High-loading ficin@AuNPs on polymer-UiO-66 surface with enhanced peroxidase-mimetic catalytic activity for colourimetric detection of dopamine.

Recently, MOFs@AuNPs composites-based catalysts via anchoring of AuNPs onto metal-organic-frameworks (MOFs) have attracted great attention. However, the influence of the AuNPs loading amounts on the catalytic activity of MOFs@AuNPs composites remains largely unexplored. Here, ficin (Fic) protected AuNPs (Fic@AuNPs) anchored onto the surface of UiO-66-NH2 (UiO) modified with poly(2-vinyl-4,4-dimethyl-2-oxazolidine) (PV) were designed and constructed. The UiOPVFic@AuNPs composites with longer PV chains leading to high-loading Fic@AuNPs exhibited intense peroxidase (POD)-mimetic activity in 3,3'5,5'-tetramethylbenzidine (TMB) oxidation. Further, following the colour-fading, dopamine (DA) was sensitively and selectively monitored in the composites-TMB-H2O2 system. The portable smartphone sensing platform-based colourimetric method had good linearity ranging from 3.34 to 36.7 µM (R2 = 0.995), with a limit of detection of 0.3 µM. This protocol explores high-loading AuNPs on polymer-MOFs composites, providing deep insights into understanding catalytic activity improvements of polymer-MOFs@AuNPs catalysts and revealing their application potential in real biological samples analysis.

Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.

BACKGROUND/AIM: Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). METHODS: We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. RESULTS: Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. CONCLUSION: TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.

17ß-Trenbolone Exposure Enhances Muscle Activity and Exacerbates Parkinson's Disease Progression in Male Mice.

Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder, and while the neuroprotective effects of estrogen are well-documented, the impact of androgens on neurological disorders remains understudied. The consequences of exposure to 17-trenbolone (17-TB), an environmental endocrine disruptor with androgen-like properties, on the mammalian nervous system have received limited attention. Therefore, in this study, we aimed to investigate the biological effects of 17-TB exposure on PD. In our investigation using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we discovered that 17-TB exposure elevated testosterone hormone levels prevented androgen receptor (AR) reduction, upregulated the expression of muscular dystrophic factors (Atrogin1, MuRF1, Musa1, and Myostatin), improved muscle strength, and enhanced locomotor activity in the open field test. However, it is noteworthy that exposure to 17-TB also led to an upregulation of neuroinflammatory cytokines (NLRP3, IL-6, IL-1α, and IL-1ß) in PD mice. Crucially, 17-TB exposure induced downregulation of nigral apoptotic proteins DJ-1 and Bcl-2 while upregulating Bax and Caspase-3 in PD mice. This exacerbated neuronal apoptosis, ultimately intensifying dopaminergic neuronal degeneration and death in the substantia nigra and striatum of PD mice. In conclusion, our findings indicate that while 17-TB mitigates muscle atrophy and enhances motor activity in PD mice, it concurrently exacerbates neuroinflammation, induces neuronal apoptosis, and worsens dopaminergic neuronal death, thereby aggravating the progression of MPTP-induced Parkinsonism. This underscores the importance of considering potential environmental risks in neurodegeneration associated with Parkinson's disease, providing a cautionary tale for our daily exposure to environmental endocrine chemical disruptors.

Phillyrin promotes autophagosome formation in A53T-αSyn-induced Parkinson's disease model via modulation of REEP1.

