Search

Sleep deprivation and insulin resistance (IR) are two risk factors for Alzheimer's disease. As the population of people with IR increases and sleep restriction (SR) due to staying up late becomes the "new normal", it is necessary to investigate the effects and molecular pathogenesis of chronic SR on cognitive function in insulin resistance. In this study, 4-week-old mice were fed a high-fat diet (HFD) for 8 weeks to establish IR model, and then the mice were subjected to SR for 21 days, and related indicators were assessed, including cognitive capacity, apoptosis, oxidative stress, glial cell activation, inflammation, blood-brain barrier (BBB) permeability and adiponectin levels, for exploring the potential regulatory mechanisms. Compared with control group, IR mice showed impaired cognitive capacity, meanwhile, SR not only promoted Bax/Bcl2-induced hippocampal neuronal cell apoptosis and Nrf2/HO1- induced oxidative stress, but also increased microglia activation and inflammatory factor levels and BBB permeability, thus aggravating the cognitive impairment in IR mice. Consequently, changing bad living habits and ensuring sufficient sleep are important intervention strategies to moderate the aggravation of IR-induced cognitive impairment. [Display omitted] • Sleep restriction (SR) induces neuronal apoptosis, oxidative stress and inflammation leading to cognitive impairment. • SR increased blood-brain barrier permeability while decreasing adiponectin levels. • SR caused further exacerbation of the above changes in insulin-resistant mice. • Poor lifestyle (SR) exacerbates neurologic complications associated with insulin resistance. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a synthetic drug with severe neurotoxicity, however, the regulation of METH‐induced neuronal programmed necrosis remains poorly understood. The aim of this study was to identify the molecular mechanisms of METH‐induced neuronal programmed necrosis. We found that neuronal programmed necrosis occurred in the striatum of brain samples from human and mice that were exposed to METH. The receptor‐interacting protein kinase 3 (RIP3) was highly expressed in the neurons of human and mice exposed to METH, and RIP3‐silenced or RIP1‐inhibited protected neurons developed neuronal programmed necrosis in vitro and in vivo following METH exposure. Moreover, the RIP1‐RIP3 complex causes cell programmed necrosis by regulating mixed lineage kinase domain‐like protein (MLKL)‐mediated cell membrane rupture and dynamin‐related protein 1 (Drp1)‐mediated mitochondrial fission. Together, these data indicate that RIP3 plays an indispensable role in the mechanism of METH‐induced neuronal programmed necrosis, which may represent a potential therapeutic target for METH‐induced neurotoxicity. [ABSTRACT FROM AUTHOR]

A vast majority of patients with NSCLC (non-small cell lung cancer) have lung adenocarcinoma (LA), and the survival rate of LA varies from 5% to 75% depending on the severity of this adenocarcinoma. PYCR1 (abnormal pyrroline-5-carboxylate reductase 1) gene and miR-328–3p have been found to be associated with cancer development. However, the underlying mechanism of interaction between miR-328–3p and PYCR1 in LA needs further investigation. The expressions of miR-328–3p and PYCR1 in samples with LA were identified by RT-qPCR. Next, we investigated the targeting relationship between these two biological factors using luciferase assay. CCK-8, BrdU, transwell-migration, and flow cytometry assays were performed to detect cell viability, cell proliferation, cell migration and cell apoptosis in LA cells. We noticed that miR-328–3p expression was downregulated in LA samples. MiR-328–3p mimic restricted cell proliferation and cell migration, while it enhanced cell apoptosis. Furthermore, the overexpression of PYCR1 promoted the proliferation and migration of LA cells, but it repressed cell apoptosis. Moreover, PYCR1 directly interacted with miR-328–3p in the LA cells, and miR-328–3p restrained the expression of PYCR1, thus suppressing LA tumorigenesis. In summary, our study revealed that miR-328–3p targeting to PYCR1 suppressed the malignancy of LA cells by impeding cell proliferation and migration, while effectively promoting cell apoptosis. • PYCR1 and miR-328–3p were selected to be the study objects. • MiR-328–3p inhibited the malignancy of LA cells. • MiR-328–3p targeting PYCR1 inhibited the expression of PYCR1. • MiR-328–3p targeting PYCR1 repressed the progression of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Developing polyamide (PA) reverse osmosis (RO) membrane with chlorine resistance is of great significance for simplifying pretreatment processes and saving operating costs. Herein, we constructed an active layer capable of highly chlorine stability and regenerative chlorine resistance by introducing p-amino diphenylamine (p-ADA) with redox activity via a facile secondary interfacial reaction (s-IR) on PA membrane surface. The calculation of resistance-in-series model indicated that the introduction of p-ADA facilitated the increase of NaCl transmembrane resistance without sacrificing membrane permeance. Chlorination experiments under acid conditions proved the protection effect of p-ADA grafted layer due to its oxidation resistance, avoiding the direct attack by free chlorine to amide bonds of polyamide membrane. By virtue of the convertible modality of the p-ADA molecule between the quinone and benzene structures during redox process, modified membranes presented the capability of regenerative chlorine resistance. After the "chlorination-reduction" cycle experiments, the normalized flux of modified membranes remained 0.522 while contrasted PA membranes showed a flux of 0.278; and the corresponding normalized NaCl rejection of modified membranes maintained at 0.998 significantly higher than that of PA membranes (0.963). This study presents a straightforward and efficient approach to enhance the chlorine resistance of PA RO membranes. [Display omitted] • p-ADA was adopted to modify the PA RO membrane by a secondary interfacial reaction. • The grafted p-ADA could cover and heal the defects of the PA membrane. • The modified membranes showed improved chlorine resistance with a higher salt rejection. • The redox feature of p-ADA molecules endowed the modified membranes with regenerative chlorine resistance. [ABSTRACT FROM AUTHOR]

