Search

Redox homeostasis contributing to the maintenance of normal cellular physiological states. On the contrary, off-kilter redox as a resolution member in the production of cardiovascular disease, rheumatoid arthritis, and even cancer. To date, a few reports have focused on ratiometric sustainable assays for ClO- and GSH cycling due to the headache of transient reactivity, ultra-low concentrations and short lifetimes. However, methods for the design of ratiometric fluorescent probes also need to be further expanded. In this paper, we present a novel approach to the construction of ratiometric fluorescent probes via controlled modification of polysiloxane backbones. We aimed at the controlled assembly of a biocompatible, more pliable and stable "Si-O-Si" bridging framework, "red gene" perylenetetracarboxylic anhydride and "green gene" molecular sensors, successfully constructing a dual-excitation, dual-emission ratiometric fluorescent probe (PBN-1) with favorable biosafety properties, excellent photostability and promising sensitivity. PBN-1 sustainability dynamically tracked ClO-/GSH oxidation fluctuations in HepG2 cells and zebrafish. Notably, PBN-1 distinguished dramatically the fluctuations of ClO-/GSH in zebrafish at different growth and developmental periods. We expect that PBN-1 could provide an effective method for the design of future ratiometric fluorescent probes and expand the application of polysiloxanes in bioimaging. [Display omitted] • A novel strategy for constructing ratiometric fluorescent probes. • Dual-excitation, dual-emission polymer ratiometric fluorescent probes. • PBN-1 demonstrated superior sensitivity to ClO- [LOD = 3 σ /k (~ 2.3 nM)]. • PBN-1 revealed fluctuating levels of ClO-/GSH in cells and zebrafish via ratiometric channels. [ABSTRACT FROM AUTHOR]

Occurrence, spatiotemporal variation, sources, and ecological risks of 20 organophosphorus flame retardants (OPFRs) in water and sediments from Hangzhou Bay (HZB) and its adjacent East China Sea (ECS) were investigated in this study. The concentrations of OPFRs (∑OPFR) in water ranged from 0.51 ng/L to 885 ng/L, with chlorinated OPFRs having the highest value. For sediments, ∑OPFR ranged from 2.93 ng/g, dry weight (dw) to 37.8 ng/g, dw. The ∑OPFR in the water and sediments of HZB in summer was significantly (p < 0.05) higher than that in autumn. Additionally, the pollution of OPFRs in HZB was higher than that in ECS, and the high-concentration areas appeared in the north and south banks of HZB and near the coast of ECS. Principal component analysis–multiple linear regression showed that the OPFRs in this region were mainly from industrial products (e.g., polyurethane foam/paint/coating/textiles/product processing). In terms of aquatic environments, ecological risks were in a low (∑RQs<0.1) to moderate (0.1<∑RQs<1) level, with regard to median exposure levels, a moderate risk (0.1<∑RQs<1) was found in the sediments during autumn. This study can provide new insights into the OPFR pollution characteristic and ecological risk in a specific eco-environment. [Display omitted] • Spatiotemporal distributions of OPFRs in aquatic environment were investigated. • The OPFRs level was significantly higher in summer than in autumn. • A Significant correlation was found between OPFRs and TOC in sediment. • The ecological risks were in a low to moderate level in HZB and ECS. [ABSTRACT FROM AUTHOR]

Autophagy is an essential process for the degradation of malfunctional organelles and the response to cancer immunotherapy. The occurrence of defective autophagy is correlated to obesity, aging, neurological diseases, inflammation and tumors. Therefore, it is urgent to accurately depict the autophagic process. We herein architecture a polysiloxane-based probe (PA-1) that was lysosome targeted and pH-responsive for discerning autophagy process. We have demonstrated that PA-1 enabled specific visualization of lysosomal autophagy. PA-1 also detected the down-regulation of the pH value that accompanied the autophagy process under starvation stimulation. During autophagy, the green fluorescence of some spots in the lysosomes gradually decreased along with the emergence of strong agglomerated red fluorescence, which might be caused by the membrane fusion of lysosomes and autophagosomes. The location of the autolysosome could be precisely displayed by the ratio image. In addition, we observed that the autophagy inhibitor CQ could increase the pH of the intracellular environment and inhibit autophagy. The design strategy will broaden the research field of polysiloxane in cellular physiological processes and serves as a candidate for basic research on autophagic processes and effective therapeutic strategies for autophagy-related diseases. [Display omitted] • Polysiloxane-based Ratiometric fluorescent probe PA-1 was designed and characterized. • PA-1 presented green fluorescence under neutral conditions and red fluorescence under acidic conditions. • PA-1 dynamically monitored the changes of H+ in HepG2 cells. • Lysosomal autophagy process in HepG2 cells was dynamically monitored by fluorescence ratio images of PA-1. • The pH upregulation behavior during lysosomal autophagy with the addition of CQ was monitored by PA-1 [ABSTRACT FROM AUTHOR]

