Protein profile of circulating extracellular vesicles reveals biomarker candidates for diagnosis of post-traumatic deep vein thrombosis.

BACKGROUND AND OBJECTIVE: Deep vein thrombosis (DVT) is a common complication after trauma and mostly without specific symptoms. Timely diagnosis and early appropriate treatment measures can prevent further development of thrombosis for patients with traumatic lower extremity fractures. Although extracellular vesicles (EVs) are confirmed as promising disease biomarkers, little is known about the role of altered levels and composition in the diagnosis of post-traumatic DVT. METHOD: The levels of circulating EVs subgroups were measured using flow cytometry. Isolated EVs were characterized and subjected to proteomics analysis to screen for differentially expressed proteins (DEPs) between DVT and non-DVT patients. Regularized logistic regression analysis based on L2 penalty terms using R's caret package was applied to build a model for DVT diagnosis. RESULTS: Compared to non-DVT patients, DVT patients had higher circulating hepatocyte-derived EVs (hEVs) with good predictive value for post-traumatic DVT diagnosis. The results of the proteomic analysis showed that differentially expressed proteins (DEPs) of circulating EVs between the DVT group and non-DVT group were enriched in the complement and coagulation cascade. Finally, an integrated model of five biomarkers including SERPING1, C8G, CFH, FIX, and hEVs level was established for post-traumatic DVT diagnosis with robust identification of the traumatic patients with and without DVT (AUC 0.972). CONCLUSION: Post-traumatic DVT patients had changed levels and composition of circulating EVs compared to non-DVT patients and healthy controls. Circulating EVs may acquire pathological protein signatures and become potential biomarkers for identifying subjects' post-traumatic DVT.

Suppression of OsSAUR2 gene expression immobilizes soil arsenic bioavailability by modulating root exudation and rhizosphere microbial assembly in rice.

One of the factors influencing the behavior of arsenic (As) in environment is microbial-mediated As transformation. However, the detailed regulatory role of gene expression on the changes of root exudation, rhizosphere microorganisms, and soil As occurrence forms remains unclear. In this study, we evidence that loss-of-function of OsSAUR2 gene, a member of the SMALL AUXIN-UP RNA family in rice, results in significantly higher As uptake in roots but greatly lower As accumulation in grains via affecting the expression of OsLsi1, OsLsi2 in roots and OsABCC1 in stems. Further, the alteration of OsSAUR2 expression extensively affects the metabolomic of root exudation, and thereby leading to the variations in the composition of rhizosphere microbial communities in rice. The microbial community in the rhizosphere of Ossaur2 plants strongly immobilizes the occurrence forms of As in soil. Interestingly, Homovanillic acid (HA) and 3-Coumaric acid (CA), two differential metabolites screened from root exudation, can facilitate soil iron reduction, enhance As bioavailability, and stimulate As uptake and accumulation in rice. These findings add our further understanding in the relationship of OsSAUR2 expression with the release of root exudation and rhizosphere microbial assembly under As stress in rice, and provide potential rice genetic resources and root exudation in phytoremediation of As-contaminated paddy soil.

Al(OTf)3-Catalyzed Regioselective N2-Arylation of Tetrazoles with Diazo Compounds.

Regioselective methods to access alkylated tetrazoles still remain a challenging goal. Herein, we describe a novel regioselective protocol for N2-arylation of tetrazoles with diazo compounds using inexpensive Al(OTf)3. This reaction could be conducted under mild conditions to access a diverse array of alkylated tetrazoles with 2-substituted tetrazoles as the major products, demonstrating a comprehensive range of substrate compatibility and excellent functional group compatibility. Mechanistic studies revealed a carbene-free process in this reaction procedure. Furthermore, the scale-up reaction and transformations of the N2-arylation of tetrazole products demonstrated the potential of this strategy.

First report of leaf spot disease caused by Pseudopithomyces chartarum on Lonicera caerulea L. in Heilongjiang Province, China.

