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Eosinophils are essential innate immune cells in allergic responses. Accumulating evidence indicates that eosinophils also participate in the pathogenesis of cardiovascular diseases (CVDs). In clinical studies, high blood eosinophil counts and eosinophil cationic protein levels have been associated with an increased risk of CVD, including myocardial infarction (MI), cardiac hypertrophy, atrial fibrillation, abdominal aortic aneurysm (AAA) and atherosclerosis. However, low blood eosinophil counts have also been reported to be a risk factor for MI, heart failure, aortic dissection, AAA, deep vein thrombosis, pulmonary embolism and ischaemic stroke. Although these conflicting clinical observations remain unexplained, CVD status, timing of eosinophil data collection, and tissue eosinophil phenotypic and functional heterogeneities might account for these discrepancies. Preclinical studies suggest that eosinophils have protective actions in MI, cardiac hypertrophy, heart failure and AAA. By contrast, cationic proteins and platelet-activating factor from eosinophils have been shown to promote vascular smooth muscle cell proliferation, vascular calcification, thrombomodulin inactivation and platelet activation and aggregation, thereby exacerbating atherosclerosis, atrial fibrillation, thrombosis and associated complications. Therefore, eosinophils seem to promote calcification and thrombosis in chronic CVD but are protective in acute cardiovascular settings. In this Review, we summarize the available clinical and preclinical data on the different roles of eosinophils in CVD., (© 2024. Springer Nature Limited.)

Chirality, an inherent characteristic of natural substances (such as sugars, peptides, proteins, and nucleic acid), plays a vital role in human metabolism and exerts substantial impacts. In general, chiral drugs can display diverse pharmacological and pharmacokinetic properties. One enantiomer may exhibit therapeutic effects, while the other could cause adverse reactions. Selective recognition of enantiomers is thus a significant task in the biomolecular and pharmaceutical fields. Despite the development of several chiral identification techniques, low-cost enantioselective sensing methods remain highly desirable. Here, we designed and developed an electrochemical sensing device for reductive enantiomer identification using natural wood channels as the substrate. The wood channels were endowed with oxidase-like activity through the in-situ growth of cerium oxide nanoparticles (CeO 2 ). Chiral recognition capability was further introduced by incorporating a layer of chiral ZIF-8 (L-ZIF) as the chiral selector. To demonstrate the enantioselective sensing performance, 3,4-dihydroxyphenylalanine (DOPA) enantiomers were employed as model analytes. Due to the oxidase-like activity and the confinement effect of the proposed channels, the captured DOPA enantiomers were effectively oxidized to their quinone structure, and the Ce(IV) in CeO 2 was reduced to Ce(III). These changes led to alterations in the surface charge of the channels, thereby modulating their ionic transport properties. This sensing mechanism also proved useful for the identification of other reductive enantiomers. The limits of detection for l-DOPA and d-DOPA were determined as 2.41 nM and 1.56 nM, respectively. The resulting wood channel-based sensing device not only can be used for the recognition and detection of reductive enantiomers, but also is expected to be applied to the non-electochemically active substances. Moreover, this study offers a novel type of solid-state channel material with low cost, reproducibility, and easy accessibility for electrochemical chiral sensing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM., Methods: We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions., Results: MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670-0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199-1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain., Conclusion: Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication., (© 2024. The Author(s).)

Immunoglobulin A nephropathy is a complex autoimmune disease with various underlying causes and significant clinical heterogeneity. There are large individual differences in its development, and the etiology and pathogenesis are still poorly understood. While it is known that immunobiological factors play a significant role in the pathophysiology of immunoglobulin A nephropathy, the specific nature of these factors has yet to be fully elucidated. Numerous investigations have verified that CD4+ and CD8+ T lymphocytes are involved in the immunopathogenesis of immunoglobulin A nephropathy. Furthermore, certain data also point to γδT cells' involvement in the pathophysiology of immunoglobulin A nephropathy. By thoroughly examining the mechanisms of action of these T cells in the context of immunoglobulin A nephropathy, this review sheds light on the immunopathogenesis of the disease and its associated factors. The review is intended to provide reference value for the future research in this field and promising treatment clues for clinical patients., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

As pure antipodes may differ in biological interactions, pharmacology, and toxicity, discrimination of enantiomers is important in the pharmaceutical and agrochemical industries. Two major challenges in enantiomer determination are transducing and amplifying the distinct chiral-recognition signals. In this study, a light-sensitive organic photoelectrochemical transistor (OPECT) with homochiral character is developed for enantiomer discrimination. Demonstrated with the discrimination of glucose enantiomers, the photoelectrochemically active gate electrode is prepared by integrating Au nanoparticles (AuNPs) and a chiral Cu(II)-metal-organic framework (c-CuMOF) onto TiO 2 nanotube arrays (TNT). The captured glucose enantiomers are oxidized to hydrogen peroxide (H 2 O 2 ) by the oxidase-mimicking AuNPs-loaded c-CuMOF. Based on the confinement effect of the mesopocket structure of the c-CuMOF and the remarkable charge transfer ability of the 1D nanotubular architecture, variations in H 2 O 2 yield are translated into significant changes in OPECT drain currents (I D ) by inducing a catalytic precipitation reaction. Variations in I D confer a sensitive discrimination of glucose enantiomers with a limit of detection (LOD) of 0.07 μM for L-Glu and 0.05 μM for D-Glu. This enantiomer-driven gate electrode response strategy not only provides a new route for enantiomer identification, but also helps to understand the origin of the high stereoselectivity in living systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Medicinal plants, increasingly utilized in functional foods, possess potent therapeutic properties and health-promoting functions, with carbohydrates playing a crucial role and exhibiting a range of effects, such as antioxidant, antitumor, immune-enhancing, antibacterial, anticoagulant, and hypoglycemic activities. However, comprehensively, accurately, rapidly, and economically assessing the quality of carbohydrate components is challenging due to their diverse and complex nature. Additionally, the purification and identification of carbohydrates also guarantee related efficacy research. This paper offers a thorough review of research progress carried out by both domestic and international scholars in the last decade on extracting, purifying, separating, identifying, and determining the content of carbohydrate components from functional foods, which are mainly composed of medicinal plants, and also explores the potential for achieving comprehensive quantitative analysis and evaluating structure-activity relationships of carbohydrate components. These findings aim to serve as a valuable reference for the future development and application of natural carbohydrate components in functional food and medicine., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hyperinflammatory responses are pivotal in the cardiomyocyte senescence pathophysiology, with IL33 serving as a crucial pro-inflammatory mediator. Our previous findings highlighted RND3's suppressive effect on IL33 expression. This study aims to explore the role of RND3 in IL33/ST2 signaling activation and in cardiomyocyte senescence. Intramyocardial injection of exogenous IL33 reduces the ejection fraction and fractional shortening of rats, inducing the appearance of senescence-associated secretory phenotype (SASP) in myocardial tissues. Recombinant IL33 treatment of AC16 cardiomyocytes significantly upregulated expression of SASP factors like IL1α, IL6, and MCP1, and increased the p-p65/p65 ratio and proportions of SA-β-gal and γH2AX-positive cells. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) and ST2 antibody astegolimab treatments mitigated above effects. RND3 gene knockout H9C2 cardiomyocytes using CRISPR/Cas9 technology upregulated IL33, ST2L, IL1α, IL6, and MCP1 levels, decreased sST2 levels, and increased SA-β-gal and γH2AX-positive cells. A highly possibility of binding between RND3 and IL33 proteins was showed by molecular docking and co-immunoprecipitation, and loss of RND3 attenuated ubiquitination mediated degradation of IL33; what's more, a panel of ubiquitination regulatory genes closely related to RND3 were screened using qPCR array. In contrast, RND3 overexpression in rats by injection of AAV9-CMV-RND3 particles inhibited IL33, ST2L, IL1α, IL6, and MCP1 expression in cardiac tissues, decreased serum IL33 levels, and increased sST2 levels. These results suggest that RND3 expression in cardiomyocytes modulates cell senescence by inhibiting the IL33/ST2/NF-κB signaling pathway, underscoring its potential as a therapeutic target in cardiovascular senescence., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alternative energy sources are required due to the decline in fossil fuel resources. Therefore, devices that utilize hydrovoltaic technology and light energy have drawn widespread attention because they are emission-free and solar energy is inexhaustible. However, previous investigations mainly focused on accelerating the water evaporation rate at the electrode interface. Here, a cooperative photoelectrochemical effect on a hydrovoltaic chip is achieved using NH 2 -MIL-125-modified TiO 2 nanotube arrays (NTs). This device demonstrated significantly improved evaporation-triggered electricity generation. Under LED illumination, the open-circuit voltage ( V OC ) of the NH 2 -MIL-125/TiO 2 NTs active layer of the hydrovoltaic chip was enhanced by 90.3% (up to 400.2 mV). Furthermore, the prepared hydrovoltaic chip showed good high-salinity tolerance, maintaining 74.6% of its performance even in 5 M NaCl. By introducing a Schiff-based reaction between the active layer and formaldehyde, a fully integrated flexible sensor was successfully fabricated for formaldehyde monitoring, and a low limit of detection of 5.2 × 10 -9 M was achieved. This novel strategy for improving the performance of hydrovoltaic devices offers a completely new general approach to construct self-powered devices for point-of-care sensing.

