The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aß1-42 oligomers through AMPK/mTOR pathway.

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

Microstructures and Rheological Properties of Short-Side-Chain Perfluorosulfonic Acid in Water/2-Propanol.

The viscosity and viscoelasticity of polyelectrolyte solutions with a single electrostatic interaction have been carefully studied experimentally and theoretically. Despite some theoretical models describe experimental results well, the influence of multiple interactions (electrostatic and hydrophobic) on rheological scaling is not yet fully resolved. Herein, we systematically study the microstructures and rheological properties of short-side-chain perfluorosulfonic acid (S-PFSA), the most promising candidate of a proton exchange membrane composed of a hydrophobic backbone with hydrophilic side-chains, in water/2-propanol. Small-angle X-ray scattering confirms that semiflexible S-PFSA colloidal particles with a length of ~38 nm and a diameter of 1-1.3 nm are formed, and the concentration dependence of the correlation length (ξ) obeys the power law ξ~c-0.5 consistent with the prediction of Dobrynin et al. By combining macrorheology with diffusing wave spectroscopy microrheology, the semidilute unentangled, semidilute entangled, and concentrated regimes corresponding to the scaling relationships ηsp~c0.5, ηsp~c1.5, and ηsp~c4.1 are determined. The linear viscoelasticity indicates that the entanglement concentration (ce) obtained from the dependence of ηsp on the polymer concentration is underestimated owing to hydrophobic interaction. The true entanglement concentration (cte) is obtained by extrapolating the plateau modulus (Ge) to the terminal modulus (Gt). Furthermore, Ge and the plateau width, τr/τe (τr and τe denote reptation time and Rouse time), scale as Ge~c2.4 and τr/τe~c4.2, suggesting that S-PFSA dispersions behave like neutral polymer solutions in the concentrated regime. This work provides mechanistic insight into the rheological behavior of an S-PFSA dispersion, enabling quantitative control over the flow properties in the process of solution coating.

Cortistatin protects against septic cardiomyopathy by inhibiting cardiomyocyte pyroptosis through the SSTR2-AMPK-NLRP3 pathway.

BACKGROUND: Although the pathophysiological mechanism of septic cardiomyopathy has been continuously discovered, it is still a lack of effective treatment method. Cortistatin (CST), a neuroendocrine polypeptide of the somatostatin family, has emerged as a novel cardiovascular-protective peptide, but the specific mechanism has not been elucidated. PURPOSE: The aim of our study is to explore the role of CST in cardiomyocytes pyroptosis and myocardial injury in sepsis and whether CST inhibits cardiomyocytes pyroptosis through specific binding with somastatin receptor 2 (SSTR2) and activating AMPK/Drp1 signaling pathway. METHODS AND RESULTS: In this study, plasma CST levels were significantly high and were negatively correlated with N-terminal pro-B type natriuretic peptide (NT-proBNP), a biomarker for cardiac dysfunction, in patients with sepsis. Exogenous administration of CST significantly improved survival rate and cardiac function in mouse models of sepsis by inhibiting the activation of the NLRP3 inflammasome and pyroptosis of cardiomyocytes (decreased cleavage of caspase-1, IL-1ß and gasdermin D). Pharmacological inhibition and genetic ablation revealed that CST exerted anti-pyroptosis effects by specifically binding to somatostatin receptor subtype 2 (SSTR2), thus activating AMPK and inactivating Drp1 to inhibit mitochondrial fission in cardiomyocytes. CONCLUSIONS: This study is the first to report that CST attenuates septic cardiomyopathy by inhibiting cardiomyocyte pyroptosis through the SSTR2-AMPK-Drp1-NLRP3 pathway. Importantly, CST specifically binds to SSTR2, which promotes AMPK phosphorylation, inhibits Drp1-mediated mitochondrial fission, and reduces ROS levels, thereby inhibiting NLRP3 inflammasome activation-mediated pyroptosis and alleviating sepsis-induced myocardial injury.

A potential pathway for identifying hypertension among urban residents aged 60+ years in China: the role of health insurance.