Blue honeysuckle (Lonicera caerulea L.) cultivation has gradually expanded in China but continues to be limited by challenges such as leaf spot disease. Between September 2022 and September 2023, a leaf spot disease was observed on approximately 30% of 'Lanjingling' blue honeysuckles grown in a 2.66 ha field (a total of about 11,000 plants) in Jiamusi city (130.47°E, 46.16°N), Heilongjiang Province, China. Affected plants displayed brown necrotic lesions on their leaves that gradually expanded in area until the leaves fell off the plant entirely. Small, 3 to 4 mm segments of infected tissue from 50 randomly selected leaves were surface sterilized with 75% ethanol for 30 s and 5% sodium hypochlorite (NaOCl) for 3 min, rinsed three times with sterile distilled water, dried on paper towels, and plated in 9 cm Petri dishes containing potato dextrose agar (PDA) (Yan et al. 2022). Five pathogens (LD-232, LD-233, LD-234, LD-235, and LD-236) were isolated on PDA and displayed a conidia morphology consistent with Pseudopithomyces spp. (Perelló et al. 2017). The fungal colonies on PDA were villiform, white, and whorled and had sparse aerial mycelium on the surface with black conidiomata. The conidia were obpyriform and dark brown, had 0 to 3 transverse and 0 to 1 longitudinal septa, and measured 9.00 to 15.30 µm × 5.70 to 9.30 µm in size (n = 50). Genomic DNA was extracted from a representative isolate, LD-232, for molecular verification and PCR amplification was performed with ITS1/ITS4 (White et al. 1990), LROR/LR7 (Carbone and Kohn 1999), and RPB2-5F2/RPB2-7CR (Liu et al. 1999) primers. Sequences of LD-232 ITS (OR835654), LSU (OR835652), and RPB2 (OR859769) revealed 99.8% (530/531 nt), 98.8% (639/647 nt), and 99.8% (1015/1017 nt) shared identity with Pseudopithomyces chartarum sequences (OP269600, OP237014, and MK434892), respectively (Wu et al. 2023). Bayesian inference (BI) was used to construct the phylogenies using Mr. Bayes v. 3.2.7 to confirm the identity of the isolates (Ariyawansa et al. 2015). Phylogenetic trees cannot be constructed based on the genes' concatenated sequences because selective strains do not have complete rDNA-ITS, LSU, and RPB2 sequences. Therefore, based on the morphological characteristics and molecular phylogeny, LD-232 was identified as P. chartarum (Perelló et al. 2017; Wu et al. 2023). A pathogenicity test was performed with six healthy, two-year-old 'Lanjingling' blue honeysuckle plants. Three plants were inoculated by spraying the LD-232 conidial suspension (1 × 106 spores/ml) or clean water as an experimental control condition (Wu et al. 2023; Yan et al. 2023). All plants were cultured in a greenhouse at 28℃ under a 12-h light/dark cycle, and each experiment was replicated three times. Typical leaf spot symptoms were observed on inoculated leaves after 10 days. The same pathogens were reisolated from infected leaves, displayed the same morphological and molecular traits, and were again identified as P. chartarum, confirming Koch's postulate. P. chartarum previously caused leaf spot disease on Tetrapanax papyrifer in China (Wu et al. 2023). To our knowledge, this is the first report of blue honeysuckle leaf spot caused by P. chartarum in China. Identification of P. chartarum as a disease agent on blue honeysuckle will help guide future management of leaf diseases for this economically important small fruit tree.

Growth increase and gonadal dysfunction of the lined seahorse triggered by zinc exposure.