BACKGROUND: The preservation of autophagosome formation presents a promising strategy for tackling neurological disorders, such as Parkinson's disease (PD). Mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) serve not only as a focal point linked to various neurological disorders but also play a crucial role in supporting the biogenesis of autophagosomes. PURPOSE: This investigation aimed to elucidate the neuroprotective properties of phillyrin against PD and its underlying mechanisms in promoting autophagosome formation. METHODS: ER and mitochondria co-localization was assessed via fluorescent staining. Annexin V-fluorescein isothiocyanate (FITC) fluorescence was employed to quantify accessible cardiolipin (CL) on mitochondrial surfaces. The levels of CL within the MAM fraction of SH-SY5Y cells were evaluated using a CL probe assay kit. Monodansylcadaverine staining was utilized to detect autophagosome formation in SH-SY5Y cells. In an A53T-alpha-synuclein (αSyn)-induced PD mouse model, the anti-PD properties of phillyrin were assessed using open field, pole climbing, and rotarod tests, as well as immunohistochemistry staining of TH+ neurons in the brain sections. RESULTS: In A53T-αSyn-treated SH-SY5Y cells, phillyrin facilitated autophagosome formation by suppressing CL externalization and restoring MAM integrity. Phillyrin enhanced the localization of receptor expression-enhancing protein 1 (REEP1) within MAM and mitochondria, bolstering MAM formation. Increased REEP1 levels in mitochondria, attributed to phillyrin, enhanced the interaction between REEP1 and NDPK-D, thereby reducing CL externalization. Furthermore, phillyrin exhibited a dose-dependent enhancement of motor function in mice, accompanied by an increase in the abundance of dopaminergic neurons within the substantia nigra. CONCLUSIONS: These findings illuminate phillyrin's ability to enhance MAM formation through upregulation of REEP1 expression within MAM, while concurrently attenuating CL externalization via the REEP1-NDPK-D interaction. These mechanisms bolster autophagosome biogenesis, offering resilience against A53T-αSyn-induced PD. Thus, our study advances the understanding of phillyrin's complex mechanisms and underscores its potential as a therapeutic approach for PD, opening new avenues in natural product pharmacology.

Cardiovascular magnetic resonance feature tracking derived strain analysis can predict return to training following exertional heatstroke.

BACKGROUND: Exertional heatstroke (EHS) is increasingly common in young trained soldiers. However, prognostic markers in EHS patients remain unclear. The objective of this study was to evaluate cardiovascular magnetic resonance (CMR) feature tracking derived left ventricle (LV) strain as a biomarker for return to training (RTT) in trained soldiers with EHS. METHODS: Trained soldiers (participants) with EHS underwent CMR cine sequences between June 2020 and August 2023. Two-dimensional (2D) LV strain parameters were derived. At 3 months after index CMR, the participants with persistent cardiac symptoms including chest pain, dyspnea, palpitations, syncope, and recurrent heat-related illness were defined as non-RTT. Multivariable logistic regression analysis was used to develop a predictive RTT model. The performance of different models was compared using the area under curve (AUC). RESULTS: A total of 80 participants (median age, 21 years; interquartile range (IQR), 20-23 years) and 27 health controls (median age, 21 years; IQR, 20-22 years) were prospectively included. Of the 77 participants, 32 had persistent cardiac symptoms and were not able to RTT at 3 months follow-up after experiencing EHS. The 2D global longitudinal strain (GLS) was significantly impaired in EHS participants compared to the healthy control group (-15.8 ± 1.7% vs -16.9 ± 1.2%, P = 0.001), which also showed significant statistical differences between participants with RTT and non-RTT (-15.0 ± 3.5% vs -16.5 ± 1.4%, P < 0.001). 2D-GLS (≤ -15.0%) (odds ratio, 1.53; 95% confidence interval: 1.08, 2.17; P = 0.016) was an independent predictor for RTT even after adjusting known risk factors. 2D-GLS provided incremental prognostic value over the clinical model and conventional CMR parameters model (AUCs: 0.72 vs 0.88, P = 0.013; 0.79 vs 0.88, P = 0.023; respectively). CONCLUSION: Two-dimensional global longitudinal strain (≤ -15.0%) is an incremental prognostic CMR biomarker to predict RTT in soldiers suffering from EHS.

