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Summary: Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Abstract Despite the abnormal expression of 18S rRNA m6A methyltransferase METTL5 being reported in some types of human malignancies, but its effect on hepatocellular carcinoma (HCC) remains to be unclear. This study aims to elucidate the influences of METTL5 on the carcinogenesis and progression of HCC. Expressions of METTL5 gene, transcript, protein, and promoter methylation in HCC were examined through multiple databases, c-BioPortal was used to confirm the genomic alterations of METTL5, the biological functions, target networks of kinases and microRNAs of METTL5, and its interactive differential genes were investigated through LinkedOmics. The possible correlation of METTL5 with the tumor-related infiltration of immune cells for HCC were explored comprehensively by using the online tools of TIMER and TISIDB. Expressions of METTL5 gene, mRNA, and protein were considerably overexpressed in HCC samples in comparison with healthy samples. The high methylation of the METTL5 promoter was observed in HCC tissues. Elevated METTL5 expression exhibited unfavorable survival outcomes in HCC patients. METTL5 expression were enriched in the signaling pathways of ribosome and oxidative phosphorylation, mismatch repair, and spliceosome through the involvement of several cancer-related kinases and miRNAs. The METTL5 expression has a positive correlation with the infiltration degree of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Marker genes of tumor immune-infiltrated cells have strong connection with METTL5. Furthermore, the upregulation of METTL5 was strongly correlated with the immune regulation of immunomodulators, chemokines, and chemokine receptors in the immune microenvironment. The oncogenesis and development of HCC are closely related to METTL5 expression, and the overexpression of METTL5 resulted in the poor survival outcome of HCC patients by regulating tumor immune microenvironment.

Introduction Robotic-assisted gait training (RAGT) has been reported to be effective in rehabilitating patients with spinal cord injury (SCI). However, studies on RAGT showed different results due to a varied number of samples. Thus, summarising studies based on robotic-related factors is critical for the accurate estimation of the effects of RAGT on SCI. This work aims to search for strong evidence showing that using RAGT is effective in treating SCI and analyse the deficiencies of current studies.Methods and analysis The following publication databases were electronically searched in December 2022 without restrictions on publication year: MEDLINE, Cochrane Library, Web of Science, Embase, PubMed, the Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure. Various combinations of keywords, including ‘motor disorders’, ‘robotics’, ‘robotic-assisted gait training’, ‘Spinal Cord Injuries’, ‘SCI’ and ‘gait analysis’ were used as search terms. All articles on randomised controlled trials (excluding retrospective trials) using RAGT to treat SCI that were published in English and Chinese and met the inclusion criteria were included. Outcomes included motor function, and gait parameters included those assessed by using the instrumented gait assessment, the Berg Balance Scale, the 10-m walk speed test, the 6-min walk endurance test, the functional ambulation category scale, the Walking index of SCI and the American Spinal Injury Association assessment scale. Research selection, data extraction and quality assessment were conducted independently by two reviewers to ensure that all relevant studies were free from personal bias. In addition, the Cochrane risk-of-bias assessment tool was used to assess the risk of bias. Review Manager V.5.3 software was used to produce deviation risk maps and perform paired meta-analyses.Ethics and dissemination Ethics approval is not required for systematic reviews and network meta-analyses. The results will be submitted to a peer-reviewed journal or presented at a conference.PROSPERO registration number CRD42022319555.

ObjectiveThis review was conducted to assess the quality of the evidence of effectiveness of repetitive transcranial magnetic stimulation (rTMS) in treating motor and language ability of cerebral palsy (CP).MethodMedline, Cochrane library, Web of Science, Embase, PubMed, and CNKI databases were searched up to July 2021 by two independent reviewers. Randomized controlled trials (RCTs) that were published in English and Chinese and met the following criteria were included. The population comprised patients who met the diagnostic criteria for CP. Intervention included the following: comparison about rTMS and sham rTMS or comparison about rTMS combine with other physical therapy and other physical therapy. Outcomes included motor function, as follows: gross motor function measure (GMFM), Gesell Development Diagnosis Scale, fine motor function measure (FMFM), Peabody developmental motor scale, and Modified Ashworth scale. For language ability, sign-significant relation (S-S) was included. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale.ResultsFinally, 29 studies were included in the meta-analysis. Results of evaluation using the Cochrane Collaborative Network Bias Risk Assessment Scale showed that 19 studies specifically explained randomization, among which two studies described allocation concealment, four studies blinded participants and persons and had low risk of bias, and six studies explained that the assessment of outcome measures was blinded. Significant improvements in motor function were observed. The GMFM of total score was determined by using the random-effect model [I2 = 88%; MD = −1.03; 95% CI (−1.35, −0.71); P

