Inhibition of mitophagy via the EIF2S1-ATF4-PRKN pathway contributes to viral encephalitis.

INTRODUCTION: Mitophagy, a selective form of autophagy responsible for maintaining mitochondrial homeostasis, regulates the antiviral immune response and acts as viral replication platforms to facilitate infection with various viruses. However, its precise role in herpes simplex virus 1 (HSV-1) infection and herpes simplex encephalitis (HSE) remains largely unknown. OBJECTIVES: We aimed to investigate the regulation of mitophagy by HSV-1 neurotropic infection and its role in viral encephalitis, and to identify small compounds that regulate mitophagy to affect HSV-1 infection. METHODS: The antiviral effects of compounds were investigated by Western blot, RT-PCR and plaque assay. The changes of Parkin (PRKN)-mediated mitophagy and Nuclear Factor kappa B (NFKB)-mediated neuroinflammation were examined by TEM, RT-qPCR, Western blot and ELISA. The therapeutic effect of taurine or PRKN-overexpression was confirmed in the HSE mouse model by evaluating survival rate, eye damage, neurodegenerative symptoms, immunohistochemistry analysis and histopathology. RESULTS: HSV-1 infection caused the accumulation of damaged mitochondria in neuronal cells and in the brain tissue of HSE mice. Early HSV-1 infection led to mitophagy activation, followed by inhibition in the later viral infection. The HSV-1 proteins ICP34.5 or US11 deregulated the EIF2S1-ATF4 axis to suppress PRKN/Parkin mRNA expression, thereby impeding PRKN-dependent mitophagy. Consequently, inhibition of mitophagy by specific inhibitor midiv-1 promoted HSV-1 infection, whereas mitophagy activation by PRKN overexpression or agonists (CCCP and rotenone) attenuated HSV-1 infection and reduced the NF-κB-mediated neuroinflammation. Moreover, PRKN-overexpressing mice showed enhanced resistance to HSV-1 infection and ameliorated HSE pathogenesis. Furthermore, taurine, a differentially regulated gut microbial metabolite upon HSV-1 infection, acted as a mitophagy activator that transcriptionally promotes PRKN expression to stimulate mitophagy and to limit HSV-1 infection both in vitro and in vivo. CONCLUSION: These results reveal the protective function of mitophagy in HSE pathogenesis and highlight mitophagy activation as a potential antiviral therapeutic strategy for HSV-1-related diseases.

Analysis of factors selectively related to herpes zoster involving peripheral sensory ganglia: Retrospective study.

Herpes zoster (HZ), resulting from the reactivation of the varicella-zoster virus, is a significant disease. This study aimed to explore the factors influencing sensory neuron involvement in HZ at different locations and its association with postherpetic neuralgia (PHN). A total of 3143 cases were retrieved from an electronic medical record system, including 2676 cases of HZ and 467 cases of PHN. Gender, age, site of onset, past surgical history, and comorbidities were analyzed using a multifactorial logistic regression model. The results revealed correlations between age, gender, comorbidities (diabetes, coronary heart disease, percutaneous coronary intervention [PCI]), and sensory neuron involvement in HZ. Specifically, older age, female gender, and comorbid conditions such as diabetes/coronary heart disease were associated with sacral dorsal root ganglion (DRG) involvement, while PCI history was associated with lumbar DRG involvement. Additionally, sensory neuron involvement at different locations by HZ was linked to PHN. Furthermore, independent risk factors for PHN included thoracic DRG involvement, older age, and comorbidities (diabetes, surgical history, malignancy). It is crucial to prevent damage to the DRG, especially in individuals with comorbidities, through activities avoidance and active treatment, to minimize the occurrence of PHN.

Oxidation of Ammonia in Water Microdroplets Produces Nitrate and Molecular Hydrogen.

