Real-time tracking of electron transfer at catalytically active interfaces in lithium-ion batteries.

Transition metals and related compounds are known to exhibit high catalytic activities in various electrochemical reactions thanks to their intriguing electronic structures. What is lesser known is their unique role in storing and transferring electrons in battery electrodes which undergo additional solid-state conversion reactions and exhibit substantially large extra capacities. Here, a full dynamic picture depicting the generation and evolution of electrochemical interfaces in the presence of metallic nanoparticles is revealed in a model CoCO3/Li battery via an in situ magnetometry technique. Beyond the conventional reduction to a Li2CO3/Co mixture under battery operation, further decomposition of Li2CO3 is realized by releasing interfacially stored electrons from its adjacent Co nanoparticles, whose subtle variation in the electronic structure during this charge transfer process has been monitored in real time. The findings in this work may not only inspire future development of advanced electrode materials for next-generation energy storage devices but also open up opportunities in achieving in situ monitoring of important electrocatalytic processes in many energy conversion and storage systems.

Fabrication of a Near-Infrared-Emissive Probe for Detecting Dipeptidyl Peptidase 4 in the Liver of Diabetic Mice and Clinical Serum.

Dipeptidyl peptidase 4 (DPP4) plays a key role in glucose metabolism, which has been a close target for diabetes pathology and treatment. It is significant for the evaluation of cellular DPP4 activity in various biological systems. Fluorescence imaging technology is currently a popular method for detecting enzymes in living cells due to its advantages of high selectivity, high sensitivity, high spatiotemporal resolution, and real-time visualization. Herein, a near-infrared (NIR)-emissive probe NEDP with a large Stokes shift (153 nm) was developed for the assay of DPP4 activity. Upon addition of DPP4, NEDP can emit a significant turn-on NIR fluorescence signal (673 nm) with high sensitivity and specificity. Moreover, NEDP can successfully be used for imaging of intracellular DPP4, confirming the regulation of DPP4 expression in hyperglucose and its treatment in living cells. Most importantly, NEDP can not only monitor the changes of DPP4 in vivo but also show that DPP4 in diabetes is mainly up-regulated in the liver, and the level of DPP4 is positively correlated with the pathological damage of the liver. In addition, NEDP can identify the serum of diabetic patients from healthy people through the fluorescence response to DPP4. These results demonstrated that the designed probe NEDP provides a prospective visual tool to explore the relationship between DPP4 and diabetes and would be applied for detecting serum of diabetes in the clinic.

Effects of vitamins and polyunsaturated fatty acids on cognitive function in older adults with mild cognitive impairment: a meta-analysis of randomized controlled trials.

PURPOSE: Vitamins and polyunsaturated fatty acids (PUFAs) have been studied extensively as safe and manageable nutrient interventions for mild cognitive impairment (MCI). The purpose of the current meta-analysis was to examine the effects of vitamins and PUFAs on cognition and to compare the effects of single and multiple nutrient subgroups in patients with MCI. METHODS: Randomized controlled trials (RCTs) written in English and Chinese were retrieved from eight databases, namely, PubMed, CENTRAL, Embase, CINAHL, Web of Science, SinoMed, CNKI, and Wanfang Data, from their respective dates of inception until 16 July 2023. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool 2.0. Meta-analyses were performed to determine the standardized mean differences (SMDs) in global cognitive function, memory function, attention, visuospatial skills, executive function, and processing speed between the supplement and control groups using 95% confidence intervals (CI) and I2. Prospero registration number: CRD42021292360. RESULTS: Sixteen RCTs that studied different types of vitamins and PUFAs were included. The meta-analysis revealed that vitamins affected global cognitive function (SMD = 0.58, 95% CI = [0.20, 0.96], P = 0.003), memory function (SMD = 2.55, 95% CI = [1.01, 4.09], P = 0.001), and attention (SMD = 3.14, 95% CI = [1.00, 5.28], P = 0.004) in patients with MCI, and PUFAs showed effects on memory function (SMD = 0.65, 95% CI = [0.32, 0.99], P < 0.001) and attention (SMD = 2.98, 95% CI = [2.11, 3.84], P < 0.001). Single vitamin B (folic acid [FA]: SMD = 1.21, 95% CI = [0.87, 1.55]) supplementation may be more effective than multiple nutrients (FA and vitamin B12: SMD = 0.71, 95% CI = [0.41, 1.01]; and FA combined with docosahexaenoic acid [DHA]: SMD = 0.58, 95% CI = [0.34, 0.83]) in global cognitive function. CONCLUSIONS: FA, vitamin B6, vitamin B12, and vitamin D may improve global cognitive function, memory function, and attention in patients with MCI. Eicosapentaenoic acid (EPA) and DHA may improve memory function and attention. We also noted that FA may exert a greater effect than a vitamin B combination (FA and vitamin B12) or the combination of FA and DHA. However, because of the low evidence-based intensity, further trials are necessary to confirm these findings.

