Inhibiting cardiac autophagy suppresses Zika virus replication.

Zika Virus (ZIKV) infection is a global threat. Other than the congenital neurological disorders it causes, ZIKV infection has been reported to induce cardiac complications. However, the precise treatment plans are unclear. Thus, illustrating the pathogenic mechanism of ZIKV in the heart is critical to providing effective prevention and treatment of ZIKV infection. The mechanism of autophagy has been reported recently in Dengue virus infection. Whether or not autophagy participates in ZIKV infection and its role remains unrevealed. This study successfully established the in vitro cardiomyocytes and in vivo mouse models of ZIKV infection to investigate the involvement of autophagy in ZIKV infection. The results showed that ZIKV infection is both time and gradient-dependent. The key autophagy protein, LC3B, increased remarkably after ZIKV infection. Meanwhile, autophagic flux was detected by immunofluorescence. Applying autophagy inhibitors decreased the LC3B levels. Furthermore, the number of viral copies was quantified to evaluate the influence of autophagy during infection. We found that autophagy was actively involved in the ZIKV infection and the inhibition of autophagy could effectively reduce the viral copies, suggesting a potential intervention strategy for reducing ZIKV infection and the undesired complications caused by ZIKV.

Water quality assessment and source identification of the Shuangji River (China) using multivariate statistical methods.

Multivariate statistical techniques, including cluster analysis (CA), discriminant analysis (DA), principal component analysis (PCA) and factor analysis (FA), were used to evaluate temporal and spatial variations in and to interpret large and complex water quality datasets collected from the Shuangji River Basin. The datasets, which contained 19 parameters, were generated during the 2 year (2018-2020) monitoring programme at 14 different sites (3192 observations) along the river. Hierarchical CA was used to divide the twelve months into three periods and the fourteen sampling sites into three groups. Discriminant analysis identified four parameters (CODMn, Cu, As, Se) loading more than 68% correct assignations in temporal analysis, while seven parameters (COD, TP, CODMn, F, LAS, Cu and Cd) to load 93% correct assignations in spatial analysis. The FA/PCA identified six factors that were responsible for explaining the data structure of 68% of the total variance of the dataset, allowing grouping of selected parameters based on common characteristics and assessing the incidence of overall change in each group. This study proposes the necessity and practicality of multivariate statistical techniques for evaluating and interpreting large and complex data sets, with a view to obtaining better information about water quality and the design of monitoring networks to effectively manage water resources.

Disrupted pathways from frontal-parietal cortex to basal ganglia and cerebellum in patients with unmedicated obsessive compulsive disorder as observed by whole-brain resting-state effective connectivity analysis - a small sample pilot study.

OBJECTIVE: To date, a systematic characterization of abnormalities in resting-state effective connectivity (rsEC) in obsessive-compulsive disorder (OCD) is lacking. The present study aimed to systematically characterize whole-brain rsEC in OCD patients as compared to healthy controls. METHODS: Using resting-state fMRI data of 50 unmedicated patients with OCD and 50 healthy participants, we constructed whole-brain rsEC networks using Granger causality analysis followed by univariate and multivariate comparisons between patients and controls. Similar analyses were performed for resting-state functional connectivity (rsFC) networks to examine how rsFC and rsEC differentially capture abnormal brain connectivity in OCD. RESULTS: Univariate comparisons identified 10 rsEC networks that were significantly disrupted in patients, and which were mainly associated with frontal-parietal cortex, basal ganglia, and cerebellum. Conversely, abnormal rsFC networks were widely distributed throughout the whole brain. Multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls using combined whole-brain rsEC and rsFC. CONCLUSIONS: The results of the present study suggest disrupted communication of information from frontal-parietal cortex to basal ganglia and cerebellum in OCD patients. Using combined whole-brain rsEC and rsFC, multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls. The alterations observed in OCD patients could aid in identifying treatment mechanisms for OCD.

Tetracycline Removal by Activating Persulfate with Diatomite Loading of Fe and Ce.

Persulfate (PS)-based oxidation technology is efficient in removing refractory organics from water. A novel diatomite (DIA) support Fe and Ce composite (Fe-Ce/DIA) was prepared for activating persulfate to degrade tetracycline in water. The Fe and Ce were uniformly loaded on DIA, and the total pore size of Fe-Ce/DIA was 6.99 × 10-2 cm3/g, and the average pore size was 12.06 nm. Fe-Ce/DIA presented a good catalytic activity and 80% tetracycline was removed under the persulfate system. The Fe-Ce/DIA also had photocatalytic activity, and the corresponding tetracycline removal efficiency was 86% under UV irradiation. Fe-Ce/DIA exhibited less iron dissolution rate compared with Fe-DIA. The tetracycline degradation rate was enhanced when the temperature increased. The optimal tetracycline removal efficiency was obtained when the conditions were of persulfate 10 mM, Fe-Ce/DIA dosage 0.02 g/L, and tetracycline concentration 50 mg/L. In addition, Fe-Ce/DIA showed a wide pH application and good reusability and stability.