Water microdroplets containing dissolved ammonia (30-300 µM) are sprayed through a copper oxide mesh with a 200 µm average pore size, resulting in the formation of nitrate (NO3-) and the release of molecular hydrogen (H2). The products result from a redox process that takes place at the liquid-solid interface through contact electrification, where no external potential is applied. Oxidation is initiated by superoxide radical anions (O2-) that originate from the oxygen in the air surrounding the microdroplets and from the hydroxyl radicals (OH•) originating from the water-air interface. Two spin traps (TEMPO and DMPO) capture these radicals as well as NH2OH+•, HNO, NO•, NO2•, and NOOH, which are detected by mass spectrometry. We also directly observed N2O2-• by the same means. We found that the hydrogen atom from the ammonia molecule can be set free not only in the form of H• but also as H2, which is detected using a residue gas analyzer. The oxidation process can be significantly enhanced by a factor of 3 when the sprayed microdroplets are irradiated with ultraviolet light (265 nm, 5 W). 35% of 300 µM ammonia can be degraded within 20 µs, and the nitrate conversion rate is estimated to be 15 nmol·mg-1·h-1.

Identification of alternative splicing regulatory patterns and characteristic splicing factors in heart failure using RNA-seq data and machine learning.

Heart failure (HF) represents the advanced stage of several cardiovascular disorders. This study aimed to build an alternative splicing regulatory network and identify potential splicing factors involved in HF utilizing RNA-seq data and machine learning algorithms. We performed bioinformatics analysis on RNA-seq datasets containing samples from HF patients and normal individuals to obtain gene expression matrices and identify differently regulated alternative splicing events in HF. By calculating percent spliced-in (PSI) value, we identified 4055 abnormal alternative splicing events of 3142 genes in HF. These genes were significantly enriched in PPAR signaling, regulation of actin cytoskeleton, and muscle contraction. Interestingly, based on abnormal alternative splicing events, two distinct clusters of HF patients with distinct molecular mechanisms and pathways were identified using unsupervised clustering. Additionally, we built a regulatory network consisting of heart failure-related alternative splicing and splicing factors. Subsequently, we identify 203 HF specific pairs between splicing factors and alternative splicing events. Four splicing factors (RBM5, ZRANB2, HnRNPF, and HnRNPA0) were found using LASSO and SVM-RFE algorithms, their expression patterns were confirmed in two other microarray datasets. Our study clarifies involvement of splicing factors and alternative splicing events in HF by thoroughly analyzing RNA-seq data with machine learning methods. The findings may advance our understanding of the regulatory systems underlying biological processes associated with heart failure by providing candidates for further investigation and markers for diagnostic and therapeutic purposes.

The relationship between intracranial atherosclerosis and white matter hyperintensity in ischemic stroke patients: a retrospective cross-sectional study using high-resolution magnetic resonance vessel wall imaging.

Background: Both intracranial atherosclerosis and white matter hyperintensity (WMH) are prevalent among the stroke population. However, the relationship between intracranial atherosclerosis and WMH has not been fully elucidated. Therefore, the aim of this study was to investigate the relationship between the characteristics of intracranial atherosclerotic plaques and the severity of WMH in patients with ischemic stroke using high-resolution magnetic resonance vessel wall imaging. Methods: Patients hospitalized with ischemic stroke and concurrent intracranial atherosclerosis at Beijing Tsinghua Changgung Hospital, a tertiary comprehensive stroke center, who underwent high-resolution magnetic resonance vessel wall imaging and conventional brain magnetic resonance imaging were continuously recruited from January 2018 to December 2018. Both intracranial plaque characteristics (plaque number, maximum wall thickness, luminal stenosis, T1 hyperintensity, and plaque length) and WMH severity (Fazekas score and volume) were evaluated. Spearman correlation or point-biserial correlation analysis was used to determine the association between clinical characteristics and WMH volume. The independent association between intracranial plaque characteristics and the severity as well as WMH score was analyzed using logistic regression. The associations of intracranial plaque characteristics with total white matter hyperintensity (TWMH) volume, periventricular white matter hyperintensity (PWMH) volume and deep white matter hyperintensity (DWMH) volume were determined using multilevel mixed-effects linear regression. Results: A total of 159 subjects (mean age: 64.0±12.5 years; 103 males) were included into analysis. Spearman correlation analysis indicated that age was associated with TWMH volume (r=0.529, P<0.001), PWMH volume (r=0.523, P<0.001) and DWMH volume (r=0.515, P<0.001). Point-biserial correlation analysis indicated that smoking (r=-0.183, P=0.021) and hypertension (r=0.159, P=0.045) were associated with DWMH volume. After adjusting for confounding factors, logistic regression analysis showed plaque number was significantly associated with the presence of severe WMH [odds ratio (OR), 1.590; 95% CI, 1.241-2.035, P<0.001], PWMH score of 3 (OR, 1.726; 95% CI, 1.074-2.775, P=0.024), and DWMH score of 2 (OR, 1.561; 95% CI, 1.150-2.118, P=0.004). Intracranial artery luminal stenosis was associated with presence of severe WMH (OR, 1.032; 95% CI, 1.002-1.064, P=0.039) and PWMH score of 2 (OR, 1.057; 95% CI, 1.008-1.109, P=0.023). Multilevel mixed-effects linear regression analysis showed that plaque number was associated with DWMH volume (ß=0.128; 95% CI, 0.016-0.240; P=0.026) after adjusted for age and sex. Conclusions: In ischemic stroke patients, intracranial atherosclerotic plaque characteristics as measured by plaque number and luminal stenosis were associated with WMH burden.