With the world pandemic of methamphetamine (METH), METH-associated cardiomyopathy (MAC) has become a widespread epidemic and is also recognized as a cause of heart failure in young people. The mechanism of occurrence and development of MAC is not clear. In this study, firstly, the animal model was evaluated by echocardiography and myocardial pathological staining. The results revealed that the animal model exhibited cardiac injury consistent with clinical alterations of MAC, and the mice developed cardiac hypertrophy and fibrosis remodeling, which led to systolic dysfunction and left ventricular ejection fraction (%LVEF) < 40%. The expression of cellular senescence marker proteins (p16 and p21) and senescence-associated secretory phenotype (SASP) was significantly increased in mouse myocardial tissue. Secondly, mRNA sequencing analysis of cardiac tissues revealed the key molecule GATA4, and Western blot, qPCR and immunofluorescence results showed that the expression level of GATA4 was significantly increased after METH exposure. Finally, knockdown of GATA4 expression in H9C2 cells in vitro significantly attenuated METH-induced cardiomyocyte senescence. Consequently, METH causes cardiomyopathy through cellular senescence mediated by the GATA4/NF-κB/SASP axis, which is a feasible target for the treatment of MAC. • Long-term administration of METH in mice induced a decrease in cardiac systolic function. • METH consumption leads to elevated expression of senescence markers in cardiac myocytes. • Consumption of METH induced significant transcriptome changes in mouse models. • Bioinformatics analysis and experimental results revealed that GATA4 is the key molecule. • GATA4/NF-κB/SASP axis-mediated cellular senescence plays an important role in METH-induced cardiomyocyte injury. [ABSTRACT FROM AUTHOR]

Objective: There are several meta-analyses of randomized controlled trials (RCTs) demonstrating the benefits of virtual reality (VR) training as an intervention for motor performance, activity of daily living (ADL) and quality of life (QoL) outcomes in patients with Parkinson's disease (PD). However, the aggregate evidence collected to date has not been thoroughly evaluated for strength, quality, and reproducibility. An umbrella review from published meta-analyses of RCTs was conducted to evaluate the strength and quality of existing evidence regarding the efficacy of VR training in improving the motor performance, ADL and QoL outcomes of patients with PD. Methods: PubMed, PsychInfo, Web of Science, and Scopus were searched to identify relevant meta-analysis of RCTs examining the effects of VR training on motor performance and quality of life outcomes in PD patients. We recalculated the effect sizes (Hedges'g) for VR training using DerSimonian and Laird (DL) random effects models. We further assessed between-study heterogeneity, prediction interval (PI), publication bias, small-size studies, and whether the results of the observed positive studies were better than would be expected by chance. Based on these calculations, the quality of evidence for each outcome was assessed by using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Results: Four meta-analysis with eight outcomes included in the umbrella review was recalculated effect size. Pooled results found VR training can large improve the basic balance ability, moderate improve the overall balance capacity and moderate improve the stride length in PD patients. For ADL and QoL, the effect sizes were pooled that suggested VR training can moderate improve ADL and QoL for PD patients. However, no statistically clear evidence was found in walking speed, motor function and gait function during VR training. The analyzed meta-analyses showed low-to-moderate methodological quality (AMSTAR2) as well as presented evidence of moderate-to-very low quality (GRADE). Tow adverse reactions were reported in the included meta-analyses. Conclusions: In this umbrella review, a beneficial correlation between VR and balance ability, stride length, ADL and QoL in PD patients was discovered, especially for the very positive effect of VR on balance because of two of the eight outcomes related to balance ability showed large effect size. The observations were accompanied by moderate- to very low-quality rating evidence, supporting VR training as a practical approach to rehabilitation. [ABSTRACT FROM AUTHOR]