The development of sensitive, selective, and rapid methods to detect bacteria in complex media is essential to ensuring human health. Virulence factors, particularly pore-forming toxins (PFTs) secreted by pathogenic bacteria, play a crucial role in bacterial diseases and serve as indicators of disease severity. In this study, a nanochannel-based label-free electrochemical sensing platform was developed for the detection of specific pathogenic bacteria based on their secreted PFTs. In this design, wood substrate channels were functionalized with a Fe-based metal-organic framework (FeMOF) and then protected with a layer of phosphatidylcholine (PC)-based phospholipid membrane (PM) that serves as a peroxidase mimetic and a channel gatekeeper, respectively. Using Staphylococcus aureus ( S. aureus ) as the model bacteria, the PC-specific PFTs secreted by S. aureus perforate the PM layer. Now exposed to the FeMOF, uncharged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) molecules in the electrolyte undergo oxidation to cationic products (ABTS •+ ). The measured transmembrane ionic current indicates the presence of S. aureus and methicillin-resistant S. aureus (MRSA) with a low detection limit of 3 cfu mL -1 . Besides excellent specificity, this sensing approach exhibits satisfactory performance for the detection of target bacteria in the complex media of food.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of immune cells in the intima of arteries. Experimental and clinical evidence shows that both innate and adaptive immunity orchestrate the progression of atherosclerosis. The heterogeneous nature of immune cells within atherosclerosis lesions is important. Studies utilizing high-dimensional mass spectrometry and single-cell RNA sequencing of leukocytes from atherosclerotic lesions show the diversity and adaptability of these immune cell subtypes. Their migration, compositional changes, phenotypic alterations, and adaptive responses are key features throughout atherosclerosis progression. Understanding how these immune cells and their subtypes affect atherogenesis would help to develop novel therapeutic approaches that control atherosclerosis progression. Precise targeting of specific immune system components involved in atherosclerosis, rather than broad suppression of the immune system with anti-inflammatory agents, can more accurately regulate the progress of atherosclerosis with fewer side effects. In this review, we cover the most recent advances in the field of atherosclerosis to understand the role of various immune cells on its development. We focus on the complex network of immune cells and the interaction between the innate immune system and adaptive immune system., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Comprehending the structure and function of rhizobacteria components and their regulation are crucial for sustainable agricultural management. However, obtaining comprehensive species information for most bacteria in the natural environment, particularly rhizobacteria, presents a challenge using traditional culture methods. To obtain diverse and pure cultures of rhizobacteria, this study primarily reviews the evolution of rhizobacteria culturomics and associated culture methods. Furthermore, it explores new strategies for enhancing the application of culturomics, providing valuable insights into efficiently enriching and isolate target bacterial strains/groups from the environment. The findings will help improve rhizobacteria's culturability and enrich the functional bacterial library.

In the 21st century, chemotherapy stands as a primary treatment method for prevalent diseases, yet drug resistance remains a pressing challenge. Utilizing electrospinning to support chemotherapy drugs offers sustained and controlled release methods in contrast to oral and implantable drug delivery modes, which enable localized treatment of distinct tumor types. Moreover, the core-sheath structure in electrospinning bears advantages in dual-drug loading: the core and sheath layers can carry different drugs, facilitating collaborative treatment to counter chemotherapy drug resistance. This approach minimizes patient discomfort associated with multiple-drug administration. Electrospun fibers not only transport drugs but can also integrate metal particles and targeted compounds, enabling combinations of chemotherapy with magnetic and heat therapies for comprehensive cancer treatment. This review delves into electrospinning preparation techniques and drug delivery methods tailored to various cancers, foreseeing their promising roles in cancer treatment.

Introduction: LMNA splicing mutations occur in 9.1% of cases with cardiac involvement cases, but the phenotype and severity of disease they cause have not yet been systematically studied. The aim of this study was to understand the clinical and pathogenic characteristics of the LMNA splice-site mutation phenotype in patients with LMNA -related dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Methods and Results: First, we reported a novel family with LMNA -related DCM and SCD, and the clinical characteristics of all current patients with LMNA splicing mutations were further summarized through the ClinVar database. Seventeen families with a total of 134 individuals, containing a total of 15 LMNA splicing mutation sites, were enrolled. A total of 42 subjects (31.3%) had SCD. Compared without with the non-DCM group ( n = 56), the patients within the DCM group ( n = 78) presented a lower incidence of atrioventricular block (AVB) ( p = 0.015) and a higher incidence rates of non-sustained ventricular tachycardia ( p = 0.004),) and implantable cardioverter defibrillator (ICD) implantation ( p = 0.005). Kaplan‒Meier survival analysis showed that the patients with pacemaker (PM) implantation had a significantly reduced the occurrence of SCD compared to patientswith those without PM implantation (log-rank p < 0.001), while there was no significant difference in ICD implantation between the two groups (log-rank p = 0.73). Second, we identified the family that we reported with a mutation in an LMNA c.513+1 G>A mutation in the reported family, and pathogenic prediction analysis showed that the mutation site was extremely harmful. Next, we conducted gene expression levels and cardiac pathological biopsy studies on the proband of this family. We found that the expression of normal LMNA mRNA from the proband was significantly downregulated in peripheral blood mononuclear cells than incompared with healthy individuals. Finally, we comprehensively summarized the pathological characteristics of LMNA -related DCM, including hypertrophy, atrophy, fibrosis, white blood cell infiltration, intercalated disc remodeling, and downregulation of desmin and connexin 43 (Cx43) expression. Discussion: Above all, Cardiaccardiac involvement in patients with LMNA splice-site mutation presented with a high rate of SCD. Implanting a pacemaker significantly reduced the SCD rate in non-DCM patients with AVB. The pathogenic characterization was not only haveinvolved suppressed the expression of the healthy LMNA allele, but was also associated with abnormal expression and distribution of desmin and Cx43., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ling, Hou, Jia, Lan, Wu, Wu, Jie, Liu, Huang, Wan, Li, Guo and Liang.)