Seahorses are characterized by unique characteristics such as a male pregnancy reproductive strategy and grasping preferences, which make these species vulnerable to various environmental risks. Zinc (Zn) is one of the most frequently occurring toxic elements in coastal waters; however, little is known about the effect of Zn exposure on seahorses. In the present study, line seahorses (Hippocampus erectus) were exposed to waterborne Zn (0.2 and 1.0 mg/L) and the impact on growth and gonadal development was investigated. Zn exposure induced growth improvement, but also led to gonadal dysfunction in the lined seahorse. Female seahorses exhibited high testosterone levels, immature follicles, and weight increase after Zn exposure, which is the typical characteristics of a polycystic ovary syndrome (PCOS)-like phenotype. Transcriptomic data suggested that the Zn-induced growth promotion resulted from the dysregulated expression of fat accumulation genes. Further investigation of gene expression profiles in the brain, ovaries, and testes indicated that Zn affected the expression of genes involved in growth, immunity, tissue remodeling, and gonadal development by regulating serum steroid hormone levels and androgen receptor expression. This study not only clarifies the complex impact of Zn on seahorses using physiological, histological, and molecular evidence but can also provide new insights into the mechanism underlying PCOS in reproductive-aged women. Moreover, this work demonstrates the risk of the common practice of Zn supplementation in the aquaculture industry as the consequent growth yield may not represent a healthy condition.

A G-quadruplex-binding platinum complex induces cancer mitochondrial dysfunction through dual-targeting mitochondrial and nuclear G4 enriched genome.

BACKGROUND: G-quadruplex DNA (G4) is a non-canonical structure forming in guanine-rich regions, which play a vital role in cancer biology and are now being acknowledged in both nuclear and mitochondrial (mt) genome. However, the impact of G4-based targeted therapy on both nuclear and mt genome, affecting mt function and its underlying mechanisms remain largely unexplored. METHODS: The mechanisms of action and therapeutic effects of a G4-binding platinum(II) complex, Pt-ttpy, on mitochondria were conducted through a comprehensive approaches with in vitro and in vivo models, including ICP-MS for platinum measurement, PCR-based genetic analysis, western blotting (WB), confocal microscope for mt morphology study, extracellular flux analyzer, JC1 and Annexin V apoptosis assay, flow cytometry and high content microscope screening with single-cell quantification of both ROS and mt specific ROS, as well as click-chemistry for IF study of mt translation. Decipher Pt-ttpy effects on nuclear-encoded mt related genes expression were undertaken via RNA-seq, Chip-seq and CUT-RUN assays. RESULTS: Pt-ttpy, shows a highest accumulation in the mitochondria of A2780 cancer cells as compared with two other platinum(II) complexes with no/weak G4-binding properties, Pt-tpy and cisplatin. Pt-ttpy induces mtDNA deletion, copy reduction and transcription inhibition, hindering mt protein translation. Functional analysis reveals potent mt dysfunction without reactive oxygen species (ROS) induction. Mechanistic study provided first evidence that most of mt ribosome genes are highly enriched in G4 structures in their promoter regions, notably, Pt-ttpy impairs most nuclear-encoded mt ribosome genes' transcription through dampening the recruiting of transcription initiation and elongation factors of NELFB and TAF1 to their promoter with G4-enriched sequences. In vivo studies show Pt-ttpy's efficient anti-tumor effects, disrupting mt genome function with fewer side effects than cisplatin. CONCLUSION: This study underscores Pt-ttpy as a G4-binding platinum(II) complex, effectively targeting cancer mitochondria through dual action on mt and nuclear G4-enriched genomes without inducing ROS, offering promise for safer and effective platinum-based G4-targeted cancer therapy.

Reproductive factors and cardiometabolic disease among middle-aged and older women: a nationwide study from CHARLS.

