The Effects of a Nonpharmacological Intervention Practice for Older Adults with Mild Cognitive Impairment and Their Family Caregivers in China.

Mild cognitive impairment (MCI) marks a critical phase in the progression to dementia. In our study, social workers utilized the Multicomponent Nonpharmacological Intervention Approach (MCNIA) to aid MCI participants (N = 52) and their caregivers, dividing into intervention and control groups. The intervention group underwent an additional regimen of non-pharmacological therapies besides pharmacological treatment. Our findings highlighted that: 1) MCNIA significantly enhanced cognitive and daily living abilities in the intervention group; 2) Caregivers experienced reduced burdens and improved social support; 3) Correlation analyses involving biomarkers indicated that MCNIA was particularly effective in alleviating depression in those with slightly more severe cognitive impairment.

Identification critical host factors for Japanese encephalitis virus replication via CRISPR screening of human sgRNA library.

Japanese encephalitis virus (JEV) is a pathogen with a substantial impact on both livestock and human health. However, the critical host factors in the virus life cycle remain poorly understood. Using a library comprising 123411 small guide RNAs (sgRNAs) targeting 19050 human genes, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based screen to identify essential genes for JEV replication. By employing knockout or knockdown techniques on genes, we identified eleven human genes crucial for JEV replication, such as prolactin releasing hormone receptor (PRLHR), activating signal cointegrator 1 complex subunit 3 (ASCC3), acyl-CoA synthetase long chain family member 3 (ACSL3), and others. Notably, we found that PRLHR knockdown blocked the autophagic flux, thereby inhibiting JEV infection. Taken together, these findings provide effective data for studying important host factors of JEV replication and scientific data for selecting antiviral drug targets.

SSK1-Loaded Neurotransmitter-Derived Nanoparticles for Alzheimer's Disease Therapy via Clearance of Senescent Cells.

Age is a significant contributor to the onset of AD. Senolysis has been recently demonstrated to ameliorate aging-associated diseases that showing a great potential in AD therapy. However, due to the presence of BBB, the anti-AD activity of senolytics are significantly diminished. SSK1 is a prodrug that can be activated by ß-gal, a lysosomal enzyme commonly upregulated in senescent cells, and thus selectively eliminates senescent cells. Furthermore, the level of ß-gal is significantly correlated with conventional AD genes from clinical sequencing data. SSK1-loaded neurotransmitter -derived lipid nanoparticles are herein developed (SSK1-NPs) that revealing good BBB penetration and bioavailability of in the body. At the brain lesion, SSK1-NP treatment significantly reduces the expression of genes associated with senescence, induced senescent cells elimination, decreased amyloid-beta accumulation, and eventually improve cognitive function of aged AD mice. SSK1-NPs, a novel nanomedicine displaying potent anti-AD activity and excellent safety profile, provides a promising strategy for AD therapy.

Exploring the Occurrence Mechanism and Early-Warning Model of Phlebitis Induced by Aescinate Based on Metabolomics in Cerebral Infarction Patients.

Objective: This study aims to explore the mechanism underlying the induction of phlebitis by aescinate and create an early-warning model of phlebitis based on metabolomics. Methods: Patients with cerebral infarction enrolled had been treated with aescinate. Plasma samples were collected either before administration of aescinate, upon the occurrence of phlebitis, or at the end of treatment. Non-targeted metabolomics and targeted amino acid metabolomics were carried out to analyze metabolic profiles and quantify the metabolites. Results: Untargeted metabolomics revealed six differential metabolites in baseline samples versus post-treatment samples and four differential metabolites in baseline samples from patients with or without phlebitis. Pathways of these differential metabolites were mainly enriched in amino acid metabolism. Ten differential amino acids with a VIP value of >1 were identified in the baseline samples, enabling us to distinguish between patients with or without phlebitis. A logistic regression model was constructed (AUC 0.825) for early warning of phlebitis of grade 2 or higher. Conclusion: The occurrence of aescinate-induced phlebitis, which can be predicted early during onset, may be associated with perturbations of the endogenous metabolic profile, especially the metabolism of amino acids.

Biomembrane-Derived Nanoparticles in Alzheimer's Disease Therapy: A Comprehensive Review of Synthetic Lipid Nanoparticles and Natural Cell-Derived Vesicles.