Background: Chronic kidney disease (CKD) is now globally recognized as a critical public health concern. Vascular calcification (VC) represents a significant risk factor for cardiovascular events in individuals with CKD. It is the accessible and precise diagnostic biomarkers for monitoring the progression of CKD and the concurrent VC are urgently needed. Methods: The adenine diet-induced CKD rat model was utilized to investigate chronic kidney injury, calcification in the kidney and thoracic aorta, and dysregulation of biochemical indices. Enzyme-linked immune sandwich assays were employed to analyze changes in calcification-related proteins. 16S rRNA sequencing was performed to delineate the microbiota characteristics in the gut and blood of CKD-afflicted rats. Additionally, transcriptome sequencing of kidney tissue was conducted to explore the relationship between CKD-associated microbiota features and alterations in kidney function. Results: The adenine diet-induced CKD inhibited body weight gain, and led to kidney injury, and pronounced calcification in kidney and thoracic aorta. The microbiota both in the gut and blood of these affected rats exhibited significantly lower alpha diversity and distinctive beta diversity than those in their healthy counterparts. CKD resulted in dysregulation of several biochemical indices (including elevated levels of creatinine, low-density lipoprotein-cholesterol, sodium, phosphorous, total cholesterol, and urea and decreased levels of albumin, calcium, lactate dehydrogenase, and total bilirubin). Moreover, it upregulated calcification-related factors (bone sialoprotein [BSP], Klotho, fibroblast growth factor [FGF]-23, and sclerostin [SOST]) and lipopolysaccharide (LPS). Notably, the increased Acinetobacter in the blood was positively associated with calcifications in the kidney and thoracic aorta, in addition to the positive correlation with gut microbiota. The enrichment of Acinetobacter was concurrent with increases in calcification factors (BSP, FGF-23, and SOST), LPS, and phosphorous. Furthermore, transcriptome sequencing revealed that the enrichment of Acinetobacter was positively correlated with the majority of upregulated genes and negatively correlated with downregulated genes involved in the mineral absorption pathway. Conclusion: Our findings, for the first time, underscore that dysbiosis of symbiotic microbiota, both in the gut and blood, is involved in the progression of CKD. Particularly, the enrichment of Acinetobacter in blood emerges as a potential risk factor for CKD and its accompanying VC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Fang, Zheng, Shi, Guo, Zhang and Zhang.)

Background: Current therapies cannot completely reverse advanced atherosclerosis. High levels of amino acids, induced by Western diet, stimulate mTORC1 (mammalian target of rapamycin complex 1)-autophagy defects in macrophages, accelerating atherosclerotic plaque progression. In addition, autophagy-lysosomal dysfunction contributes to plaque necrotic core enlargement and lipid accumulation. Therefore, it is essential to investigate the novel mechanism and molecules to reverse amino acid-mTORC1-autophagy signaling dysfunction in macrophages of patients with advanced atherosclerosis., Methods: We observed that Gpr137b-ps (G-protein-coupled receptor 137B, pseudogene) was upregulated in advanced atherosclerotic plaques. The effect of Gpr137b-ps on the progression of atherosclerosis was studied by generating advanced plaques in ApoE -/- mice with cardiac-specific knockout of Gpr137b-ps. Bone marrow-derived macrophages and mouse mononuclear macrophage cell line RAW264.7 cells were subjected to starvation or amino acid stimulation to study amino acid-mTORC1-autophagy signaling. Using both gain- and loss-of-function approaches, we explored the mechanism of Gpr137b-ps-regulated autophagy., Results: Our results demonstrated that Gpr137b-ps deficiency led to enhanced autophagy in macrophages and reduced atherosclerotic lesions, characterized by fewer necrotic cores and less lipid accumulation. Knockdown of Gpr137b-ps increased autophagy and prevented amino acid-induced mTORC1 signaling activation. As the downstream binding protein of Gpr137b-ps, HSC70 (heat shock cognate 70) rescued the impaired autophagy induced by Gpr137b-ps. Furthermore, Gpr137b-ps interfered with the HSC70 binding to G3BP (Ras GTPase-activating protein-binding protein), which tethers the TSC (tuberous sclerosis complex) complex to lysosomes and suppresses mTORC1 signaling. In addition to verifying that the NTF2 (nuclear transport factor 2) domain of G3BP binds to HSC70 by in vitro protein synthesis, we further demonstrated that HSC70 binds to the NTF2 domain of G3BP through its W90-F92 motif by using computational modeling., Conclusions: These findings reveal that Gpr137b-ps plays an essential role in the regulation of macrophage autophagy, which is crucial for the progression of advanced atherosclerosis. Gpr137b-ps impairs the interaction of HSC70 with G3BP to regulate amino acid-mTORC1-autophagy signaling, and these results provide a new potential therapeutic direction for the treatment of advanced atherosclerosis., Competing Interests: Disclosures None.

Background: The prognostic nutritional index (PNI) and different glucose metabolisms have been separately reported to be correlated with long-term prognosis in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). However, PNI application in patients with an impaired glucose metabolism has not been well validated, especially in pre-diabetic patients. This study evaluated whether PNI influences a long-term risk of mortality along different glucose metabolism statuses., Methods: A total of 17,697 patients with AMI and a history of PCI were enrolled in this retrospective observational cohort study from January 2007 to December 2020. Three subgroups with different glucose metabolism statuses, including normal glucose regulation (NGR), pre-diabetes mellitus (pre-DM), and diabetes mellitus (DM), were divided into three groups according to the tertiles of PNI, respectively., Results: All-cause mortality occurred in 2613 (14.8%) patients within a median of 4.1 years of follow-up. Upon analyzing the Kaplan-Meier plots for the NGR, pre-DM, and DM groups, the incidence of all-cause or cardiovascular mortality in the low PNI (PNI-L, ≤ 42.7) subgroup was significantly higher than that in the median PNI (PNI-M, > 42.7 and ≤ 48.2) and high PNI (PNI-H, > 48.2) subgroups (all, P < 0.001). After adjusting for confounding factors, the hazard ratio (HR) for all-cause mortality in the PNI-L group significantly increased compared to that in the PNI-H subgroups of the NGR group (HR, 1.35; 95% CI 1.14-1.66; P < 0.001), pre-DM group (HR, 1.29; 95% CI 1.02-1.62; P < 0.001), and DM group (HR, 1.36; 95% CI 1.13-1.63; P < 0.001). Given that there was evidence of interactions between PNI and different glucose statuses (P for interaction < 0.001), patients were divided into nine subgroups, and we found that DM patients with PNI-L statuses had the highest risk of all-cause mortality compared to NGR patients with PNI-H statuses (HR, 1.69; 95% CI 1.42-2.01; P < 0.001)., Conclusion: Lower PNI is a significant and independent risk factor for all-cause mortality in AMI patients undergoing PCI with different glucose metabolism statuses, and this risk further increases with DM compared to NGR or pre-DM statuses., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Alzheimer's disease (AD) is an irreversible brain disorder, which has been found to be associated with neurotoxic amyloid-β oligomers (AβO). The early diagnosis of AD is still a great challenge. Herein, inspired by the hierarchical channel structure of natural wood, we design and demonstrate a low-cost and sensitive wood channel-based fluidic membrane for electrochemical sensing of AβO 1-42 . In this design, Zn/Cu-2-methylimidazole (Zn/Cu-Hmim) with artificial peroxidase (POD)-like activity was asymmetrically fabricated at one side of the wood channels by biomimetic mineralization and a subsequent ion exchange reaction. The strong affinity between Cu(II) and AβO 1-42 enables Cu(II) species in Zn/Cu-Hmim to be extracted by AβO 1-42 , thus suppressing the POD-like performance via Zn/Cu-Hmim disassembly. Using Zn/Cu-Hmim to catalyze the oxidation reaction of 2,2'-diazo-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) by H 2 O 2 , the current-voltage (I-V) properties of wood channels are influenced by the generated oxidation product (ABTS •+ ), thus providing information useful for the quantitative analysis of AβO 1-42 . Importantly, the three aggregation states of Aβ 1-42 (AβM 1-42 , AβO 1-42 , and AβF 1-42 ) can also be identified, owing to the affinity difference and available reaction sites. The proposed wood membrane provides a novel, assessable, and scalable channel device to develop sensitive electrochemical sensors; moreover, the sustainable wood materials represent alternative candidates for developing channel-structured sensing platforms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Enantioselective identification of chiral molecules is regarded as one of the key issues in biological and medical sciences because of their configuration-dependent effects on biological systems. In this study, we developed an electrochemical platform based on a tandem recognition-reaction zone design in TiO 2 nanochannels for the specific recognition of reducing enantiomers. In this system, MIL-125(Ti) Ti-metal-organic frameworks, in situ grown in TiO 2 nanochannels, provided a homochiral recognition environment via postmodification with l-tartaric acid (l-TA); MnO 2 nanosheets possessing both glucose oxidase (GOD)- and peroxidase (POD)-mimicking activities served as the target-reactive zone at the end of the nanochannels. The use of penicillamine (Pen) enantiomers as model-reducing targets facilitated the passage of d-Pen through the homochiral recognition zone, owing to its lower affinity with l-TA. The passed Pen molecules reached the responsive zone and induced a target concentration-dependent MnO 2 disassembly. Such target recognition event impaired the cascade GOD- and POD-like activities of MnO 2 . Combining the enantioselectivity of the recognition nanochannels with the cascade enzyme-like activity of MnO 2 toward glucose and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate), the quantitative identification of l- and d-Pen was achieved through the changes in transmembrane ionic current induced by the generated charged products. This recognition-reaction zone design paves an effective way for developing a promising electrochemical platform for the identification of reducing enantiomers with improved selectivity and sensitivity.