All-Optical Control of Ultrafast Switching between the Hybridized Plasmonic Fields of Au Nanorod Dimer in fs-nm Scale with Dispersed Femtosecond Laser.

With the increasing demand for ultrafast communication and information processing in future optical chips, arbitrary manipulation of electromagnetic fields in the femtosecond-nanometer spatiotemporal scale has attracted great attention in integrated optics. Manipulation of the nanoscale light field in the real femtosecond temporal domain is challenging work. Here, we have demonstrated all-optical control of ultrafast switching between the hybridized plasmonic fields of a Au nanorod dimer in the fs-nm scale using a dispersed femtosecond laser and revealed the transformation process with ultrahigh spatiotemporal resolved technology via the combination of a pump-probe technique and photoemission electron microscopy (PEEM). The results show that we can actively and coherently control the transformation sequence and time (with the shortest temporal interval of around 15 fs) of the two hybridized modes in the Au nanorod dimer by tuning the dispersion of the laser pulse. The nanoscale light manipulation achieved by all-optical control may contribute to the design of high-speed miniaturized signal-processing systems.

Emission characteristics and health effects of PM2.5 from vehicles in typical areas.

Introduction: Vehicle emissions have become an important source of urban air pollution, and the assessment of air pollution emission characteristics and health effects caused by specific pollution sources can provide scientific basis for air quality management. Methods: In this paper, vehicle PM2.5 pollution in typical urban agglomerations of China (the Beijing-Tianjin-Hebei urban agglomeration (BTHUA), the triangle of the Central China urban agglomeration (TCCUA) and the Chengdu-Chongqing urban agglomeration (CCUA)) were used as research samples to evaluate the emission characteristics, health effects and economic losses of vehicle PM2.5 pollution based on the emission inventory, air quality model and exposure-response function from 2010 to 2020. Results: The results indicated that PM2.5 emissions from vehicles in the three urban agglomerations during 2010-2020 first showed an upward yearly trend and then showed a slow decrease in recent years. Heavy-duty trucks and buses are the main contribution vehicles of PM2.5, and the contribution rates of light-duty vehicles to PM2.5 is increasing year by year. The contribution rate of PM2.5 in Beijing decreased significantly. In addition to capital cities and municipalities directly under the central Government, the emission of pollutants in other cities cannot be ignored. The evaluation results of the impact of PM2.5 pollution from vehicles on population health show that: the number of each health endpoint caused by PM2.5 pollution from vehicles in the BTHUA and CCUA showed an overall upward trend, while the TCCUA showed a downward trend in recent years. Among them, PM2.5 pollution from vehicles in the three major urban agglomerations cause about 78,200 (95% CI: 20,500-138,800) premature deaths, 122,800 (95% CI: 25,600-220,500) inpatients, and 628,400 (95% CI: 307,400-930,400) outpatients and 1,332,400 (95% CI: 482,700-2,075,600) illness in 2020. The total health economic losses caused by PM2.5 pollution from vehicles in the three major urban agglomerations in 2010, 2015 and 2020 were 68.25 billion yuan (95% CI: 21.65-109.16), 206.33 billion yuan (95% CI: 66.20-326.20) and 300.73 billion yuan (95% CI: 96.79-473.16), accounting for 0.67% (95% CI: 0.21-1.07%), 1.19% (95% CI: 0.38%-1.88%) and 1.21% (95% CI: 0.39%-1.90%) of the total GDP of these cities. Discussion: Due to the differences in vehicle population, PM2.5 concentration, population number and economic value of health terminal units, there are differences in health effects and economic losses among different cities in different regions. Among them, the problems of health risks and economic losses were relatively prominent in Beijing, Chengdu, Chongqing, Tianjin and Wuhan.

