to elucidate the pathogenesis of this condition. However, despite these efforts, effective treatment strategies remain elusive. To collate the current research advances in myocarditis, and thereby provide possible directions for further research, this review summarizes the mechanisms involved in viral invasion of the organism and primarily focuses on how viruses trigger excessive inflammatory responses and in result in different types of cell death. Furthermore, this article outlines existing therapeutic approaches and potential therapeutic targets for the acute phase of myocarditis. In particular, immunomodulatory treatments are emphasized and suggested as the most extensively studied and clinically promising therapeutic options.

Differential responses of soil bacteria, fungi and protists to root exudates and temperature.

The impact of climate warming on soil microbes has been well documented, with studies revealing its effects on diversity, community structure and network dynamics. However, the consistency of soil microbial community assembly, particularly in response to diverse plant root exudates under varying temperature conditions, remains an unresolved issue. To address this issue, we employed a growth chamber to integrate temperature and root exudates in a controlled experiment to examine the response of soil bacteria, fungi, and protists. Our findings revealed that temperature independently regulated microbial diversity, with distinct patterns observed among bacteria, fungi, and protists. Both root exudates and temperature significantly influenced microbial community composition, yet interpretations of these factors varied among prokaryotes and eukaryotes. In addition to phototrophic bacteria and protists, as well as protistan consumers, root exudates determined to varying degrees the enrichment of other microbial functional guilds at specific temperatures. The effects of temperature and root exudates on microbial co-occurrence patterns were interdependent; root exudates primarily simplified the network at low and high temperatures, while responses to temperature varied between single and mixed exudate treatments. Moreover, temperature altered the composition of keystone species within the microbial network, while root exudates led to a decrease in their number. These results emphasize the substantial impact of plant root exudates on soil microbial community responses to temperature, underscoring the necessity for future climate change research to incorporate additional environmental variables.

Specific and Sensitive Visual Proviral DNA Detection of Major Pathogenic Avian Leukosis Virus Subgroups Using CRISPR-Associated Nuclease Cas13a.

Avian leukosis viruses (ALVs) include a group of avian retroviruses primarily associated with neoplastic diseases in poultry, commonly referred to as avian leukosis. Belonging to different subgroups based on their envelope properties, ALV subgroups A, B, and J (ALV-A, ALV-B, and ALV-J) are the most widespread in poultry populations. Early identification and removal of virus-shedding birds from infected flocks are essential for the ALVs' eradication. Therefore, the development of rapid, accurate, simple-to-use, and cost effective on-site diagnostic methods for the detection of ALV subgroups is very important. Cas13a, an RNA-guided RNA endonuclease that cleaves target single-stranded RNA, also exhibits non-specific endonuclease activity on any bystander RNA in close proximity. The distinct trans-cleavage activity of Cas13 has been exploited in the molecular diagnosis of multiple pathogens including several viruses. Here, we describe the development and application of a highly sensitive Cas13a-based molecular test for the specific detection of proviral DNA of ALV-A, B, and J subgroups. Prokaryotically expressed LwaCas13a, purified through ion exchange and size-exclusion chromatography, was combined with recombinase polymerase amplification (RPA) and T7 transcription to establish the SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) molecular detection system for the detection of proviral DNA of ALV-A/B/J subgroups. This novel method that needs less sample input with a short turnaround time is based on isothermal detection at 37 °C with a color-based lateral flow readout. The detection limit of the assay for ALV-A/B/J subgroups was 50 copies with no cross reactivity with ALV-C/D/E subgroups and other avian oncogenic viruses such as reticuloendotheliosis virus (REV) and Marek's disease virus (MDV). The development and evaluation of a highly sensitive and specific visual method of detection of ALV-A/B/J nucleic acids using CRISPR-Cas13a described here will help in ALV detection in eradication programs.

Functional traits of exotic submerged macrophytes mediate diversity-invasibility relationship in freshwater communities under eutrophication.