Background: Cardiometabolic disease is skyrocketing to epidemic proportions due to the high prevalence of its components and the aging of the worldwide population. More efforts are needed to improve cardiometabolic health. The aim of this nationally representative study based on the China Health and Retirement Longitudinal Study (CHARLS, 2014-2018) was to examine the association between reproductive factors and cardiometabolic disease among Chinese women aged ≥45 years. Methods: The CHARLS is an ongoing longitudinal study initiated in 2011, and the latest follow-up was completed in 2018. In total, 6,407 participants were analyzed. Effect-sizes are expressed as odds ratios (OR) and 95% confidence intervals (CI). Confounding was considered from statistical adjustment, subsidiary exploration, and unmeasured confounding assessment aspects. Results: Of 6,407 accessible participants, 60.9% were recorded as having one or more of five predefined cardiovascular or metabolic disorders. Compared to those with two children, participants who had 0-1 child were found to have a lower risk of cardiometabolic disease (OR = 0.844, 95% CI: 0.714-0.998), and those who had ≥3 children had a greater risk (OR = 1.181, 95% CI: 1.027-1.357). Age at menarche of 16-18 years was a protective factor compared with ≤16 years of age (OR = 0.858, 95% CI: 0.749-0.982). In contrast, participants with a history of abortion were 1.212 times more likely to have cardiometabolic disorders (OR = 1.212, 95% CI: 1.006-1.465). The likelihood for the presence of unmeasured confounding was low, as reflected by E-values. Conclusions: Our findings demonstrate that number of children, age at menarche, and history of abortion were associated with a significant risk of cardiometabolic disease among Chinese women aged ≥45 years.

Near-infrared fluorescent probe for the imaging of viscosity in fatty liver mice and valuation of drug efficacy.

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

BCKDK modification enhances the anticancer efficacy of CAR-T cells by reprogramming branched chain amino acid metabolism.

Altered branched chain amino acids (BCAAs), including leucine, isoleucine, and valine, are frequently observed in patients with advanced cancer. We evaluated the efficacy of chimeric antigen receptor (CAR) T cell-mediated cancer cell lysis potential in the immune microenvironment of BCAA supplementation and deletion. BCAA supplementation increased cancer cell killing percentage, while accelerating BCAA catabolism and decreasing BCAA transporter decreased cancer cell lysis efficacy. We thus designed BCKDK engineering CAR T cells for the reprogramming of BCAA metabolism in the tumor microenvironment based on the genotype and phenotype modification. BCKDK overexpression (OE) in CAR-T cells significantly improved cancer cell lysis, while BCKDK knockout (KO) resulted in inferior lysis potential. In an in vivo experiment, BCKDK-OE CAR-T cell treatment significantly prolonged the survival of mice bearing NALM6-GL cancer cells, with the differentiation of central memory cells and an increasing proportion of CAR-T cells in the peripheral circulation. BCKDK-KO CAR-T cell treatment resulted in shorter survival and a decreasing percentage of CAR-T cells in the peripheral circulation. In conclusion, BCKDK-engineered CAR-T cells exert a distinct phenotype for superior anticancer efficiency.

miR-4685-3p Alleviates Human Brain Microvascular Endothelial Cells Injury by Regulating MMP9.

OBJECTIVE: Cerebral microbleeds (CMBs) are punctate hemorrhagic lesions within the brain parenchyma and are a classic manifestation of cerebral small vessel disease (CSVD). The primary objective of this study is to investigate the potential role of miR-4685-3p and underlying mechanisms by which miR-4685-3p modulates matrix metalloproteinase-9 (MMP9) in cerebral microvascular endothelial cell injury. METHODS: We employed high-throughput sequencing to screen for differentially expressed miRNAs in the peripheral blood of patients with CMBs and healthy controls. Employing lipopolysaccharide (LPS) to induce cellular damage, we aim to establish a model of human brain microvascular endothelial cells (hCMEC/D3) injury. We also had cells transfected with miR-4685-3p mimic and MMP9 overexpression plasmid. We utilized quantitative polymerase chain reaction (qPCR) to assess the expression levels of miR-4685-3p and performed Western blot analysis to examine MMP9 expression levels in the cells. We employed the CCK-8 assay, TUNEL assay, and tube formation assay to evaluate cellular viability, apoptotic rates, and angiogenic capabilities. Furthermore, dual-luciferase reporter assay analysis was conducted to confirm the relationship between miR-4685-3p and MMP9. RESULTS: The sequencing results indicated a downregulation of miR-4685-3p in the peripheral blood of patients with CMBs. Within the context of LPS-induced injury to hCMEC/D3 cells, miR-4685-3p exhibits reduced expression, whereas MMP9 expression levels are elevated. The elevation of miR-4685-3p expression levels attenuates LPS-induced cellular apoptosis and enhances the viability and tube-forming capacity of hCMEC/D3 cells. Concomitant transfection with MMP9 overexpression constructs effectively reversed the detrimental effects of LPS on hCMEC/D3 cell integrity. We further confirmed that miR-4685-3p overexpression directly targets MMP9, leading to negative regulation of MMP9 expression. CONCLUSION: Upregulating miR-4685-3p, which targets the MMP9 axis, mitigated LPS-induced cerebral microvascular endothelial cell injury, potentially playing a protective role in the progression of CMBs.

Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy.

The sulfate radical (SO4•-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4•- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.

Can energy saving and emission reduction policies promote green transformation of industrial enterprises--The Case of China.

In the context of the continued advancement of the green economy transition, the proactive pursuit of carbon emissions reduction and the early attainment of carbon neutrality goals have emerged as essential components in promoting high-quality economic development. Not only does it contribute to the creation of a community of human destiny, but it is also vital to the realization of sustainable development for human civilization. A dynamic evolutionary game model, which encompasses the interactions among government, enterprises, and the public, was constructed to examine the inherent impact mechanisms of the behavior of three players on the development of a green economy under the context of energy saving and emission reduction subsidies. The results showed that the incentive and punishment mechanisms served as effective tools for harmonizing the interests of system members. Within the mechanisms, the public demonstrated a higher sensitivity to rewards, while enterprises exhibited greater responsiveness to fines. Consequently, the government could influence the behavior of enterprises by incentivizing the public to serve as a third-party inquiry and oversight body. Simultaneously, the government could encourage enterprises to expedite green technology innovation by employing a combination of incentive and punishment mechanisms.

Structure-based characterization and compound identification of the wild-type THF class-II riboswitch.

Riboswitches are conserved regulatory RNA elements participating in various metabolic pathways. Recently, a novel RNA motif known as the folE RNA motif was discovered upstream of folE genes. It specifically senses tetrahydrofolate (THF) and is therefore termed THF-II riboswitch. To unravel the ligand recognition mechanism of this newly discovered riboswitch and decipher the underlying principles governing its tertiary folding, we determined both the free-form and bound-form THF-II riboswitch in the wild-type sequences. Combining structural information and isothermal titration calorimetry (ITC) binding assays on structure-based mutants, we successfully elucidated the significant long-range interactions governing the function of THF-II riboswitch and identified additional compounds, including alternative natural metabolites and potential lead compounds for drug discovery, that interact with THF-II riboswitch. Our structural research on the ligand recognition mechanism of the THF-II riboswitch not only paves the way for identification of compounds targeting riboswitches, but also facilitates the exploration of THF analogs in diverse biological contexts or for therapeutic applications.

Bifidobacterium longum K5 Prevents Enterohaemorrhagic Escherichia coli O157:H7 Infection in Mice through the Modulation of the Gut Microbiota.

Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is a commonly encountered foodborne pathogen that can cause hemorrhagic enteritis and lead to hemolytic uremic syndrome (HUS) in severe cases. Bifidobacterium is a beneficial bacterium that naturally exists in the human gut and plays a vital role in maintaining a healthy balance in the gut microbiota. This study investigated the protective effects of B. longum K5 in a mouse model of EHEC O157:H7 infection. The results indicated that pretreatment with B. longum K5 mitigated the clinical symptoms of EHEC O157:H7 infection and attenuated the increase in myeloperoxidase (MPO) activity in the colon of the mice. In comparison to the model group, elevated serum D-lactic acid concentrations and diamine oxidase (DAO) levels were prevented in the K5-EHEC group of mice. The reduced mRNA expression of tight junction proteins (ZO-1, Occludin, and Claudin-1) and mucin MUC2, as well as the elevated expression of virulence factors Stx1A and Stx2A, was alleviated in the colon of both the K5-PBS and K5-EHEC groups. Additionally, the increase in the inflammatory cytokine levels of TNF-α and IL-1ß was inhibited and the production of IL-4 and IL-10 was promoted in the K5-EHEC group compared with the model group. B. longum K5 significantly prevented the reduction in the abundance and diversity of mouse gut microorganisms induced by EHEC O157:H7 infection, including blocking the decrease in the relative abundance of Roseburia, Lactobacillus, and Oscillibacter. Meanwhile, the intervention with B. longum K5 promoted the production of acetic acid and butyric acid in the gut. This study provides insights into the use of B. longum K5 for developing probiotic formulations to prevent intestinal diseases caused by pathogenic bacterial infections.