Objective: To elucidate the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in the antituberculosis (anti-TB) immune response mediated by dendritic cells (DCs)., Methods: In vivo, C57BL/6J mice infected with the Mycobacterium tuberculosis strain H37Rv. Before infection, the mice were pretreated with the PC-PLC inhibitor D609. Bacillary loads in lung and spleen tissues were quantified through colony-forming unit (CFU) assays. Hematoxylin and eosin (H&E) staining was performed to assess inflammatory infiltration and tissue damage. Levels of inflammatory mediators in peripheral venous blood were quantified using enzyme-linked immunosorbent assays (ELISAs). Flow cytometry was employed to determine the proportions of conventional DCs (cDCs) and their subsets, cDC1 and cDC2, within lung, spleen, and lymph node tissues. In vitro, mouse bone marrow-derived dendritic cells (BMDCs) pretreated with D609. The expression levels of chemokines and pro-inflammatory cytokines were assessed via quantitative polymerase chain reaction (qPCR) and ELISA. BMDCs were loaded with H37Rv expressing red fluorescent protein (RFP-H37Rv) or DQ-OVA, and flow cytometry was utilized to analyze the impact of D609 on antigen phagocytosis and processing. Furthermore, flow cytometry was employed to evaluate the effect of D609 pretreatment on the expression levels of costimulatory molecules on BMDCs. The capacity of D609-treated BMDCs to activate and proliferate T cells, as well as to induce interferon-gamma (IFN-γ) secretion, was assessed through a DC-T cell coculture system., Results: In vivo analysis revealed that mice pretreated with D609 exhibited a marked increase in tissue bacterial load, enhanced inflammatory infiltration, and a reduction in pro-inflammatory mediator expression in peripheral venous blood. There was a notable decrease in the number of cDCs in lung and lymph node tissues, with a pronounced reduction in cDC1 in the lungs and cDC2 in the lymph nodes. In vitro studies demonstrated that D609 pretreated BMDCs displayed a significant decline in inflammatory mediator production, antigen phagocytosis, and antigen processing capabilities, potentially due to altered expression of costimulatory molecules. Coculture experiments indicated that D609 pretreated BMDCs showed a substantial reduction in their ability to stimulate T cell activation, proliferation, and IFN-γ secretion., Conclusion: Our findings suggest that PC-PLC plays a critical role in the functionality of DCs, including the production of chemokines and pro-inflammatory cytokines, migration to lymph nodes, and antigen presentation to T cells, which collectively contribute to T cell activation and effective clearance of Mycobacterium tuberculosis. Further investigation into the regulatory mechanisms of PC-PLC in DCs may uncover novel therapeutic targets for the development of advanced anti-TB treatments., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objective: This study aimed to assess the impact of corn straw-based unfermented and fermented total mixed rations (TMR) supplemented with exogenous cellulase on the in vitro fermentation characteristics, growth performance, feeding behavior, apparent digestibility, rumen fermentation and digestive enzyme activities of Chinese Simmental bulls., Methods: Unfermented (direct spraying of exogenous cellulase onto TMR, TMR) and fermented (exogenous cellulase fermentation for more than 7 d, fermented total mixed rations [FTMR]) TMR were collected, dried, powdered and used as fermentation substrates. The fermentation liquid was ruminal fluid collected from Chinese Simmental bulls. The artificial rumen culture fluid were continuously cultured in vitro for 48 h. Based on the diets they were fed, 24 healthy Chinese Simmental bulls (average weight of 495.93±10.89 kg) were randomly divided into two groups, with 12 bulls in each group, which were fed TMR or FTMR. The study lasted 56 d., Results: In in vitro experiments, the neutral detergent fiber (NDF) degradability and total volatile fatty acid, propionate, iso-butyrate, iso-valerate and valerate concentrations were greater in the FTMR group (p<0.05) than in the TMR group. However, the methane production, pH and acetate/propionate (A/P) of the FTMR group tended to be lower (p<0.05) than those of the TMR group. In the in vivo experiments, the average daily gain, eating rate, and feed efficiency of the FTMR groups were greater (p<0.05) than those of the TMR group. Similarly, the NDF degradability of the FTMR group was greater (p<0.05) than that of the TMR group. Compared to those in the TMR group, the concentrations of total volatile fatty acids, iso-butyrate, propionate and butyrate were greater in the FTMR group (p<0.05), and the A/P ratio was lower (p<0.05). Similarly, cellulase, xylanase, and β-glucosidase activities were greater (p<0.05) in the FTMR group than in the TMR group., Conclusion: Corn straw-based FTMR supplemented with exogenous cellulase play a vital role in decreasing the structural carbohydrate content of TMR and ruminal methane production in vitro, improving nutrient digestion and absorption, optimizing rumen fermentation, and improving the growth performance of beef cattle.

Visible-light photooxidation sensitized by surface attachment of small colorless organics on semiconductor photocatalysts has emerged as an economical method for photocatalytic synthesis or degradation. In particular, heteroatom (X = N and Cl)-containing substrates could undergo either C-N coupling or dechlorination degradation via sensitizing TiO 2 , but the mechanism in conducting the competitive visible-light sensitized photooxidations is still vague. Herein, the visible-light photooxidation of colorless 4-chlorobenzene-1,2-diamine ( o -CAN) on TiO 2 was revealed, contributing to selective C-N coupling rather than dechlorination. Oxygen vacancies (OVs) were in situ generated on the TiO 2 surface, which could be dominant in weakening the Cl-Ti adsorption of o -CAN and regulating the activation of O 2 for selective C-N coupling. The C-N coupling product, functionalized as the sensitizer, further promoted the visible-light photooxidation upon N-Ti and Cl-Ti coordination. This process was then confirmed by on-line mass spectrometric analysis, and the intermediates as well as their kinetics were determined. Thereby, theoretical calculations were employed to verify the roles of OVs in competitive photooxidation and lowering the energy barriers as well. Based on the comprehensive characterizations of both the catalysts and intermediates, this work has provided insights into competitive photooxidations under visible light., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Controlling intracranial pressure, nerve cell regeneration, and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury. There is currently a lack of effective treatment methods. Hibernation has the characteristics of low temperature, low metabolism, and hibernation rhythm, as well as protective effects on the nervous, cardiovascular, and motor systems. Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body's metabolism, lowering the body's core temperature, and allowing the body to enter a state similar to hibernation. This review introduces artificial hibernation technology, including mild hypothermia treatment technology, central nervous system regulation technology, and artificial hibernation-inducer technology. Upon summarizing the relevant research on artificial hibernation technology in acute brain injury, the research results show that artificial hibernation technology has neuroprotective, anti-inflammatory, and oxidative stress-resistance effects, indicating that it has therapeutic significance in acute brain injury. Furthermore, artificial hibernation technology can alleviate the damage of ischemic stroke, traumatic brain injury, cerebral hemorrhage, cerebral infarction, and other diseases, providing new strategies for treating acute brain injury. However, artificial hibernation technology is currently in its infancy and has some complications, such as electrolyte imbalance and coagulation disorders, which limit its use. Further research is needed for its clinical application., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Single-atom enzymes (SAzymes) exhibit great potential for chemodynamic therapy (CDT); while, general application is still challenged by their instability and unavoidable side effects during delivery. Herein, a manganese-based polyoxometalate single-atom enzyme (Mn-POM SAE) is first introduced into tumor-specific CDT, which exhibits tumor microenvironment (TME)-activated transition of nontoxicity-to-toxicity. Different from traditional POM materials, the aggregates of low-toxic Mn-POM SAE nanospheres are obtained at neutral conditions, facilitating efficient delivery and avoiding toxicity problems in normal tissues. Under acid TME conditions, these nanospheres are degraded into smaller units of toxic Mn(II)-PW 11 ; thus, initiating cancer cell-specific therapy. The released active units of Mn(II)-PW 11 exhibit excellent multienzyme-like activities (including peroxidase (POD)-like, oxidase (OXD)-like, catalase (CAT)-like, and glutathione peroxidase (Gpx)-like activities) for the synergistic cancer therapy due to the stabilized high valence Mn species (Mn III /Mn IV ). As demonstrated by both intracellular evaluations and in vivo experiments, ROS is generated to cause damage to lysosome membranes, further facilitating acidification and impaired autophagy to enhance cancer therapy. This study provides a detailed investigation on the acid-triggered releasing of active units and the electron transfer in multienzyme-mimic-like therapy, further enlarging the application of POMs from catalytical engineering into cancer therapy., (© 2024 Wiley‐VCH GmbH.)