Background: Identification is the first step for treatment of hypertension. However, the awareness rate of hypertension was not high globally. This study aimed to examine the potential role of health insurance for early-identifying hypertension among urban older residents in China. Methods: In this cross-sectional study, urban residents aged 60+ years were chosen from Nanjing municipality of China in 2018. The outcome measure was hypertension status ("no hypertension," "diagnosed hypertension" or "un-diagnosed hypertension"). Independent variable was health insurance ("Urban Employee Basic Medical Insurance scheme, UEBMI" or "Urban Resident Basic Medical Insurance scheme, URBMI"). Logistic regression models were introduced to estimate odds ratio (OR) and 95% confidence interval (CI) to examine the association between health insurance and hypertension. Results: Totally, 19,742 participants completed the study. Among overall, URBMI and UEBMI participants, 47.2% (95%CI = 46.5, 47.9%), 38.4% (95%CI = 37.3, 39.6%) and 52.1% (95%CI = 51.2, 53.0%), separately, were diagnosed with hypertension, while the prevalence of un-diagnosed hypertension was 12.7% (95%CI = 12.2, 13.2%), 18.5% (95%CI = 17.6, 19.4%) and 9.6% (95%CI = 9.1, 10.1%), respectively. For overall participants, those with UEBMI were more likely to have hypertension identified (OR = 1.20; 95%CI = 1.11, 1.29) and at lower odds to experience un-diagnosed hypertension (OR = 0.68; 95%CI = 0.61, 0.76) compared to their counterparts with URBMI after control for potential confounders. Moreover, such associations of health insurance with diagnosed and un-diagnosed hypertension were also observed among participants stratified by age and gender. Conclusion: Favorable health insurance may be a pathway for identifying hypertension among urban older residents in China. This study has important public health implications that hypertension may be identified early through favorable health insurance policies for older residents in China.

Hyperbranched Vitrimer for Ultrahigh Energy Dissipation.

Polymers are ideally utilized as damping materials due to the high internal friction of molecular chains, enabling effective suppression of vibrations and noises in various fields. Current strategies rely on broadening the glass transition region or introducing additional relaxation components to enhance the energy dissipation capacity of polymeric damping materials. However, it remains a significant challenge to achieve high damping efficiency through structural control while maintaining dynamic characteristics. In this work, we propose a new strategy to develop hyperbranched vitrimers (HBVs) containing dense pendant chains and loose dynamic crosslinked networks. A novel yet weak dynamic transesterification between the carboxyl and boronic acid ester was confirmed and used to prepare HBVs based on poly (hexyl methacrylate-2-(4-ethenylphenyl)-5,5-dimethyl-1,3,2-dioxaborinane) P(HMA-co-ViCL) copolymers. The A B n ${{AB}_{n}}$ -type of macromonomers, the crosslinking points formed by the dynamic covalent connection via the associative exchange, and the weak yet dynamic exchange reaction are the three keys to developing high-performance HBV damping materials. We found that P(HMA-co-ViCL) 20k-40-60 HBV exhibited ultrahigh energy-dissipation performance over a broad frequency and temperature range, attributed to the synergistic effect of dense pendant chains and weak dynamic covalent crosslinks. This unique design concept will provide a general approach to developing advanced damping materials.

Bicontinuous Ionogel Electrolyte with Conductive Nanochannels for Flexible Supercapacitors.

Ionogels with excellent mechanical performance and conductivity have been considered as ideal candidates for flexible ionotronics. However, current ionogels suffer from the well-known trade-off between mechanical strength and conductivity. Herein, we construct an ionogel with bicontinuous phase structures, a polymer-rich phase, and a solvent-rich phase. The synergy of the polymer-rich phase as an energy dissipation mechanism and the solvent-rich phase as a conductive nanochannel enables the resultant bicontinuous ionogel to show comprehensive properties, a tensile strength of 4.2 MPa, a toughness of 14.4 MJ/m3, a conductivity of 4.3 mS/cm, excellent self-healing capability, and reprocessability. Benefiting from the remarkable mechanical performance and high conductivity, the integrated supercapacitor achieves a high specific capacitance of 118 mF/cm2 (at a current density of 0.2 mA/cm2) and a capacitance retention of up to 90% (1000 charge-discharge cycles). More significantly, the resultant supercapacitor retains outstanding electrochemical performance even after being subjected to various deformations and even under harsh conditions. This study provides a reliable strategy for developing a high-performance ionogel electrolyte and broadens its application in flexible ionotronics.