Plant diversity may respond differently in terms of whether it can drive plant invasions in freshwater ecosystem. Linkages and interactions between diversity and invasibility have not been clearly resolved, and it is unclear how nutrient enrichment (e.g., eutrophication) will affect this relationship. As a key predictor of plant growth, the ability of functional traits to mediate trade-offs in the diversity-invasibility relationship is unknown. Here, we conducted a series of experiments to determine the role of exotic plant functional traits in the diversity-invasibility relationship of submerged macrophyte communities under eutrophication. We selected common native and exotic submerged macrophytes in the subtropics to construct different diverse submerged macrophyte communities to simulate invasion. Meanwhile, to test the adaptability and importance of functional traits, we experimentally verified the differences in functional traits between exotic and native species. Our results showed a positive correlation between native plant diversity and community invasibility. Moreover, the invader's performance was predominantly determined by functional traits of exotic species, such as plant biomass and tissue nutrients, which were significantly altered by species diversity. Furthermore, our results suggested that functional traits contribute significantly more to the invasiveness of exotic submerged macrophytes than the other factors to which they are subjected. Plant functional traits can mediate the diversity-invasibility relationship because of the higher intrinsic dominance of exotic submerged macrophyte species. In summary, our study revealed diversity-invasibility relationship in submerged macrophyte communities and highlighted functional traits as key drivers of invasion of high-risk exotic submerged macrophyte species. Although previous studies have elucidated the importance of functional trait studies for plant invasions, our study provides the only current evidence demonstrating the important role of invaders' functional traits in mediating the diversity-invasibility relationship. This novel perspective offers valuable insights into the management and control of invasive aquatic plants.

Hypomethylation-associated Sox11 upregulation promotes oncogenesis via the PI3K/AKT pathway in OLP-associated OSCC.

Oral lichen planus (OLP) is a particularly prevalent oral disorder with the potential to progress to oral squamous cell carcinoma (OSCC). SRY-box transcription factor 11 (Sox11) has been reported to serve as a prognostic marker for various cancers. However, the role and mechanism of Sox11 in OLP-related OSCC are unknown. Our results indicated that Sox11 was highly expressed, and that Sox11 promoter methylation was significantly reduced in OLP-associated OSCC tissues. High Sox11 expression and Sox11 promoter hypomethylation indicate a poor patient prognosis. According to in vivo and in vitro experiments, the knockdown of Sox11 inhibited proliferation, invasion, and migration while driving its apoptotic death in OSSC cells; Sox11 overexpression exerted the opposite effect as Sox11 knockdown. Mechanistically, knockdown of Sox11 inhibited PI3K/AKT and glycolysis pathway, and overexpression of Sox11 enhanced the PI3K/AKT and glycolysis pathways in OSCC cells. In addition, we demonstrated that Sox11 overexpression accelerated the progression of OSCC, at least in part by promoting PI3K/AKT pathway activation. In conclusion, our data indicated that the DNA hypomethylation-associated upregulation of Sox11 could promote oncogenic transformation via the PI3K/AKT pathway in OLP-associated OSCC. Therefore, Sox11 might be a reliable biomarker for predicting the progression of precancerous oral tissues.

All-RNA-mediated targeted gene integration in mammalian cells with rationally engineered R2 retrotransposons.

All-RNA-mediated targeted gene integration methods, rendering reduced immunogenicity, effective deliverability with non-viral vehicles, and a low risk of random mutagenesis, are urgently needed for next-generation gene addition technologies. Naturally occurring R2 retrotransposons hold promise in this context due to their site-specific integration profile. Here, we systematically analyzed the biodiversity of R2 elements and screened several R2 orthologs capable of full-length gene insertion in mammalian cells. Robust R2 system gene integration efficiency was attained using combined donor RNA and protein engineering. Importantly, the all-RNA-delivered engineered R2 system showed effective integration activity, with efficiency over 60% in mouse embryos. Unbiased high-throughput sequencing demonstrated that the engineered R2 system exhibited high on-target integration specificity (99%). In conclusion, our study provides engineered R2 tools for applications based on hit-and-run targeted DNA integration and insights for further optimization of retrotransposon systems.

Synthesis of Boronate Affinity-Based Oriented Dummy Template-Imprinted Magnetic Nanomaterials for Rapid and Efficient Solid-Phase Extraction of Ellagic Acid from Food.