ObjectiveRhythmic auditory stimulation (RAS) belongs to neurologic music therapy, which has attracted clinical attention because of its efficacy in motor function after stroke. This study aimed to summarize the effectiveness of rhythmic auditory stimulation (RAS) for the treatment of motor function and balance ability in stroke through a systematic review and meta-analysis.MethodsAll studies were retrieved from six databases. The effects of RAS on stroke were determined using the following indicators: motor function including step length, step cadence, velocity, Fugl–Meyer assessment (FMA); and balance ability including overall balance index (OBI) and Berg Balance Scale (BBS). The risk map of bias of the quality of the studies and the meta-analysis results of the indicators was prepared using RevMan 5.2 software.ResultsA total of 1,363 abstracts were retrieved. Among them, 325 duplicate studies were eliminated, and 971 studies were excluded after reading the titles and abstracts. In addition, by downloading the full text for further reading and screening, 47 studies were excluded. A total of 22 studies were included in the systematic review, and 18 studies were included in the meta-analysis. Assessment of quality, based on the PEDro scale, two studies had low quality, three studies had excellent quality, and the other studies had good quality; based on the Cochrane Collaborative Network Bias Risk Assessment Scale. A total of 15 studies specifically explained the random methods used. Meanwhile, seven studies did not report random sequence generation. A total of 10 studies reported that the evaluation of experimental results was blinded. In the meta-analysis, the results of motor function [namely, velocity (SMD = 0.99, 95% CI (0.43, 1.55)), step length (SMD = 0.97, 95% CI (0.74, 1.20)), and step cadence (MD = 5.16, 95% CI (4.17, 6.14)), FMA (MD = 2.93, 95% CI (2.04, 3.83))], were statistically significant (P < 0.01). The results of balance ability [OBI (MD = −0.51, 95% CI (−0.86, −0.16)) and BBS (MD = 2.93, 95% CI (1.67, 4.20))], were also statistically significant (P < 0.01). Among all the outcome indicators, three indicators were included in more than 10 studies: these are step length, step cadence, and velocity. The results showed that the two sides of the funnel chart were asymmetrical, thus these results all showed heterogeneity. The GRADEpro GDT online tool was used to evaluate the quality of evidence for the outcome indicators in the included studies. Five outcome indicators were included, of which three were low-quality indicators and two were moderate-quality indicators.ConclusionsRAS could improve gait parameters, walking function, and balance ability of individuals with stroke. However, studies or samples of outcome indicators for balance ability of stroke patients is relatively insufficient, which also requires further research in the future.Systematic review registrationPROSPERO, identifier: CRD42021225102.

ObjectiveThis study aimed to summarize the effectiveness of rhythmic auditory stimulation (RAS) for the treatment of gait and motor function in Parkinson's disease (PD) through a systematic review and meta-analysis.MethodsAll studies were retrieved from eight databases. The effects of RAS on PD were determined using the following indicators: gait parameters including step length, stride width, step cadence, velocity, stride length; motor function including 6 min walk test (6MWT) and timed up-and-go test (TUGT); the Unified Parkinson's Disease Rating Scale (UPDRS); and the Berg Balance Scale (BBS). The risk map of bias of the quality of the studies and the meta-analysis results of the indicators was prepared with RevMan 5.2 software.ResultsTwenty-one studies were included in the systematic review, and 14 studies were included in the meta-analysis. In the meta-analysis, the results of gait parameters, namely, velocity, step length, and stride length, were statistically significant (P < 0.05), whereas the results of cadence and stride width were not statistically significant (P ≧ 0.05). The results of 6MWT and TUGT for motor function as well as UPDRS-II, UPDRS-III, and BBS were statistically significant (P < 0.05).ConclusionsRAS could improve gait parameters, walking function, balance function, and daily living activities of individuals with PD. The application of RAS in conventional rehabilitation approaches can enhance motor performance in PD. Future studies should use a large sample size and a rigorous design to obtain strong conclusions about the advantages of RAS for the treatment of gait and motor function in PD.

Research is presented describing the substitution of proline by 5,5-dimethylproline in a variety of protein problems to contain the X-Pro peptide group in its cis conformation.