This paper seeks to determine the effect of combination anti-PD-1 and antiretroviral therapy (ART) on people living with HIV (PLWH) with advanced gastric cancer. In our case, a PLWH with recurrent locally advanced gastric cancer was treated with anti-PD-1 inhibitor and ART. A significant reduction in tumor lesions (as demonstrated by contrast-enhanced CT imaging) and a better quality of life were achieved following treatment. There have been limited studies on the treatment of PLWH with advanced gastric cancer. Chemotherapy is most often used, however, with unsatisfactory outcomes. to date, there have been no published reports on the use of PD-1 inhibitors in PLWH with advanced gastric cancer. Our report provides a valuable reference for future management of such patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is updating the diagnostic criteria for AD, which changed the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." Previously, most of studies focus on the correlation between the gut microbiome and amyloid beta deposition ("A"), the initial AD pathological feature triggering the "downstream" tauopathy and neurodegeneration. However, limited research investigated the interactions between the gut microbiome and other AD pathogenesis ("TNIVS"). In this review, we summarize current findings of the gut microbial characteristics in the whole spectrum of AD. Then, we describe the association of the gut microbiome with updated biomarker categories of AD pathogenesis. In addition, we outline the gut microbiome-related therapeutic strategies for AD. Finally, we discuss current key issues of the gut microbiome research in the AD field and future research directions. HIGHLIGHTS: The new revised criteria for Alzheimer's disease (AD) proposed by the Alzheimer's Association Workgroup have updated the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." The associations of the gut microbiome with updated biomarker categories of AD pathogenesis are described. Current findings of the gut microbial characteristics in the whole spectrum of AD are summarized. Therapeutic strategies for AD based on the gut microbiome are proposed., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Pyroptosis has attracted widespread concerns in cancer therapy, while the therapeutic efficiency could be significantly restricted by using the crucial pyroptosis checkpoint of autophagy and tumor hypoxia. Herein, a DNA nanocomplex (DNFs@ZnMn), containing cascade DNAzymes, promoter-like ZnO 2 -Mn nanozymes and photosensitizers, was constructed in one pot through rolling circle amplification reactions to induce pyroptosis through disrupting autophagy. After targeting cancer cells with a high expression of H + and glutathione, DNFs@ZnMn decomposed to expose DNAzymes and promoter-like ZnO 2 -Mn nanozymes. Then, sufficient metal ions and O 2 were released to promote cascade DNA/RNA cleavage and relieving of tumor hypoxia. The released DNAzyme-1 self-cleaved long DNA strands with Zn 2+ as the cofactor and simultaneously exposed DNAzyme-2 to cleave ATG-5 mRNA (with Mn 2+ as the cofactor). This cascade DNAzyme-mediated gene regulation process induced downregulation of ATG-5 proteins to disrupt autophagy. Simultaneously, the released ZnO 2 donated sufficient H 2 O 2 to generate adequate O 2 to relieve tumor hypoxia, obtaining highly cytotoxic 1 O 2 to trigger pyroptosis. By using dynamic cascade gene silencing to disrupt the pyroptosis checkpoint and synergistic relieving of hypoxia, this DNA nanocomplex significantly weakened cellular resistance to achieve efficient pyroptosis therapy both in vitro and in vivo ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The mixture of whole-plant soybean and whole-plant corn silage (WPSCS) is nutrient balanced and is also a promising roughage for ruminants. However, few studies have investigated the changes in bacterial community succession in WPSCS inoculated with homofermentative and heterofermentative lactic acid bacteria (LAB) and whether WPSCS inoculated with LAB can improve fermentation quality by reducing nutrient losses. This study investigated the effect of Lactobacillus plantarum ( L. plantarum ) or Lactobacillus buchneri ( L. buchneri ) on the fermentation quality, aerobic stability, and bacterial community of WPSCS. A 40:60 ratio of whole-plant soybean corn was inoculated without (CK) or with L. plantarum (LP), L. buchneri (LB), and a mixture of LP and LB (LPB), and fermented for 14, 28, and 56 days, followed by 7 days of aerobic exposure. The 56-day silage results indicated that the dry matter content of the LP and LB groups reached 37.36 and 36.67%, respectively, which was much greater than that of the CK group (36.05%). The pH values of the LP, LB, and LPB groups were significantly lower than those of the CK group ( p  < 0.05). The ammoniacal nitrogen content of LB was significantly lower than that of the other three groups ( p  < 0.05), and the ammoniacal nitrogen content of LP and LPB was significantly lower than that of CK ( p  < 0.05). The acetic acid content and aerobic stability of the LB group were significantly greater than those of the CK, LP, and LPB groups ( p  < 0.05). High-throughput sequencing revealed a dominant bacteria shift from Proteobacteria in fresh forage to Firmicutes in silage at the phylum level. Lactobacillus remained the dominant genus in all silage. Linear discriminant analysis effect size (LEFSe) analysis identified Lactobacillus as relatively abundant in LP-treated silage and Weissella in LB-treated groups. The results of KEGG pathway analysis of the 16S rRNA gene of the silage microbial flora showed that the abundance of genes related to amino acid metabolism in the LP, LB, and LPB groups was lower than that in the CK group ( p  < 0.05). In conclusion, LAB application can improve the fermentation quality and nutritional value of WPSCS by regulating the succession of microbial communities and metabolic pathways during ensiling. Concurrently, the LB inoculant showed the potential to improve the aerobic stability of WPSCS., 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 Xu, Ma, Sa, Sui, Wang, Li, Zhu, Wu, Hu and Niu.)

Background: Clear cell renal cell carcinoma (ccRCC) is corelated with tumor-associated material (TAM), coagulation system and adipocyte tissue, but the relationships between them have been inconsistent. Our study aimed to explore the cut-off intervals of variables that are non-linearly related to ccRCC pathological T stage for providing clues to understand these discrepancies, and to effectively preoperative risk stratification., Methods: This retrospective analysis included 218 ccRCC patients with a clear pathological T stage between January 1st, 2014, and November 30th, 2021. The patients were categorized into two cohorts based on their pathological T stage: low T stage (T1 and T2) and high T stage (T3 and T4). Abdominal and perirenal fat variables were measured based on preoperative CT images. Blood biochemical indexes from the last time before surgery were also collected. The generalized sum model was used to identify cut-off intervals for nonlinear variables., Results: In specific intervals, fibrinogen levels (FIB) (2.63-4.06 g/L) and platelet (PLT) counts (>200.34 × 10 9 /L) were significantly positively correlated with T stage, while PLT counts (<200.34 × 10 9 /L) were significantly negatively correlated with T stage. Additionally, tumor-associated material exhibited varying degrees of positive correlation with T stage at different cut-off intervals (cut-off value: 90.556 U/mL)., Conclusion: Preoperative PLT, FIB and TAM are nonlinearly related to pathological T stage. This study is the first to provide specific cut-off intervals for preoperative variables that are nonlinearly related to ccRCC T stage. These intervals can aid in the risk stratification of ccRCC patients before surgery, allowing for developing a more personalized treatment planning., Competing Interests: 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., (© 2024 The Authors.)