Non-invasive brain stimulation in the treatment of generalized anxiety disorder: A systematic review and meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), and transcranial direct current stimulation (tDCS), is an emerging intervention that has been used to treat various mental illnesses. However, previous studies have not comprehensively compared the efficacies of various NIBS modalities in alleviating anxiety symptoms among patients with generalized anxiety disorder (GAD). Therefore, this study conducted a systematic review and meta-analysis to assess the efficacy of NIBS for patients with GAD. METHODS: A systematic search of four major bibliographic databases (Embase, PubMed, Web of Science and The Cochrane Library) was conducted from inception dates to November 26, 2023 to identify eligible studies. The data were analyzed using a random-effects model. RESULTS: Seven randomized controlled trials (RCTs) were included in the meta-analysis. Significant differences were found in changes in Hamilton anxiety rating scale (HARS) scores, study-defined response, and remission between the intervention and control groups. Moreover, the intervention groups experienced a significantly higher frequency of headaches. CONCLUSION: The results revealed that interventions improved GAD compared to control groups. cTBS and rTMS exhibited better treatment efficacy than tDCS, which did not appear to have a significant therapeutic effect. Longer follow-up periods and larger sample sizes are required in future RCTs. TRIAL REGISTRATION: This meta-analysis was conducted in accordance with PRISMA guidelines and registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, CRD42023466285).

[Risk Factors for Returning of Pediatric Liver Transplant Recipients to the Intensive Care Unit].

Objective To explore the risk factors for the returning of pediatric liver transplant recipients to the intensive care unit (ICU) and provide reference for the clinical decision-making after surgery. Methods A retrospective analysis was conducted with the information of all the pediatric patients who underwent liver transplantation in Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine and were returned to the ICU from 2019 to 2021.The patients returned to the ICU during hospitalization and the reasons for the return were recorded.Each patient of ICU return was matched with three pediatric patients who did not return to the ICU during hospitalization.The basic information,the vital signs and laboratory indicators on the day of transfer from ICU,immunosuppressants and drug concentrations were compared between the two groups.Multivariate Logistic regression analysis was performed to explore the risk factors for the returning of pediatric liver transplant recipients to the ICU. Results The returning rate of pediatric liver transplant recipients to the ICU was 4.36%,and it was 16.00% within 48 h.The main reasons for the return included respiratory complications,abdominal infections,and hepatic vascular occlusion.Multivariate Logistic regression analysis showed that post-operative red blood cell transfusion (OR=4.554,95%CI=1.743-11.901,P=0.002) and high serum level of uric acid (OR=1.005,95%CI=1.001-1.009,P=0.014) were the risk factors for returning to the ICU.High diastolic blood pressure (OR=0.922,95%CI=0.885-0.960,P<0.001) and high total protein level (OR=0.937,95%CI=0.891-0.986,P=0.012) were the protective factors for returning to the ICU. Conclusion Post-operative red blood cell transfusion and high serum level of uric acid are independent risk factors for the returning of pediatric liver transplant recipients to the ICU.

Increasing Influenza Vaccination Rates among Patients with Type 2 Diabetes Mellitus in Chongqing, China: A Cross-Sectional Analysis Using Behavioral and Social Drivers Tools.

BACKGROUND: Influenza vaccination is essential for type 2 diabetes mellitus (T2DM) patients due to their higher risks of severe complications and mortality from influenza. This study investigated the willingness of T2DM patients in Chongqing, China, to receive the influenza vaccination during the 2023/2024 season, using behavioral and social drivers (BeSD) tools to improve vaccination uptake in this high-risk group. METHODS: A multi-stage sampling method was used to select participants, and face-to-face surveys were conducted in community health centers between March 1 and May 1, 2023. Binary logistic regression was used to analyze the factors influencing vaccination willingness, and standardized scores identified barriers and drivers. RESULTS: Among 1672 T2DM patients, 11.7% had been vaccinated during the 2022/2023 season, and 59.6% were willing to receive the vaccination in the 2023/2024 season. Higher willingness was associated with ethnic minorities (odds ratio [OR], 3.18, 95% confidence interval [CI]: 1.58-6.39), being unemployed individuals (OR 2.69, 95% CI: 1.60-4.52), higher monthly household income per capita (OR 2.72, 95% CI: 1.65-4.50), having diabetes complications (OR 1.76, 95% CI: 1.23-2.51), sufficient vaccine knowledge (OR 1.87, 95% CI: 1.48-2.37), and previous vaccination (OR 7.75, 95% CI: 4.83-12.44). Concerning BeSDs, fear of infecting friends or family members and trust in vaccine efficacy were the predominant drivers, while high vaccine costs were the greatest barrier. CONCLUSIONS: Future strategies should focus on improving vaccine knowledge, supporting healthcare workers and peer recommendations, and enhancing vaccination policies. Key interventions such as health education among high-risk groups, such as unemployed individuals, advocacy campaigns, pay-it-forward strategies, and policies for free vaccination could improve coverage in Chongqing.