In recent years, an increasing number of scientists have focused on conducting experiments on laser ablation of bone tissue. The purpose of this study was to summarize the prognosis of tissue and the extent of thermal damage in past hard tissue ablation experiments, and review the evidence for the feasibility of laser osteotomy in surgery. An electronic search of PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science (WOS) for relevant English-language articles published through June 2023 was conducted. This review includes 48 literature reports on laser ablation of hard tissues from medical and biological perspectives. It summarizes previous studies in which the ideal ablation rate, depth of ablation, and minimal damage to bone tissue and surrounding soft tissues were achieved by changing the laser type, optimizing the laser parameter settings, or adding adjuvant devices. By observing their post-operative healing and inflammatory response, this review aims to provide a better understanding of pulsed laser ablation of hard tissues. Previous studies suggest that laser osteotomy has yielded encouraging results in bone resection procedures. We believe that low or even no thermal damage can be achieved by experimentally selecting a suitable laser type, optimizing laser parameters such as pulse duration and frequency, or adding additional auxiliary cooling devices. However, the lack of clinical studies makes it difficult to conclusively determine whether laser osteotomy is superior in clinical applications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Glutathione (GSH) plays a vital role in many physiological processes, and its abnormal levels have been found to be associated with several diseases. In contrast to traditional methods using electron donor-containing electrolytes for photoelectrochemical (PEC) sensing, in this study, a target-driven electron donor generation in a PEC electrode was developed to detect GSH. Using well-aligned TiO 2 nanotube arrays (TNTs) as the PEC substrate, mesoporous MIL-125(Ti) was grown in the TNTs through an in situ solvothermal method and subsequent two-step annealing treatment. The accommodation capacity of mesoporous MIL-125(Ti) allows a well loading of cystine and Pt nanoclusters (NCs). Taking advantage of the specific cleavage ability of disulfide bonds by GSH, cystine was converted to cysteine, which served as the electron donor for the PEC process. Benefiting from the confinement effect of mesoporous MIL-125(Ti), cysteine was effectively oxidized to cysteine sulfinic acid by the photogenerated holes. Importantly, the highly active Pt NCs decorated in the mesopores not only improved the charge transfer but also accelerated the above oxidation reaction. The synergistic effect of these factors enabled the efficient separation of the photogenerated electron-hole pairs, which induced a significant photocurrent increase and in turn led to the high-sensitivity detection of GSH. Consequently, the proposed PEC biosensor exhibited excellent performance in the detection of GSH in serum specimens. The target-driven electron donor generation designed in this study might open a new route for developing sensitive and selective PEC biosensors with application in complex biological environments.

Metal-organic frameworks (MOFs) demonstrate strong potential in biosample separation. However, the obtained MOFs powders are unsuitable for recovery techniques in an aqueous solution, especially the challenges of withdrawing MOFs particles and expanding their functions for specific applications. Herein, a general strategy is designed utilizing metal oxide-nanochannel arrays as precursors and templates for in-situ selective growth of MOFs structures. The exemplary MOFs (Ni-bipy) with tailored composition are selectively grown in NiO/TiO 2 nanochannel membrane (NM) using NiO as the sacrificial precursor, which enables one to achieve a ∼262 times concentration of histidine-tagged proteins within 100 min. The significantly improved adsorption efficiency in a wide pH range and the effective enrichment from a complex matrix as a nanofilter illustrate the great potential of MOFs in nanochannels membranes for the high-efficiency recovery of essential proteins in complex biological samples. The porous self-aligned Ni-MOFs/TiO 2 NM exhibits biocompatibility and flexible functionalities, which is desirable for the generation of multifunctional nanofilter devices and developing biomacromolecule delivery vehicles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Enzyme-mimicking nanoparticles play a key role in important catalytic processes, from biosensing to energy conversion. Therefore, understanding and tuning their performance is crucial for making further progress in biological applications. We developed an efficient and sensitive electrochemical method for the real-time monitoring of the glucose oxidase (GOD)-like activity of single nanoparticle through collision events. Using brush-like sulfonate (-SO 3 - )-doped polyaniline (PANI) decorated on TiO 2 nanotube arrays (TiNTs-SPANI) as the electrode, we fabricated a proton reservoir with excellent response and high proton-storage capacity for evaluating the oxidase-like activity of individual Au nanoparticles (AuNPs) via instantaneous collision processes. Using glucose electrocatalysis as a model reaction system, the GOD-like activity of individual AuNPs could be directly monitored via electrochemical tests through the nanoparticle collision-induced proton generation. Furthermore, based on the perturbation of the electrical double layer of SPANI induced by proton injection, we investigated the relationship between the measured GOD-like activities of the plasmonic nanoparticles (NPs) and the localized surface plasmon resonance (LSPR) as well as the environment temperature. This work introduces an efficient platform for understanding and characterizing the catalytic activities of nanozymes at the single-nanoparticle level.