Decreased flow in ischemic stroke with coexisting intracranial artery stenosis and white matter hyperintensities.

Background: Stroke patients with coexisting intracranial artery stenosis (ICAS) and white matter lesions (WML) usually have a poor outcome. However, how WML affects stroke prognosis has not been determined. Objective: To investigate the quantitative forward flow at the middle cerebral artery in ICAS patients with different degrees of WML using 4D flow. Design: Single-center cross-sectional cohort study. Methods: Ischemic stroke patients with symptomatic middle cerebral artery (MCA) atherosclerosis were included, and they were divided into 2 groups based on Fazekas scale on Flair image (mild group = Fazekas 0-2, and severe group = Fazekas >2), TOF-MRA and 4D flow were performed to quantify the stenosis degree and forward flow at the proximal of stenosis. The flow parameters were compared between different white matter hyperintensity (WMH) groups, as well as in different MCA stenosis groups, logistic regression was used to validate the association between forward flow and WMH. Results: A total of 66 patients were included in this study (mean age 56 years old, 68.2% male). 77.3% of them presented with WMH (Fazekas 1-5). Comparison of flow index between mild and severe WMH groups found a significantly lower forward flow (2.34 ± 1.09 vs 3.04 ± 1.35), higher PI (0.75 ± 0.43 vs 0.66 ± 0.32), and RI (0.49 ± 0.19 vs 0.46 ± 0.15) at ipsilateral infarction MCA in the severe WMH group, all P-values <0.05. After adjusting for other covariates, forward mean flow at ipsilateral infarction MCA is still associated with severe WMH independently, OR = 0.537, 95% CI (0.294, 0.981), P = 0.043. Conclusion: Intracranial artery stenosis patients with coexisting severe WMH suffer from significantly decreased flow, which could explain the poor clinical outcome in this population, and also provide some insight into recanalization therapy in the future.

Why was the study done? stroke patients with intracranial artery stenosis (ICAS) have a high prevalence of white matter hyperintensities (WMH), a surrogate biomarker of small vessel disease (SVD), and patients with coexisting ICAS and WMH are more likely to have unfavorable clinical outcomes and higher stroke recurrence risk. However, how WMH affects stroke outcomes has been unknown. What did the researchers do? In this study, we compared the flow and perfusion index between different WMH groups, as well as in different ICAS groups using 4D flow combined with ASL, to obtain the quantitative flow relationship in this population. What did the researchers find? As a result, we found that both the degree of intracranial artery stenosis and WMH burden is associated with decreased flow, and the flow decrease is more significant at the ipsilateral of infarct. What do the findings mean? This is the first study investigating the complicated hemodynamic status using 4D flow combined with ASL in stroke patients with coexisting ICAS and WMH. The results in this study could not only provide some evidence for unfavorable clinical outcomes in ICAS patients with severe WMH burden but also give us some insight into recanalization therapy in this population.

How does green credit affect industrial green transformation? Mechanism discussion and empirical test.