A key role of the gut microbiota in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), has been identified over the past decades. Increasing clinical and preclinical evidence implicates that there is bidirectional communication between the gut microbiota and the central nervous system (CNS), which is also known as the microbiota-gut-brain axis. Nevertheless, current knowledge on the interplay between gut microbiota and the brain remains largely unclear. One of the primary mediating factors by which the gut microbiota interacts with the host is peripheral metabolites, including blood or gut-derived metabolites. However, mechanistic knowledge about the effect of the microbiome and metabolome signaling on the brain is limited. Neuroimaging techniques, such as multi-modal magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET), have the potential to directly elucidate brain structural and functional changes corresponding with alterations of the gut microbiota and peripheral metabolites in vivo . Employing a combination of gut microbiota, metabolome, and advanced neuroimaging techniques provides a future perspective in illustrating the microbiota-gut-brain pathway and further unveiling potential therapeutic targets for AD treatments., 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 Sheng, Du, Liang, Xu, Ding, Chen, Jia and Wang.)

The remodulation of H + /Ca 2+ gradients in the mitochondria matrix could be effective to induce mitochondria depolarization for the enhancement of cancer therapy. However, it is still challenged by H + homeostasis, insufficient Ca 2+ , uncoordinated regulations, and inefficient loading/delivery strategies. Herein, a supramolecular DNA nanocomplex (Ca@DNA-MF) was prepared to synergistically remodulate H + /Ca 2+ gradients for mitochondrial depolarization. Upon targeted functionalization and TME-triggered delivery, multiple reagents were released in cancer cells for synergistic three-channel mitochondrial depolarization: the gene reagent of siMCT4 blocked the LA metabolism to induce mitochondrial acidification by downregulating monocarboxylate transporter 4 (MCT4); released Ca 2+ disrupted Ca 2+ homeostasis to facilitate Ca 2+ -based mitochondrial depolarization; specifically, TME-activated glutathione (GSH) depletion facilitated efficient generation of hydroxyl radicals (˙OH), further enhancing the mitochondrial depolarization. The remodulation not only triggered apoptosis but also led to ferroptosis to generate abundant ROS for efficient LPO-based apoptosis, providing a synergistic strategy for enhanced synergistic cancer therapy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Pelophylax nigromaculatus is a common commercial specie of frogs that generally cultured throughout China. With the application of high-density culture, P. nigromaculatus can be co-infected by two or more pathogens, which thereby induce synergistic influence on the virulence of the infection. In this study, two bacterial strains were simultaneously isolated from diseased frogs by incubating on Luria-Bertani (LB) agar. Isolates were identified as Klebsiella pneumoniae and Elizabethkingia miricola by morphological, physiological and biochemical features, as well as 16S rRNA sequencing and phylogenetic analysis. The whole genome of K. pneumoniae and E. miricola isolates consist single circular chromosome of 5,419,557 bp and 4,215,349 bp, respectively. The genomic sequence analysis further indicated that K. pneumoniae isolate conserved 172 virulent and 349 antibiotic-resistance genes, whereas E. miricola contained 24 virulent and 168 antibiotic resistance genes. In LB broth, both isolates could grow well at 0%-1% NaCl concentration and pH 5-7. Antibiotic susceptibility testing revealed that both K. pneumoniae and E. miricola were resistant to kanamycin, neomycin, ampicillin, piperacillin, carbenicillin, enrofloxacin, norfloxacin and sulfisoxazole. Histopathological studies showed that co-infection caused considerable lesions in the tissues of brain, eye, muscle, spleen, kidney and liver, including cell degeneration, necrosis, hemorrhage and inflammatory cell infiltration. The LD 50 of K. pneumoniae and E. miricola isolates were 6.31 × 10 5  CFU/g and 3.98 × 10 5  CFU/g frog weight, respectively. Moreover, experimentally infected frogs exhibited quick and higher mortality under coinfection with K. pneumoniae and E. miricola than those single challenge of each bacterium. To date, no natural co-infection by these two bacteria has been reported from frogs and even amphibians. The results will not only shed light on the feature and pathogenesis of K. pneumoniae and E. miricola, but also highlight that co-infection of these two pathogen is a potential threat to black-spotted frog farming., 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 Ltd. All rights reserved.)

This study investigated the effects of dietary chitosan on growth, antioxidant, immunity, intestinal morphology and resistance against Aeromonas hydrophila of hybrid sturgeon (Acipenser baerii♀ × Acipenser schrenckii♂). Sturgeons (18.18 ± 0.08 g) were randomly divided into four groups, fed with chitosan-supplemented diets for 8 weeks and then infected with A. hydrophila. The results showed significant differences of body weight gain, specific growth rate and feed conversion ratio in sturgeon fed chitosan and control diets. The oral administration of chitosan significantly increased the acid phosphatase, alkaline phosphatase, lysozyme, myeloperoxidase, superoxide dismutase, glutathione peroxidase and catalase activities, as well as the complement 3 and 4 contents and disease resistance against A. hydrophila. Moreover, enhancement of muscular thickness and goblet cells in mid intestine and increase of muscular thickness and villus height in spiral valve were observed in the chitosan supplemented groups. In addition, dietary chitosan-supplemented diets mitigated the changes of antioxidant and immune activity induced by A. hydrophila challenge, as well as prevented fish from bacterial invasion. The optimal dose was 3.00 g chitosan/kg diet for hybrid sturgeon., 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 © 2022 Elsevier B.V. All rights reserved.)