Serum soluble alpha-klotho klotho and cognitive functioning in older adults aged 60 and 79: an analysis of cross-sectional data of the National Health and Nutrition Examination Survey 2011 to 2014.

OBJECTIVES: Klotho, consisting of membrane klotho and soluble alpha-klotho, is found to be associated with better cognitive outcomes in small samples of the aged population. We aimed to examine the association of serum soluble alpha-klotho with cognitive functioning among older adults using a nationally representative sample of U.S. older adults. METHOD: A total of 2,173 U.S. older adults aged 60-79 years in the National Health and Nutrition Examination Survey from 2011 to 2014 were included in this cross-sectional analysis. Serum soluble alpha-klotho was measured in the laboratory and analyzed with an ELISA kit. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD-WL) immediate and delayed memory, the Animal fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on sample means and standard deviations. Multivariable linear regression models were applied to examine the association of quartiles and continuous value of serum soluble alpha-klotho with test-specific and global cognition z-scores. Subgroup analysis was conducted by sex. The following covariates were included in the analysis- age, sex, race/ethnicity, education, depressive symptoms, smoking status, body mass index (BMI), physical activity, stroke, prevalent coronary heart disease, total cholesterol, and systolic blood pressure. All the information was self-reported or obtained from health exams. RESULTS: Serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (beta [ß] =-0.13, 95% confidence interval [CI]: -0.25, -0.01). For subgroup analysis, serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (ß=-0.16, 95% CI: -0.32, -0.003) and global cognition (ß=-0.14, 95% CI: -0.28, -0.01) among female participants. No association was found between continuous serum soluble alpha-klotho and cognitive functioning among the participants. CONCLUSIONS: Lower serum soluble alpha-klotho quartile was associated with poorer cognitive functioning among older women. Future studies are expected to examine the longitudinal association between klotho levels and cognitive outcomes.

Prevalence and risk factors of depression among elderly people in nursing homes from 2012 to 2022: a systematic review and meta-analysis.

OBJECTIVES: To determine a pooled prevalence of depression and its influencing factors among nursing home residents. METHOD: PsycINFO, PubMed, Embase, and Web of Science were searched for studies investigating the prevalence and risk factors of late-life depression among nursing home residents between January 2012 and November 2022. Two reviewers independently completed the literature screening, data extraction and quality assessment. A random-effects model was utilized to pool the prevalence of depression and summarize the influencing factors. RESULTS: This meta-analysis included 48 studies involving 28,501 participants. The pooled prevalence of depressive mood and major depressive disorder was 53% and 27%, respectively. The rate of depressive mood is higher in lower-middle-income countries (60.0%), compared with high- (53.0%) and upper-middle-income countries (44.0%). The rate of depressive mood (35.0%) is higher among females than male (19.0%). Depression was influenced by factors, including male (OR = 0.28), insufficient income (OR = 3.53), comorbidities (OR = 2.66), pain (OR = 2.67; r = 0.31), functional disability (r = 0.33), loneliness (r = 0.43), number of chronic health problems (r = 0.18), social support (r = -0.28), activities of daily living (r = -0.43), subjective health (r = -0.28), autonomy (r = -0.41), environment (r = -0.50) and physical (r = -0.57) and psychological health (r = -0.65). CONCLUSION: The prevalence of depressive mood is high among nursing home residents, especially in lower-middle-income countries. It is influenced by factors including gender, income, social support, daily activities, environment, physical and psychological health and autonomy. Understanding those factors can provide evidence-based recommendations for improved awareness, prevention and better management of late-life depression.