Aims: Blood eosinophil count and eosinophil cationic protein (ECP) concentration are risk factors of cardiovascular diseases. This study tested whether and how eosinophils and ECP contribute to vascular calcification and atherogenesis., Methods and Results: Immunostaining revealed eosinophil accumulation in human and mouse atherosclerotic lesions. Eosinophil deficiency in ΔdblGATA mice slowed atherogenesis with increased lesion smooth muscle cell (SMC) content and reduced calcification. This protection in ΔdblGATA mice was muted when mice received donor eosinophils from wild-type (WT), Il4-/-, and Il13-/- mice or mouse eosinophil-associated-ribonuclease-1 (mEar1), a murine homologue of ECP. Eosinophils or mEar1 but not interleukin (IL) 4 or IL13 increased the calcification of SMC from WT mice but not those from Runt-related transcription factor-2 (Runx2) knockout mice. Immunoblot analyses showed that eosinophils and mEar1 activated Smad-1/5/8 but did not affect Smad-2/3 activation or expression of bone morphogenetic protein receptors (BMPR-1A/1B/2) or transforming growth factor (TGF)-β receptors (TGFBR1/2) in SMC from WT and Runx2 knockout mice. Immunoprecipitation showed that mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2. Immunofluorescence double-staining, ligand binding, and Scatchard plot analysis demonstrated that mEar1 bound to BMPR-1A and BMPR-1B with similar affinity. Likewise, human ECP and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation. In a cohort of 5864 men from the Danish Cardiovascular Screening trial and its subpopulation of 394 participants, blood eosinophil counts and ECP levels correlated with the calcification scores of different arterial segments from coronary arteries to iliac arteries., Conclusion: Eosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway., Competing Interests: Conflict of interest All authors declare no conflict of interest for this contribution., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

As a biomarker of periodontitis, sensitive and timely monitoring of hydrogen sulfide (H 2 S) in exhaled breath at room temperature (RT) is important for the early intervention of oral diseases. However, the required high operation temperature to achieve high sensitivity is still a technical challenge for directly monitoring exhaled breath. In this study, by integrating metal-organic frameworks (MOFs) into self-aligned TiO 2 nanotube arrays (NTs), a chemiresistor gas sensor with outstanding sensitivity and selectivity was constructed for the detection of H 2 S at RT. The precise regulation of a Co(III)-based MOF CoBDC-NH 2 (BDC-NH 2 = 2-aminoterephthalic acid) not only induced more active surface for the preconcentration of the target gas but also caused a buildup of Z-scheme heterojunctions in the H 2 S atmosphere that induced an ultrahigh sensitivity at RT via 365 nm light-emitting diode irradiation. The response and recovery times decreased to ∼50 and ∼28%, respectively, when this system was exposed to UV light. The sensing chips based on the as-prepared TiO 2 /CoBDC-NH 2 NTs exhibited the highest-ranking H 2 S sensing performance, i.e., a limit of detection of 1.3 ppb and excellent selectivity even to 100 times high concentration of interference gases, owing to the synergistic chemical environment provided by NH 2 -functionalized Co-MOFs and abundant photogenerated electrons provided by Z-scheme heterojunctions. This sensing chip was also used in a practical application for the timely monitoring of halitosis from direct exhaled breath. This study provides a reliable and sensitive design for clinically aiding the timely detection of H 2 S in a complex oral environment.

Virtualization and resource isolation techniques have enabled the efficient sharing of networked resources. How to control network resource allocation accurately and flexibly has gradually become a research hotspot due to the growth in user demands. Therefore, this paper presents a new edge-based virtual network embedding approach to studying this problem that employs a graph edit distance method to accurately control resource usage. In particular, to manage network resources efficiently, we restrict the use conditions of network resources and restrict the structure based on common substructure isomorphism and an improved spider monkey optimization algorithm is employed to prune redundant information from the substrate network. Experimental results showed that the proposed method achieves better performance than existing algorithms in terms of resource management capacity, including energy savings and the revenue-cost ratio., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sepsis is a systemic inflammatory response syndrome caused by bacteria and other pathogenic microorganisms. Every year, approximately 31.5 million patients are diagnosed with sepsis, and approximately 5.3 million patients succumb to the disease. In this study, we identified biomarkers for diagnosing sepsis analyzed the relationships between genes and Immune cells that were differentially expressed in specimens from patients with sepsis compared to normal controls. Finally, We verified its effectiveness through animal experiments. Specifically, we analyzed datasets from four microarrays(GSE11755、GSE12624、GSE28750、GSE48080) that included 106 blood specimens from patients with sepsis and 69 normal human blood samples. SVM-RFE analysis and LASSO regression model were carried out to screen possible markers. The composition of 22 immune cell components in patients with sepsis were also determined using CIBERSORT. The expression level of the biomarkers in Sepsis was examined by the use of qRT-PCR and Western Blot (WB). We identified 50 differentially expressed genes between the cohorts, including 2 significantly upregulated and 48 significantly downregulated genes, and KEGG pathway analysis identified Salmonella infection, human T cell leukemia virus 1 infection, Epstein-Barr virus infection, hepatitis B, lysosome and other pathways that were significantly enriched in blood from patients with sepsis. Ultimately, we identified COMMD9, CSF3R, and NUB1 as genes that could potentially be used as biomarkers to predict sepsis, which we confirmed by ROC analysis. Further, we identified a correlation between the expression of these three genes and immune infiltrate composition. Immune cell infiltration analysis revealed that COMMD9 was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, et al. CSF3R was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, et al. NUB1 was correlated with T cells regulatory (Tregs), T cells gamma delta, T cells follicular helper, et al. Taken together, our findings identify potential new diagnostic markers for sepsis that shed light on novel mechanisms of disease pathogenesis and, therefore, may offer opportunities for therapeutic intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wang, Zhang, Tao, Guo, Liu, Liu, Liu, Mei and Chen.)

Fructus gardeniae (FG) is a traditional Chinese medicine and health food for thousands of years of application throughout Chinese history and is still widely used in clinical Chinese medicine. FG has a beneficial impact on anxiety, depression, insomnia, and psychiatric disorders; however, its mechanism of action requires further investigation. This study aimed to investigate the effects and mechanisms of FG on sleep deprivation (SD)-induced anxiety-like behavior in rats. A model of SD-induced anxiety-like behavior in rats was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). This was accompanied by neuroinflammation and metabolic abnormalities in the hippocampus and disturbance of intestinal microbiota. However reduced SD-induced anxiety-like behavior and decreased levels of pro-inflammatory cytokines including TNF-α and IL-1β were observed in the hippocampus of rats after 7 days of FG intervention. In addition, metabolomic analysis demonstrated that FG was able to modulate levels of phosphatidylserine 18, Phosphatidylinositol 18, sn-glycero-3-phosphocholine, deoxyguanylic acid, xylose, betaine and other metabolites in the hippocampus. The main metabolic pathways of hippocampal metabolites after FG intervention involve carbon metabolism, glycolysis/gluconeogenesis, pentose phosphate, and glycerophospholipid metabolism. 16S rRNA sequencing illustrated that FG ameliorated the dysbiosis of gut microbiota in anxious rats, mainly increased the abundance of Muribaculaceae and Lactobacillus, and decreased the abundance of Lachnospiraceae&#95;NK4A136&#95;group. In addition, the correlation analysis demonstrated that there was a close relationship between hippocampal metabolites and intestinal microbiota. In conclusion, FG improved the anxiety behavior and inhibited of neuroinflammation in sleep-deprived rats, and the mechanism may be related to the FG regulation of hippocampal metabolites and intestinal microflora composition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Wang, Li, Yuan, Liu, Guo, Li, Zhang, Tao and Mei.)

Chiral recognition is a crucial issue in the biomedical and pharmaceutical research communities. Due to the need for expensive equipment, reagents, and external energy, enantiomer identification is difficult to perform outside of a laboratory. Based on water evaporation-induced hydrovoltaic effect, a power-free sensing platform with sensitive chiral recognition capability is proposed for the discrimination of enantiomers. The chiral recognizer was bovine serum albumin (BSA), a naturally occurring protein. Using arginine (Arg) enantiomers as the sensing targets, the difference in enantioselectivity between l-Arg and d-Arg on a BSA-modified porous carbon substrate can be measured directly from the output voltage. By combining the cyclization reaction between NO and O -phenylenediamine (OPD), it has been discovered that the sensitivity and specificity of enantioselective identification can be significantly enhanced based on the surface charges. The limit of detection (LOD) could be as low as 76.0 nM. In addition, the proposed chips are extremely flexible and can function under deformation without sacrificing output performance. This self-powered chiral recognition chip paves a new path for the detection of chiral molecules at any time, any place, and it also has excellent potential for use in flexible wearable technology.