Growing evidence supports that Alzheimer's disease (AD) could be regarded as a metabolic disease, accompanying central and peripheral metabolic disturbance. Nowadays, exploring novel and potentially alternative hallmarks for AD is needed. Peripheral metabolites based on blood and gut may provide new biochemical insights about disease mechanisms. These metabolites can influence brain energy homeostasis, maintain gut mucosal integrity, and regulate the host immune system, which may further play a key role in modulating the cognitive function and behavior of AD. Recently, metabolomics has been used to identify key AD-related metabolic changes and define metabolic changes during AD disease trajectory. This review aims to summarize the key blood- and microbial-derived metabolites that are altered in AD and identify the potential metabolic biomarkers of AD, which will provide future targets for precision therapeutic modulation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Considerable attention has been paid to interindividual differences in the cardiorespiratory fitness (CRF) response to exercise. However, the complex multifactorial nature of CRF response variability poses a significant challenge to our understanding of this issue. We aimed to explore whether unsupervised clustering can take advantage of large amounts of clinical data and identify latent subgroups with different CRF exercise responses within a healthy population., Methods: 252 healthy participants (99 men, 153 women; 36.8 ± 13.4 yr) completed moderate endurance training on 3 days/week for 4 months, with exercise intensity prescribed based on anaerobic threshold (AT). Detailed clinical measures, including resting vital signs, ECG, cardiorespiratory parameters, echocardiography, heart rate variability, spirometry and laboratory data, were obtained before and after the exercise intervention. Baseline phenotypic variables that were significantly correlated with CRF exercise response were identified and subjected to selection steps, leaving 10 minimally redundant variables, including age, BMI, maximal oxygen uptake (VO 2max ), maximal heart rate, VO 2 at AT as a percentage of VO 2max , minute ventilation at AT, interventricular septal thickness of end-systole, E velocity, root mean square of heart rate variability, and hematocrit. Agglomerative hierarchical clustering was performed on these variables to detect latent subgroups that may be associated with different CRF exercise responses., Results: Unsupervised clustering revealed two mutually exclusive groups with distinct baseline phenotypes and CRF exercise responses. The two groups differed markedly in baseline characteristics, initial fitness, echocardiographic measurements, laboratory values, and heart rate variability parameters. A significant improvement in CRF following the 16-week endurance training, expressed by the absolute change in VO 2max , was observed only in one of the two groups (3.42 ± 0.4 vs 0.58 ± 0.65 ml⋅kg -1 ∙min -1 , P = 0.002). Assuming a minimal clinically important difference of 3.5 ml⋅kg -1 ∙min -1 in VO 2max , the proportion of population response was 56.1% and 13.9% for group 1 and group 2, respectively ( P< 0.001). Although group 1 exhibited no significant improvement in CRF at group level, a significant decrease in diastolic blood pressure (70.4 ± 7.8 vs 68.7 ± 7.2 mm Hg, P = 0.027) was observed., Conclusions: Unsupervised learning based on dense phenotypic characteristics identified meaningful subgroups within a healthy population with different CRF responses following standardized aerobic training. Our model could serve as a useful tool for clinicians to develop personalized exercise prescriptions and optimize training effects., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2022 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

DNA nanoframeworks, with great biological information and controlled framework structures, exhibit great potentials in biological applications. Their applications are normally limited by unstable structures susceptible to hydrolysis, depurination, depyrimidination, oxidation, alkylation, or nuclease degradations. Herein, to ensure the mechanical and chemical stabilities of DNA nanoframeworks for intracellular applications, biomineralization of multifunctional DNA nanoframeworks with a tetrahedral skeleton is employed. Via silicification, the S-S bond is simultaneously introduced to obtain the silica-armored DNA nanoframeworks (Si-DNA nanoframeworks), mechanically and chemically stabilized for efficient intracellular deliveries. This successfully prevents degradations and leakages of reagents loaded on Si-DNA nanoframeworks, including biomolecular siRNA and small DOX drugs. Furthermore, the nucleic acid strands of the nanoframeworks are labeled with FAM and the quencher, facilitating miRNA detection upon "turn-on" signals from hybridizations. Therefore, the nanoframeworks collapse via double responses of the silica coating (silica acidic dissolution and S-S reduction by GSH) in cancer cells, realizing on-demand reagent release for miRNA detection and synergistic treatments (by siRNA and DOX). Demonstrated by both in vivo and in vitro experiments, the biomineralization has stabilized DNA nanomaterials for biological applications.

The relationship of cognitive reserve and measures of reserve with longitudinal cognitive change and the duration of preclinical, prodromal, and mild Alzheimer disease (AD) dementia remains to be fully characterized. In our study, 660 β-amyloid-positive participants staged with preclinical AD, prodromal AD, and dementia due to AD from the Alzheimer's Disease Neuroimaging Initiative were selected. Cognitive reserve and brain reserve were defined by conventional proxies or the residual method at baseline. We evaluated the utility of these reserves in predicting longitudinal cognitive change by mixed effects models and used a multi-state model to estimate stage duration stratified by reserve groups. Corrected for age, sex, and APOE-ε4 status, reserve was associated with cognitive decline, and the effects changed depending on the specific measures of reserve and the stage of AD. Reserves defined by the residual method were stronger predictors of cognitive change than those defined by conventional proxies. The estimated time from preclinical to mild AD dementia varied from 15-24 years based on the different reserve groups, and we observed a linear trend for the longest duration in individuals with high cognitive reserve/high brain reserve, followed by those with high cognitive reserve/low brain reserve, low cognitive reserve/high brain reserve, and low cognitive reserve/low brain reserve. This study showed a reduced risk of cognitive decline for individuals with higher level of reserve regardless of methods for measuring reserve. Interindividual differences in reserve may be important for clinical practice and trial design., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to analyze the clinical features and prognostic factors of imaging progression and survival in patients with antisynthetase syndrome (ASS) complicated by interstitial lung disease (ILD) in a large Chinese cohort., Methods: Medical records, imaging, and serological data of 111 patients with ASS-ILD (positive for at least one of the following autoantibodies: anti-Jo1, anti-PL7, anti-PL12, and anti-EJ) from the Affiliated Yantai Yuhuangding Hospital of Qingdao University database were retrospectively investigated. According to the changes in high-resolution computed tomography (HRCT) outcomes at 1 year follow-up, Patients were categorized into three groups: the regression, stability, and deterioration groups. Univariate analysis was performed to evaluate the possible prognostic factors of ILD outcome and death, and multivariate analysis was performed to determine the independent predictors of ASS-ILD outcome and death by logistic regression., Results: The number of CD3-CD19+ cells and initial glucocorticoid dosage were correlated with imaging progression, and may be independent risk factors for ILD deterioration. Dyspnea as the first symptom, hypohemoglobinemia, the serum ferritin level, oxygen partial pressure at diagnosis, and different treatment types were important factors affecting survival, and the initial serum ferritin level may be an independent risk factor for survival., Conclusions: The clinical characteristics of patients with ASS-ILD with different antisynthetase antibody subtypes are different. An increase in the CD3-CD19+ cell level is an independent risk factor for the deterioration of HRCT imaging. Early intensive treatment with high-dose glucocorticoids can effectively improve imaging prognosis of ILD. Patients with significantly elevated serum ferritin levels should be treated intensively., 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 Zhao, Jiang, Wu, Wang, Wang, Bai, Li, Tang and Liu.)