Safety, immunogenicity, and efficacy of a modified COVID-19 mRNA vaccine, SW-BIC-213, in healthy people aged 18 years and above: a phase 3 double-blinded, randomized, parallel controlled clinical trial in Lao PDR (Laos).

Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos. Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital. The primary outcomes were safety and immunogenicity, with efficacy as an exploratory endpoint. Participants who were fully immunized with a two-dose inactivated vaccine for more than 6 months were assigned equally to either the SW-BIC-213 group (25 µg) or BBIBP group. The primary safety endpoint was to describe the safety profile of all participants in each group up to 6 months post-booster immunization. The primary immunogenic outcome was to demonstrate the superiority of the neutralizing antibody response, in terms of geometric mean titers (GMTs) of SW-BIC-213, compared with BBIBP 28 days after the booster dose. The exploratory efficacy endpoint aimed to assess the relative efficacy of SW-BIC-213 compared to BBIBP against virologically confirmed symptomatic COVID-19 over a 6-month period. The trial was registered with ClinicalTrials.gov (NCT05580159). Findings: Between October 10, 2022, and January 13, 2023, 1200 participants were assigned to SW-BIC-213 group and 1203 participants in the BBIBP group. All adverse reactions observed during the study were tolerable, transient, and resolved spontaneously. Solicited local reactions were the main adverse reactions in both the SW-BIC-213 group (43.8%) and BBIBP group (14.8%) (p < 0.001). Heterologous boosting with SW-BIC-213 induced higher live virus neutralizing antibodies to SARS-CoV-2 wildtype and BA.5 strains with GMTs reaching 750.1 and 192.9 than homologous boosting with BBIBP with GMTs of 131.5 (p < 0.001) and 47.5 (p < 0.001) on day 29. The statistical findings revealed that, following a period of 14-day to 6-month after booster vaccination, the SW-BIC-213 group exhibited a relative vaccine efficacy (VE) of 70.1% (95% CI: 34.2-86.4) against symptomatic COVID-19 when compared to the BBIBP group. Interpretation: A heterologous booster with the COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and proves highly immunogenic and efficacious in preventing symptomatic COVID-19 in individuals who have previously received two doses of inactivated vaccine. Funding: Shanghai Strategic Emerging Industries Development Special Fund, Biomedical Technology Support Special Project of Shanghai "Science and Technology Innovation Action Plan", Shanghai Municipal Science and Technology Commission.

Role of confinement in the shear banding and shear jamming in noncolloidal fiber suspensions.

The jamming effect is critical in processing short fiber-reinforced thermoplastics (FRTs). Fiber jamming can induce discontinuous shear thickening (DST) in simple shear and result in fiber-matrix separation in more complex flows such as injection molding and compression molding of FRTs. The confinement effect commonly induces local jams and strongly enhances fiber jamming. However, the transient evolution of local fiber jams under confinement and its correlation with the tumbling of fibers are still elusive. In this study, we adopted rheo-PIV (particle image velocity) techniques to study this effect for glass fiber-reinforced thermoplastics (FRTs). The translational and tumbling motion of fiber were determined during rheological measurements, and the distribution of fiber orientation was determined by X-ray CT. Three shear banding regions appeared after the viscosity overshoot under high shear stress in suspensions with high fiber content, which was associated with the three regions of fiber orientation across the gap due to confinement. Shear banding was ascribed to the different tumbling speeds across the gap because of the different initial orientations and different wall confinements near and far from the wall. The local shear thickening and jamming behavior became most significant under intermediate confinement, and were affected by shear strain, shear stress, and fiber contents. 3D state diagrams were constructed to show the confinement effect on the evolution of shear banding and jamming.

Annexin A5 derived from matrix vesicles protects against osteoporotic bone loss via mineralization.

Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the skeletal system due to their membranous vesicle characteristics and abundant calcium and phosphorus content. However, the role of MVs in the progression of osteoporosis is poorly understood. Here, we report that annexin A5, an important component of the matrix vesicle membrane, plays a vital role in bone matrix homeostasis in the deterioration of osteoporosis. We first identified annexin A5 from adherent MVs but not dissociative MVs of osteoblasts and found that it could be sharply decreased in the bone matrix during the occurrence of osteoporosis based on ovariectomized mice. We then confirmed its potential in mediating the mineralization of the precursor osteoblast lineage via its initial binding with collagen type I to achieve MV adhesion and the subsequent activation of cellular autophagy. Finally, we proved its protective role in resisting bone loss by applying it to osteoporotic mice. Taken together, these data revealed the importance of annexin A5, originating from adherent MVs of osteoblasts, in bone matrix remodeling of osteoporosis and provided a new strategy for the treatment and intervention of bone loss.

Paeoniflorin, ferulic acid, and atractylenolide III improved LPS-induced neuroinflammation of BV2 microglia cells by enhancing autophagy.

Microglia hyperactivation is an important cause of neuroinflammation in Alzheimer's disease (AD). Paeoniflorin (PF), ferulic acid (FA), and atractylenolide III (ATL) are potent in anti-inflammation and neuroprotection. Multiple components can act on different targets simultaneously to exert synergistic therapeutic effects and exploring the synergistic potential between compounds is an important area of research. We investigated the effects of PF, FA, and ATL, alone or in combination, on LPS-induced neuroinflammation and autophagy in BV2 microglia cells. We found that PF, FA, and ATL, alone or in combination, significantly reduced the production of inflammatory factors such as IL-6, IL-1ß, and TNF-α, especially in the PF + FA + ATL group, which performed the best. In addition, the combination of PF, FA, and ATL significantly increased the expression of autophagy-related proteins p-AMPK, p-ULK1, Beclin1, LC3, and TFEB and decreased the expression of p62. Moreover, the restoration of autophagic flux by the combination of PF, FA, and ATL was abrogated by the addition of the autophagy inhibitor Wortmannin. In conclusion, PF, FA, and ATL have a synergistic effect in reducing LPS-induced inflammatory factor release from BV2 microglia cells, and its protective effect may be through activation of the AMPK/ULK1/TFEB autophagic signaling pathway.

Protective Effect of Ferulic Acid on Lipopolysaccharide-Induced BV2 Microglia Inflammation via AMPK/mTOR Signaling Pathway.

In neurodegenerative diseases, microglial activation and neuroinflammation are essential for the control and progression of neurodegenerative diseases. Mitigating microglium-induced inflammation is one strategy for hindering the progression of neurodegenerative diseases. Ferulic acid (FA) is an effective anti-inflammatory agent, but its potential role and regulation mechanism in neuroinflammatory reactions have not been fully studied. In this study, the neuroinflammation model was established by lipopolysaccharide (LPS), and the inhibitory effect of FA on neuroinflammation of BV2 microglia was studied. The results showed that FA significantly reduced the production and expression of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), leukocyte-6 (IL-6) and interleukin-1ß (IL-1ß). We further studied the mechanism of FA's regulation of LPS-induced BV2 neuroinflammation and found that FA can significantly reduce the expression of mTOR in BV2 microglia induced by LPS, and significantly increase the expression of AMPK, indicating that FA may have an anti-inflammatory effect by activating the AMPK/mTOR signaling pathway to regulate the release of inflammatory mediators (such as NLRP3, caspase-1 p20 and IL-1ß). We further added an autophagy inhibitor (3-MA) and an AMPK inhibitor (compound C, CC) for reverse verification. The results showed that FA's inhibitory effects on TNF-α, IL-6 and IL-1ß and its regulatory effect on AMPK/mTOR were destroyed by 3-MA and CC, which further indicated that FA's inhibitory effect on neuroinflammation is related to its activation of the AMPK/mTOR autophagy signaling pathway. In a word, our experimental results show that FA can inhibit LPS-induced neuroinflammation of BV2 microglia by activating the AMPK/mTOR signaling pathway, and FA may be a potential drug for treating neuroinflammatory diseases.

Impact-Protective Bicontinuous Hydrogel/Ultrahigh-Molecular Weight Polyethylene Fabric Composite with Multiscale Energy Dissipation Structures for Soft Body Armor.