Optical properties and radiative forcing of carbonaceous aerosols in a valley city under persistent high temperature.

Carbonaceous aerosols were collected in the valley city of Baoji city in Northern China in August 2022. The light absorption characteristics and influencing factors of black carbon (BC) and brown carbon (BrC) were analyzed, and their radiative forcing was estimated. The results showed that the light absorption of secondary brown carbon [AbsBrC,sec (370)] was 7.5 ± 2.4 Mm-1, which was 2.5 times that of primary brown carbon [AbsBrC,pri (370), 3.0 ± 1.2 Mm-1]. During the study period, the absorption Ångström exponent (AAE) of aerosol was 1.6, indicating that there was obvious secondary aerosol formation or carbonaceous aerosol aging in the valley city of Baoji. Except for secondary BrC (BrCsec), the light absorption coefficient (Abs) and mass absorption efficiency (MAE) of BC and primary BrC (BrCpri) during the persistent high temperature period (PHT) were higher than those during the normal temperature period (NT) and the precipitation period (PP), which indicated that the light absorption capacity of black carbon and primary brown carbon increased, while the light absorption capacity of secondary brown carbon decreased under persistent high temperature period. Secondary aerosols sulfide (SO42-), nitrate (NO3-) and secondary organic carbon (SOC) are important factors for promoting the light absorption enhancemen of BC and BrCpri and photobleaching of BrCsec during persistent high temperature period. The Principal Component Analysis-Multiple Linear Regression (PCA-MLR) model showed that traffic emissions was the most important source of pollution in Baoji City. Based on this, the secondary source accelerates the aging of BC and BrC, causing changes in light absorption. During PHT, the radiative forcing of BC and BrCpri were enhanced, while the radiative forcing of BrCsec was weakened, but the positive radiative forcing generated by them may aggravate the high-temperature disaster.

Ultrasound­targeted microbubble destruction technology delivering ß­klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post­myocardial infarction.

Fibroblast growth factor (FGF)21 is a peptide hormone that improves mitochondrial function and energy metabolism, and the deficiency of its co­receptor ß­klotho (KLB) causes decreased FGF21 sensitivity. The present study examined whether the cardiac delivery of plasmids containing the KLB gene via ultrasound­targeted microbubble destruction (UTMD) enhances the efficacy of FGF21 against heart failure post­acute myocardial infarction (AMI). For this purpose, the levels of FGF21 in patients and rats with heart dysfunction post­infarction were determined using ELISA. Sprague­Dawley rats received the 3X UTMD­mediated delivery of KLB@cationic microbubbles (KLB@CMBs) 1 week following the induction of AMI. Echocardiography, histopathology and biochemical analysis were performed at 4 weeks following the induction of AMI. The results revealed that patients with heart failure post­infarction had higher serum FGF21 levels than the healthy controls. However, the downstream signal, KLB, but not α­klotho, was reduced in the heart tissues of rats with AMI. As was expected, treatment with FGF21 did not substantially attenuate heart remodeling post­infarction. It was found that decreased receptors KLB in the heart may result in the insensitivity to FGF21 treatment. In vivo, the UTMD technology­mediated delivery of KLB@CMBs to the heart significantly enhanced the effects of FGF21 administration on cardiac remodeling and mitochondrial dysfunction in the rats following infarction. The delivery of KLB to the heart by UTMD and the administration of FGF21 attenuated mitochondrial impairment and oxidative stress by activating nuclear factor erythroid 2­related factor 2 signals. On the whole, the present study demonstrates that the cardiac delivery of KLB significantly optimizes the cardioprotective effects of FGF21 therapy on adverse heart remodeling. UTMD appears a promising interdisciplinary approach with which to improve heart failure post­myocardial infarction.