siRNA therapeutics are challenged by homogeneous and efficient loading, maintenance of biological activities, and precise, dynamic and monitorable site-release. Herein, supramolecular nanomaterials of WP5⊃G-siRNA were constructed by modular and hierarchical self-assembly of siRNA with guest (3,6-di(thiophen-2-yl)pyrrolo[3,4- c ]pyrrole-1,4(2 H ,5 H )-dione derivative, G) and host (pillar[5]arene, WP5) molecules in the same system. Demonstrated by experiments and theoretical calculations, WP5⊃G-siRNA was constructed via comprehensive weak interactions including electrostatic, hydrophobic-hydrophilic, host-guest and π-π interactions. Therefore, siRNAs were efficiently loaded, maintaining good stability, bioactivities and biocompatibilities. At pH 6.8, G was protonated to give weak acidic-responsive "turn-on" fluorescent signals, which realized the precise location of cancer sites. This triggered a subsequent delivery and a dynamic release of siRNA in cancer cells under acidic conditions for the entire collapse of WP5⊃G-siRNA by the protonation of both WP5 and G. By both in vitro and in vivo experiments, precise and visualized delivery to cancer sites was achieved to exhibit effective tumour inhibition. This provided an efficient and soft strategy of siRNA therapies and expanded the application of supramolecular nanomaterials in diagnosis and treatment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The pollution characteristics, potential sources, and potential ecological risk of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were investigated in the Hangzhou Bay (HZB) and East China Sea (ECS). Total OCPs concentration ranged from 2.62 to 102.07 ng/L and 4.41 to 75.79 μg/kg in the seawater and sediment samples, with PCBs concentration in the range of 0.40-51.75 ng/L and 0.80-45.54 μg/kg, respectively. The OCPs were positively correlated with nutrients, whereas PCBs presented a negative correlation. The newly imported dichlorodiphenyltrichloroethane (DDT) in HZB is mainly the mixing of technical DDT and dicofol sources. The PCB source composition is more likely related to the mixture of Kanechlor 300, 400, Aroclor 1016, 1242, and Aroclor 1248. Risk assessment results indicate that OCPs posed low risk in seawater. The potential risk of DDTs in the sediments is a cause of concern., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Subjective cognitive decline (SCD)-related worries are indicative of an increased risk for developing Alzheimer's disease (AD) dementia. However, the influence of SCD-related worries on the relationship between amyloid and gray matter (GM) atrophy remains unknown. A total of 93 SCD participants underwent 18 F-florbetapir PET and T1-weighted MRI scans. SCD individuals were classified into amyloid-positive or amyloid-negative groups based on global amyloid uptake. Three-step statistical analyses were performed: (1) partial correlation analysis was conducted to determine whether global amyloid relates to GM volume in amyloid-positive and amyloid-negative groups; (2) linear regression analysis was conducted to determine whether the interaction term (worries × global amyloid) predicts GM volume; and (3) post hoc subgroup linear regression analysis was conducted to determine the association between amyloid and GM volume in the subgroups with and without worries. Age, sex, education and total intracranial volume were adjusted in all models. We found a negative relationship between global amyloid load and GM volume in the right hemisphere (r = 0.441, p = 0.012) and right temporal cortex (r = 0.506, p = 0.003) in the amyloid-positive group. Moreover, in the amyloid-positive group, a significant worries × amyloid interaction effect on GM volume was found in the bilateral hemisphere (right: p interaction =0.037; left: p interaction =0.036), left temporal cortex (p interaction =0.044) and bilateral frontal cortex (right: p interaction =0.010; left: p interaction =0.011). Subsequent post hoc analysis revealed a significant amyloid-GM association only in the subgroup with worries but not in the subgroup without worries. In preclinical AD cases, SCD-related worries may occur as a symptom in those cases where amyloid affects GM to a greater extent and may thus represent a high-risk population for future cognitive decline., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The objective of this study is to investigate the protective effect of kaempferol against ischemia/reperfusion (IR) injury and the underlying molecular mechanisms., Methods: H9C2 cells were pretreated with kaempferol for 24 hours and further insulted with IR injury. Cell vitality, reactive oxygen species (ROS) level, glutathione (GSH) level, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and sirtuin-3 (SIRT3), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) expressions were evaluated. Moreover, short interfering ribonucleic acid targeting SIRT3 was used to investigate the role of SIRT3 against IR mediated by kaempferol in vitro. IR mice models were also established to confirm the protective effects of kaempferol on IR in vivo., Results: After IR injury, H9C2 cells vitality was reduced, ROS levels, NADPH oxidase activity, and Bax expressions were increased, and GSH levels and Bcl2 expressions were decreased. After kaempferol pretreatment, the vitality of H9C2 cells was increased. The levels of ROS, NADPH oxidase activity, and Bax expression were decreased. In addition, levels of GSH and Bcl2 expression were enhanced. Furthermore, silencing SIRT3 attenuated the protective effect mediated by kaempferol, with increased ROS levels, NADPH oxidase activity, and Bax expression, along with reduced GSH level and Bcl2 expression. In vivo IR model showed that kaempferol could preserve IR-damaged cardiac function., Conclusion: Kaempferol has the capability of attenuating H9C2 cells IR injury through activating SIRT3 to inhibit oxidative stress.

Objective: Blood-based biomarkers for the early diagnosis of Alzheimer's disease (AD) are a 'Holy Grail' of AD research. Growing evidence shows that levels of apolipoproteins and various inflammation-related factors are altered in the peripheral blood of patients with AD. The purpose of this study was to clear and definite whether these biomarkers are differentially expressed at the early stages of AD, and could be a biomarker as an early diagnosis of the disease., Design: Observation study., Setting: This study was a part of the Sino Longitudinal Study on Cognitive Decline, an ongoing prospective cohort study (ClinicalTrials.gov identifier: NCT03370744) that centres on Xuanwu Hospital (Beijing, China) in cooperation with an alliance of 94 hospitals from 50 cities across China., Participants: In the present study, 416 right-handed Chinese Han subjects were recruited through standardised public advertisements from 2014 to 2019., Outcome Measures: Concentrations of plasma apolipoprotein A1, apolipoprotein CIII (ApoCIII), apolipoprotein E (ApoE), A-2-macroglobulin (A2M), complement C3 (C3) and complement factor H (FH) were determined using a commercial multiplex Luminex-based panel in normal controls (NC), subjective cognitive decline (SCD), mild cognitive impairment and AD groups., Results: For individual analysis, pairwise comparisons showed that: (1) For SCD versus NC, no biomarker showed significant difference; (2) For amnestic mild cognitive impairment (aMCI) versus NC, levels of ApoCIII, ApoE, A2M, C3 and FH increased significantly; and (3) For AD versus NC, amounts of C3 increased. For models differentiating clinical groups, discriminant analysis was performed by including all protein markers, age, sex, genotype and education level in the model. This approach could distinguish between patients with aMCI (area under the curve (AUC): 0.743) and AD (AUC: 0.837) from NC., Conclusion: Our results suggest that concentrations of certain apolipoproteins and inflammation-related factors are altered at the early stage of AD, and could be useful biomarkers for early diagnosis., Trial Registration Number: NCT03370744., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Group B coxsackieviruses (CVBs) are the main cause of virus-induced myocarditis. CVBs use coxsackievirus and adenovirus receptor (CAR) for infection and targeting CAR has been shown to ameliorate CVBs-induced myocarditis. Ligand-of-Numb protein X1 (LNX1) is an E3 ubiquitin ligase that was shown to interact with CAR. However, the precise effect of LNX1 on CAR and the roles of LNX1 on CVBs-induced myocarditis remain unknown. In the present study, we generated mice deficient in LNX1 in the heart and evaluated the symptoms of myocarditis after CVB3 infection. We also monitored the expression and ubiquitination of CAR in LNX1-deficient cardiomyocytes after CVBs infection. We found that CVBs infection decreased CAR expression while promoted the expression of LNX1. Mice with deficiency of LNX1 in the heart had normal myocardial development while had deteriorated myocarditis symptoms after CVB3 infection. In LNX1-deficient cardiomyocytes, decreased ubiquitination of CAR and upregulation of CAR were observed after CVB3 infection. In summary, LNX1 controls CVB3-induced myocarditis by regulating the expression of CAR., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We aimed to investigate the mechanism and effect of photodynamic treatment mediated by 5-aminoketovalerate (5-ALA-PDT) on human ovarian cancer cells (OVCAR3 cells) and to provide a theoretical basis for the subsequent experimental step in vivo. Human ovarian cancer OVCAR3 cells were randomly divided into four groups: control group, laser irradiation alone group, photosensitizer alone group, and photodynamic treatment group. Alterations in cell morphology were observed with an inverted light microscope; cell viability was examined by CCK-8 assays. The ROS content and apoptosis rate were examined by flow cytometry analysis. Western blot was used to detect the expression of apoptosis-related proteins, such as caspase-3, Bax, and Bcl-2, and the expression of cleaved caspase-3 in live cells was detected by a cleaved caspase-3 assay kit. Inverted light microscopy showed alterations in cell morphology in different stages. Comparison with the three other groups indicated that tumor cell proliferation was significantly decreased in the photodynamic treatment group (P < 0.05). Flow cytometry analysis revealed that the content of ROS was higher in the photodynamic group than in the other three groups, and the apoptosis rate was higher in the photodynamic treatment group. The difference compared with the other three groups was statistically significant (P < 0.001). The western blot results indicated that the protein expression of Bcl-2 and caspase-3 was decreased in the photodynamic treatment group, and the protein expression level of Bax was increased (P < 0.05). The expression of cleaved caspase-3 was increased in the photodynamic treatment group compared with the other groups according to the data obtained with a microplate reader. Thus, our results demonstrated that the apoptosis and viability of OVCAR3 cells are altered in response to 5-ALA-PDT; however, no remarkable effects were observed in ovarian cancer cells treated with laser irradiation or photosensitizer alone. 5-ALA-PDT can significantly inhibit the growth of human ovarian cancer cells, and the mechanism of this effect is related to the tumor cell apoptosis mediated by the downregulation of Bcl-2 and caspase-3 and upregulation of Bax protein expression., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature.)