Sustainable development has become a strategic consensus in response to the global environmental problems. Green credit is a major policy innovation that promotes the transformation of economic development mode and industrial green transformation (IGT). Using provincial panel data from 2005 to 2020, we investigate the effect of green credit on IGT using a systematic GMM model, a dynamic threshold model, as well as the possible nonlinear relationship. Benchmark regression results show that green credit can encourage industrial green transformation. In addition, there is a single green credit threshold with a value of 0.2612. The trend is "negative to positive". According to the moderating effect results, environmental regulation moderates in a negative manner. As environmental regulations become more stringent, the contribution of green credit to IGT will diminish. The intermediary mechanism test demonstrates that green technology innovation and marketization level play a partial intermediary role. Heterogeneity testing confirms that the function of green credit in promoting industrial green transformation is more significant in regions with a higher level of green finance development and a lower degree of government intervention. Therefore, the government should encourage financial institutions to provide green credit products and services to meet the financing needs of different green projects, thereby facilitating the industrial green transformation.

Intestinal flora influences the progression of subarachnoid hemorrhage by affecting peripheral and central inflammatory pathways.

Subarachnoid hemorrhage (SAH) is a debilitating condition that leaves survivors with neurological disability for the rest of their lives. No effective treatment for early brain injury (EBI) has been developed. Gut microbiome (GM) impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the GM has an impact on the outcome of SAH brain injury. Here, we wondered whether microbiota could relieve the injury. We changed the microbiota of 8-week-old male rats by administering antibiotic-containing water for 2 weeks. Composition of the GM was profiled by using 16S rRNA. We induced SAH by puncture the internal carotid artery of control rats and rats with altered GM. Additionally, we studied inflammatory cells using HE stains, Intestinal lymphocyte flow cytometry, and Neuroinflammatory factor WB. SAH was significantly averted by alterations in GM using antibiotics. The altered GM significantly increased the intestinal and intracranial inflammation after SAH. This was manifested by Mosin (MSN) inflammatory cytokines. Our findings demonstrated that the brain injury following SAH is associated with GM.

Frailty Predicts Dementia and Death in Older Adults Living in Long-Term Care.

OBJECTIVES: To investigate how the accumulation of deficits traditionally related and not traditionally related to dementia predicts dementia and mortality. DESIGN: A retrospective cohort study with up to 9 years of follow-up. SETTING AND PARTICIPANTS: Long-term care residents aged ≥65 with or without dementia. METHODS: Frailty indices based on health deficit accumulation were constructed. The FI-t consisted of 27 deficits traditionally related to dementia; the FI-n consisted of 27 deficits not traditionally related to dementia; the FI-a consisted of all 54 deficits taken from the FI-t and the FI-n. RESULTS: In this long-term care sample (n = 29,758; mean age = 84.6 ± 8.0; 63.8% female), 91% of the residents had at least 1 impairment in activities of daily living, 61% had a diagnosis of dementia, and the vast majority were frail (53% had FI-a > 0.2). Residents with dementia had a higher FI-t compared with those without dementia (0.278 ± 0.110 vs. 0.272 ± 0.108), whereas residents without dementia had a higher FI-n (0.143 ± 0.082 vs. 0.136 ± 0.079). Within 9 years, 97% of the sample had died; a 0.01 increase of the FI-a was associated with a 4% increase of the mortality risk, adjusting for age, sex, admission year, stay length, and dementia type. Residents who developed dementia after admission to long-term care had higher baseline FI-t and FI-a (P's < .003) than those who remained without dementia. CONCLUSIONS AND IMPLICATIONS: Frailty is highly prevalent in older adults living in long-term care, irrespective of the presence or absence of dementia. Accumulation of deficits, either traditionally related or unrelated to dementia, is associated with risks of death and dementia, and more deficits increases the probability. Our findings have implications for improving the quality of care of older adults in long-term care, by monitoring the degree of frailty at admission, managing distinct needs in relation to dementia, and enhancing frailty level-informed care and services.