Current therapies for Alzheimer's disease used in the clinic predominantly focus on reducing symptoms with limited capability to control disease progression; thus, novel drugs are urgently needed. While nanoparticles (liposomes, high-density lipoprotein-based nanoparticles) constructed with synthetic biomembranes have shown great potential in AD therapy due to their excellent biocompatibility, multifunctionality and ability to penetrate the BBB, nanoparticles derived from natural biomembranes (extracellular vesicles, cell membrane-based nanoparticles) display inherent biocompatibility, stability, homing ability and ability to penetrate the BBB, which may present a safer and more effective treatment for AD. In this paper, we reviewed the synthetic and natural biomembrane-derived nanoparticles that are used in AD therapy. The challenges associated with the clinical translation of biomembrane-derived nanoparticles and future perspectives are also discussed.

Assessment of the Fruit Chemical Characteristics and Antioxidant Activity of Different Mulberry Cultivars (Morus spp.) in Semi-Arid, Sandy Regions of China.

As a traditional cash crop with ecological and nutritional values, mulberry is gradually expanding its consumption worldwide due to its great regional adaptability and superior health functions. The widespread interest in nutrients has led to a growing need to explore in depth the health benefits of mulberries. Many studies are actively being conducted to investigate the adaptability of the diversity of mulberries in different applications. This study systematically investigated the physicochemical properties and antioxidant activity of four mulberry genotypes cultivated in China's semi-arid sandy regions to better understand the composition and health-promoting potential of this super crop. Chemical composition identification was identified via HPLC and antioxidant activity was further determined via DPPH and FRAP. The moisture, crude protein, ash, soluble solids, phenolics, anthocyanins, and flavonoids contents of mulberry were comparatively analyzed. The study revealed that the four mulberry genotypes showed significant differences in quality and content of the analyzed characteristics. The greatest antioxidant activity was found in Shensang 1, which had the most soluble solids (17%) and the highest amounts of free sugar (fructose: 5.14% and glucose: 5.46%). Ji'an had the most minerals (K: 2.35 mg/g, Ca: 2.27 mg/g, and Fe: 467.32 mg/kg) and it also contained chlorogenic acid, which has the potential to be turned into a natural hypoglycemic agent. PCA and Pearson correlation analysis indicated that the antioxidant activity was closely related to the chemical contents of total phenols, flavonoids, anthocyanins, and soluble sugars. If the antioxidant activity and nutrient content of the developed plants are considered, Shen Sang 1 is the most favorable variety. This finding can be used to support the widespread cultivation of mulberries to prevent desertification as well as to promote the development of the mulberry industry.

Cell primitive-based biomimetic nanomaterials for Alzheimer's disease targeting and therapy.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is not just confined to the older population. Although developments have been made in AD treatment, various limitations remain to be addressed. These are partly contributed by biological hurdles, such as the blood-brain barrier and peripheral side effects, as well as by lack of carriers that can efficiently deliver the therapeutics to the brain while preserving their therapeutic efficacy. The increasing AD prevalence and the unavailability of effective treatments have encouraged researchers to develop improved, convenient, and affordable therapies. Functional materials based on primitive cells and nanotechnology are emerging as attractive therapeutics in AD treatment. Cell primitives possess distinct biological functions, including long-term circulation, lesion site targeting, and immune suppression. This review summarizes the challenges in the delivery of AD drugs and recent advances in cell primitive-based materials for AD treatment. Various cell primitives, such as cells, extracellular vesicles, and cell membranes, are presented together with their distinctive biological functions and construction strategies. Moreover, future research directions are discussed on the basis of foreseeable challenges and perspectives.

Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease.