As an essential gasotransmitter, carbon monoxide (CO) had gradually become a research hotspot in that it possessed important physiological functions and unique pharmacological properties. However, to date, no report has focused on the topic of detecting CO both in vivo and using films. To open up a new field of CO probes, for the first time, we designed a probe ( PMAH-CO ) that showed a distinctive ratio emission characteristic and displayed the quantitative distribution of CO in HeLa cells and zebrafish with a higher signal-to-noise ratio. Meanwhile, the fluorescent polysiloxane-based film ( PMF ) containing PMAH-CO exhibited an excellent response to CO. Due to the addition of the Si-O bond, the probe exhibited a broad transparency in the visible light range and had excellent photostability. Moreover, the probe was economically viable, easy to handle, and suitable for biological research. Hence, PMAH-CO and PMF would open up the road to broaden the application of silicone materials in the field of fluorescence imaging.

Noninvasive assessment of autonomic nervous system (ANS) activity is of great importance, but the accuracy of the method used, which is primarily based on electrocardiogram-derived heart rate variability (HRV), has long been suspected. We investigated the feasibility of photoplethysmography (PPG) in ANS evaluation. Data of 32 healthy young men under four different ANS activation patterns were recorded: baseline, slow deep breathing (parasympathetic activation), cold pressor test (peripheral sympathetic activation), and mental arithmetic test (cardiac sympathetic activation). We extracted 110 PPG-based features to construct classification models for the four ANS activation patterns. Using interpretable models based on random forest, the main PPG features related to ANS activation were obtained. Results showed that pulse rate variability (PRV) exhibited similar changes to HRV across the different experiments. The four ANS patterns could be better classified using more PPG-based features compared with using HRV or PRV features, for which the classification accuracies were 0.80, 0.56, and 0.57, respectively. Sensitive features of parasympathetic activation included features of nonlinear (sample entropy), frequency, and time domains of PRV. Sensitive features of sympathetic activation were features of the amplitude and frequency domain of PRV of the PPG derivatives. Subsequently, these sensitive PPG-based features were used to fit the improved HRV parameters. The fitting results were acceptable ( p < 0.01), which might provide a better method of evaluating ANS activity using PPG., 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 © 2021 Liu, Zhang, Di, Wang, Xie, Xie and Zhang.)

Objective: To define resilience metrics for cognitive decline based on plasma and cerebrospinal fluid (CSF) amyloid-β (Aβ) and examine the demographic, genetic, and neuroimaging factors associated with interindividual differences among metrics of resilience and to demonstrate the ability of such metrics to predict the diagnostic conversion to mild cognitive impairment (MCI). Methods: In this study, cognitively normal (CN) participants with Aβ-positive were included from the Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 100) and Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 144). Using a latent variable model of data, metrics of resilience [brain resilience (BR), cognitive resilience (CR), and global resilience (GR)] were defined based on the plasma Aβ and CSF Aβ. Linear regression analyses were applied to investigate the association between characteristics of individuals (age, sex, educational level, genetic, and neuroimaging factors) and their resilience. The plausibility of these metrics was tested using linear mixed-effects models and Cox regression models in longitudinal analyses. We also compared the effectiveness of these metrics with conventional metrics in predicting the clinical progression. Results: Although individuals in the ADNI cohort were older (74.68 [5.65] vs. 65.38 [4.66], p < 0.001) and had higher educational levels (16.3 [2.6] vs. 12.6 [2.8], p < 0.001) than those in the SILCODE cohort, similar loadings between resilience and its indicators were found within both models. BR and GR were mainly associated with age, women, and brain volume in both cohorts. Prediction models showed that higher CR and GR were related to better cognitive performance, and specifically, all types of resilience to CSF Aβ could predict longitudinal cognitive decline. Conclusion: Different phenotypes of resilience depending on cognition and brain volumes were associated with different factors. Such comprehensive resilience provided insight into the mechanisms of susceptibility for Alzheimer's disease (AD) at the individual level, and interindividual differences in resilience had the potential to predict the disease progression in CN people., 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 © 2021 Lin, Sun, Wang, Su, Wang and Han.)

Subjective cognitive decline (SCD) is the preclinical stage of Alzheimer's disease (AD), the most common neurodegenerative disease in the elderly. We collected resting-state functional MRI data and applied novel graph-theoretical analyses to investigate the dynamic spatiotemporal cerebral connectivities in 63 individuals with SCD and 67 normal controls (NC). Temporal flexibility and spatiotemporal diversity were mapped to reflect dynamic time-varying functional interactions among the brain regions within and outside communities. Temporal flexibility indicates how frequently a brain region interacts with regions of other communities across time; spatiotemporal diversity describes how evenly a brain region interacts with regions belonging to other communities. SCD and NC differed in large-scale brain dynamics characterized by the two measures, which, with support vector machine, demonstrated higher classification accuracies than conventional static parameters and structural metrics. The findings characterize dynamic network dysfunction that may serve as a biomarker of the preclinical stage of AD.