Aims: Group 2 innate lymphoid cells (ILC2s) regulate adaptive and innate immunities. In mouse heart, production of myocardial infarction (MI) increased ILC2 accumulation, suggesting a role for ILC2 in cardiac dysfunction post-MI., Methods and Results: We produced MI in ILC2-deficeint Rorafl/flIl7rCre/+ mice and in Icosfl-DTR-fl/+Cd4Cre/+ mice that allowed diphtheria toxin-induced ILC2 depletion. Genetic or induced deficiency of ILC2 in mice exacerbated cardiac dysfunction post-MI injury along with increased myocardial accumulation of neutrophils, CD11b+Ly6Chi monocytes, and CD4+ T cells but deficiency of eosinophils (EOS) and dendritic cells (DC). Post-MI hearts from genetic and induced ILC2-deficient mice contained many more apoptotic cells than those of control mice, and Rorafl/flIl7rCre/+ mice showed thinner and larger infarcts and more collagen-I depositions than the Il7rCre/+ mice only at early time points post-MI. Mechanistic studies revealed elevated blood IL5 in Il7rCre/+ mice at 1, 7, and 28 days post-MI. Such increase was blunted in Rorafl/flIl7rCre/+ mice. Administration of recombinant IL5 reversed EOS losses in Rorafl/flIl7rCre/+ mice, but IL5 did not correct the DC loss in these mice. Adoptive transfer of ILC2, EOS, or DC from wild-type mice, but not ILC2 from Il5-/- mice improved post-MI cardiac functions in Rorafl/flIl7rCre/+ recipient mice. EOS are known to protect cardiomyocytes from apoptosis. Here we showed that DC acted like EOS in blocking cardiomyocyte apoptosis. Yet, ILC2 or IL5 alone did not directly affect cardiomyocyte apoptosis or TGF-β (transforming growth factor-β)-induced cardiac fibroblast Smad signalling., Conclusion: This study revealed an indirect cardiac reparative role of ILC2 in post-MI hearts via the IL5, EOS, and DC mechanism., Competing Interests: Conflict of interest: The authors have declared no conflicts ofinterest.., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The space-agile optical composite detection (SOCD) system with a pointing mirror possesses flexible and fast response ability. Like other space telescopes, if the stray light is not properly eliminated, it may result in a false response or noise that floods the real light signal due to the low illuminance and large dynamic range of the target. The paper shows the optical structure layout, the decomposition of the optical processing index and roughness control index, the stray light suppression requirements, and the detailed stray light analysis process. The pointing mirror and ultra-long afocal optical path increase the difficulty of stray light suppression in the SOCD system. This paper presents the design method of a special-shaped aperture diaphragm and entrance baffle, black baffle surface testing, simulating, selection, and stray light suppression analysis process. The special-shaped entrance baffle has a significant effect on the suppression of stray light and reduced dependence on the platform posture of the SOCD system.

Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), also known as lysine (K)-specific demethylase 6A (KDM6A), functions as a tumor suppressor gene or oncogene depending on the tumor type and context. However, its tumor-suppressive mechanisms remain largely unknown. Here, we investigated the clinical significance and biological effects of UTX expression in pancreatic ductal adenocarcinoma (PDA) and determined the potential mechanisms of its dysregulation. UTX expression and its association with clinicopathologic characteristics of PDA patients were analyzed using immunohistochemistry. UTX mRNA and protein expression and their regulation in PDA cell lines were measured using quantitative polymerase chain reaction and Western blot analyses. The biological functions of UTX in PDA cell growth, migration, and invasion were determined using gain- and loss-of-function assays with both in vitro and in vivo animal models. UTX expression was reduced in human PDA cell lines and specimens. Low UTX expression was associated with poor differentiation and prognosis in PDA. Forced UTX expression inhibited PDA proliferation, migration, and invasion in vitro and PDA growth and metastasis in vivo , whereas knockdown of UTX expression did the opposite. Mechanistically, UTX expression was trans-activated by GATA6 activation. GATA6-mediated PDA progression could be blocked, at least partially, by silencing UTX expression. In conclusion, loss of GATA6-mediated UTX expression was evident in human PDA and restored UTX expression suppressed PDA growth and metastasis. Thus, UTX is a tumor suppressor in PDA and may serve as a prognostic biomarker and therapeutic target., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Enantioselective identification of chiral molecules is of paramount importance in medical science, biochemistry, and pharmaceutics owing to the configuration-dependent activities of enantiomers. However, the identical physicochemical properties of enantiomers remain challenging in chiral sensing. In this study, inspired by the peroxidase-mimicking activity of Fe(III)-based nanomaterials, an enantioselective artificial architecture is constructed on TiO 2 nanochannels. Homochiral Ti-based metal-organic frameworks (MOFs) use a 2,2'-bipyridine-5,5'-dicarboxylic acid ligand as the artificial enzyme skeleton, Fe(III) as peroxidase-mimicking centers, and l-tartaric acid (TA) as a chiral recognition selector. Using l-/d-cystine as model enantiomers, the chiral moieties of l-TA on Ti-MOFs allow stereoselective recognition of guest molecules through hydrogen bonds formed between chiral cystine and the host. In a tris(2-carboxyethyl)phosphine hydrochloride-containing environment, the disulfide bonds in cystine molecules are further cleaved, and the HS-tails react with Fe(III) active sites, causing the loss of peroxidase-like performance of nanochannels. Benefitting from the nanochannel architecture's current-potential ( I - V ) properties, the selective recognition of cystine enantiomers is directly monitored through the peroxidase-like activity change-induced ionic current signatures. This study provides a new and universal strategy for distinguishing disulfide- and thiol-containing chiral molecules.

Aims: Blood eosinophil (EOS) counts and EOS cationic protein (ECP) levels associate positively with major cardiovascular disease (CVD) risk factors and prevalence. This study investigates the role of EOS in cardiac hypertrophy., Methods and Results: A retrospective cross-section study of 644 consecutive inpatients with hypertension examined the association between blood EOS counts and cardiac hypertrophy. Pressure overload- and β-adrenoreceptor agonist isoproterenol-induced cardiac hypertrophy was produced in EOS-deficient ΔdblGATA mice. This study revealed positive correlations between blood EOS counts and left ventricular (LV) mass and mass index in humans. ΔdblGATA mice showed exacerbated cardiac hypertrophy and dysfunction, with increased LV wall thickness, reduced LV internal diameter, and increased myocardial cell size, death, and fibrosis. Repopulation of EOS from wild-type (WT) mice, but not those from IL4-deficient mice ameliorated cardiac hypertrophy and cardiac dysfunctions. In ΔdblGATA and WT mice, administration of ECP mEar1 improved cardiac hypertrophy and function. Mechanistic studies demonstrated that EOS expression of IL4, IL13, and mEar1 was essential to control mouse cardiomyocyte hypertrophy and death and cardiac fibroblast TGF-β signalling and fibrotic protein synthesis. The use of human cardiac cells yielded the same results. Human ECP, EOS-derived neurotoxin, human EOS, or murine recombinant mEar1 reduced human cardiomyocyte death and hypertrophy and human cardiac fibroblast TGF-β signalling., Conclusion: Although blood EOS counts correlated positively with LV mass or LV mass index in humans, this study established a cardioprotective role for EOS IL4 and cationic proteins in cardiac hypertrophy and tested a therapeutic possibility of ECPs in this human CVD., Competing Interests: Conflict of interest: The authors have declared no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Development of abdominal aortic aneurysms (AAA) enhances lesion group-2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rora fl/fl Il7r Cre/+ mice or induced ILC2 depletion in Icos fl-DTR-fl/+ Cd4 Cre/+ mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS. IL5 or ILC2 from wild-type (WT) mice, but not ILC2 from Il5 -/- mice induces EOS differentiation in bone-marrow cells from Rora fl/fl Il7r Cre/+ mice. IL5, IL13, and EOS or ILC2 from WT mice, but not ILC2 from Il5 -/- and Il13 -/- mice block SMC apoptosis and promote SMC proliferation. EOS but not ILC2 from WT or Il5 -/- mice block endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6C hi monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5 -/- ILC2 slows AAA growth in Rora fl/fl Il7r Cre/+ mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Accurate detection of trace biomarkers in biological samples is a key task in diagnostic testing, but it remains challenging due to the high concentration of other physiologically relevant interferences. This work presents a new electrochemiluminescence (ECL) sensing device based on a bio-inspired nanochannel membrane (NM) guarded with two differential gates. The recognition event at the aptamer gate is followed by the permitting of stimulator transport toward the metal-organic framework (MOF) gate. Proof of concept application is evaluated using cytochrome C (Cytc) as the analyte, and glucose, a commonly existing nutriment as the stimulator. The oxidase-mimic plasmonic nanoparticles induce an effective release of ECL luminophore from the MOF gate. This cascade-gates guarded NM can effectively separate biological matrices from the detection cell. Consequently, the proposed system can achieve direct sensing of 1.0 nm Cytc in undiluted serum within the threshold concentrations of leukemia and lymphoma, making it attractive for point-of-care applications., (© 2022 Wiley-VCH GmbH.)