Effect of biochar addition on the anaerobic digestion of food waste: microbial community structure and methanogenic pathways.

This study assessed the effects of the addition of biochar prepared at 700 °C with different dosages on the anaerobic digestion of food waste. The biochar addition at a concentration of 10.0 g/L increased the cumulative methane yield by 128%, and daily methane production was also significantly promoted. The addition of biochar derived from poplar sawdust significantly increased the relative abundance of dominant bacteria for anaerobic digestion by 85.54-2530% and promoted the degradation of refractory organic matter and the transfer of materials between the hydrolysis and acid production stages. Further analysis has demonstrated that Bathyarchaeia and hydrogenotrophic methanogens were enriched by the biochar addition. Meanwhile, the relative abundances of functional genes, including C5-branched dibasic acid metabolism, and pyruvate metabolism, were increased by 11.38-26.27%. The relative abundances of genes related to major amino acid metabolism, including histidine metabolism, lysine biosynthesis, and phenylalanine, tyrosine, and tryptophan biosynthesis, were increased by 11.96-15.71%. Furthermore, the relative abundances of genes involved in major replication and repair were increased by 14.76-22.76%, and the major folding, sorting, degradation, and translation were increased by 14.47-19.95%, respectively. The relative abundances of genes related to major membrane transport and cell motility were increased by 10.02 and 83.09%, respectively.

Acceptance level of advance care planning and its associated factors among the public: A nationwide survey.

BACKGROUND: Advance care planning (ACP) can contribute to individuals making decisions about their healthcare preferences in advance of serious illness. Up to now, the acceptance level and associated factors of ACP among the public in China remain unclear. This study aims to investigate the acceptance level of ACP in China and identify factors associated with it based on the socioecological model. METHODS: A total of 19,738 participants were included in this survey. We employed a random forest regression analysis to select factors derived from the socioecological model. Multivariate generalized linear model analysis was then conducted to explore the factors that were associated with the acceptance level of ACP. RESULTS: On a scale ranging from 0 to 100, the median score for acceptance level of ACP was 64.00 (IQR: 48.00-83.00) points. The results of the multivariate generalized linear model analysis revealed that participants who scored higher on measures of openness and neuroticism personality traits, as well as those who had greater perceptions of social support, higher levels of health literacy, better neighborly relationships, family health, and family social status, were more likely to accept ACP. Conversely, participants who reported higher levels of subjective well-being and greater family communication levels demonstrated a lower likelihood of accepting ACP. CONCLUSIONS: This study identified multiple factors associated with the acceptance level of ACP. The findings offer valuable insights that can inform the design and implementation of targeted interventions aimed at facilitating a good death and may have significant implications for the formulation of end-of-life care policies and practices in other countries facing similar challenges.

Nursing management of intracranial hypertension in adults with severe brain injury in a neurosurgery intensive care unit: a best practice implementation project.