Ellagic acid (EA) is a natural polyphenol and possesses excellent in vivo bioactivity and antioxidant behaviors, which play an important role in the treatment of oxidative stress-related diseases, such as cancer. Additionally, EA is also known as a skin-whitening ingredient. The content of EA would determine its efficacy. Therefore, the accurate analysis of EA content can provide more information for the scientific consumption of EA-rich foods and cosmetics. Nevertheless, the analysis of EA in these samples is challenging due to the low concentration level and the presence of interfering components with high abundance. Molecularly imprinted polymers are highly efficient pretreatment materials in achieving specific recognition of target molecules. However, the traditional template molecule (EA) could not be absolutely removed. Hence, template leakage continues to occur during the sample preparation process, leading to a lack of accuracy in the quantification of EA in actual samples, particularly for trace analytes. In addition, another drawback of EA as an imprinting template is that EA possesses poor solubility and a high price. Gallic acid (GA), called dummy templates, was employed for the synthesis of MIPs as a solution to these challenges. The approach used in this study was boronate affinity-based oriented surface imprinting. The prepared dummy-imprinted nanoparticles exhibited several significant advantages, such as good specificity, high binding affinity ((4.89 ± 0.46) × 10-5 M), high binding capacity (6.56 ± 0.35 mg/g), fast kinetics (6 min), and low binding pH (pH 5.0) toward EA. The reproducibility of the dummy-imprinted nanoparticles was satisfactory. The dummy-imprinted nanoparticles could still be reused even after six adsorption-desorption cycles. In addition, the recoveries of the proposed method for EA at three spiked levels of analysis in strawberry and pineapple were 91.0-106.8% and 93.8-104.0%, respectively, which indicated the successful application to real samples.

Dihydroartemisinin induces ferroptosis in T cell acute lymphoblastic leukemia cells by downregulating SLC7A11 and activating the ATF4­CHOP signaling pathway.

The present study aimed to investigate the anti-leukemic effects of dihydroartemisinin (DHA) on T-cell acute lymphoblastic leukemia (T-ALL) cell lines, Jurkat and Molt-4, and the underlying mechanisms. Cell Counting Kit-8 was performed to measure cell viability. Cell apoptosis and cell cycle distribution were assessed by flow cytometry. The expression levels of ATF4 and CHOP mRNA were assessed by reverse transcription-quantitative PCR, while the protein abundance of SLC7A11, GPX4, ATF4 and CHOP was determined by western blotting. Moreover, malondialdehyde, glutathione (GSH) and reactive oxygen species (ROS) assays were used to detect the levels of ferroptosis. The results showed that DHA suppressed T-ALL cell viability in vitro, and induced cell cycle arrest at S or G2/M phase. DHA also induced ROS burst, activated endoplasmic reticulum (ER) stress, disrupted the system Xc--GSH-GSH peroxidase 4 antioxidant system, and increased lipid peroxide accumulation, resulting in cell death. By contrast, the pharmacological inhibition of ferroptosis alleviated DHA-induced cell death, confirming that DHA induces T-ALL cell death via ferroptosis. Mechanistically, the effect of DHA on ferroptosis was partly mediated by downregulating SLC7A11 and upregulating the ATF4-CHOP signaling pathway, which is associated with ER stress. These results indicated that DHA may induce ferroptosis in T-ALL cell lines and could represent a promising therapeutic agent for treating T-ALL.

Miniature CRISPR-Cas12 Systems: Mechanisms, Engineering, and Genome Editing Applications.

The therapeutic application of CRISPR-based gene editing technology is hindered by the delivery challenges of large Cas nucleases. The emergence of miniature editing tools derived from type V CRISPR systems and their ancestor TnpB nucleases presents promising solutions to counter these obstacles. Notably, the type V CRISPR-Cas12f and -Cas12n systems exhibit not only a concise gene size but also remarkable precision in targeted editing, thereby underscoring their potential as supreme gene editing tools. Although both systems are considered as intermediates in the evolution of TnpB to mature Cas12 effectors, they exhibit distinct biochemical and structural characteristics, demonstrating the diversity and complexity of TnpB's evolutionary outcomes. The diverse evolutionary branches indicate the existence of numerous unexplored compact CRISPR systems in nature, the mining and development of which could potentially revolutionize gene manipulation techniques and pave the way for innovative applications in gene therapy. In this Account, we summarize the recent advances from our group with the research and development of Cas12f and Cas12n genome editing systems, including the identification, characterization, and engineering for improving the editing efficiency. Additionally, we discuss the evolutionary process of the ancestral nuclease TnpB growing into various type V CRISPR systems, giving insight into the discovery of novel compact gene editing systems.

Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox.

Experimental studies on DNA transposable elements (TEs) have been limited in scale, leading to a lack of understanding of the factors influencing transposition activity, evolutionary dynamics, and application potential as genome engineering tools. We predicted 130 active DNA TEs from 102 metazoan genomes and evaluated their activity in human cells. We identified 40 active (integration-competent) TEs, surpassing the cumulative number (20) of TEs found previously. With this unified comparative data, we found that the Tc1/mariner superfamily exhibits elevated activity, potentially explaining their pervasive horizontal transfers. Further functional characterization of TEs revealed additional divergence in features such as insertion bias. Remarkably, in CAR-T therapy for hematological and solid tumors, Mariner2_AG (MAG), the most active DNA TE identified, largely outperformed two widely used vectors, the lentiviral vector and the TE-based vector SB100X. Overall, this study highlights the varied transposition features and evolutionary dynamics of DNA TEs and increases the TE toolbox diversity.

