Deoxyribozyme and aptamer selections are typically conducted in aqueous buffer solutions. Using nonaqueous cosolvents in selection experiments will help expand the activity of deoxyribozymes with non-oligonucleotide substrates and will allow identification of new aptamers for nonprotein targets. We undertook in vitro selections utilizing a small amount of methanol in the reaction to keep the herbicides alachlor and atrazine in solution with the goal of identifying deoxyribozymes that require these herbicides for activity. The resulting deoxyribozymes successfully catalyze RNA ligation, but do not require alachlor or atrazine. Surprisingly, some of these deoxyribozymes displayed better catalytic activity in the presence of methanol over just aqueous buffer. We investigated several organic cosolvents to see if this enhancement was limited to methanol and found that other cosolvents, including ethanol, DMSO, and DMF, supported activity; in some cases, greater enhancement was observed. On the basis of these results, we tested two other previously identified RNA-ligating deoxyribozymes to assess their tolerance of cosolvents and determined that different deoxyribozymes showed different responses to the cosolvents. Our results demonstrate that deoxyribozymes can tolerate and, in some cases, display enhanced activity in alternative solvent conditions. These findings will facilitate the development of responsive deoxyribozyme systems utilizing components with limited water solubility.

Background: Minimally invasive diagnostic biomarkers of neurodegenerative diseases such as Alzheimer’s disease (AD) facilitate patient selection and cognitive progressive decline monitoring. However, the diagnostic value of circulating microRNAs (miRNAs) for early cognitive impairment and progression to dementia is currently under debate. Thus, this study aimed to assess the diagnostic performance of circulating, cerebrospinal fluid (CSF) and exosomal miRNAs in the detection of clinical cognitive impairment in mild cognitive impairment (MCI), AD, and MCI-AD. Methods: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Chinese Science and Technology Journals Database (CQVIP), and Chinese Medicine Premier (Wanfang) to identify potentially eligible studies related to noncoding RNAs and cognitive dysfunction biomarkers published before November 2018. The quality assessment of the studies was performed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Meta-analysis of the literature data was performed using Stata/MP 14.0 software. The corresponding effects models were selected to calculate the summary sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), and diagnostic odds ratio (DOR) and to plot the summary receiver operating characteristic curves (SROCs) and calculate the areas under the curves (AUCs). Results: A total of 18 studies involving 729 patients with AD, 283 patients with MCI, and 15 patients with MCI-AD were pooled. The results revealed that the sensitivity and specificity of miRNAs in the diagnosis of AD were 0.78 and 0.79, respectively, and the area under the summary receiver operating characteristic curve (AUSROC) was 0.90. The sensitivity and specificity of miRNAs in the diagnosis of MCI were 0.89 and 0.85, respectively, and the AUSROC was 0.94. The sensitivity and specificity of microRNAs in the diagnosis of MCI-AD were 0.87 and 0.84, respectively, and the AUSROC was 0.92. Conclusion: Our study found that miRNAs have certain diagnostic value for cognitive impairment, with high sensitivity and specificity, especially in diagnostics with multiple miRNAs and serum-based miRNA assays.

Background Depression is seriously affecting the physical and mental health of young people worldwide. Subthreshold depression, as an early stage of depression, is essential for early prevention and treatment of depression. Tai Chi, as a traditional Chinese mind-body therapy, may become an alternative intervention. However, the neurophysiological mechanism of Tai Chi for young people with subthreshold depression remains unclear, restricting its further promotion and application. Therefore, rigorous randomized clinical trials are needed to further observe the intervention effect of Tai Chi on young adults with subthreshold depression and explore the neurophysiological mechanism. Method/design This report describes a two-arm, randomized, parallel controlled trial with allocation concealment and assessor blinding. A total of 64 eligible participants are randomly allocated to the Tai Chi group and the waiting list group in a 1:1 ratio. Participants in the Tai Chi group receive 12 weeks of Tai Chi training, with a total of 36 times and each for 60 min. Specifically, the participants in the waiting list group are requested to maintain their routine lifestyle. In this study, the primary outcome measure is the mean change in scores on the PHQ-9 and HAMD-17 between baseline and 12 weeks; the secondary outcomes are the mean change in the scores on CES-D, CPSS, GAD-7, and PSQI. Besides, the saliva cortisol levels and fMRI are monitored to explore the mechanism of action of Tai Chi on subthreshold depression. Discussion The protocol uses a randomized controlled trial to examine the effectiveness of Tai Chi for young adults with subthreshold depression and explore neurophysiological mechanisms. If the test results are positive, it can be verified that Tai Chi can promote the physical and mental health of young adults with subthreshold depression. Trial registration Chinese Clinical Trial Registry ChiCTR1900028289. Registered on 17 December 2019