INTRODUCTION: The nursing management of intracranial hypertension in adult patients with severe brain injury is crucial for maintaining the stability of intracranial pressure, which ultimately improves patient outcomes. OBJECTIVES: This project aimed to implement evidence-based practices for the nursing management of intracranial hypertension in adult patients with severe brain injury. METHODS: This evidence implementation project was conducted in a neurosurgery intensive care unit in a large tertiary hospital in Guangzhou, China. The project was guided by the JBI Evidence Implementation Framework, which is an audit and feedback model with seven stages. The Ottawa Model of Research Use was used to identify barriers and facilitators to best practices and to develop improvement strategies. RESULTS: Thirty-three nurses and 50 patients with severe brain injury participated in the baseline and follow-up audits. After project implementation, follow-up audits revealed significantly improved compliance with best practices compared with baseline. Nurses' awareness of best practices increased (41% to 96%); nursing assessment, monitoring, and interventions related to intracranial hypertension rose significantly (from 82%, 75%, and 59% to 98%, 84%, and 87%, respectively); and patients' optic nerve sheath diameter was notably lower (6.002±0.677 mm to 5.698±0.730 mm). CONCLUSIONS: The systematic integration of consistent training and education, together with the refinement of care processes and the creation of relevant tools, led to a significant improvement in awareness and adherence to best practices. Further testing of this program in more hospitals is needed. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A243.

A novel AP2/ERF transcription factor, NtERF10, positively regulates plant height in tobacco.

Ethylene response factors have been shown to be involved in the effects of plant developmental processes and to regulate stress tolerance. The aim of this study was to recognize the regulatory mechanisms of ethylene response factors on tobacco plant height. In this study, a gene-edited mutant (ERF10-KO) and wild type (WT) were utilized as experimental materials. Transcriptome and metabolome analyses were used to investigate the regulatory mechanism of NtERF10 gene editing on plant height in tobacco. Here, through the analysis of differentially expressed genes (DEGs), 2051 genes were upregulated and 1965 genes were downregulated. We characterized the different ERF10-KO and WT plant heights and identified key genes for photosynthesis, the plant hormone signal transduction pathway and the terpene biosynthesis pathway. NtERF10 was found to affect the growth and development of tobacco by regulating the expression levels of the PSAA, PSBA, GLY17 and GGP3 genes. Amino acid metabolism was analyzed by combining analyses of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs). In addition, we found that members of the bHLH, NAC, MYB, and WRKY transcription factor families have vital roles in regulating plant height. This study not only provides important insights into the positive regulation of the ethylene response factor NtERF10 on plant height during plant growth and development but also provides new research ideas for tobacco molecular breeding.

Ginsenoside Rg3 Restores Mitochondrial Cardiolipin Homeostasis via GRB2 to Prevent Parkinson's Disease.

Regulating cardiolipin to maintain mitochondrial homeostasis is a promising strategy for addressing Parkinson's disease (PD). Through a comprehensive screening and validation process involving multiple models, ginsenoside Rg3 (Rg3) as a compound capable of enhancing cardiolipin levels is identified. This augmentation in cardiolipin levels fosters mitochondrial homeostasis by bolstering mitochondrial unfolded protein response, promoting mitophagy, and enhancing mitochondrial oxidative phosphorylation. Consequently, this cascade enhances the survival of tyrosine hydroxylase positive (TH+) dopaminergic neurons, leading to an amelioration in motor performance within PD mouse models. Using limited proteolysis-small-molecule mapping combined with molecular docking analysis, it has confirmed Growth Factor Receptor-Bound Protein 2 (GRB2) as a molecular target for Rg3. Furthermore, these investigations reveal that Rg3 facilitates the interaction between GRB2 and TRKA (Neurotrophic Tyrosine Kinase, Receptor, Type 1), thus promotes EVI1 (Ecotropic Virus Integration Site 1 Protein Homolog) phosphorylation by ERK, subsequently increases CRLS1 (Cardiolipin Synthase 1) gene expression and boosts cardiolipin synthesis. The absence of GRB2 or CRLS1 significantly attenuates the beneficial effects of Rg3 on PD symptoms. Finally, Tenofovir Disoproxil Fumarate (TDF) that also promotes the binding between GRB2 and TRKA is further identified. The identified compounds, Rg3 and TDF, exhibit promising potential for the prevention of PD by bolstering cardiolipin expression and reinstating mitochondrial homeostasis.

