Repetitive transcranial magnetic stimulation (rTMS) acts as a kind of widely-applied and non-invasive method in the intervention of some neurological disorders. This prospective, randomized, double-blind, placebo-controlled trial investigates the effect of rTMS on 30 cases of Alzheimer’s disease (AD) participants, who were classified into mild and moderate groups. Neuropsychological tests were carried out using the AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA AVLT) before, immediately after, and 6 weeks after the intervention. In this work, data from 30 AD patients revealed that there was no obvious interaction effect of time-by-group. The ADAS-cog, MMSE and WHO-UCLA AVLT score in the rTMS group was significantly improved compared with baselines at 6 weeks after treatment (all p<0.05). Meanwhile, MoCA scores were also obviously ameliorated in the mild AD patients with rTMS. Besides, subgroup analysis showed that the effect of rTMS on the memory and language of mild AD patients was superior to those of moderate AD patients. In conclusion, our findings suggested that repetitive transcranial magnetic stimulation improves cognitive function, memory and language level of AD patients, especially in the mild stage of AD. Thus, rTMS can be recommended as a promising adjuvant therapy combined with cholinesterase inhibitors at the mild stage of AD patients.

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New‐era soft microrobots for biomedical applications need to mimic the essential structures and collective functions of creatures from nature. Biocompatible interfaces, intelligent functionalities, and precise locomotion control in a collective manner are the key parameters to design soft microrobots for the complex bio‐environment. In this work, a biomimetic magnetic microrobot (BMM) inspired by magnetotactic bacteria (MTB) with speedy motion response and accurate positioning is developed for targeted thrombolysis. Similar to the magnetosome structure in MTB, the BMM is composed of aligned iron oxide nanoparticle (MNP) chains embedded in a non‐swelling microgel shell. Linear chains in BMMs are achieved due to the interparticle dipolar interactions of MNPs under a static magnetic field. Simulation results show that, the degree and speed of assembly is proportional to the field strength. The BMM achieves the maximum speed of 161.7 µm s−1 and accurate positioning control under a rotating magnetic field with less than 4% deviation. Importantly, the locomotion analyses of BMMs demonstrate the frequency‐dependent synchronization under 8 Hz and asynchronization at higher frequencies due to the increased drag torque. The BMMs can deliver and release thrombolytic drugs via magneto‐collective control, which is promising for ultra‐minimal invasive thrombolysis.

Several biological processes as well as infectious agents, physiological or environmental stress, and perturbed antioxidant response can promote oxidative stress. Oxidative stress usually happens when cells are exposed to more electrically charged reactive oxygen species (ROS) such as HO or O. ROS are well known for being both beneficial and deleterious. Recent studies have indicated that ROS are deleterious to cells, leading to programmed cell death (PCD) at high concentrations. At low concentrations, however, ROS can act as signaling molecules in a variety of cellular processes. In this review, we present an update of our current understanding of the role and regulation of reactive oxygen species in various viral infections, cellular signaling pathways and immune responses. We then discuss how the antioxidant defense system acts as an antiviral effector to limit cell damage.

Background: To investigate the effect of creatine and coenzyme Q10 (CoQ10) combination therapy on mild cognitive impairment (MCI) in Parkinson's disease (PD; PD-MCI) and its influences on plasma phospholipid (PL) levels in PD-MCI. Methods: The demographic data of 75 PD-MCI patients who enrolled in this collaborative PD study were collected. These patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) III and the Montreal Cognitive Assessment (MoCA). These 75 PD-MCI patients were randomly treated with creatine monohydrate 5 g b.i.d. and CoQ10 100 mg t.i.d. orally or placebo. MoCA evaluation and PL level measurements were performed after 12 and 18 months of treatment. Results: After 12 and 18 months of treatment, the differences in the MoCA scores of the combination therapy and control groups were statistically significant (p < 0.05 at 12 months and p < 0.01 at 18 months), and the plasma PL levels of the combination therapy group were significantly lower than those of the control group (p < 0.01 at 12 months and p < 0.001 at 18 months). Conclusions: Combination therapy with creatine and CoQ10 could delay the decline of cognitive function in PD-MCI patients and could lower their plasma PL levels; therefore, this combination therapy may have a neuroprotective function.