Soft body armor greatly improves the comfort and security of the wearers. Although laminates based on high-performance fabrics have been adopted, it remains an enormous challenge to develop fabric laminates having flexibility, low bulge deformation, and ballistic protection capability simultaneously. Herein, we report a bullet-proof bicontinuous hydrogel (BH)/ultrahigh-molecular weight polyethylene fabric (UPF) composite. The presence of the BH significantly improves the impact resistance performance of the UPF, without compromising its flexibility. In specific, the multiscale energy dissipation structures composed of hydrogen bond associations in the chain scale, bicontinuous phase structures in the nanoscale, and fibers in the microscale are broken to dissipate energy. As a result, the impact energy of the bullet is greatly absorbed and the bulge height of the composites is significantly reduced in contrast to the neat UPF laminates. This study indicates that the flexible BH-UPF composites with multiscale energy dissipation structures have a promising application in soft body armor.

The Association between Burnout, Social Support, and Psychological Capital among Primary Care Providers in Togo: A Cross-Sectional Study.

Background and Objectives: Job burnout is prevalent among primary care providers (PCPs) in different countries, and the factors that can alleviate burnout in these countries have been explored. However, no study has addressed the prevalence and the correlates of job burnout among Togolese PCPs. Therefore, we aimed to examine the prevalence of burnout and its association with social support and psychological capital among PCPs in Togo. Material and Methods: We conducted a cross-sectional study in Togo from 5 to 17 November 2020 among 279 PCPs of 28 peripheral care units (PCUs). Participants completed the Maslach Burnout Inventory, Job Content Questionnaire, and Psychological Capital Questionnaire. Data were analyzed using the Mann-Whitney U test, Kruskal-Wallis H test, Pearson correlation analysis, and multiple linear regression. Results: We received 279 responses, out of which 37.28% experienced a high level of emotional exhaustion (EE), 13.62% had a high level of depersonalization (DP), and 19.71% experienced low levels of personal accomplishment (PA). EE had a significant negative correlation with the supervisor's support. In contrast, self-efficacy, hope, optimism, and resilience had a significant negative correlation with DP and a significant positive correlation with PA. Furthermore, supervisors' support significantly predicted lower levels of EE. Optimism significantly predicted lower levels of DP and higher levels of PA. Conclusions: Burnout is common among Togolese PCPs, and self-efficacy, optimism, and supervisors' support significantly contribute to low levels of job burnout among Togolese PCPs. This study provided insight into intervention programs to prevent burnout among PCPs in Togo.

An impact resistant hydrogel enabled by bicontinuous phase structure and hierarchical energy dissipation.

High performance hydrogels have essential applications in many fields such as tissue engineering and soft robot. Herein, we develop an impact resistant hydrogel composed of bicontinuous structures of polymer-hard phase and polymer-soft phase. This unique bicontinuous phase structure is formed by modulating various hydrogen bonding interactions. During loading, the polymer-hard phase is broken accompanied by the dissociation of hydrogen bonds to dissipate energy, while the polymer-soft phase distributes the load to avoid stress concentration, thus enabling the bicontinuous hydrogel to achieve excellent strength and toughness simultaneously. Furthermore, the fracture of hierarchical energy dissipation structures efficiently reduces impact strength and increases buffer time. Owing to the synergy of the bicontinuous phase structure and hierarchical energy dissipation, the resulting bicontinuous hydrogel remains intact even if it undergoes impact at a strain rate of ∼13 000 s-1. Based on these findings, it is expected that the bicontinuous hydrogel has a potential application in the field of articular cartilage repair.

Regulation of different protonated states of two intimate histidine residues on the reductive half-reaction of glucose oxidase.