Unsupervised adversarial neural network for enhancing vasculature in photoacoustic tomography images using optical coherence tomography angiography.

Photoacoustic tomography (PAT) is a powerful imaging modality for visualizing tissue physiology and exogenous contrast agents. However, PAT faces challenges in visualizing deep-seated vascular structures due to light scattering, absorption, and reduced signal intensity with depth. Optical coherence tomography angiography (OCTA) offers high-contrast visualization of vasculature networks, yet its imaging depth is limited to a millimeter scale. Herein, we propose OCPA-Net, a novel unsupervised deep learning method that utilizes the rich vascular feature of OCTA to enhance PAT images. Trained on unpaired OCTA and PAT images, OCPA-Net incorporates a vessel-aware attention module to enhance deep-seated vessel details captured from OCTA. It leverages a domain-adversarial loss function to enforce structural consistency and a novel identity invariant loss to mitigate excessive image content generation. We validate the structural fidelity of OCPA-Net on simulation experiments, and then demonstrate its vascular enhancement performance on in vivo imaging experiments of tumor-bearing mice and contrast-enhanced pregnant mice. The results show the promise of our method for comprehensive vessel-related image analysis in preclinical research applications.

Effectiveness of influenza vaccine among the population in Chongqing, China, 2018-2022: A test negative design-based evaluation.

Influenza vaccination is the most cost-effective strategy for influenza prevention. Influenza vaccines have been found to be effective against symptomatic and medically attended outpatient influenza illnesses. However, there is currently a lack of data regarding the effectiveness of inactivated influenza vaccines in Chongqing, China. We conducted a prospective observational test-negative design study. Outpatient and emergency cases presenting with influenza-like illnesses (ILI) and available influenza reverse transcription polymerase chain reaction (RT-PCR) were selected and classified as cases (positive influenza RT-PCR) or controls (negative influenza RT-PCR). A total of 7,307 cases of influenza and 7,905 control subjects were included in this study. The overall adjusted influenza vaccine effectiveness (IVE) was 44.4% (95% confidence interval (CI): 32.5-54.2%). In the age groups of less than 6 years old, 6-18 years old, and 19-59 years old, the adjusted IVE were 32.2% (95% CI: 10.0-48.9%), 48.2% (95% CI: 30.6-61.4%), and 72.0% (95% CI: 43.6-86.1%). The adjusted IVE for H1N1, H3N2 and B (Victoria) were 71.1% (95% CI: 55.4-81.3%), 36.1% (95% CI: 14.6-52.2%) and 33.7% (95% CI: 14.6-48.5%). Influenza vaccination was effective in Chongqing from 2018 to 2022. Evaluating IVE in this area is feasible and should be conducted annually in the future.

Alterations of resting-state network dynamics in Alzheimer's disease based on leading eigenvector dynamics analysis.

Alzheimer's disease (AD) is a neurodegenerative disease, and mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia. Early detection of MCI can help slow down the progression of AD. At present, there are few studies exploring the characteristics of abnormal dynamic brain activity in AD. This article uses a method called leading eigenvector dynamics analysis (LEiDA) to study resting-state functional magnetic resonance imaging (rs-fMRI) data of AD, MCI, and cognitively normal (CN) participants. By identifying repetitive states of phase coherence, intergroup differences in brain dynamic activity indicators are examined, and the neurobehavioral scales were used to assess the relationship between abnormal dynamic activities and cognitive function. The results showed that in the indicators of occurrence probability and lifetime, the globally synchronized state of the patient group decreased. The activity state of the limbic regions significantly detected the difference between AD and the other two groups. Compared to CN, AD and MCI have varying degrees of increase in default and visual region activity states. In addition, in the analysis related to the cognitive scales, it was found that individuals with poorer cognitive abilities were less active in the globally synchronized state and more active in limbic region activity state and visual region activity state. Taken together, these findings reveal abnormal dynamic activity of resting-state networks in patients with AD and MCI, provide new insights into the dynamic analysis of brain networks, and contribute to a deeper understanding of abnormal spatial dynamic patterns in AD patients.NEW & NOTEWORTHY Alzheimer's disease (AD) is a neurodegenerative disease, but few studies have explored the characteristics of abnormal dynamic brain activity in AD patients. Here, our report reveals the abnormal dynamic activity of the patients' resting-state network, providing new insights into the dynamic analysis of brain networks and helping to gain a deeper understanding of the abnormal spatial dynamic patterns in AD patients.