The relationship between health insurance and economic performance: an empirical study based on meta-analysis.

Health insurance stands as a pivotal facet of social wellbeing, with profound implications for the overarching landscape of economic development. The existing research, however, lacks consensus on the relationship between health insurance and economic performance and provides no evidence about the magnitude of the correlation. This lack of information seriously impedes the high-quality development of the healthcare system. Therefore, to scientifically elucidate the relationship between the two, this study involved a meta-analysis, analyzing 479 effect values derived from 34 independent research samples. The results reveal a strongly positive correlation between health insurance and economic performance [r = 0.429, 95% CI = (0.381, 0.475)]. Findings show that health insurance in developed countries more effectively fosters economic performance than in developing countries. Moreover, public health insurance exerts a stronger promoting effect on economic performance than commercial health insurance. The relationship between health insurance and economic performance is moderated by data type, research method, country of sample origin, literature type, journal impact factor, publication year, type of health insurance, and the research populations. Based on meta-analysis, this study not only scientifically responds to the controversy of the relationship between health insurance and economic performance, and the magnitude of a correlation, but also further reveals the inner conduction mechanism between the two. Our research findings are meaningful for policymakers to choose an appropriate healthcare strategy according to their unique attributes, propelling sustainable economic development.

Aggregation-induced-emission red carbon dots for ratiometric sensing of norfloxacin and anti-counterfeiting.

The detection of trace antibiotic residues holds significant importance because it's related to food safety and human health. In this study, we developed a new high-yield red-emitting carbon dots (R-CDs) with aggregation-induced emission properties for ratiometric sensing of norfloxacin. R-CDs were prepared in 30 min using an economical and efficient microwave-assisted method with tartaric acid and o-phenylenediamine as precursors, achieving a high yield of 34.4 %. R-CDs showed concentration-dependent fluorescence and aggregation-induced-emission properties. A ratiometric fluorescent probe for detecting the norfloxacin was developed. In the range of 0-40 µM, the intensity ratio of two emission peaks (I445 nm/I395 nm) towards norfloxacin show good linear relationship with its concentrations and a low detection limit was obtained (36.78 nM). In addition, complex patterns were developed for anti-counterfeiting based on different emission phenomenon at different concentrations. In summary, this study designed a novel ratiometric fluorescent probe for detection of norfloxacin, which greatly shortens the detection time and improves efficiency compared with high-performance liquid chromatography and other methods. The study will promote the application of carbon dots in anti-counterfeiting and other related fields, laying the foundation for the preparation of low-cost photosensitive anti-counterfeiting materials.

Biomarkers for neuromyelitis optica: a visual analysis of emerging research trends.

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis. Over the past 20 years, the search for biomarkers for neuromyelitis optica has been ongoing. Here, we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica. Research in this area is consistently increasing, with China and the United States leading the way on the number of studies conducted. The Mayo Clinic is a highly reputable institution in the United States, and was identified as the most authoritative institution in this field. Furthermore, Professor Wingerchuk from the Mayo Clinic was the most authoritative expert in this field. Keyword analysis revealed that the terms "neuromyelitis optica" (261 times), "multiple sclerosis" (220 times), "neuromyelitis optica spectrum disorder" (132 times), "aquaporin 4" (99 times), and "optical neuritis" (87 times) were the most frequently used keywords in literature related to this field. Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis. Furthermore, aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder. Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarker for myelin oligodendrocyte glycoprotein antibody-associated disease. Recent biomarkers for neuromyelitis optica include cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein, serum astrocyte damage biomarkers like FAM19A5, serum albumin, and gamma-aminobutyric acid. The latest prospective clinical trials are exploring the potential of these biomarkers. Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder. The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity, specificity, and safety for the accurate diagnosis of neuromyelitis optica.