Sustained frailty remission and dementia risk in older adults: A longitudinal study.

INTRODUCTION: Physical frailty is reversible, but little is known about the sustainability of frailty remission and its impact on dementia. METHODS: Data were derived from the National Health and Aging Trends Study (NHATS) (2011 to 2021). Physical frailty was assessed using the Fried frailty phenotype, and frailty transition patterns across three waves were defined. The relationship of sustained frailty remission with incident dementia was examined using Cox proportional regression, stratified by age and gender. RESULTS: Among 1931 participants, 348 (18.0%) were capable of sustained frailty remission. During the 8-year follow-up, 279 participants developed dementia. In a fully adjusted model, sustained remission was associated with a lower risk of dementia (hazard ratio = 0.66, 95% confidence interval = 0.47 to 0.93). The association was more pronounced among younger-old and male participants but not observed among their counterparts. DISCUSSION: Sustained frailty remission was associated with a reduced risk of developing dementia. Physical frailty could be an essential forewarning of dementia and a target for interventions. HIGHLIGHTS: We provided new insights into the natural progression of frailty and its impact on dementia risk using a nationally representative sample Sustained frailty remission reduced risk of incident dementia. Age and gender played a role in the frailty-dementia link, and thus individualized dementia risk screening is necessary. Physical frailty could be an essential forewarning of cognitive decline and an ideal target for interventions to prevent dementia.

The association of cardiometabolic multimorbidity and fear of falling among older adults: Data from the national health and aging trends study.

OBJECTIVES: Cardiometabolic diseases (CMDs) have been individually associated with fall-related outcomes, but their combined effect on fear of falling (FOF) has not been investigated. This study aims to examine the association between cardiometabolic multimorbidity and FOF in older adults. METHODS: Data from the National Health and Aging Trends Study, 4,295 community-dwelling older adults ≥ 65 years were analyzed in this longitudinal study. CMDs were assessed at baseline, including heart disease, diabetes, stroke, and hypertension. FOF was evaluated by asking participants if they worried about falling in the past month. Data were analyzed using multi-adjusted logistic regression. RESULTS: Cardiometabolic multimorbidity was associated with a higher risk of FOF. The combination of heart disease and diabetes showed the highest risk of FOF (OR = 3.47, 95 % CI: 1.63-7.40). CONCLUSIONS: These findings underscore the need for targeted interventions to mitigate the combined impact of cardiometabolic multimorbidity on FOF in older adults.

Demographics moderated the association of symptom burden with falls and fall-related outcomes.

OBJECTIVES: To examine whether (1) prior-year symptom burden predicted later-year falls and fall-related outcomes and (2) demographics moderated the longitudinal effects of symptom burden on falls and fall-related outcomes among community-dwelling older adults. METHODS: We used 2011-2018 National Health and Aging Trends Study data that included 9,060 community-dwelling older adults (contributed 34,327 observations). Falls and fall-related outcomes included self-reported falls, multiple falls, fear of falling (FOF), and FOF limiting activity. Symptom burden was defined as the presence of pain, insomnia, breathing difficulty, depressive symptoms, anxiety, and fatigue, and calculated the number of symptoms (range from 0 to 6). Binomial logistic regression was used to examine the associations between symptom burden and falls and fall-related outcomes and the moderation effects of demographic factors. RESULTS: The majority of the sample were aged between 65 and 79 years old (57.7%), non-Hispanic White (70.5%), and female (58.4%). Each additional symptom was associated with an increased risk of falls (Adjusted Odds Ratio [AOR]: 1.13, 95% CI: 1.10-1.15), multiple falls (AOR: 1.15, 95% CI: 1.12-1.18), FOF (AOR: 1.20, 95% CI: 1.18-1.23), and FOF limiting activity (AOR: 1.24, 95% CI: 1.20-1.28). Age, race/ethnicity, education, and living arrangement statistically significantly moderated the relationships between symptom burden and falls and fall-related outcomes. CONCLUSIONS: Symptom burden predicted falls, multiple falls, FOF and FOF limiting activity, and demographics may differentially modify this risk. Individually tailored symptom assessment and management plans should be incorporated into fall risk assessment and interventions for community-dwelling older adults living.