Glucose oxidase (GOx) can catalyze the oxidation of ß-D-glucose under mild conditions to directly convert biological energy into electrical energy, which has great potential for applications in the fields of enzyme biofuel cells and glucose biosensors. In enzymatic biofuel cells, GOx is often used as an anodic catalyst to improve the performance. The important role of two intimate histidine residues, His505 and His548 (PDB code 4YNU), in the GOx active center has been highlighted in the catalytic oxidation of ß-D-glucose, but there is still a lack of systematic examination on the influence of different protonated states of His505 and His548 on the catalytic oxidation of ß-D-glucose in GOx. Therefore, in the present work, the GOx active center under the possible protonated states of His548 and His505 is systematically examined by using ONIOM calculations, as well as the influence of remote Arg210 is considered. The calculations reveal that the intimate His505 and His548 can modulate the interaction of the ß-D-glucose substrate with isoalloxazine and then control the deprotonization of the hydroxyl group bound to the anomeric carbon of ß-D-glucose like controllers. The remote Arg210 provides the driving force for the transfer of two electrons from ß-D-glucose to isoalloxazine of FAD via the long-range electrostatic attraction like a horse. Specially, the protonated His505 can serve as a good helper of Arg210 to promote the occurring of the two-proton-coupled two-electron transfer from ß-D-glucose to isoalloxazine and His548 in the active center of GOx. These findings provide much insight into the catalytic reactions of GOx in a low pH environment, which may be beneficial to expand the applications of GOx.

Uncovering Brain Differences in Preschoolers and Young Adolescents with Autism Spectrum Disorder Using Deep Learning.

Identifying brain abnormalities in autism spectrum disorder (ASD) is critical for early diagnosis and intervention. To explore brain differences in ASD and typical development (TD) individuals by detecting structural features using T1-weighted magnetic resonance imaging (MRI), we developed a deep learning-based approach, three-dimensional (3D)-ResNet with inception (I-ResNet), to identify participants with ASD and TD and propose a gradient-based backtracking method to pinpoint image areas that I-ResNet uses more heavily for classification. The proposed method was implemented in a preschool dataset with 110 participants and a public autism brain imaging data exchange (ABIDE) dataset with 1099 participants. An extra epilepsy dataset with 200 participants with clear degeneration in the parahippocampal area was applied as a verification and an extension. Among the datasets, we detected nine brain areas that differed significantly between ASD and TD. From the ROC in PASD and ABIDE, the sensitivity was 0.88 and 0.86, specificity was 0.75 and 0.62, and area under the curve was 0.787 and 0.856. In a word, I-ResNet with gradient-based backtracking could identify brain differences between ASD and TD. This study provides an alternative computer-aided technique for helping physicians to diagnose and screen children with an potential risk of ASD with deep learning model.

HHcy Induces Pyroptosis and Atherosclerosis via the Lipid Raft-Mediated NOX-ROS-NLRP3 Inflammasome Pathway in apoE-/- Mice.

Lipid rafts play important roles in signal transduction, particularly in responses to inflammatory processes. The current study aimed to identify whether lipid raft-mediated inflammation contributes to hyperhomocysteinemia (HHcy)-accelerated atherosclerosis (AS), and to investigate the underlying mechanisms. THP-1-derived macrophages were used for in vitro experiments. ApoE-/- mice were fed a high-fat diet for 12 weeks to establish an AS model, and a high-fat plus high-methionine diet was used to induce HHcy. We found that homocysteine (Hcy) increased the expression of p22phox and p67phox and promoted their recruitment into lipid rafts (indicating the assembly of the NOX complex), thereby increasing ROS generation and NOX activity, NLRP3 inflammasome activation, and pyroptosis. Mechanistically, Hcy activated the NOX-ROS-NLRP3 inflammasome pathway and induced pyroptosis by increasing the expression of acid sphingomyelinase (ASM) to promote the formation of lipid raft clustering. Importantly, lipid raft-mediated pyroptosis was confirmed in HHcy mice, and HHcy-promoted macrophage recruitment in atherosclerotic lesions and HHcy-aggravated AS were blocked by the lipid raft disruptor methyl-ß-cyclodextrin. The study findings indicate that Hcy promotes lipid raft clustering via the upregulation of ASM, which mediates the assembly of the NOX complex, causing an increase in ROS generation, NLRP3 inflammasome activation, and pyroptosis, and contributes to HHcy-induced AS.

Outbound medical tourists: The interplay of perceived quality, length of stay, group-size, post-visit destination image and revisit intention.