Accumulating evidence has demonstrated a significant relationship between prefrontal lobe and hypertension. Elevated blood pressure is usually associated with a prefrontal hemodynamic abnormality. However, the detailed process is still unclear. In this study, we designed a startle protocol and tested the response of the cerebral cortex and cardiovascular system in young normotensive subjects with a family history of hypertension (FH+). Additionally, the cold forehead test (CFT) was performed in hypertensive subjects. In total, 40 young normotensive subjects (21 with FH+ and 19 without a family history of hypertension (FH-)) and 49 middle-aged subjects (21 normotensives (NT) and 28 hypertensives (HT)) were recruited. Our results showed that the magnitude of startle-evoked alpha oscillation at the parasympathetic-related prefrontal cortex (FP1 and FP2) in the FH+ group was significantly smaller than in the FH- group. Acute bradycardia (RRI increase) was observed in FH- subjects but disappeared in the FH+ group. The coupling between instant cardiac acute response (increased RRI) and prefrontal arousal (magnitude of evoked oscillation) was significantly weakened in the FH+ group compared with the FH- group. Furthermore, the decrease in HR induced by parasympathetic outflow during CFT was absent in HT subjects. Hence, we concluded that the impairment of parasympathetic outflow derived from the prefrontal lobe occurs in both healthy young offspring of hypertensive and hypertensive patients.

SCN- is one of the most important anions in metabolic processes. However, the investigation of SCN- in living systems is restricted by the lack of stable functional molecular tools. Herein, the first fluorene-based polymer fluorescent probe V1 was synthesized through rational design. Compared with small molecule fluorescent probes, V1 exhibited excellent fluorescence stability in bovine serum albumin (BSA) solution. Furthermore, the V1-based paper sensor was highly selective toward SCN- in aqueous solution. Significantly, these merits of the probe V1 enable the detection of SCN- in different living cell lines and zebrafish.

Background: Subjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer's disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ε4 as well as neuropsychiatric symptoms in SCD., Methods: A total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD., Results: Compared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ε4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers., Conclusions: Individuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD., Trial Registration: ClinicalTrials.gov (Identifier: NCT03370744 ). Registered 15 March 2017.

Objectives: Although recent animal studies have highlighted the importance of cardiorespiratory coupling in the pathogenesis of hypertension, little research has assessed the cardiorespiratory coupling in humans at high risk of developing hypertension. The aim of this study was to investigate the cardiorespiratory coupling in healthy young individuals genetically predisposed to hypertension at both rest and mental stress conditions., Methods: We studied 39 normotensive male participants [21 with (FH+) and 18 without (FH-) a family history of hypertension]. Electrocardiography, impedance cardiography, beat-to-beat blood pressure and respiratory signal were simultaneously recorded during 5 min of rest and 5 min of mental arithmetic task (MAT). Stroke volume, cardiac output, systemic vascular resistance, baroreflex sensitivity and aortic pulse wave velocity were calculated. Autonomic activity was approximated noninvasively by the spectral analysis of cardiovascular variability. Respiratory sinus arrhythmia (RSA) and cardiorespiratory phase synchronization (CRPS) were used to define the amplitude and phase relationships of cardiorespiratory coupling., Results: All resting parameters were similar between FH- and FH+ groups except resting CRPS, which was lower in FH+ group. Furthermore, the changes in hemodynamic parameters and cardiovascular variability at MAT were comparable in FH- and FH+ groups. Moreover, MAT elicited a decrease in CRPS of FH- group, whereas CRPS of participants in FH+ group remained unchanged during MAT., Conclusion: Healthy offspring of hypertensive parents have lower CRPS at rest, indicating an early impairment of cardiorespiratory coupling. Furthermore, CRPS decreased under mental stress in participants without a family history of hypertension, whereas this reactivity of CRPS was absent in participants with a family history of hypertension.

The connectome-wide association studies exploring association between brain connectome and disease phenotypes have suffered from massive number of comparisons. In this paper, we propose to apply a multivariate distance-based analytic framework on brain white matter (WM) structural networks invaded by Alzheimer's disease (AD). Eighty-three subjects including patients with AD, amnestic mild cognitive impairment (aMCI) and healthy subjects were scanned with dMRI. By constructing WM structural network for each individual, we used both multivariate and traditional univariate statistical models to complimentarily analyze network pattern and fiber strength changes due to AD. WM connections linked with several brain structures were found significantly changed between AD group and normal controls. No significant findings were observed between aMCI group and normal controls. Our results demonstrate the sensitivity of the combined connectome-based analytic framework in detecting abnormalities of structural brain network.

Genome-wide association studies have identified that TERT gene was associated with telomere length and age-related diseases. However, little study directly focused on the association between TERT gene polymorphisms and risk of coronary heart disease (CHD). We conducted a case-control study to examine the effect of TERT polymorphisms on CHD risk among 596 CHD patients and 603 healthy controls from China. Five significant single nucleotide polymorphisms (SNP) in TERT were selected and genotyped using Sequenom Mass-ARRAY technology. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age and gender. Allelic model analysis revealed that for TERT rs10069690, allele frequency distributions differed between cases and controls (OR= 1.267, 95%CI = 1.018-1.576; p = 0.034). Genotypic model analysis revealed that genotype frequency distributions of rs10069690 differed between cases and controls after adjusted by age and sex (TC vs. CC: adjusted OR = 1.352, 95% CI = 1.007-1.815; p = 0.045). Genetic model analysis revealed that rs10069690 was associated with an increased risk of CHD under co-dominant, dominant, over-dominant and log-additive models. After adjustments, it remained significant under over-dominant model (adjusted OR = 1.35, 95% CI = 1.01-1.81; p = 0.044). Our results shed new light on the association between telomere-related gene TERT polymorphisms and CHD susceptibility in a Chinese Han population., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to report.

The use of wireless sensor networks for wearable computing in health care is growing quickly. Numerous applications are already in use, such as blood pressure monitors and heart rate monitors. As such, it is very important for system designers to consider how to protect patient privacy, especially in wireless sensor networks. After studying and analyzing the features of wireless sensor networks in medical systems, a data division scheme was proposed in this paper, provided the advantages of homomorphic encryption. In the proposed scheme, even if a forwarding node is compromised, the attacker will not be able to eavesdrop on the data, resulting in much stronger privacy than existing schemes. Experimental results shows that the scheme provides a good trade off in resources consumed and system security, and is efficient for encrypting or decrypting sensitive medical data.