Effectiveness of psychological interventions among community-dwelling older adults with subthreshold depression: A systematic review and meta-analysis.

BACKGROUND: Little is known about the effectiveness of psychological interventions among older adults with subthreshold depression in the community. This systematic review and meta-analysis aimed to examine the effectiveness of psychological interventions on depressive symptoms, anxiety symptoms and quality of life. METHODS: We searched five databases from inception to 20th September 2022 and included RCTs that evaluated the effectiveness of psychological interventions among older adults with subthreshold depression in the community. Standardized mean difference (SMD) and 95 % confidence intervals (CI) were used to calculate the effect sizes of treatment outcomes in the meta-analysis, using RevMan 5.4.1 and Stata 16.0. RESULTS: This meta-analysis included thirteen RCT studies involving 2079 participants. Psychological interventions could significantly reduce depressive symptoms (post-intervention time: SMD = -0.58, 95 % CI = -0.76 to -0.40; follow-up time: SMD = -0.31, 95 % CI = -0.41 to -0.22) and anxiety symptoms (post-intervention time: SMD = -0.33, 95 % CI = -0.49 to -0.17; follow-up time: SMD = -0.24, 95 % CI = -0.36 to -0.12) and improve quality of life (post-intervention time: SMD = 0.30, 95 % CI = 0.05 to 0.55; follow-up time: SMD = 0.15, 95 % CI = 0.01 to 0.28). CONCLUSION: Evidence suggests that psychological interventions could significantly reduce depressive symptoms and anxiety symptoms, and improve quality of life among community-dwelling older adults with subthreshold depression.

A single mitochondria-targetable fluorescent probe for visualizing cysteine and glutathione in ferroptosis of myocardial ischemia/reperfusion injury.

Ferroptosis plays an important role in the early stage of myocardial ischemia/reperfusion (MI/R) injury, which is closely associated with the antioxidant damage of mitochondrial cysteine (Cys)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis. Visualization of Cys and GSH in mitochondria is meaningful to value ferroptosis and further contributes to understanding and preventing MI/R injury. Herein a mitochondria-targetable thiols fluorescent probe (MTTP) was designed and synthesized based on sulfonyl benzoxadiazole (SBD) chromophore with a triphenylphosphine unit as the mitochondria-targeted functional group. Cys and GSH can be differentiated by MTTP with two distinguishable emission bands (583 nm and 520 nm) through the controllable aromatic substitution-rearrangement reaction. Importantly, MTTP is capable of monitoring ferroptosis and its inhibition by measuring mitochondrial Cys and GSH. MTTP was also employed to non-invasively detect ferroptosis during oxygen and glucose deprivation/reoxygenation (OGD/R)-induced MI/R injury in H9C2 cells. In a word, MTTP provides a visual tool that can simultaneously detect Cys and GSH to monitor ferroptosis processes during MI/R injury, which helps for more deeper understanding of the role of ferroptosis in MI/R injury-related diseases.

The impact of frailty on short-term prognosis in discharged adult stroke patients: A multicenter prospective cohort study.