Confinement-Induced Biocatalytic Activity Enhancement of Light- and Thermoresponsive Polymer@Enzyme@MOF Composites.

Metal-organic frameworks (MOFs) are favorable hosting materials for fixing enzymes to construct enzyme@MOF composites and to expand the applications of biocatalysts. However, the rigid structure of MOFs without tunable hollow voids and a confinement effect often limits their catalytic activities. Taking advantage of the smart soft polymers to overcome the limitation, herein, a protection protocol to encapsulate the enzyme in zeolitic imidazolate framework-8 (ZIF-8) was developed using a glutathione-sensitive liposome (L) as a soft template. Glucose oxidase (GOx) and horseradish peroxidase (HRP) were first anchored on a light- and thermoresponsive porous poly(styrene-maleic anhydride-N,N-dimethylaminoethyl methacrylate-spiropyran) membrane (PSMDSP) to produce PSMDSP@GOx-HRP, which could provide a confinement effect by switching the UV irradiation or varying the temperature. Afterward, embedding PSMDSP@GOx-HRP in L and encapsulating PSMDSP@GOx-HRP@L into hollow ZIF-8 (HZIF-8) to form PSMDSP@GOx-HRP@HZIF-8 composites were performed, which proceeded during the crystallization of the framework following the removal of L by adding glutathione. Impressively, the biocatalytic activity of the composites was 4.45-fold higher than that of the free enzyme under UV irradiation at 47 °C, which could benefit from the confinement effect of PSMDSP and the conformational freedom of the enzyme in HZIF-8. The proposed composites contributed to the protection of the enzyme against harsh conditions and exhibited superior stability. Furthermore, a colorimetric assay based on the composites for the detection of serum glucose was established with a linearity range of 0.05-5.0 mM, and the calculated LOD value was 0.001 mM in a cascade reaction system. This work provides a universal design idea and a versatile technique to immobilize enzymes on soft polymer membranes that can be encapsulated in porous rigid MOF-hosts. It also holds potential for the development of smart polymer@enzyme@HMOFs biocatalysts with a tunable confinement effect and high catalytic performance.

Image reconstruction of multispectral sparse sampling photoacoustic tomography based on deep algorithm unrolling.

Photoacoustic tomography (PAT), as a novel medical imaging technology, provides structural, functional, and metabolism information of biological tissue in vivo. Sparse Sampling PAT, or SS-PAT, generates images with a smaller number of detectors, yet its image reconstruction is inherently ill-posed. Model-based methods are the state-of-the-art method for SS-PAT image reconstruction, but they require design of complex handcrafted prior. Owing to their ability to derive robust prior from labeled datasets, deep-learning-based methods have achieved great success in solving inverse problems, yet their interpretability is poor. Herein, we propose a novel SS-PAT image reconstruction method based on deep algorithm unrolling (DAU), which integrates the advantages of model-based and deep-learning-based methods. We firstly provide a thorough analysis of DAU for PAT reconstruction. Then, in order to incorporate the structural prior constraint, we propose a nested DAU framework based on plug-and-play Alternating Direction Method of Multipliers (PnP-ADMM) to deal with the sparse sampling problem. Experimental results on numerical simulation, in vivo animal imaging, and multispectral un-mixing demonstrate that the proposed DAU image reconstruction framework outperforms state-of-the-art model-based and deep-learning-based methods.

From inflammatory signaling to neuronal damage: Exploring NLR inflammasomes in ageing neurological disorders.

The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.