In the original article, Zaiqiang Zhang was affiliated to Department of Neurology, Beijing Hospital, National Center of Gerontology, Beijing, China. The corrected affiliation should be: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [ABSTRACT FROM AUTHOR]

Vascular dementia (VD) is the second most common cause of dementia after Alzheimer's disease. Neuroinflammation contributes to pathogenesis of VD. Neurotropin (NTP) is an analgesic that has been shown to suppress inflammation and neural repair. But its effects on VD are still unclear. Therefore, this study aimed to investigate the therapeutic effects and potential mechanisms of NTP in the VD model mice established by bilateral common carotid artery stenosis method. In VD mice, we found that NTP treatment increased cerebral blood flow by Laser speckle imaging, reduced neuron loss by Nissl, HE and immunochemistry staining, attenuated white matter damage by magnetic resonance imaging and ultrastructural damage by transmission electron microscope, improved cognitive functions by new object recognition test and three-chamber test, Y maze test and Morris water maze test, inhibited significantly glial activation by immunofluorescence methods, reduced the expression of TLR4, down-regulated expression of MyD88 and phosphorylation of NF-κB P65, decreased the levels of pro-inflammatory cytokines IL-1β, IL-6 and TNFα. Further, we showed that administration of a TLR4 inhibitor TAK242 had a similar effect to NTP, while the TLR4 agonist CRX-527 attenuated the effect of NTP in the VD mice. Collectively, our study suggested that NTP alleviates cognitive impairment by inhibiting TLR4/MyD88/NF-κB inflammation signaling pathway in the VD mice. Thus, NTP may be a promising therapeutic approach and a potential TLR4 inhibitor for VD. [Display omitted] • VD mice showed neuronal loss and glial activation. • NTP ameliorated cognitive impairment in VD mice, decreased white matter degeneration and reduced levels of pro-inflammatory cytokines. • TAK242 had a similar effect to NTP, while CRX-527 attenuated the effects of NTP in VD mice. [ABSTRACT FROM AUTHOR]

Diversified ion-selective separation applications have dramatically incentivized the exploitation and performance modulation of highly ion-selective nanofiltration (NF) membranes. However, the ion selectivity of NF membranes is synergistically governed by multi-scale factors of membrane structural parameters and operational parameters, with the intrinsic ion-selective mechanism still ambiguous. Herein, we proposed an ensemble machine learning (ML) method to decouple key factors affecting the ionic selectivity of polyamide NF membranes. Membrane structural parameters and operational parameters were typically extracted as input variables and linked to mono−/divalent ion selectivity by model training based on Random Forest and XGBoost algorithms. The feature importance assessment indicated the critical role of membrane structure parameters on ion selectivity, wherein pore radius dominated the mono−/divalent anionic selectivity while zeta potential for mono−/divalent cationic selectivity. Partial dependence analyses further depicted intensive insights regarding the influence of membrane structural parameters on ion selectivity. Moreover, stochastic dataset splitting measurements demonstrated the accurate predictive capability of the model simultaneously possessing excellent stability and reliability. We anticipated that the implementation of ensemble ML in explicating the intricate ion-selective mechanism created platforms for understanding the structure-membrane performance correlation and orientally manufacturing highly ion-selective NF membranes. [Display omitted] • Ensemble machine learning was implemented to decouple the key features affecting ion selectivities of polyamide membranes. • RF and XGBoost algorithms were adopted to learn from relevant variables and evaluate permutation features importance. • Mono-/divalent anionic selectivity was dominated by pore size while zeta potential for mono-/divalent cationic selectivity. [ABSTRACT FROM AUTHOR]