BACKGROUND: Frailty is commonly observed in stroke patients and it is associated with adverse outcomes. However, there remains a gap in longitudinal studies investigating the causal relationship between baseline frailty and short-term prognosis in discharged adult stroke patients. OBJECTIVE: To examine the causal impact of frailty on non-elective readmission and major adverse cardiac and cerebral events, and investigate its associations with cognitive impairment and post-stroke disability. DESIGN: A multicenter prospective cohort study. SETTING: Two tertiary hospitals in Central and Northwest China. PARTICIPANTS: 667 adult stroke patients in stroke units were included from January 2022 to June 2022. METHODS: Baseline frailty was assessed by the Frailty Scale. Custom-designed questions were utilized to assess non-elective readmission and major adverse cardiac and cerebral events as primary outcomes. Cognitive impairment, assessed using the Mini-Mental State Examination Scale (MMSE), and post-stroke disability, measured with the Modified Rankin Scale (mRS), were considered secondary outcomes at a 3-month follow-up. The impact of baseline frailty on non-elective readmission and major adverse cardiac and cerebral events was examined using bivariate and multiple Cox regression analyses. Furthermore, associations between baseline frailty and cognitive impairment, or post-stroke disability, were investigated through generalized linear models. RESULTS: A total of 5 participants died, 12 had major adverse cardiac and cerebral events, and 57 had non-selective readmission among 667 adult stroke patients. Frailty was an independent risk factor for non-selective readmission (hazard ratio [HR]: 2.71, 95 % confidence interval [CI]: 1.59, 4.62) and major adverse cardiac and cerebral events (HR: 3.77, 95 % CI: 1.07, 13.22) for stroke patients. Baseline frailty was correlated with cognitive impairment (regression coefficient [ß]: -2.68, 95 % CI: -3.78, -1.58) adjusting for socio-demographic and clinical factors and follow-up interval. However, the relationship between frailty and cognitive impairment did not reach statistical significance when further adjusting for baseline MMSE (ß: -0.39, 95 % CI: -1.43, 0.64). Moreover, baseline frailty was associated with post-stroke disability (ß: 0.36, 95 % CI: 0.08, 0.65) adjusting for socio-demographic and clinical variables, follow-up interval, and baseline mRS. CONCLUSIONS: The finding highlights the importance of assessing baseline frailty in discharged adult stroke patients, as it is significantly associated with non-elective readmission, major adverse cardiac and cerebral events, and post-stroke disability at 3 months. These results highlight the crucial role of screening and evaluating frailty status in improving short-term prognosis for adult stroke patients. Interventions should be developed to address baseline frailty and mitigate the short-term prognosis of stroke. TWEETABLE ABSTRACT: Baseline frailty predicts non-elective readmission, major adverse cardiac and cerebral events, and post-stroke disability in adult stroke patients. @haiyanhexyyy.

Influences of Social Disengagement and Depressive Symptoms on Sleep Disturbance in Dementia Caregiving Dyads: A Nationally Representative Study.

OBJECTIVES: To examine the influence of social disengagement and depressive symptoms on sleep disturbance among dementia caregiving dyads and the actor-partner interdependence nature of these influences. DESIGN: Actor-partner interdependence model through structural equation modeling for dyadic analyses. SETTING AND PARTICIPANTS: A total of 310 dyads of older adults with dementia and their care partners from 2 national representative studies in the United States, the National Health and Aging Trends Study (NHATS) and its companion study, the National Study of Caregiving (NSOC). METHODS: Data from the NHATS Round 11 and NSOC IV were analyzed using descriptive statistics, Pearson correlation analysis, and the actor-partner interdependence model. Structural equation modeling was used to assess the mediation effects of depressive symptoms within the actor-partner interdependence models. RESULTS: In the model of caregivers, social disengagement had a direct impact on sleep disturbance (ß = 0.49, P < .001) and an indirect impact through depressive symptoms (ß = 0.25, P < .001). In the model of older adults with dementia, social disengagement only had an indirect effect on sleep disturbance through depressive symptoms. In models examining partner effects, caregivers' social disengagement directly influenced their care partners' depressive symptoms (ß = 0.20, P = .019), which subsequently affected caregivers' sleep disturbance (ß = 0.17, P < .001). Social disengagement (ß = 0.17, P = .001) and depressive symptoms (ß = 0.17, P < .001) in older adults with dementia directly impacted their caregivers' sleep disturbance. Depressive symptoms of older adults with dementia served as multiple mediators linking one member's social disengagement to both their own and partner's sleep. CONCLUSIONS AND IMPLICATIONS: This study represents one of the first attempts to investigate the influencing mechanism of sleep disturbances among older adults with dementia and their informal caregivers through a dyadic perspective. The sleep disturbance of caregivers may be directly influenced by the social disengagement and depressive symptoms exhibited by both members of the dyad, whereas the sleep disturbance experienced by older adults with dementia can only be indirectly influenced by the dyad's social disengagement via their own depressive symptoms. Dyadic social activities targeting depressive symptoms could be designed to address sleep disturbances in dementia caregiving dyads.