Breast cancer clinical outcomes and tumor immune microenvironment: cross-dialogue of multiple epigenetic modification profiles.

The discovery of RNA methylation alterations associated with cancer holds promise for their utilization as potential biomarkers in cancer diagnosis, prognosis, and prediction. RNA methylation has been found to impact the immunological microenvironment of tumors, but the specific role of methylation-related genes (MRGs), particularly in breast cancer (BC), the most common cancer among women globally, within the tumor microenvironment remains unknown. In this study, we obtained data from TCGA and GEO databases to investigate the expression patterns of MRGs in both genomic and transcriptional domains in BC. By analyzing the data, we identified two distinct genetic groupings that were correlated with clinicopathological characteristics, prognosis, degree of TME cell infiltration, and other abnormalities in MRGs among patients. Subsequently, an MRG model was developed to predict overall survival (OS) and its accuracy was evaluated in BC patients. Additionally, a highly precise nomogram was created to enhance the practical usability of the MRG model. In low-risk groups, we observed lower TBM values and higher TIDE scores. We further explored how MRGs influence a patient's prognosis, clinically significant characteristics, response to therapy, and the TME. These risk signatures have the potential to improve treatment strategies for BC patients and could be applied in future clinical settings. Moreover, they may also be utilized to determine prognosis and biological features in these patients.

Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia.

INTRODUCTION: A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required. METHODS AND ANALYSIS: A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19-69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire. ETHICS AND DISSEMINATION: The trial has been authorised by Health Canada and approved by The University of British Columbia/Children's and Women's Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT05430152.

Combating Barriers to the Development of a Patient-Oriented Frailty Website.

Unlabelled: This viewpoint article, which represents the opinions of the authors, discusses the barriers to developing a patient-oriented frailty website and potential solutions. A patient-oriented frailty website is a health resource where community-dwelling older adults can navigate to and answer a series of health-related questions to receive a frailty score and health summary. This information could then be shared with health care professionals to help with the understanding of health status prior to acute illness, as well as to screen and identify older adult individuals for frailty. Our viewpoints were drawn from 2 discussion sessions that included caregivers and care providers, as well as community-dwelling older adults. We found that barriers to a patient-oriented frailty website include, but are not limited to, its inherent restrictiveness to frail persons, concerns over data privacy, time commitment worries, and the need for health and lifestyle resources in addition to an assessment summary. For each barrier, we discuss potential solutions and caveats to those solutions, including assistance from caregivers, hosting the website on a trusted source, reducing the number of health questions that need to be answered, and providing resources tailored to each users' responses, respectively. In addition to screening and identifying frail older adults, a patient-oriented frailty website will help promote healthy aging in nonfrail adults, encourage aging in place, support real-time monitoring, and enable personalized and preventative care.

Brain vital signs as a quantitative measure of cognition: Methodological implementation in a care home environment.

Introduction: Managing cognitive function in care homes is a significant challenge. Individuals in care have a variety of scores across standard clinical assessments, such as the Mini-Mental Status Exam (MMSE), and many of them have scores that fall within the range associated with dementia. A recent methodological advance, brain vital sign monitoring through auditory event-related potentials, provides an objective and sensitive physiological measurement to track abnormalities, differences, or changes in cognitive function. Taking advantage of point-of-care accessibility, the current study evaluated the methodological feasibility, the assessment of whether a particular research method can be successfully implemented, of quantitatively measuring cognition of care home residents using brain vital signs. Secondarily, the current study examined the relationship between brain vital signs, specifically the cognitive processing associated N400 component, and MMSE scores in care home residents. Materials and methods: Brain vital signs used the established N100 (auditory sensation), P300 (basic attention), and N400 (cognitive processing) event-related potential (ERP) components. A total of 52 residents were enrolled, with all participants evaluated using the MMSE. Participants were assigned into homogeneous groups based on their MMSE scores, and were categorized into low (n = 14), medium (n = 17), and high (n = 13) MMSE groups. Both brain vital sign measures and underlying ERP waveforms were examined. Statistical analyses used partial least squares correlation (PLS) analyses in which both MMSE and age were included as factors, as well as jackknife approaches, to test for significant brain vital sign changes. Results: The current study successfully measured and analyzed standardized, quantifiable brain vital signs in a care home setting. ERP waveform data showed specific N400 changes between MMSE groups as a function of MMSE score. PLS analyses confirmed significant MMSE-related and age-related differences in the N400 amplitude (p < 0.05, corrected). Similarly, the jackknife approach emphasized the N400 latency difference between the low and high MMSE groups. Discussion and conclusion: It was possible to acquire brain vital signs measures in care home residents. Additionally, the current study evaluated brain vital signs relative to MMSE in this group. The comparison revealed significant decreasing in N400 response amplitude (cognitive processing) as a function of both MMSE score and age, as well as a slowing of N400 latency. The findings indicate that objective neurophysiological measures of impairment are detectable in care home residents across the span of MMSE scores. Direct comparison to MMSE- and age-related variables represents a critical initial step ahead of future studies that will investigate relative improvements in sensitivity, validity, reliability and related advantages of brain vital sign monitoring.