Nanofiltration (NF) plays an increasingly central role in water/salts separation, which puts forward tailored requirements on NF membranes in a variety of application scenarios. However, the ambiguous separation mechanisms of NF including membrane structure parameters and operating conditions hinder the rational design of versatile NF membranes. Herein, machine learning was used to explore the correlation between membrane structure parameters and operating conditions with water/salts selectivity, and reveal the importance of the diverse features based on literature data. Two structural features of polyamide NF membrane (pore radius and zeta potential) and two operating parameters (pressure and feed concentration) were typically extracted and associated with water/salts selectivity. Random Forest and XGBoost models were employed to learn from relevant variables and assess their importance. The results showed that membrane structure parameters attached more importance to water/salts selectivity than that of operating conditions accompanying the variable influence for different typed salts, where symmetrical salts were mainly governed by size sieving while Donnan exclusion for asymmetrical salts. Structure-performance relationships between pore radius, zeta potential and diverse water/salts selectivity were established using partial dependence plot analysis. It is anticipated that the constructed comprehensive insights can be further leveraged to tackle performance modulation and oriented design of multi-scenarios NF membranes. [Display omitted] • Machine learning was used to understand NF separation mechanisms. • Random Forest and XGBoost models were employed to learn from relevant variables and assess features importance. • Symmetrical salts were mainly governed by size sieving while Donnan exclusion for asymmetrical salts. • The integrated management of pore size and zeta potential for the oriented design of versatile NF membranes was highlighted. [ABSTRACT FROM AUTHOR]

Objective: It was recently found that structural changes in the substantia nigra (SN) and motor symptoms become more prominent in Parkinson's disease (PD) patients with striatal silent lacunar infarction (SSLI) than in those without SSLI. Hyperhomocysteinemia (HHCY) was an independent risk factor for SSLI in PD patients. In this follow-up study, we investigated the relationship between HHCY and structural changes of the SN in PD patients.Methods: A total of 72 untreated early PD patients without SSLI, divided into control and HHCY groups, were enrolled in this study. All participants underwent conventional MRI and diffusion kurtosis imaging (DKI) twice; at baseline and at the 2-year visit. The differences of the following variables between the two groups were analyzed: mean kurtosis (MK) values of the SN, the severity of disease, daily dosage of levodopa, and the variation of these indexes from baseline to 2-year visit. Logistic regression analysis was used to identify the relationship between HHCY and structural changes of the SN in PD patients.Results: 1.All variables mentioned above showed significant differences between the two groups. 2. The variation in MK values of the SN were positively correlated with the variation in the severity of disease. 3. HHCY was an independent risk factor for the variation in MK values of the SN in PD patients.Conclusion: HHCY is associated with the structural changes of the SN in PD patients. As PD progresses, motor symptoms become aggravated with increased structural changes to the SN, especially in patients with HHCY. [ABSTRACT FROM AUTHOR]

Renal insufficiency is associated with the prognosis of acute ischemic stroke (AIS) and homocysteine (Hcy) levels. This study investigated the association between plasma Hcy levels and renal insufficiency in patients with AIS. A total of 987 patients with AIS who had been treated at the First People's Hospital of Foshan between 2011 and 2014 were retrospectively studied. Based on their cystatin C (Cys C) levels, the patients were divided into the normal renal function group (Cys C ≤ 1.25 mg/L) or the renal impairment group (Cys C > 1.25 mg/L). Multivariate regression analysis was applied to reveal the association between hyperhomocysteinemia (HHcy) and renal impairment. The renal impairment group showed more advanced age of onset, higher percentage of prior stroke and hypertension, higher baseline National Institute of Health Stroke Scale score, lower high-density lipoprotein cholesterol levels, and higher Hcy levels compared with the normal renal function group. A multivariate analysis revealed a relationship between early renal impairment and Hcy levels: an increase of Hcy by 1 μmol/L was associated with an increase of 12-18% of the risk of renal impairment among patients with AIS and HHcy. Patients with AIS and HHcy had a 2.42-3.51 fold increase of the risk of renal impairment compared with patients with normal Hcy level ( P < 0.001). In conclusion, patients with stroke and HHcy could be more prone to renal impairment. [ABSTRACT FROM AUTHOR]