With the increase of population aging, the number of Alzheimer's disease (AD) patients is also increasing. According to current estimates, approximately 11% of people over 65 suffer from AD, and that percentage rises to 42% among people over 85. However, no effective treatment capable of decelerating or stopping AD progression is available. Furthermore, AD-targeted drugs composed of synthetic molecules pose concerns regarding biodegradation, clearance, immune response, and neurotoxicity. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are essential intercellular communication mediators holding great promise as AD therapeutics owing to their biocompatibility, versatility, effortless storage, superior safety, and the ability to transport messenger and noncoding RNAs, proteins, lipids, DNAs, and other bioactive compounds derived from cells. The functionalisation and engineering strategies of MSC-EVs are highlighted (e.g. preconditioning, drug loading, surface modification, and artificial EV fabrication), which could improve AD treatment by multiple therapeutic effects, including clearing abnormal protein accumulation and achieving neuroprotection and immunomodulatory effects. Herein, this review summarises state-of-the-art strategies to engineer MSC-EVs, discusses progress in their use as AD therapeutics, presents the perspectives and challenges associated with the related clinical applications, and concludes that engineered MSC-EVs show immense potential in AD therapy.

Characteristics of Soil Physicochemical Properties and Microbial Community of Mulberry (Morus alba L.) and Alfalfa (Medicago sativa L.) Intercropping System in Northwest Liaoning.

Medicinal plant intercropping is a new intercropping method. However, as a new intercropping model, the influence of intercropping of alfalfa on microorganisms has not been clarified clearly. In this study, the composition and diversity of microbial communities in alfalfa intercropping were studied, and the differences of bacterial and fungal communities and their relationships with environmental factors are discussed. Intercropping significantly decreased soil pH and significantly increased soil total phosphorus (TP) content, but did not increase soil total carbon (TC) and total nitrogen (TN). Intercropping can increase the relative abundance of Actinobacteria and reduce the relative abundance of Proteobacteria in soil. The relative abundance and diversity of bacteria were significantly correlated with soil pH and TP, while the diversity of fungi was mainly correlated with TC, TN and soil ecological stoichiometry. The bacterial phylum was mainly related to pH and TP, while the fungal phylum was related to TC, TN, C: P and N: P. The present study revealed the stoichiometry of soil CNP and microbial community characteristics of mulberry-alfalfa intercropping soil, clarified the relationship between soil stoichiometry and microbial community composition and diversity, and provided a theoretical basis for the systematic management of mulberry-alfalfa intercropping in northwest Liaoning.

Sleep Parameters and Plasma Biomarkers for Cognitive Impairment Evaluation in Patients With Cerebral Small Vessel Disease.

OBJECTIVES: Cognitive impairment caused by cerebrovascular disease accounts for more than half of vascular dementia. However, neuropsychological tests are limited by their subjectivity. Additional effective approaches to evaluate cognitive impairment in patients with cerebrovascular disease are necessary. METHOD: One hundred and thirty-two patients with cerebrovascular disease were recruited. One hundred participants met the criteria and completed neuropsychological scales. Sixty-nine participants proceeded with polysomnography, and 63 of them had their peripheral blood biomarkers measured. According to Mini-Mental State Examination scores, patients were divided into cognitively impaired and cognitively normal groups. The differences in biomarkers and sleep parameters between the groups were compared, and decision tree models were constructed to evaluate the evaluation ability of these indicators on cognitive decline. RESULTS: The integrated decision tree model of sleep parameters yielded an area under curve (AUC) of 0.952 (95% confidence interval [CI]: 0.911-0.993), while that of plasma biomarkers yielded an AUC of 0.872 (95% CI: 0.810-0.935) in the assessment of cognition status. Then the participants were automatically clustered into mild and severe cognitive impairment groups by multiple neuropsychological test results. The integrated plasma biomarker model showed an AUC of 0.928 (95% CI: 0.88-0.977), and the integrated sleep parameter model showed an AUC of 0.851 (95% CI: 0.783-0.919) in the assessment of mild/severe cognitive impairment. DISCUSSION: Integrated models which consist of sleep parameters and plasma biomarkers can accurately evaluate dementia status and cognitive impairment in patients with cerebral small vessel disease. This innovative study may facilitate drug development, early screening, clinical diagnosis, and prognosis evaluation of the disease.

Involvement of microRNA/cystine/glutamate transporter in cold-stressed gastric mucosa injury.

