The C-C chemokine receptor 7: An immune molecule that modulates central nervous system function in homeostasis and disease.

The interaction between the central nervous system (CNS) and the peripheral immune system is key for brain function in homeostasis and disease. Recent studies have revealed that the C-C chemokine receptor 7 (CCR7) is expressed in both CNS resident cells and peripheral immune cells, and plays an important role in regulating behavior in homeostasis and neuroinflammation in disease. This review integrates studies examining the role of CCR7 in CNS resident and peripheral immune cells in homeostasis and disease, as well as the pathways of peripheral immune cell migration in and out of the brain via CCR7. A special emphasis is placed on the CCR7-dependent migration of peripheral immune cells into the recently discovered meningeal lymphatic vessels surrounding the brain and nasal lymphatics, its migration into cervical lymph nodes, and the implications that this migration might have for CNS function.

High-performance mode decomposition using physics- and data-driven deep learning.

A novel physics- and data-driven deep-learning (PDDL) method is proposed to execute complete mode decomposition (MD) for few-mode fibers (FMFs). The PDDL scheme underlies using the embedded beam propagation model of FMF to guide the neural network (NN) to learn the essential physical features and eliminate unexpected features that conflict with the physical laws. It can greatly enhance the NN's robustness, adaptability, and generalization ability in MD. In the case of obtaining the real modal weights (ρ2) and relative phases (θ), the PDDL method is investigated both in theory and experiment. Numerical results show that the PDDL scheme eliminates the generalization defect of traditional DL-based MD and the error fluctuation is alleviated. Compared with the DL-based MD, in the 8-mode case, the errors of ρ2 and θ can be reduced by 12 times and 100 times for beam patterns that differ greatly from the training dataset. Moreover, the PDDL maintains high accuracy even in the 8-mode MD case with a practical maximum noise factor of 0.12. In terms of adaptation, with a large variation of the core radius and NA of the FMF, the error keeps lower than 0.43% and 2.08% for ρ2 and θ, respectively without regenerating new dataset and retraining NN. The experimental configuration is set up and verifies the accuracy of the PDDL-based MD. Results show that the correlation factor of the real and reconstructed beam patterns is higher than 98%. The proposed MD-scheme shows much potential in the application of practical modal coupling characterization and laser beam quality analysis.

The Mechanisms of the Potential Probiotic Lactiplantibacillus plantarum against Cardiovascular Disease and the Recent Developments in its Fermented Foods.

Cardiovascular disease (CVD) has become the leading cause of death worldwide. Many recent studies have pointed out that Lactiplantibacillus plantarum (Lb. plantarum) has great potential in reducing the risk of CVD. Lb. plantarum is a kind of lactic acid bacteria (LAB) widely distributed in fermented food and the human intestinal tract, some strains of which have important effects on human health and the potential to be developed into probiotics. In this review, we summarize the mechanism of potential probiotic strains of Lb. plantarum against CVD. It could regulate the body's metabolism at the molecular, cellular, and population levels, thereby lowering blood glucose and blood lipids, regulating blood pressure, and ultimately reducing the incidence of CVD. Furthermore, since Lb. plantarum is widely utilized in food industry, we highlight some of the most important new developments in fermented food for combating CVD; providing an insight into these fermented foods can assist scientists in improving the quality of these foods as well as alleviating patients' CVD symptoms. We hope that in the future functional foods fermented by Lb. plantarum can be developed and incorporated into the daily diet to assist medication in alleviating CVD to some extent, and maintaining good health.

Case Report: Clinical Outcome From Pallidal Stimulation in a Patient With Levodopa-Resistant Dopa-Responsive Dystonia.

Dopa-responsive dystonia (DRD) is a group of movement disorders with genetic and clinical heterogeneity. Dramatic response to levodopa is the hallmark of DRD. Therefore, DRD cases with poor response to levodopa are rarely reported. In addition, the clinical outcomes from deep brain stimulation (DBS) in levodopa-resistant patients remain unclear. Here, we described the clinical outcome of pallidal stimulation in a DRD patient having a poor response to levodopa. The patient was a 25-year-old man and had a 7-year history of cervical dystonia. A novel frameshift mutation in the GCH1 gene was found in the patient as well as his elder sister and mother. Unfortunately, he had no response to a large dosage of levodopa/benserazide (600/150 mg per day) and onabotulinumtoxin A injection. Therefore, bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) was performed. With parameter adjustments, the severity of his torticollis was gradually improved and relieved substantially in the 8-month follow-up visit. Our current report highlights that GPi-DBS therapy leads to promising clinical outcomes for levodopa-resistant DRD.

Transcranial alternating current stimulation for treating depression: a randomized controlled trial.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

Clinical profile of fatal familial insomnia: phenotypic variation in 129 polymorphisms and geographical regions.

OBJECTIVE: Elucidate the core clinical and genetic characteristics and identify the phenotypic variation between different regions and genotypes of fatal familial insomnia (FFI). METHODS: A worldwide large sample of FFI patients from our case series and literature review diagnosed by genetic testing were collected. The prevalence of clinical symptoms and genetic profile were obtained, and then the phenotypic comparison between Asians versus non-Asians and 129Met/Met versus 129Met/Val were conducted. RESULTS: In total, 131 cases were identified. The age of onset was 47.51±12.53 (range 17-76) years, 106 patients died and disease duration was 13.20±9.04 (range 2-48) months. Insomnia (87.0%) and rapidly progressive dementia (RPD; 83.2%) occurred with the highest frequency. Hypertension (33.6%) was considered to be an objective indicator of autonomic dysfunction. Genotype frequency at codon 129 was Met/Met (84.7%) and Met/Val (15.3%), and allele frequency was Met (92.4%) and Val (7.6%).129 Met was a risk factor (OR: 3.728, 95% CI: 2.194 to 6.333, p=0.000) for FFI in the non-Asian population. Comparison of Asians and non-Asians revealed clinical symptoms and genetic background to show some differences (p<0.05). In the comparison of 129 polymorphisms, a longer disease duration was found in the 129 MV group, with alleviation of some clinical symptoms (p<0.05). After considering survival probability, significant differences in survival time between genotypes remained (p<0.0001). CONCLUSIONS: Insomnia, RPD and hypertension are representative key clinical presentations of FFI. Phenotypic variations in genotypes and geographic regions were documented. Prion protein gene 129 Met was considered to be a risk factor for FFI in the non-Asian population, and 129 polymorphisms could modify survival duration.