Monosaccharides play significant roles in daily metabolism in living organisms. Although various devices have been constructed for monosaccharide identification, most rely on the specificity of the natural enzyme. Herein, inspired by natural ionic channels, an asymmetrical MOF-in-nanochannel architecture is developed to discriminate monosaccharide enantiomers based on cascade reactions by combining oxidase-mimicking and Fenton-like catalysis in homochiral mesoporous CuMOF pockets. The identification performance is remarkably enhanced by the increased oxidase-mimicking activity of Au nanoparticles under a local surface plasmon resonance (LSPR) excitation. The apparent steady-state kinetic parameters and nano-fluidic simulation indicate that the different affinities induced by Au-LSPR excitation and the confinement effect from MOF pockets precipitate the high chiral sensitivity. This study offers a promising strategy for designing an enantiomer discrimination device and helps to gain insight into the origin of stereoselectivity in a natural enzyme., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Recent study has shown that the transient receptor potential vanilloid 2 (TRPV2) channel was exclusively upregulated in patients with atrial fibrillation (AF), and that this overexpression might be detrimental for occurrence and maintenance of AF. We aimed to characterize the expression levels of TRPV2 mRNA in peripheral blood mononuclear cells (PBMCs) with/without early recurrence of atrial fibrillation (ERAF) after radiofrequency catheter ablation (RFCA), and to find a reliable predictor for ERAF., Methods: 65 patients of AF, who underwent RFCA successfully, then divided into two groups according to ERAF during following 3 months. PBMCs were isolated from whole blood by Ficoll gradient centrifugation before and after RFCA. Gene set enrichment analysis was performed to evaluate TRPV channels expression levels and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping was used for pathway enrichment analysis., Results: There was no significant difference in the TRPV2 mRNA expression level between the two groups before RFCA, while without ERAF group of TRPV2 expression was markedly reduced compared to ERAF group after RFCA. Moreover, the number of TRPV2 expression was confirmed as an independent predictor for the first time through receiver operating characteristic and Kaplan-Meier survival curve analysis. It should be pointed out that the above results were only used to predict ERAF, and have no predictive significance for late recurrence of atrial fibrillation according to the current data. Additionally, ERAF was inversely correlated with P wave dispersion. KEGG mapping further clustered 41 pathways, revealing that ''cyclic guanosine monophosphate-protein kinase G signaling pathway'' was significantly enriched., Conclusions: We firstly assume that downregulated expression of peripheral TRPV2 appear in patients without ERAF after RFCA. TRPV2 may thus represent a novel predictor of early phase after successful radiofrequency ablation., (© 2022. The Author(s).)

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease with high disability and mortality. Its susceptible risk factors include old age, being male, smoking, hypertension, and aortic atherosclerosis. With the improvement of screening techniques, AAA incidence and number of deaths caused by aneurysm rupture increase annually, attracting much clinical attention. Due to the lack of non-invasive treatment, early detection and development of novel treatment of AAA is an urgent clinical concern. The pathophysiology and progression of AAA are characterized by inflammatory destruction. The gut microbiota is an "invisible organ" that directly or indirectly affects the vascular wall inflammatory cell infiltration manifested with enhanced arterial wall gut microbiota and metabolites, which plays an important role in the formation and progression of AAA. As such, the gut microbiome may become an important risk factor for AAA. This review summarizes the direct and indirect effects of the gut microbiome on the pathogenesis of AAA and highlights the gut microbiome-mediated inflammatory responses and discoveries of relevant therapeutic targets that may help manage the development and rupture of AAA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ling, Jie, Qin, Zhang, Shi, Li and Guo.)

Panax notoginseng, a traditional medicinal and edible plant, is widely used in medicine, health care, cosmetics, and other industries. Affected by the discrepancy between market supply and demand and price, the adulteration of P. notoginseng products with other plant-derived ingredients occurs at times. With the continuous development of technologies such as spectroscopy, chromatography, and DNA barcoding, the detection techniques for rapid and sensitive determination of the authenticity identification and origin of P. notoginseng have become more diversified to meet the needs of different regulatory goals and could effectively control practices that mislead consumers and promote false labeling. This review analyzes and summarizes the existing technologies for determining the authenticity and origin of P. notoginseng from these three aspects: morphological, chemical, and molecular biology methods from the literature since 2001; on this basis, the current problems and future research directions are discussed to provide a reference for the establishment of rapid and accurate methods to verify authenticity and origin to promote the further development and improvement of quality control technology systems for P. notoginseng., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

As a marker molecule in respiratory gases for the pulmonary disease asthma, nitric oxide (NO) has attracted much attention for real-time gas monitoring. However, low sensitivity, poor selectivity, and high operating temperature limit the practical applications of metal oxide semiconductor (MOS) based chemiresistor gas sensors. Herein, by deliberately introducing metal-organic frameworks (MOFs) in free-standing TiO 2 nanochannels (NCs), a chemiresistor gas sensor with excellent detection ability and outstanding selective traits is developed for sensing NO at room temperature (RT). The precisely engineered Cu(II)-based MOF Cu-TCA (H 3 TCA = tricarboxytriphenyl amine) induces more active surface in the NCs, causing the buildup of CuTCA/TiO 2 p-n heterojunctions that improve the sensing response at RT just via a simple UV irradiation (λ = 365 nm). Importantly, the specialized reductive reaction of Cu(II) by NO enables a remarkable selectivity toward NO analysis. Owing to the synergistic large active surface and chemical sensitization effects from Cu-TCA, the resulting Cu-TCA/TiO 2 NCs show outstanding sensing performance; i.e., the response (( R gas - R air )/ R air ) reaches 124% at 50 ppm of NO with a detection limit of 140 ppb at RT. In addition, the response time decreases to 25.6% if the system is subjected to UV irradiation. The as-formed sensing membrane is also demonstrated to be practically effective for flexible and wearable sensing devices for quantitative NO analysis. This study facilitates the use of MOFs to achieve synergistically enhanced selectivity and sensitivity to develop high-performance gas sensors.

Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice; the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory effects of JTKY in poly(I:C)-induced pneumonia model mice were studied using untargeted metabolomics. Our results showed that JTKY treatment decreased the wet-to-dry ratio in the lung tissue, total protein concentration, and total cell count of the bronchoalveolar lavage fluid (BALF). Hematoxylin and Eosin (HE) and Masson staining indicated that the JTKY treatment alleviated the pathological changes and decreased the fibrotic contents in the lungs. JTKY treatment also decreased the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α)] and increased the levels of immunomodulatory cytokines (IL-4 and IL-10) in the BALF and serum. Flow cytometry analysis showed that the JTKY treatment lowered the ratio of CD86 + /CD206 + macrophages in the BALF, decreased inducible nitric oxide synthase (iNOS) level, and increased arginase 1 (Arg-1) level in lung. JTKY also lowered CD11b + Ly6G + neutrophils in BALF and decreased myeloperoxidase (MPO) activity in lung. Moreover, it also elevated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) level in lung. Untargeted metabolomic analysis showed that the JTKY treatment could affect 19 metabolites in lung, such as L-adrenaline, L-asparagine, ornithine, and alpha-ketoglutaric acid. These metabolites are associated with the synthesis and degradation of ketone bodies, butanoate, alanine, aspartate, and glutamate metabolism, and tricarboxylic acid (TCA) cycle processes. In conclusion, our study demonstrated that treatment with JTKY ameliorated poly(I:C)-induced pneumonia. The mechanism of action of JTKY may be associated with the inhibition of the inflammatory response, the reduction of oxidative stress, and the regulation of the synthesis and degradation of ketone bodies, TCA cycle, and metabolism of alanine, aspartate, glutamate, and butanoate processes in lung., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cui, Wang, Yu, Wu, Zhang, Guo, Luo, Li, Li, He, Wen, Liao and Wang.)

It is important to detect cancer biomarkers at an early stage of tumor development for the effective diagnosis and treatment of cancer. As a well-known probe for detecting superoxide (·O 2 - ) radicals, nitro blue tetrazolium (NBT) can rapidly react with ·O 2 - to form a hydrophobic formazan precipitate. In this study, by deliberately utilizing this reaction, Pt asymmetrically decorated on a TiO 2 nanochannel membrane (Pt/TiNM) is explored to fabricate an electrochemical immunosensing platform with outstanding selectivity and ultrahigh sensitivity. Using NBT as the substrate, hydrophobic formazan precipitation induces a substantial block of ionic diffusion flux in nanochannels. Using alpha fetoprotein (AFP) as the target analyte, the established immunorecognition event was used to induce MoS 2 -Ab 2 conjugates. Thanks to the excellent light-shielding ability of MoS 2 nanosheets, the production of ·O 2 - radicals from the photocatalysis of Pt/TiNM is effectively depressed because of the attenuated arrival of light. The reduced formazan precipitation results in ionic transport changes in nanochannels, which in turn enables the selective recognition of AFP down to 2 ng mL -1 . This target-modulated sensing strategy is also capable of sensing other immune targets, thus paving a new way for designing nanochannel-based sensing platforms.

As an intriguing and intrinsic feature of life, chirality is highly associated with many significant biological processes. Simultaneous recognition and quantification of enantiomers remains a major challenge. Here, a sensitive enantiomer identification device is developed on TiO 2 nanochannels via the design of cascade recognition-quantification zones along the nanochannels. In this system, β-cyclodextrin (β-CD) is self-assembled on one side of the nanochannels for the selective recognition of enantiomers; CuMOFs are designed as the target-responsive partners on the other side of the nanochannels for the quantification of enantiomers that pass through the nanochannels. As a proof-of-principle of the cascade design, arginine (Arg) enantiomers are tested as the identification targets. The l-Arg molecules selectively bind in the recognition zone; d-Arg molecules pass through the recognition zone and then interact with the quantification zone via a specialized reduction reaction. As verified by nanofluidic simulations, because of the confinement effect of nanoscale channels combined with the condensation effect of porous structure, the in situ reaction in the quantification zone contributes to an unprecedented variation in transmembrane K + flux, leading to an improved identification signal. This novel cascade-zone nanochannel membrane provides a smart strategy to design multifunctional nanofluidic devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Diabetic patients show elevated plasma IL18 concentrations. IL18 has two receptors: the IL18 receptor (IL18r) and the Na-Cl co-transporter (NCC). Here, we report that IL18 is expressed on islet α cells, NCC on β cells, and IL18r on acinar cells in human and mouse pancreases. The deficiency of these receptors reduces islet size, β cell proliferation, and insulin secretion but increases β cell apoptosis and exocrine macrophage accumulation after diet-induced glucose intolerance or streptozotocin-induced hyperglycemia. Together with the glucagon-like peptide-1 (GLP1), IL18 uses the NCC and GLP1 receptors on β cells to trigger β cell development and insulin secretion. IL18 also uses the IL18r on acinar cells to block hyperglycemic pancreas macrophage expansion. The β cell-selective depletion of the NCC or acinar-cell-selective IL18r depletion reduces glucose tolerance and insulin sensitivity with impaired β cell proliferation, enhanced β cell apoptosis and macrophage expansion, and inflammation in mouse hyperglycemic pancreas. IL18 uses NCC, GLP1r, and IL18r to maintain islet β cell function and homeostasis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Enrichment and separation of specific endogenous molecules are essential for disease diagnosis and the pharmaceutical industry. Although many solid sorbents have been developed for target molecule enrichment, simultaneous separation of multitargets is still a challenge for adsorbents. In this study, we develop a multitarget selective sorbent based on a nanochannel membrane prepared by the anodization of a Ti-Cu alloy. The in situ growth of a metal-organic framework (MOF, herein using Cu-based HKUST-1) in the nanochannels enables the resulting MOF-in-nanochannel membrane to act as a nanofilter. Benefitting from the size-exclusion effect of MOFs and the distinct surface characteristics of each component in the HKUST-1/TiO 2 nanochannels, the as-proposed membranes can be simply operated as a filter and exhibit satisfactory selectivities and enrichment capacities in the separation of aromatic amino acids, histidine-rich proteins, and phosphoproteins. More importantly, the adsorbed multitargets can be further controllably released from the membrane in a sequence via a staged recovery process. The use of this system is envisioned to provide an innovative and potential design for efficient sorption media for the selective enrichment and staged separation of specific biomolecules.

Asthma is an allergic airway disease in which type 2-mediated inflammation has a pathogenic role. Cardiovascular diseases (CVDs) are type 1-dominant inflammatory diseases in which type 2 cytokines often have a protective role. However, clinical studies demonstrate that allergic asthma and associated allergies are essential risk factors for CVD, including coronary heart diseases, aortic diseases, peripheral arterial diseases, pulmonary embolism, right ventricular dysfunction, atrial fibrillation, cardiac hypertrophy and even hypertension. Mast cells, eosinophils, inflammatory cytokines and immunoglobulin (Ig)E accumulate in asthmatic lungs and in the injured heart and vasculature of patients with CVD. Clinical studies show that many anti-asthmatic therapies affect the risk of CVD. As such, allergic asthma and CVD may share common pathogenic mechanisms. Preclinical investigations indicate that anti-asthmatic drugs have therapeutic potential in certain CVDs. In this Review, we discuss how asthma and allied allergic conditions may contribute to the prevalence, incidence and progression of CVD and vice versa., (© 2022. Springer Nature Limited.)

Chiral enantiomers have different effects on biological processes. Enantiomer separation is significant and necessary. Herein, a photothermal (PT) effect-derived enantioselective desorption strategy based on homochiral Au/TiO 2 nanotubes (NTs) is developed. Using 3,4-dihydroxyphenylalanine (DOPA) as the model enantiomer, an obvious selective desorption of L/D-DOPA can be achieved by the NIR light-triggered local temperature enhancement. Molecular docking simulation further verifies that the distinct affinity precipitated by the different hydrogen bonds between homochiral sorbent and target enantiomers is the origin of enantioselective desorption. This desorption strategy provides a green and alternative approach for the selective separation of chiral molecules.