Correlation between newborn weight and serum BCAAs in pregnant women with diabetes.

BACKGROUND: Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids for mammals. Maternal BCAAs during pregnancy have been associated with newborn development. Meanwhile, BCAAs have been tightly linked with insulin resistance and diabetes in recent years. Diabetes in pregnancy is a common metabolic disorder. The current study aims to assess the circulating BCAA levels in pregnant women with diabetes and their relationship with neonatal development. METHODS: The serum concentrations of BCAAs and their corresponding branched-chain α-keto acids (BCKAs) catabolites in 33 pregnant women with normal glucose tolerance, 16 pregnant women with type 2 diabetes before pregnancy (PDGM), and 15 pregnant women with gestational diabetes mellitus (GDM) were determined using a liquid chromatography system coupled to a mass spectrometer. The data were tested for normal distribution and homogeneity of variance before statistical analysis. Correlations were computed with the Pearson correlation coefficient. RESULTS: The maternal serum BCAAs and BCKAs levels during late pregnancy were higher in women with PGDM than those in healthy women. Meanwhile, the circulating BCAAs and BCKAs showed no significant changes in women with GDM compared with those in healthy pregnant women. Furthermore, the circulating BCAA and BCKA levels in women with PGDM were positively correlated with the weight of the newborn. The circulating leucine level in women with GDM was positively correlated with the weight of the newborn. BCAA and BCKA levels in healthy pregnant women showed no correlation with newborn weight. CONCLUSIONS: The serum BCAAs in pregnant women with diabetes, which was elevated in PGDM but not GDM, were positively correlated with newborn weight. These findings highlight potential approaches for early identification of high-risk individuals and interventions to reduce the risk of adverse pregnancy outcomes.

AHNAK2 Regulates NF-κB/MMP-9 Signaling to Promote Pancreatic Cancer Progression.

Early metastasis of pancreatic cancer (PaC) is a major cause of its high mortality rate. Previous studies have shown that AHNAK2 is involved in the progression of some tumors and is predicted to be an independent prognostic factor for PaC; however, the specific mechanisms through which AHNAK2 regulates PaC remain unclear. In this study, we examined the role of AHNAK2 in PaC and its potential molecular mechanisms. AHNAK2 mRNA and protein expression in PaC tissues and cells were measured using qRT-PCR and western blot analysis. After AHNAK2 knockdown using small interfering RNA, PaC cells were subjected to CCK-8 scratch, and Transwell assays to assess cell proliferation, migration, and invasion, respectively. Furthermore, the validation of the mechanistic pathway was achieved by western blot analysis. AHNAK2 mRNA and protein levels were up-regulated in PaC and silencing AHNAK2 significantly inhibited the proliferation, migration, and invasion of PaC cells. Mechanistically, AHNAK2 knockdown decreased the expression of phosphorylated p65, phosphorylated IκBα, and matrix metalloproteinase-9 (MMP-9), suggesting that activation of the NF-κB/MMP-9 signaling pathway was inhibited. Importantly, activation of NF-κB reversed the effects of AHNAK2 knockdown. Our findings indicate that AHNAK2 promotes PaC progression through the NF-kB/MMP-9 pathway and provides a theoretical basis for targeting AHNAK2 for the treatment of PaC.

Characterization and Engineering of a Novel Miniature Eubacterium siraeum CRISPR-Cas12f System.

Cas12f nucleases are one of the most compact genome editors, exhibiting promising potential for in vivo therapeutic applications. However, the availability of active Cas12f genome editors remains relatively limited in the field. Here, we report the characterization and engineering of a novel miniature Cas12f endonuclease from Eubacterium siraeum (EsCas12f1, 433 amino acids). We elucidate the specific Protospacer Adjacent Motifs preference and the detailed biochemical properties for DNA targeting and cleavage. By employing rational design strategies, we systematically optimize the guide RNA of EsCas12f1, converting the initially ineffective CRISPR-EsCas12f1 system into an efficient bacterial genome editor. Furthermore, we demonstrate the capacity of EsCas12f1 for in vitro nucleic-acid diagnostics. In summary, our results enrich the miniature CRISPR-Cas toolbox and pave the way for the application of EsCas12f1 for both genome editing and in vitro diagnostics.