Stress ulcers are complicated by severe trauma and other critical diseases, the mechanism of which remains unclear. An increasing number of studies have shown that microRNAs (miRNAs) are important regulators of stress responses such as hypoxia, abnormal temperature, and inflammation. The evidence indicates that miRNAs are also involved in regulating stress-induced ulcers. Recently, we demonstrated that gastric mucosal injury induced by aspirin is related to the reduction of glutamate levels by inhibition of cystine/glutamate transporter (xCT) activity. In the present study, the effect of a miRNA/xCT on gastric mucosal injury induced by cold stimulation was investigated. We found that cold stimulation induced gastric mucosa injury with a reduction in glutamate levels and xCT activity and upregulation of miR-143, miR-152, and miR-181 expression. Exogenous glutamate significantly alleviated gastric mucosa injury by cold stimulation. In vitro experiments demonstrated that treatment with miR-143, miR-152, or miR-181 mimics directly induced cell damage. The effects of these mimics were alleviated by exogenous glutamate. The present study suggests that miR-143, miR-152, and miR-181 are involved in cold stimulation-induced acute gastric mucosal injury. Furthermore, the regulatory effect of miRNAs on gastric mucosa injury induced by cold stimulation is related to a decrease in glutamate release by reduction of cystine/glutamate transporter activity.

Nanoparticles-based anti-aging treatment of Alzheimer's disease.

Age is the strongest risk factor for Alzheimer's disease (AD). In recent years, the relationship between aging and AD has been widely studied, with anti-aging therapeutics as the treatment for AD being one of the mainstream research directions. Therapeutics targeting senescent cells have shown improvement in AD symptoms and cerebral pathological changes, suggesting that anti-aging strategies may be a promising alternative for AD treatment. Nanoparticles represent an excellent approach for efficiently crossing the blood-brain barrier (BBB) to achieve better curative function and fewer side effects. Thereby, nanoparticles-based anti-aging treatment may exert potent anti-AD therapeutic efficacy. This review discusses the relationship between aging and AD and the application and prospect of anti-aging strategies and nanoparticle-based therapeutics in treating AD.

Gold nanoparticle-directed autophagy intervention for antitumor immunotherapy via inhibiting tumor-associated macrophage M2 polarization.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

Effects of Mixed Decomposition of Pinus sylvestris var. mongolica and Morus alba Litter on Microbial Diversity.

Pinus sylvestris var. mongolica is widely planted in China as a windbreak and sand fixation tree. To improve the current situation of large-scale declines of forested areas planted as P. sylvestris var. mongolica monocultures, we investigated the biological and microbial effects of stand establishment using mixed tree species. The interactions during the mixed decomposition of the litter and leaves of different tree species are an important indicator in determining the relationships among species. In this experiment, a method of simulating the mixed decomposition of P. sylvestris var. mongolica and Morus alba litter under P. sylvestris var. mongolica forest was used to determine the total C, total N, and total P contents in the leaf litter, and the microbial structures were determined by using Illumina MiSeq high-throughput sequencing. It was found that with samples with different proportions of P. sylvestris var. mongolica and M. alba litters, the decomposition rate of P. sylvestris var. mongolica × M. alba litter was significantly higher than that of the pure P. sylvestris var. mongolica forest, and the microbial community and composition diversity of litter in a pure P. sylvestris var. mongolica forest could be significantly improved. The possibility of using M. alba as a mixed tree species to address the declines of pure P. sylvestris var. mongolica forest was verified to provide guidance for pure P. sylvestris var. mongolica forests by introducing tree species with coordinated interspecific relationships and creating a mixed forest.

Linking tree water use efficiency with calcium and precipitation.

Water use efficiency (WUE) is a key physiological trait in studying plant carbon and water relations. However, the determinants of WUE across a large geographical scale are not always clear, limiting our capacity to predict WUE in response to future global climate change. We propose that tree WUE is influenced by calcium (Ca) availability and precipitation. In addition, although it is well-known that transpiration is the major driving force for passive nutrient uptake, the linkage between these two processes has not been well-established. Because Ca uptake is an apoplastic and passive process that purely relies on transpiration, and there is no translocation once assimilated, we further developed a theoretical model to quantify the relationship between tree Ca accumulation and WUE using soil-to-plant calcium ratio (SCa/BCa) and tree WUE derived from δ13C. We tested our theoretical model and predicted relationships using three common tree species across their native habitats in Northern China, spanning 2300 km and a controlled greenhouse experiment with soil Ca concentrations manipulated. We found that tree WUE was negatively related to precipitation of the growing season (GSP) and positively with soil Ca. A multiple regression model and a path analysis suggested a higher contribution of soil Ca to WUE than GSP. As predicted by our theoretical model, we found a positive relationship between WUE and SCa/BCa across their distribution ranges in all three tree species and in the controlled experiment for one selected species. This relationship suggests a tight coupling between water and Ca uptake and the potential use of SCa/BCa to indicate WUE. A negative relationship between SCa/BCa and GSP also suggests a possible decrease in tree Ca accumulation efficiency in a drier future in Northern China.

