Care stressors and perceived stress among family caregivers of Chinese older adults with disabilities: The mediation effect of resilience.

OBJECTIVES: Guided by the Stress Process Model, this study examined the mediating effect of resilience on the relationship between care stressors and perceived caregiving stress. METHODS: Data were based on 234 older adults with disabilities and their caregivers from 6 urban districts and 6 rural counties from Jinan, China. Descriptive analysis, analysis of variance, ordinary least squares regression, and mediation analysis were performed. RESULTS: Perceived stress among family caregivers of Chinese older adults with disabilities was affected by the physical and mental health of both themselves and the care recipients, as well as care intensity and financial difficulties. Resilience played a partial mediating role in the associations among three stressors (i.e. older adults' disability levels, number of chronic diseases, and caregivers' self-reported mental) and perceived caregiving stress. CONCLUSIONS: Enhanced resilience aids caregivers' adaptation to their roles, suggesting the need for societal, spiritual, emotional, and behavioral resilience training.

Improving the Thermostability of Thermomyces lanuginosus Lipase by Restricting the Flexibility of N-Terminus and C-Terminus Simultaneously via the 25-Loop Substitutions.

(1) Lipases are catalysts widely applied in industrial fields. To sustain the harsh treatments in industries, optimizing lipase activities and thermal stability is necessary to reduce production loss. (2) The thermostability of Thermomyces lanuginosus lipase (TLL) was evaluated via B-factor analysis and consensus-sequence substitutions. Five single-point variants (K24S, D27N, D27R, P29S, and A30P) with improved thermostability were constructed via site-directed mutagenesis. (3) The optimal reaction temperatures of all the five variants displayed 5 °C improvement compared with TLL. Four variants, except D27N, showed enhanced residual activities at 80 °C. The melting temperatures of three variants (D27R, P29S, and A30P) were significantly increased. The molecular dynamics simulations indicated that the 25-loop (residues 24-30) in the N-terminus of the five variants generated more hydrogen bonds with surrounding amino acids; hydrogen bond pair D254-I255 preserved in the C-terminus of the variants also contributes to the improved thermostability. Furthermore, the newly formed salt-bridge interaction (R27…E56) in D27R was identified as a crucial determinant for thermostability. (4) Our study discovered that substituting residues from the 25-loop will enhance the stability of the N-terminus and C-terminus simultaneously, restrict the most flexible regions of TLL, and result in improved thermostability.

Electroencephalography microstates as novel functional biomarkers for insomnia disorder.

Background: Insomnia disorder (ID) is one of the most common mental disorders. Research on ID focuses on exploring its mechanism of disease, novel treatments and treatment outcome prediction. An emerging technique in this field is the use of electroencephalography (EEG) microstates, which offer a new method of EEG feature extraction that incorporates information from both temporal and spatial dimensions. Aims: To explore the electrophysiological mechanisms of repetitive transcranial magnetic stimulation (rTMS) for ID treatment and use baseline microstate metrics for the prediction of its efficacy. Methods: This study included 60 patients with ID and 40 age-matched and gender-matched good sleep controls (GSC). Their resting-state EEG microstates were analysed, and the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) were collected to assess sleep quality. The 60 patients with ID were equally divided into active and sham groups to receive rTMS for 20 days to test whether rTMS had a moderating effect on abnormal microstates in patients with ID. Furthermore, in an independent group of 90 patients with ID who received rTMS treatment, patients were divided into optimal and suboptimal groups based on their median PSQI reduction rate. Baseline EEG microstates were used to build a machine-learning predictive model for the effects of rTMS treatment. Results: The class D microstate was less frequent and contribute in patients with ID, and these abnormalities were associated with sleep onset latency as measured by PSG. Additionally, the abnormalities were partially reversed to the levels observed in the GSC group following rTMS treatment. The baseline microstate characteristics could predict the therapeutic effect of ID after 20 days of rTMS, with an accuracy of 80.13%. Conclusions: Our study highlights the value of EEG microstates as functional biomarkers of ID and provides a new perspective for studying the neurophysiological mechanisms of ID. In addition, we predicted the therapeutic effect of rTMS on ID based on the baseline microstates of patients with ID. This finding carries great practical significance for the selection of therapeutic options for patients with ID.

Effects on resting-state EEG phase-amplitude coupling in insomnia disorder patients following 1 Hz left dorsolateral prefrontal cortex rTMS.