Long-term exposure to fine particulate matter constituents and cognitive impairment among older adults: An 18-year Chinese nationwide cohort study.

BACKGROUND: Although growing evidence has shown independent links of long-term exposure to fine particulate matter (PM2.5) with cognitive impairment, the effects of its constituents remain unclear. This study aims to explore the associations of long-term exposure to ambient PM2.5 constituents' mixture with cognitive impairment in Chinese older adults, and to further identify the main contributor. METHODS: 15,274 adults ≥ 65 years old were recruited by the Chinese Longitudinal Healthy Longevity Study (CLHLS) and followed up through 7 waves during 2000-2018. Concentrations of ambient PM2.5 and its constituents (i.e., black carbon [BC], organic matter [OM], ammonium [NH4+], sulfate [SO42-], and nitrate [NO3-]) were estimated by satellite retrievals and machine learning models. Quantile-based g-computation model was employed to assess the joint effects of a mixture of 5 PM2.5 constituents and their relative contributions to cognitive impairment. Analyses stratified by age group, sex, residence (urban vs. rural), and region (north vs. south) were performed to identify vulnerable populations. RESULTS: During the average 3.03 follow-up visits (89,296.9 person-years), 4294 (28.1%) participants had developed cognitive impairment. The adjusted hazard ratio [HR] (95% confidence interval [CI]) for cognitive impairment for every quartile increase in mixture exposure to 5 PM2.5 constituents was 1.08 (1.05-1.11). BC held the largest index weight (0.69) in the positive direction in the qg-computation model, followed by OM (0.31). Subgroup analyses suggested stronger associations in younger old adults and rural residents. CONCLUSION: Long-term exposure to ambient PM2.5, particularly its constituents BC and OM, is associated with an elevated risk of cognitive impairment onset among Chinese older adults.

Efficient Dlx2-mediated astrocyte-to-neuron conversion and inhibition of neuroinflammation by NeuroD1.

In vivo astrocyte-to-neuron (AtN) conversion induced by overexpression of neural transcriptional factors has great potential for neural regeneration and repair. Here, we demonstrate that a single neural transcriptional factor, Dlx2, converts mouse striatal astrocytes into neurons in a dose-dependent manner. Lineage-tracing studies in Aldh1l1-CreERT2 mice confirm that Dlx2 can convert striatal astrocytes into DARPP32+ and Ctip2+ medium spiny neurons (MSNs). Time-course studies reveal a gradual conversion from astrocytes to neurons in 1 month, with a distinct intermediate state in between astrocytes and neurons. Interestingly, when Dlx2-infected astrocytes start to lose astrocytic markers, the other local astrocytes proliferate to maintain astrocytic levels in the converted areas. Unexpectedly, although Dlx2 efficiently reprograms astrocytes into neurons in the gray matter striatum, it also induces partial reprogramming of astrocytes in the white matter corpus callosum. Such partial reprogramming of white matter astrocytes is associated with neuroinflammation, which can be suppressed by the addition of NeuroD1. Our results highlight the importance of investigating AtN conversion in both the gray matter and white matter to thoroughly evaluate therapeutic potentials. This study also unveils the critical role of anti-inflammation by NeuroD1 during AtN conversion.

Prognostic Significance of Phenylalanine in Heart Failure: Clinical Insights and Inter-Organ Crosstalk Snapshot.