Milk proteins are prone to changes during the heat treatment process. Here, we aimed to study the changes in caprine milk fat globule membrane (MFGM) proteins with three heat treatment processes—ultra-pasteurization (85 °C, 30 min), ultra-high-temperature instant sterilization (135 °C, 5 s), and spray-drying (inlet, 160 °C and outlet, 80 °C)—using the label-free proteomics technique. A total of 1015, 637, 508, and 738 proteins were identified in the raw milk, ultra-pasteurized milk, ultra-high-temperature instant sterilized milk, and spray-dried reconstituted milk by using label-free proteomics techniques, respectively. Heat treatment resulted in a significant decrease in the relative intensity of MFGM proteins, such as xanthine dehydrogenase/oxidase, butyrophilin subfamily 1 member A, stomatin, and SEA domain-containing protein, which mainly come from the membrane, while the proteins in skimmed milk, such as β-lactoglobulin, casein, and osteopontin, increased in MFGM after heat treatment. Among these different heat treatment groups, the procedure of spray-drying resulted in the least abundance reduction of caprine milk MFGM proteins. Additionally, it showed heating is the key process affecting the stability of caprine MFGM protein rather than the spray-drying process. These findings provide new insights into the effects of heat treatment on caprine MFGM protein composition and potential biological functions.

Background: Neuromyelitis optica spectrum disorders (NMOSD) is an inflammatory and heterogeneous astrocyte disorder of the central nervous system (CNS), concerned because of its high pathogenicity, high risk of recurrence, and poor prognosis. Optic neuritis (ON) is the first manifestation in 30% to 50% of NMOSD patients, and eventually involved optic nerve in 70% of patients. The idiopathic ON associated with NMO is called NMO-associated ON(NMO-ON). There are substantial costs to the countries and individuals associated with treatment of NMO-ON. Intravenous corticosteroids (IVCSs), as the first-line therapy, leads to unsatisfactory outcomes for NMO-ON and is associated with potential adverse events (AEs). Emerging evidences have proved the important value and potential prospect of plasma exchange (PLEX) in NMO-ON. Although PLEX is increasingly used in NMO-ON, its therapeutic effect and safety are still controversial. There are no systematic reviews yet that evaluated the effects of PLEX against other therapies in patients with NMO-NO. It is therefore timely to perform a systematic review to assess the efficacy and safety of PLEX on current research for its potential use in clinical practice in treating NMO-ON. Methods: The systematic review will include all of the randomized controlled trials (RCT) on the efficacy and safety of PLEX for NMO-ON. A relevant literature search by sensitive search strategies was conducted using the following electronic databases from their inception to November 30, 2019: PubMed, Web of Science, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal database (VIP) and CBM. We will also search registers of clinical trials, potential gray literature, and conference abstracts. There are no limits on language and publication status. The literature screening, data extraction, and quality assessment will be conducted by 2 reviewers independently. The reporting quality and risk of bias will be assessed by other 2 researchers. Best-corrected visual acuity (BCVA), annualized relapse rate (ARR), the frequency and extent of adverse events (AEs) will be evaluated as the primary outcome. The secondary outcomes will include expanded disability status scales (EDSS), relapse-free rate, peri-papillary retinal nerve fibers layer (pRNFL) or macular volume, visual electrophysiology examinations, standard automated perimetry examinations, time to the next attack. Meta-analysis will be performed using RevMan5.3 software provided by the Cochrane Collaboration and Stata 12.0. Results: This study will provide a comprehensive review based on current evidence of PLEX treatment for NMO-ON in several aspects, including BCVA, ARR, the frequency and extent of adverse events (AEs), EDSS, relapse-free rate, etc. Conclusion: The conclusion of this study will provide evidence to determine whether PLEX is an effective and...