The power of microdroplet photochemistry.

This study presents compelling evidence demonstrating that irradiation of the air-solution interface, whether achieved through the spraying of microdroplets into the air or by bubbling air through a solution, significantly accelerates the rate of photochemical reactions by orders of magnitude compared to identical reaction conditions in bulk solutions. We propose this approach as a novel and versatile method for harnessing solar energy in chemical transformations.

Regulatory mechanisms of long non-coding RNAs on mitochondrial function in congestive heart failure.

Congestive heart failure (CHF) is a multifaceted cardiovascular condition that imposes significant economic and social burdens on society, while also presenting a dearth of efficacious treatment modalities. Long non-coding RNAs (lncRNAs) possess the ability to influence the pathophysiological mechanisms underlying cardiac disease through their regulation of gene transcription, translation, and post-translational modifications. Additionally, certain lncRNAs can be encoded by the mitochondrial genome, hence impacting mitochondrial function. The heart relies heavily on mitochondrial oxidative phosphorylation for approximately 95 % of its ATP production. Consequently, the primary determinant linking mitochondrial dysfunction to heart failure is the impairment of cardiac energy supply resulting from mitochondrial injury. Cardiac dysfunction can arise as a result of various factors, including metabolic disease, disturbances in calcium homeostasis, oxidative stress, apoptosis, and mitochondrial phagocytosis, all of which are facilitated by mitochondrial damage. Currently, an increasing body of research indicates that lncRNA plays a significant role in the regulation of mitochondrial activity, hence impacting heart failure. As a result, the goal of this paper is to propose new ideas and targets for clinical research and therapy of heart failure by reviewing recent research on the regulatory mechanism of mitochondrial function by novel lncRNAs.

Abnormal expression of PRKAG2-AS1 in endothelial cells induced inflammation and apoptosis by reducing PRKAG2 expression.

PRKAG2 is required for the maintenance of cellular energy balance. PRKAG2-AS1, a long non-coding RNA (lncRNA), was found within the promoter region of PRKAG2. Despite the extensive expression of PRKAG2-AS1 in endothelial cells, the precise function and mechanism of this gene in endothelial cells have yet to be elucidated. The localization of PRKAG2-AS1 was predominantly observed in the nucleus, as revealed using nuclear and cytoplasmic fractionation and fluorescence in situ hybridization. The manipulation of PRKAG2-AS1 by knockdown and overexpression within the nucleus significantly altered PRKAG2 expression in a cis-regulatory manner. The expression of PRKAG2-AS1 and its target genes, PRKAG2b and PRKAG2d, was down-regulated in endothelial cells subjected to oxLDL and Hcy-induced injury. This finding suggests that PRKAG2-AS1 may be involved in the mechanism behind endothelial injury. The suppression of PRKAG2-AS1 specifically in the nucleus led to an upregulation of inflammatory molecules such as cytokines, adhesion molecules, and chemokines in endothelial cells. Additionally, this nuclear suppression of PRKAG2-AS1 facilitated the adherence of THP1 cells to endothelial cells. We confirmed the role of nuclear knockdown PRKAG2-AS1 in the induction of apoptosis and inhibition of cell proliferation, migration, and lumen formation through flow cytometry, TUNEL test, CCK8 assay, and cell scratching. Finally, it was determined that PRKAG2-AS1 exerts direct control over the transcription of PRKAG2 by its binding to their promoters. In conclusion, downregulation of PRKAG2-AS1 suppressed the proliferation and migration, promoted inflammation and apoptosis of endothelial cells, and thus contributed to the development of atherosclerosis resulting from endothelial cell injury.