Background: Heart failure (HF) remains a leading cause of morbidity and mortality globally, necessitating the identification of reliable prognostic biomarkers to guide therapeutic interventions. Recent clinical observations have underscored phenylalanine (PHE) as a prognostic marker in HF, although the mechanisms involving inter-organ crosstalk remain understood. Methods: This study adopted a dull approach, with a retrospective analysis of 550 HF patients to establish the prognostic value of pre-discharge PHE levels and a study on the inter-organ crosstalk of PHE among 24 patients. We analyzed the correlations between PHE concentrations and clinical outcomes, alongside a comprehensive examination of PHE metabolism across the skeletal muscle, liver, heart, kidney, and lung. Results: In the clinical prognostic analysis of 550 patients hospitalized for acute decompensated HF, elevated PHE levels (≥65.6 µM) were significantly and independently associated with increased all-cause mortality during a median follow-up of 4.5 years (log rank = 36.7, p < 0.001), underscoring its value as a prognostic marker in HF. The inter-organic crosstalk study elucidated the mechanism associated with PHE elevation in patients with HF, characterized by an increase in PHE output in skeletal muscle and a decrease in hepatic and cardiac PHE uptakes. Notably, PHE concentration gradients across these organs were correlated with HF severity, such as the NYHA functional class, B-type natriuretic peptide levels, and the presence of acute HF. Conclusions: Our findings confirm the prognostic significance of PHE in patients with HF and unveil the complex metabolic interplay among key organs that contribute to PHE dysregulation. These insights not only reinforce the importance of metabolic monitoring in HF management but also open avenues for therapeutic targets.

Two-photon live imaging of direct glia-to-neuron conversion in the mouse cortex.

JOURNAL/nrgr/04.03/01300535-202408000-00032/figure1/v/2023-12-16T180322Z/r/image-tiff Over the past decade, a growing number of studies have reported transcription factor-based in situ reprogramming that can directly convert endogenous glial cells into functional neurons as an alternative approach for neuroregeneration in the adult mammalian central nervous system. However, many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry. In addition, concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tracing mice. In this study, we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ectopic expression of the neural transcription factor NeuroD1 in both proliferating reactive astrocytes and lineage-traced astrocytes in the mouse cortex. Time-lapse imaging over several weeks revealed the step-by-step transition from a typical astrocyte with numerous short, tapered branches to a typical neuron with a few long neurites and dynamic growth cones that actively explored the local environment. In addition, these lineage-converting cells were able to migrate radially or tangentially to relocate to suitable positions. Furthermore, two-photon Ca2+ imaging and patch-clamp recordings confirmed that the newly generated neurons exhibited synchronous calcium signals, repetitive action potentials, and spontaneous synaptic responses, suggesting that they had made functional synaptic connections within local neural circuits. In conclusion, we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuroregeneration and neural circuit reconstruction.

Feasibility of therapeutic Chinese massage (tui na) for peripheral neuropathy among people with human immunodeficiency virus: findings of a pilot randomized controlled trial.

Background: Peripheral neuropathy (PN) is prevalent in people with human immunodeficiency virus (PHIV) with no Food and Drug Administration-approved treatment. Therapeutic Chinese massage (TCM) is a promising noninvasive and non-harmful intervention for HIV-related PN. However, relevant research is lacking. The purpose of this study is to evaluate the feasibility of TCM for HIV-related PN. Method: We conducted a pilot, single-centered, two-arm, double-blinded, randomized controlled trial. Twenty eligible PHIV were recruited primarily from the AIDS Foundation Houston, Inc. in Texas and were randomly assigned into two groups. Ten participants in the intervention group received three weekly 25-min TCM sessions by a certified TCM therapist. The remaining ten control group participants received the same therapist's three weekly 25-min placebo massage sessions on their lower extremities. The outcome was the feasibility of this study as measured by recruitment and completion rates, participant safety, and treatment adherence and compliance, as well as the effect size of the intervention. Results: The study population comprised 20 PHIV (mean age 55.23). This study showed high feasibility as measured by a high rate of recruitment, a 100% rate of completion, and zero serious adverse events. As we inquired 21 respondents for eligibility for the study, all except one had HIV-related PN. All respondents were willing to participate in the study and adhered to the group assignment after they enrolled in the study. The participants' baseline pain was at a medium to a high level (6.30 [2.15] out of 10). Conclusion: Chinese massage is a feasible intervention in PHIV. Future relevant randomized controlled trials are expected. Clinical trial registration: https://clinicaltrials.gov/, NCT05379140.