Acute stroke and transient ischemic attack (TIA) is a great burden not only during hospitalization but also after hospital discharge. The objective of this meta-analysis was to evaluate the hospital readmissions, causes and risk factors after survival of acute stroke and TIA. Pubmed, Web of Science, Cochrane Library, OVID and EMBASE databases were searched to identify studies reporting hospital readmissions after acute stroke and TIA. The primary outcomes were hospital readmission rates during 30 days and 1 year after discharge. The primary causes and risk factors of hospital readmissions were also identified. Ten studies with 253,680 patients were eligible for inclusion. The pooled 30-day and 1-year hospital readmission rates were 17.4 % (95 % CI, 12.7-23.5 %) and 42.5 % (95 % CI, 34.1-51.3 %), respectively. The three major causes of 30-day hospital readmissions were infection (19.9 %), coronary artery disease (CAD) (17.8 %) and recurrent stroke (16.0 %) successively, while the three major causes were recurrent stroke (19.4 %), infection (19.3 %) and CAD (16.3 %) during 1 year's follow-up. There were more patients with CAD in readmits group than that in control group (p = 0.030). The length of index admission, defined as any eligible admission to an acute care hospital assessed in the measure for the outcome, was longer (p = 0.000) and admission National Institutes of Health Stroke Score (NIHSS) was higher (p = 0.002) in readmits group than these in control group. In conclusion, there is high risk of early and long-term hospital readmissions after survival of acute stroke and TIA. These patients with coronary artery disease, longer length of index admission and higher NIHSS deserve deep attention after hospital discharge.

Parkinson’s disease (PD) is mainly managed by pharmacological therapy (e.g., Benserazide and dopamine agonists). However, prolonged use of these drugs would gradually diminish their dopaminergic effect. Gut dysbiosis was observed in some patients with PD, suggesting close association between the gut microbiome and PD. Probiotics modulate the host’s gut microbiota beneficially. A 3-month randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the beneficial effect of probiotic co-administration in patients with PD. Eighty-two PD patients were recruited and randomly divided into probiotic [n = 48; Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8), Benserazide, dopamine agonists] and placebo (n = 34; placebo, Benserazide, dopamine agonists) groups. Finally, 45 and 29 patients from Probio-M8 and placebo groups provided complete fecal and serum samples for further omics analysis, respectively. The results showed that Probio-M8 co-administration conferred added benefits by improving sleep quality, alleviating anxiety, and gastrointestinal symptoms. Metagenomic analysis showed that, after the intervention, there were significantly more species-level genome bins (SGBs) of Bifidobacterium animalis, Ruminococcaceae, and Lachnospira, while less Lactobacillus fermentum and Klebsiella oxytoca in Probio-M8 group (P < 0.05). Interestingly, Lactobacillus fermentum correlated positively with the scores of UPDRS-III, HAMA, HAMD-17, and negatively with MMSE. Klebsiella oxytoca correlated negatively with feces hardness. Moreover, co-administering Probio-M8 increased SGBs involved in tryptophan degradation, gamma-aminobutyric acid, short-chain fatty acids, and secondary bile acid biosynthesis, as well as serum acetic acid and dopamine levels (P < 0.05). Taken together, Probio-M8 synergized with the conventional regimen and strengthened the clinical efficacy in managing PD, accompanied by modifications of the host’s gut microbiome, gut microbial metabolic potential, and serum metabolites.

Our previous studies indicated that recombinant rabies viruses (rRABV) expressing chemokines or cytokines (including GM-CSF) could enhance the immunogenicity by recruiting and/or activating dendritic cells (DC). In this study, bacterial flagellin was cloned into the RABV genome and recombinant virus LBNSE-Flagellin was rescued. To compare the immunogenicity of LBNSE-Flagellin with recombinant virus expressing GMCSF (LBNSE-GMCSF), mice were immunized with each of these rRABVs by intramuscular (i.m.) or oral route. The parent virus (LBNSE) without expression of any foreign molecules was included for comparison. The i.m.-immunized mice were bled at three weeks after the immunization for the measurement of virus neutralizing antibody (VNA) and then challenged with 50 LD50 challenge virus standard (CVS-24). Orally immunized mice were boosted after three weeks and then bled and challenged one week after the booster immunization. It was found that both LBNSE-GMCSF and LBNSE-Flagellin recruited/activated more DCs and B cells in the periphery, stimulated higher levels of adaptive immune responses (VNA), and protected more mice against challenge infection than the parent virus LBNSE in both the i.m. and the orally immunized groups. Together, these studies suggest that recombinant RABV expressing GM-CSF or flagellin are more immunogenic than the parent virus in both i.m. and oral immunizations.