Using halo effect as the underlying theory, we examined how perceived quality of medical care influenced components of post-visit destination image (infrastructure, attraction, value for money, and enjoyment) and how each component influenced Bangladeshi outbound medical tourists' revisit intentions. Additionally, we examined how these relationships varied based on their length of stay (LOS) and travel-group size (TGS). Results showed a significant positive effect of the perceived quality of medical care on all four components of the post-visit destination image. Except for enjoyment, all three components had a significant positive influence on revisit intentions. All the proposed relationships were supported for medical tourists with higher LOS and TGS. However, for medical tourists with low LOS, the perceived quality of medical care did not influence value for money. Furthermore, value for money and enjoyment did not significantly influence revisit intentions for medical tourists with low LOS and TGS.

Predictive performance of lipid parameters in identifying undiagnosed diabetes and prediabetes: a cross-sectional study in eastern China.

BACKGROUND: Dyslipidaemia is a risk factor for abnormal blood glucose. However, studies on the predictive values of lipid markers in prediabetes and diabetes simultaneously are limited. This study aimed to assess the associations and predictive abilities of lipid indices and abnormal blood glucose. METHODS: A sample of 7667 participants without diabetes were enrolled in this cross-sectional study conducted in 2016, and all of them were classified as having normal glucose tolerance (NGT), prediabetes or diabetes. Blood glucose, blood pressure and lipid parameters (triglycerides, TG; total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; non-high-density lipoprotein cholesterol, non-HDL-C; and triglyceride glucose index, TyG) were evaluated or calculated. Logistic regression models were used to analyse the association between lipids and abnormal blood glucose. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the discriminatory power of lipid parameters for detecting prediabetes or diabetes. RESULTS: After adjustment for potential confounding factors, the TyG was the strongest marker related to abnormal blood glucose compared to other lipid indices, with odds ratios of 2.111 for prediabetes and 5.423 for diabetes. For prediabetes, the AUCs of the TG, TC, HDL-C, LDL-C, TC/HDL-C, TG/HDL-C, non-HDL-C and TyG indices were 0.605, 0.617, 0.481, 0.615, 0.603, 0.590, 0.626 and 0.660, respectively, and the cut-off points were 1.34, 4.59, 1.42, 2.69, 3.39, 1.00, 3.19 and 8.52, respectively. For diabetes, the AUCs of the TG, TC, HDL-C, LDL-C, TC/HDL-C, TG/HDL-C, non-HDL-C and TyG indices were 0.712, 0.679, 0.440, 0.652, 0.686, 0.692, 0.705, and 0.827, respectively, and the cut-off points were 1.35, 4.68, 1.42, 2.61, 3.44, 0.98, 3.13 and 8.80, respectively. CONCLUSIONS: The TyG, TG and non-HDL-C, especially TyG, are accessible biomarkers for screening individuals with undiagnosed diabetes.

miR-125a attenuates the malignant biological behaviors of cervical squamous cell carcinoma cells through Rad51.

Cervical squamous cell carcinoma (CSCC), the most common cervical malignancy, is more likely to invade and metastasize than other cervical cancers. miR-125a, a tumor suppressor gene, has been confirmed to be associated with cancer metastasis. However, the role of miR-125a in CSCC and the underlying mechanism are unknown. miR-125a expression was confirmed by real-time quantitative PCR (RT-qPCR), and the Rad51 expression level was measured by western blotting analysis. CSCC cell proliferation, migration and invasion were assessed with functional assays, including CCK-8, colony formation, wound healing and Transwell assays. Our data confirmed that miR-125a is expressed at low levels in CSCC tissues and cells. Functionally, the overexpression of miR-125a greatly prevented the proliferation, migration and invasion of CSCC cells, and the inhibition of miR-125a expression strongly enhanced these behaviors in CSCC cells. Moreover, the expression of Rad51, a miR-125a target gene, greatly reversed the miR-125-mediated inhibition of CSCC cell proliferation, migration and invasion. In addition, we discovered that miR-125a downregulated the levels of phosphorylated PI3K, AKT and mTOR through Rad51 in CSCC cells. miR-125a, a tumor suppressor, can attenuate the malignant behaviors of CSCC cells by targeting Rad51. Therefore, the miR-125a/Rad51 axis might be a target for CSCC therapy.