Despite burgeoning evidence for cortical hyperarousal in insomnia disorder, the existing results on electroencephalography spectral features are highly heterogeneous. Phase-amplitude coupling, which refers to the modulation of the low-frequency phase to a high-frequency amplitude, is probably a more sensitive quantitative measure for characterizing abnormal neural oscillations and explaining the therapeutic effect of repetitive transcranial magnetic stimulation in the treatment of patients with insomnia disorder. Sixty insomnia disorder patients were randomly divided into the active and sham treatment groups to receive 4 weeks of repetitive transcranial magnetic stimulation treatment. Behavioral assessments, resting-state electroencephalography recordings, and sleep polysomnography recordings were performed before and after repetitive transcranial magnetic stimulation treatment. Forty good sleeper controls underwent the same assessment. We demonstrated that phase-amplitude coupling values in the frontal and temporal lobes were weaker in Insomnia disorder patients than in those with good sleeper controls at baseline and that phase-amplitude coupling values near the intervention area were significantly enhanced after active repetitive transcranial magnetic stimulation treatment. Furthermore, the enhancement of phase-amplitude coupling values was significantly correlated with the improvement of sleep quality. This study revealed the potential of phase-amplitude coupling in assessing the severity of insomnia disorder and the efficacy of repetitive transcranial magnetic stimulation treatment, providing new insights on the abnormal physiological mechanisms and future treatments for insomnia disorder.

The potential of electroencephalography coherence to predict the outcome of repetitive transcranial magnetic stimulation in insomnia disorder.

BACKGROUND: It is unknown whether repetitive Transcranial Magnetic Stimulation (rTMS) could improve sleep quality by modulating electroencephalography (EEG) connectivity of insomnia disorder (ID) patients. Great heterogeneity had been found in the clinical outcomes of rTMS for ID. The study aimed to investigate the potential mechanisms of rTMS therapy for ID and develop models to predict clinical outcomes. METHODS: In Study 1, 50 ID patients were randomly divided into active and sham groups, and subjected to 20 sessions of treatment with 1 Hz rTMS over the left dorsolateral prefrontal cortex. EEG during awake, Polysomnography, and clinical assessment were collected and analyzed before and after rTMS. In Study 2, 120 ID patients were subjected to active rTMS stimulation and were then separated into optimal and sub-optimal groups due to the median of Pittsburgh Sleep Quality Index reduction rate. Machine learning models were developed based on baseline EEG coherence to predict rTMS treatment effects. RESULTS: In Study 1, decreased EEG coherence in theta and alpha bands were observed after rTMS treatment, and changes in theta band (F7-O1) coherence were correlated with changes in sleep efficiency. In Study 2, baseline EEG coherence in theta, alpha, and beta bands showed the potential to predict the treatment effects of rTMS for ID. CONCLUSION: rTMS improved sleep quality of ID patients by modulating the abnormal EEG coherence. Baseline EEG coherence between certain channels in theta, alpha, and beta bands could act as potential biomarkers to predict the therapeutic effects.

Synthesis, biological evaluation and preliminary mechanisms of 6-amino substituted harmine derivatives as potential antitumor agents.

To explore the effect of the introduction of the amino and substituted amino groups on the antitumor activity of harmine, twenty-five novel 6-amino substituted harmine derivatives (3a-3j and 5a-5o) were synthesized and evaluated for anti-proliferative activity on a panel of cancer cell lines. Compounds 3i and 5n exhibited the most potent antiproliferative activity with IC50 values lower than 2.2 µM. Especially, compound 5n possessed extremely potent antitumor activity with IC50 values of 0.34 µM and 0.65 µM against HL-60 and A549 cell lines, respectively. Further, the preliminary studies of mechanisms showed that compound 5n could significantly induce cell apoptosis in a dose-dependent manner, cause cell cycle arrest at the G2/M phase and intercalate into ct-DNA via the competition with EB, while displaying very weak topoisomerase I (Topo I) inhibition activity. More importantly, 5n showed mild cytotoxicity against human normal lung epithelial cells BEAS-2B. Based on these considerations, 5n may be a good antitumor candidate compound for further exploration.

Caregiving stress among family caregivers of older adults living with disabilities in China.

OBJECTIVES: This study aimed to describe caregiving stress among family caregivers of Chinese older adults living with disabilities, and explore how care intensity, financial expenses, and care difficulties are associated with caregiving stress. METHODS: Data of 220 older adult-caregiver dyads were collected from 6 urban districts and 6 rural counties from Shandong province, China. Descriptive analyses and multivariate ordinal logistic regression analyses were performed. RESULTS: Family caregivers providing nine or more hours of care per day reported higher caregiving stress than those who provided fewer than nine hours. Caregivers who experienced insufficient care abilities, economic hardships, or time conflicts were more likely to report caregiving stress. Financial support provided to older adults was not associated with caregiving stress. CONCLUSIONS: Family caregivers of Chinese older adults with disabilities are experiencing excessive caregiving stress. Social support groups and China's long-term care insurance system should be promoted to better assist family caregivers.