Single-cell RNA sequencing analysis provides novel insights into the role of apoptosis-related genes in muscle aging.

OBJECTIVE: This study employed a comprehensive single-cell analysis approach to explore the role of cell apoptosis-related genes in muscle aging. METHODS: The single-cell RNA sequencing data from the GSE143704 dataset were used to identify distinct cell clusters and assess gene expression patterns related to apoptosis activation. The "limma" package was used to identify hub genes, after which we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify relevant pathways. Additionally, Gene Set Enrichment Analysis(GSEA) and Gene Set Variation Analysis (GSVA) were used to uncover relevant biological pathways. The Receiver Operating Characteristic Curve (ROC) was used to evaluate the diagnostic value of the hub genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to analyze the immune cell infiltration levels. RESULTS: Single-cell sequencing data from muscle aging patients allowed the identification of various cell types, including epithelial cells, adipocytes, and tissue-resident macrophages. By conducting a differential expression analysis that intersected active and nonactive apoptosis, as well as comparing elderly and young samples, a total of 22 hub genes were identified (p < 0.05). The 22 hub genes have discriminative ability as potential biomarkers for diagnosing muscle aging. The enrichment analysis indicated that these genes were closely associated with diverse pathways, including "response to UV-B" and "extracellular matrix organization" (p < 0.05). Furthermore, GSEA and GSVA indicated that multiple pathways emerged-for example, the "complement and coagulation cascades", "proteasome", "insulin signaling pathway", and "MAPK signaling pathway". Additionally, the analysis of immune cell infiltration revealed positive correlations between most of the hub genes and immune cells. CONCLUSION: Our study identified 22 apoptosis-related genes involved in muscle aging and indicated their potential diagnostic value. These findings offer a novel perspective on the pathogenesis of muscle aging and present potential targets for therapeutic interventions.

Understanding the rapid spread of antimicrobial resistance genes mediated by IS26.

Insertion sequences (ISs) promote the transmission of antimicrobial resistance genes (ARGs) across bacterial populations. However, their contributions and dynamics during the transmission of resistance remain unclear. In this study, we selected IS26 as a representative transposable element to decipher the relationship between ISs and ARGs and to investigate their transfer features and transmission trends. We retrieved 2656  translocatable  IS 26 -bounded  units with  ARGs (tIS26-bUs-ARGs) in complete bacterial genomes from the NCBI RefSeq database. In total, 124 ARGs spanning 12 classes of antibiotics were detected, and the average contribution rate of IS26 to these genes was 41.2%. We found that  IS 26 -bounded  units (IS26-bUs) mediated extensive ARG dissemination within the bacteria of the Gammaproteobacteria class, showing strong transfer potential between strains, species, and even phyla. The IS26-bUs expanded in bacterial populations over time, and their temporal expansion trend was significantly correlated with antibiotic usage. This wide dissemination could be due to the nonspecific target site preference of IS26. Finally, we experimentally confirmed that the introduction of a single copy of IS26 could lead to the formation of a composite transposon mediating the transmission of "passenger" genes. These observations extend our knowledge of the IS26 and provide new insights into the mediating role of ISs in the dissemination of antibiotic resistance.

Immunological Characteristics of Hepatic Dendritic Cells in Patients and Mouse Model with Liver Echinococcus multilocularis Infection.

The cestode Echinococcus multilocularis, which mainly dwells in the liver, leads to a serious parasitic liver disease called alveolar echinococcosis (AE). Despite the increased attention drawn to the immunosuppressive microenvironment formed by hepatic AE tissue, the immunological characteristics of hepatic dendritic cells (DCs) in the AE liver microenvironment have not been fully elucidated. Here, we profiled the immunophenotypic characteristics of hepatic DC subsets in both clinical AE patients and a mouse model. Single-cell RNA sequencing (scRNA-Seq) analysis of four AE patient specimens revealed that greater DC numbers were present within perilesional liver tissues and that the distributions of cDC and pDC subsets in the liver and periphery were different. cDCs highly expressed the costimulatory molecule CD86, the immune checkpoint molecule CD244, LAG3, CTLA4, and the checkpoint ligand CD48, while pDCs expressed these genes at low frequencies. Flow cytometric analysis of hepatic DC subsets in an E. multilocularis infection mouse model demonstrated that the number of cDCs significantly increased after parasite infection, and a tolerogenic phenotype characterized by a decrease in CD40 and CD80 expression levels was observed at an early stage, whereas an activated phenotype characterized by an increase in CD86 expression levels was observed at a late stage. Moreover, the expression profiles of major immune checkpoint molecules (CD244 and LAG3) and ligands (CD48) on hepatic DC subsets in a mouse model exhibited the same pattern as those in AE patients. Notably, the cDC and pDC subsets in the E. multilocularis infection group exhibited higher expression levels of PD-L1 and CD155 than those in the control group, suggesting the potential of these subsets to impair T cell function. These findings may provide valuable information for investigating the role of hepatic DC subsets in the AE microenvironment and guiding DC targeting treatments for AE.