Morning blood pressure surge and intracranial atherosclerotic plaque characteristics: a high-resolution magnetic resonance vessel wall imaging study.

OBJECTIVE: To investigate the relationship between morning blood pressure surge (MBPS) and intracranial atherosclerotic plaque burden and vulnerability. METHODS: A total of 267 ischaemic stroke patients were retrospectively analysed. Sleep-trough and prewaking MBPS were calculated from ambulatory blood pressure monitoring (ABPM). Plaque characteristics, including intraplaque haemorrhage (IPH), maximum wall thickness (max WT), and stenosis degree, were obtained from high-resolution MR vessel wall imaging (HR-vwMRI). Linear and logistic regression were used to detect the association. RESULTS: Subjects with the top tertile of sleep-trough MBPS (≥15.1 mmHg) had a lower prevalence (9.1% vs. 19.6%, P = .029) of severe stenosis (≥70%) than others. Subjects within the top tertile of prewaking MBPS (≥7.6 mmHg) had a lower percentage of IPH (27.3% vs. 40.4%, P = .035) than others. After adjusting for stroke risk factors (age, sex, diabetes, hyperlipidaemia, hyperhomocysteinaemia, smoking, and family stroke history) and 24-h mean systolic blood pressure, 10 mmHg sleep-trough MBPS increment was associated with 0.07mm max WT reduction, and the top tertile MBPS group was associated with a lower chance of severe stenosis (odd ratio = 0.407, 95% CI, 0.175-0.950). Additionally, an increased prewaking MBPS is associated with a lower incidence of IPH, with OR = 0.531 (95% CI, 0.296-0.952). Subgroup analysis demonstrated that the positive findings could only be seen in non-diabetic subjects. CONCLUSION: Increment of MBPS is negatively associated with intracranial atherosclerotic plaque burden and vulnerability, and this relationship remains significant in the non-diabetic subgroup. ADVANCES IN KNOWLEDGE: This study provided evidence that MBPS was associated with the intracranial atherosclerotic plaque burden and vulnerability on HR-vwMRI.

LRENet: a location-related enhancement network for liver lesions in CT images.

Objective. Liver cancer is a major global health problem expected to increase by more than 55% by 2040. Accurate segmentation of liver tumors from computed tomography (CT) images is essential for diagnosis and treatment planning. However, this task is challenging due to the variations in liver size, the low contrast between tumor and normal tissue, and the noise in the images. APPROACH: In this study, we propose a novel method called location-related enhancement network (LRENet) which can enhance the contrast of liver lesions in CT images and facilitate their segmentation. LRENet consists of two steps: (1) locating the lesions and the surrounding tissues using a morphological approach and (2) enhancing the lesions and smoothing the other regions using a new loss function. MAIN RESULTS: We evaluated LRENet on two public datasets (LiTS and 3Dircadb01) and one dataset collected from a collaborative hospital (Liver cancer dateset), and compared it with state-of-the-art methods regarding several metrics. The results of the experiments showed that our proposed method outperformed the compared methods on three datasets in several metrics. We also trained the Swin-Transformer network on the enhanced datasets and showed that our method could improve the segmentation performance of both liver and lesions. SIGNIFICANCE: Our method has potential applications in clinical diagnosis and treatment planning, as it can provide more reliable and informative CT images of liver tumors.