Disrupted pathways from the frontal-parietal cortices to basal nuclei and the cerebellum are a feature of the obsessive-compulsive disorder spectrum and can be used to aid in early differential diagnosis.

A marker for distinguishing patients with obsessive-compulsive disorder (OCD) spectrum has not yet been identified. Whole-brain resting-state effective and functional connectivity (rsEC and rsFC, respectively) networks were constructed for 50 unmedicated OCD (U-OCD) patients, 45 OCD patients in clinical remission (COCD), 47 treatment-resistant OCD (T-OCD) patients, 42 chronic schizophrenia patients who exhibit OCD symptoms (SCHOCD), and 50 healthy controls (HCs). Multivariate pattern analysis (MVPA) was performed to investigate the accuracy of using connectivity alterations to distinguished among the aforementioned groups. Compared to HCs, rsEC connections were significantly disrupted in the U-OCD (n = 15), COCD (n = 8), and T-OCD (n = 19) groups. Additionally, 21 rsEC connections were significantly disrupted in the T-OCD group compared to the SCHOCD group. The disrupted rsEC networks were associated mainly with the frontal-parietal cortex, basal ganglia, limbic regions, and the cerebellum. Classification accuracies for distinguishing OCD patients from HCs and SCHOCD patients ranged from 66.6% to 98.0%. In conclusion, disrupted communication from the frontal-parietal cortices to subcortical basal nuclei and the cerebellum may represent a functional pathological feature of the OCD spectrum. MVPA based on both abnormal rsEC and rsFC patterns may aid in early differential diagnosis of OCD.

Block copolymer@ZIF-8 nanocomposites as a pH-responsive multi-steps release system for controlled drug delivery.

Developing the hybrid nanosystems for controlled drug release is still a challenging task. In this work, pH-responsive core-shell nanocomposites have been prepared by the growth of zeolitic imidazolate framework-8 (ZIF-8) on the surface of polymeric aggregates self-assembled from poly(ε-caprolactone)-block-poly (quaternized vinylbenzyl chloride/bipyridine) (PCL-b-q(PVBC/BPy), BCP for short) in water. The core of the micelles or the inner cavity of vesicles serves as the drug storage reservoir for the doxorubicin hydrochloride (DOX) and the ZIF-8 shells act as the gatekeepers to prevent drug premature release at physiological environment. Upon pH stimulus, the core-shell nanocomposites (BCP@ZIF-8) show a retarded drug release behavior compared with DOX-loaded polymeric aggregates counterparts (without the shell of ZIF-8). Moreover, the as-prepared nanocomposites perform good biocompatibility towards MCF-7 cell. Meanwhile, the DOX-loaded BCP@ZIF-8 nanocomposites present lower cytotoxicity compared with DOX-loaded BCP and free DOX. The confocal microscopy study shows the core-shell nanocomposites could be efficiently internalized by cancer cells, and the loaded DOX could be successfully released under acidic intracellular environment. The above result shows that the core-shell nanocomposite could be a promising candidate for pH-responsive drug delivery system in the cancer therapy.

Redox and pH responsive polymeric vesicles constructed from a water-soluble pillar[5]arene and a paraquat-containing block copolymer for rate-tunable controlled release.

Herein, for rate-tunable controlled release, pH and redox dual responsive polymeric vesicles were constructed based on host-guest interaction between a water soluble pillar[5]arene (WP5) and a paraquat-containing block copolymer (BCP) in water. The yielding polymeric vesicles can be further applied in the controlled release of a hydrophilic model drug, doxorubicin hydrochloride (DOX). The drug release rate is regulated depending on the type of single stimulus or the combination of two stimuli. Meanwhile, DOX-loaded polymeric vesicles present anticancer activity in vitro comparable to free DOX under the studied conditions, which may be important for applications in the therapy of cancers as a controlled-release drug carrier.

Glucose- and H2O2-Responsive Polymeric Vesicles Integrated with Microneedle Patches for Glucose-Sensitive Transcutaneous Delivery of Insulin in Diabetic Rats.

Herein, a dual-responsive insulin delivery device by integrating glucose- and H2O2-responsive polymeric vesicles (PVs) with transcutaneous microneedles (MNs) has been designed. This novel microneedle delivery device achieves a goal of fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from a triblock copolymer including poly(ethylene glycol), poly(phenylboronic acid) (glucose-sensitive block), and poly(phenylboronic acid pinacol ester) (H2O2-sensitive block). After loading with insulin and glucose oxidase (GO x), the drug-loaded PVs display a basal insulin release as well as a promoted insulin release in response to hyperglycemic states. The insulin release rate responds quickly to elevated glucose and can be further promoted by the incorporated GO x, which will generate the H2O2 at high glucose levels and further break the chemical links of phenylboronic acid pinacol ester group. Finally, the transdermal delivery of insulin to the diabetic rats ((insulin + GO x)-loaded MNs) presents an effective hypoglycemic effect compared to that of subcutaneous injection or only insulin-loaded MNs, which indicates the as-prepared MNs insulin delivery system could be of great importance for the applications in the therapy of diabetes.