Objective: Striatal silent lacunar infarction (SSLI) is associated with structural changes to the substantia nigra (SN), detectable by diffusion kurtosis imaging (DKI). In this follow-up study, we investigated the effects of SSLI on the SN and movement disorders in patients with Parkinson's disease (PD).Methods: A total of 60 untreated patients with early-stage PD, divided into control and SSLI groups, were enrolled in this study. All participants underwent conventional MRI and DKI twice; at baseline and after a 1-year period. We analyzed the differences of the following variables between the two groups: mean kurtosis (MK) values of the SN, the severity of disease, daily dosage of levodopa, and the variation of these indexes from baseline to 1-year visit. Logistic regression analysis was used to identify the major risk factors for SSLI in PD patients.Results: 1. All variables showed significant differences between the two groups. 2. The variation in MK values of the SN had a positive correlation with the variation in the severity of disease. 3. Hypertension and hyperhomocysteinemia were independent factors for SSLI in patients with PD.Conclusion: As PD progresses, movement disorders become more prominent, with increased structural changes to the SN, especially in patients with SSLI. Furthermore, PD patients with hypertension and hyperhomocysteinemia are more likely to have SSLI. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) abuse is a significant public health concern globally. Cardiac toxicity is one of the important characteristics of METH, in addition to its effects on the nervous system. However, to date, research on the cardiotoxic injury induced by METH consumption has been insufficient. To systematically analyze the potential molecular mechanism of cardiac toxicity in METH-associated heart failure (HF), a rat model was constructed with a dose of 10 mg/kg of METH consumption. Cardiac function was evaluated by echocardiography, and HE staining was used to clarify the myocardial histopathological changes. Integrated analyses, including mRNA, miRNA and lncRNA, was performed to analyze the RNA expression profile and the potential molecular mechanisms involved in METH-associated HF. The results showed that METH caused decreased myocardial contractility, with a decreased percent ejection fraction (%EF). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the RNAs with expression changes revealed abnormal circadian rhythm regulation in the METH groups, with circadian rhythm-related genes and their downstream effectors expressed differentially, especially the aryl hydrocarbon receptor nuclear translocator-like (Arntl). Competing endogenous RNA (ceRNA) networks associated with circadian rhythm, including Arntl, was also observed. Therefore, this study revealed that long-term METH consumption was associated with the HF in a rat model by decreasing the %EF, and that the abnormal circadian rhythm could provide new directions for investigating the METH-associated HF, and that the differentially expressed genes in this model could provide candidate genes for the identification and assessment of cardiac toxicity in METH-associated HF, which is fundamental for further understanding of the disease. • Long-term consumption of METH in rat induces the decrease of cardiac systolic function. • METH consumption induces the significant transcriptomic changes of rat model. • Integrated analysis and experimental results revealed irregular circadian rhythm. • METH consumption affects the abnormal of effectors of circadian rhythm. • METH consumption increased the expression ARNTL in the left ventricle of heart. [ABSTRACT FROM AUTHOR]

• Polyesteramide-based membrane was successfully prepared via interfacial polymerization. • The polyesteramide membrane with high free volume showed high water flux. • Acid and alkali stabilities of polyesteramide membranes were obtained. A novel aromatic polyesteramide-based membrane with high free volume for water desalination was prepared by adding a rigid cardo-contorted biphenol monomer to the aqueous phase solution of m-phenylenediamine (MPD) and then carrying out the interfacial polymerization. Compared with the polyamide (PA) membrane, the polyesteramide membrane with high free volume and ultrathin separating layer exhibited 250% increase in flux and 1.2% loss in salt rejection. Moreover, acid and alkali stabilities of polyesteramide membranes were studied by immersing the polyesteramide membranes into acid, aid/ethyl alcohol (EA), alkali and alkali/EA aqueous solutions. After acid/alkali treatments, the surface contact angles of acid/alkali-treated PA/9,9-bis(4-hydroxyphenyl)fluorine (PA/BHPF) membranes were much smaller than the pristine PA/BHPF membrane. With EA, both the acid/EA-treated and alkali/EA-treated polyesteramide membranes exhibited a significant increase in water flux; moreover, the acid/EA-treated membranes showed a simultaneous increase in water flux and salt rejection within a treatment time of 24 h, due to the increase in hydrophilicity and the partial dissolution of small polymer fragments on membrane surface. [ABSTRACT FROM AUTHOR]