Calcium-sensing receptor-mediated macrophage polarization improves myocardial remodeling in spontaneously hypertensive rats.

Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (Mφs) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis. R568 can increase the content of CaSR and M2 macrophages (M2Mφs, exert an anti-inflammatory effect) in myocardial tissue, reduce M1 macrophages (M1Mφs), which have a pro-inflammatory effect in this process. In contrast, NPS2143, a negative state regulator of CaSR, exerted the opposite effect in all of the above experiments. Following this study, R568 increased CaSR content in SHR myocardial tissue, lowered blood pressure, promoted macrophages to M2Mφs and improved myocardial fibrosis, but interestingly, both M1Mφs and M2Mφs were increased in the peritoneal cavity of SHRs, the number of M2Mφs remained lower than M1Mφs. In vitro, R568 increased CaSR content in RAW264.7 cells (a macrophage cell line), regulating intracellular Ca2+ ([Ca2+]i) inhibited NOD-like receptor family protein 3 (NLRP3) inflammasome activation and ultimately prevented its conversion to M1Mφs. The results showed that a decrease in CaSR in hypertensive rats causes further development of hypertension and cardiac damage. EH myocardial remodeling can be improved by CaSR overexpression by suppressing NLRP3 inflammasome activation and macrophage polarization toward M1Mφs and increasing M2Mφs.

A mitochondrial targeted dual ratiometric near-infrared fluorescent probe based on ICT effect for the detection of SO2 derivative and its bioimaging.

SO2 derivatives play an important role in many metabolic processes, excessive ingestion of them can lead to serious complications of various diseases. In this work, a novel dual ratiometric NIR fluorescent probe XT-CHO based on ICT effect was synthesized for detecting SO2 derivative. In the design of the probe, the α, ß-unsaturated bond formed between benzopyran and coumarin was used as the reaction site for SO2, meanwhile, the extended π-conjugate system promoted maximum emission wavelength of the probe up to 708 nm. Notably, the probe exhibited high selectivity and sensitivity for detecting SO2, the limit of detection reached 2.13 nM and 58.5 nM in fluorescence spectra and UV-Vis absorption spectra, respectively. The reaction mechanism of SO2 and XT-CHO had been verified by 1H NMR, ESI-MS spectra and DFT calculation. Moreover, the probe was successfully applied in detecting endogenous and exogenous SO2 in living cells and proved possessed the mitochondrial targeted ability.

Air Pollution and Influenza: A Systematic Review and Meta-Analysis.

Background: Influenza is the first infectious disease that implements global monitoring and is one of the major public health issues in the world. Air pollutants have become an important global public health issue, in recent years, and much epidemiological and clinical evidence has shown that air pollutants are associated with respiratory diseases. Methods: We comprehensively searched articles published up to 15 November 2022 in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Database of Chinese sci-tech periodicals, and Wanfang Database. The search strategies were based on keyword combinations related to influenza and air pollutants. The air pollutants included particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3). Meta-analysis was performed using the R programming language (R4.2.1). Results: A total of 2926 records were identified and 1220 duplicates were excluded. Finally, 19 studies were included in the meta-analysis according to inclusion and exclusion criteria. We observed a significant association between partial air pollutants (PM2.5, NO2, PM10 and SO2) and the incidence risk of influenza. The RRs were 1.0221 (95% CI: 1.0093~1.0352), 1.0395 (95% CI: 1.0131~1.0666), 1.007 (95% CI: 1.0009~1.0132), and 1.0352 (95% CI. 1.0076~1.0635), respectively. However, there was no significant relationship between CO and O3 exposure and influenza, and the RRs were 1.2272 (95% CI: 0.9253~1.6275) and 1.0045 (95% CI: 0.9930~1.0160), respectively. Conclusion: Exposure to PM2.5, NO2, PM10, and SO2 was significantly associated with influenza, which may be risk factors for influenza. The association of CO and O3 with influenza needs further investigation.