Caregiver burden and its associated factors among family caregivers of persons with dementia in Shanghai, China: a cross-sectional study.

OBJECTIVE: To assess the level of caregiver burden and factors associated with it among family caregivers of persons with dementia (PWD) living in communities of Shanghai, China. DESIGN: Cross-sectional study. SETTING: Communities in Hongkou District of Shanghai, China. PARTICIPANTS: A random sample of 109 older adults with dementia and their primary family caregivers. MAIN OUTCOME MEASURE: Caregiver burden measured by the Caregiver Burden Inventory (CBI), and the Caregivers' depressive symptom measured by the simplified Chinese version of Self-rating Depression Scale was the outcome variable of the study. The independent variables, including the cognitive function (measured by Montreal Cognitive Assessment (MoCA), sleep quality assessed by the Pittsburgh Sleep Quality Index, abilities of daily life assessed by the Activities of Daily Living Scale, and behavioural and psychological symptoms assessed by the Neuropsychiatric Inventory of PWDs, the community service utilisation (measured by the Community Service Utilisation Measurement), perceived social support (assessed by three questions), positive aspects of caregiving (PAC) (assessed by the PAC) of dementia caregivers, were analysed. Multivariate linear regression was employed to determine the factors related to caregiver burden. RESULTS: The average level of CBI was 65.92±16.74. The score of MoCA, PAC and perceived social support of caregivers were negatively associated with caregiver burden (ß=-0.84, p<0.001, ß=-3.61, p=0.03 and ß=-1.22, p=0.001, respectively). Community service utilisation was positively associated (ß=3.46, p<0.001) with caregiver burden. Perceived social support by the caregiver moderated the relationship between caregiver burden and caregivers' depression symptoms. CONCLUSION: Dementia caregivers experienced a high level of caregiver burden. The cognitive function of PWD, PAC, social support and community service utilisation were factors associated with caregiver burden. Strengthening social support, providing more high-quality home care services, promoting PAC are imperative to reduce caregiver burden.

Effect of strip clear-cutting on the natural regeneration of Pinus tabuliformis plantations in northeastern China.

In this study, the effect of strip clear-cutting on the natural regeneration performance of mature Pinus tabuliformis plantations in the three locations in western part of the Liaoning Province was analyzed. Strip clear-cutting, with clear-cut and uncut strip widths of 15, 20, 25 m, and 10 and 18 m, respectively, was conducted in spring 2014, and control, in each study location. Field investigations were conducted in 2017. Fifteen sample plots with sizes of 4 m2 (2 m × 2 m) were established in each clear-cut strip, uncut strip, and control. One to four saplings were randomly selected to measure the current year increment, and the lengths and numbers for branch of the first whorl. Three saplings were randomly selected from the center of the strip to measure the photosynthetic rate. Three sample plots with sizes of 4 m2 (2 m × 2 m) and 1 m2 (1 m × 1 m) were developed in each strip and control to determine the biodiversity of shrubs and herbs as well as the water content of the decomposition and semi-decomposition layer. The results show that the current year increment and branch length of the first whorl can be ordered as follows: clear-cut strips > control > uncut strips. Number of the branches of the first whorl can be ordered as follows: clear-cut strips > uncut strips > control. Strip clear-cutting was a statistically significant treatment for the current year increment and length and number of branches of the first whorl. The saplings from the clear-cut strip with a width of 25 m have the largest photosynthetic capacity compared with those from the other strips and control. The transpiration rates of the large, medium, and small saplings from clear-cut strips are the largest and those of saplings from the control are the smallest. The water content of the decomposition and semi-decomposition layer in the control is the highest, but no significant difference was confirmed between the strip clear-cutting approaches.