Interactions between circulating inflammatory factors and autism spectrum disorder: a bidirectional Mendelian randomization study in European population.

Background: Extensive observational studies have reported an association between inflammatory factors and autism spectrum disorder (ASD), but their causal relationships remain unclear. This study aims to offer deeper insight into causal relationships between circulating inflammatory factors and ASD. Methods: Two-sample bidirectional Mendelian randomization (MR) analysis method was used in this study. The genetic variation of 91 circulating inflammatory factors was obtained from the genome-wide association study (GWAS) database of European ancestry. The germline GWAS summary data for ASD were also obtained (18,381 ASD cases and 27,969 controls). Single nucleotide polymorphisms robustly associated with the 91 inflammatory factors were used as instrumental variables. The random-effects inverse-variance weighted method was used as the primary analysis, and the Bonferroni correction for multiple comparisons was applied. Sensitivity tests were carried out to assess the validity of the causal relationship. Results: The forward MR analysis results suggest that levels of sulfotransferase 1A1, natural killer cell receptor 2B4, T-cell surface glycoprotein CD5, Fms-related tyrosine kinase 3 ligand, and tumor necrosis factor-related apoptosis-inducing ligand are positively associated with the occurrence of ASD, while levels of interleukin-7, interleukin-2 receptor subunit beta, and interleukin-2 are inversely associated with the occurrence of ASD. In addition, matrix metalloproteinase-10, caspase 8, tumor necrosis factor-related activation-induced cytokine, and C-C motif chemokine 19 were considered downstream consequences of ASD. Conclusion: This MR study identified additional inflammatory factors in patients with ASD relative to previous studies, and raised a possibility of ASD-caused immune abnormalities. These identified inflammatory factors may be potential biomarkers of immunologic dysfunction in ASD.

Neurotrophin-4 promotes in vitro development and maturation of human secondary follicles yielding metaphase II oocytes and successful blastocyst formation.

STUDY QUESTION: Does a matrix-free culture system supplemented with neurotrophic factor 4 (NT4) improve human in vitro follicular development and meiotic maturation, ultimately resulting in fertilizable oocytes? SUMMARY ANSWER: NT4 supplementation of in vitro culture significantly enhances the growth, steroid hormone production, and maturity potential of human secondary follicles derived from fresh ovarian medulla (from post- and pre-pubertal patients), thereby yielding fertilizable oocytes. WHAT IS KNOWN ALREADY: Reconstituting folliculogenesis in vitro is of paramount importance in the realms of fertility preservation, reproductive biology research, and reproductive toxicity assessments. However, the efficiency of in vitro culture systems remains suboptimal, as the attainment of fertilizable oocytes from in vitro growth (IVG) of human follicles remains unachieved, with the data being particularly scant regarding follicles from prepubertal girls. We have previously found that mouse oocytes from secondary follicles derived from IVG are deficient in neuroendocrine regulation. NT4 and its corresponding receptor have been identified in human follicles. Significantly, the addition of NT4 during the IVG process markedly enhances both follicle growth and oocyte maturation rates in mice. STUDY DESIGN SIZE DURATION: Fresh medulla tissue obtained during tissue preparation for ovarian tissue cryopreservation (OTC) were collected from 10 patients aged from 6 to 21 years old, all of whom had undergone unilateral oophorectomy as a means of fertility preservation. Isolated secondary follicles were individually cultured in vitro with or without NT4 in a matrix-free system. PARTICIPANTS/MATERIALS SETTING METHODS: Secondary follicles, extracted via enzymatic digestion and mechanical disruption from each patient, were randomly allocated to either a control group or an NT4-supplemented group (100 ng/ml), followed by individual culture on an ultra-low attachment plate. Follicle growth and viability were assessed by microscopy. Levels of anti-Müllerian hormone (AMH), estradiol, and progesterone in the medium were quantified. An oocyte-specific marker was identified using confocal fluorescence microscopy following DEAD box polypeptide 4 (DDX4) staining. The competence of individual oocytes for maturation and fertilization were assessed after IVM and ICSI with donated sperm samples. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, isolated follicles from both groups survived up to 6 weeks with increasing diameters over the duration (P < 0.05), reaching terminal diameters of almost 1 mm with confirmed steroidogenesis and expression of oocyte marker (DDX4), and producing morphologically normal MII oocytes. When compared with the control group, the NT4 group had a similar initial follicular diameter (206 ± 61.3 vs 184 ± 93.4 µm) but exhibited a significant increase in follicular diameter from the ninth day of culture onwards (P < 0.05). From Week 3, estradiol and progesterone production were significantly increased in the NT4 group, while no significant difference was observed in AMH production between groups. The proportion of 'fast-growth' follicles in the NT4 group was significantly higher than that in the control group (13/23 vs 6/24, P < 0.05). An increased efficiency of MII oocyte maturation per live follicle in the NT4 group was also observed (control group vs NT4 group, 4/24 vs 10/23, P < 0.05). It is noteworthy that an MII oocyte obtained from the control group exhibited abnormal fertilization after ICSI. In contrast, an MII oocyte acquired from the NT4 group progressed to the blastocyst stage and showed potential for transfer. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The cohort examined in this study was all patients diagnosed with beta-thalassemia major. Whether this culture system is effective for patients with other diseases remains unknown. Since the chosen dose of NT4 was established based on dose finding in mice, the optimal dose for use in a human IVG system needs further confirmation. The oocytes and embryos procured from this study have not been quantified for ploidy status or epigenetic signatures. WIDER IMPLICATIONS OF THE FINDINGS: Fresh medulla tissue obtained during tissue preparation for OTC may serve as a precious source of fertilizable oocytes for female fertility preservation, even for pre-pubertal girls, without the threat of tumour reintroduction. After further characterization and optimization of the system, this culture system holds the potential to provide a powerful future research tool, for the comprehensive exploration of human follicular development mechanisms and for conducting reproductive toxicity evaluations. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Key R&D Program of China (grant number 2022YFC2703000) and National Natural Science Foundation of China (grant numbers 82271651 and 81871214). The medium used in human follicle in vitro culture in this study has been applied for a national invention patent in China (No. 202211330660.7). The inventors of the patent, in order, are: Y.G., C.F., and X.L.

Predictors of Cognitive Functions After Stroke Assessed Using the Wechsler Adult Intelligence Scale: A Retrospective Study.

Background: The mechanism(s) of cognitive impairment remains complex, making it difficult to confirm the factors influencing poststroke cognitive impairment (PSCI). Objective: This study quantitatively investigated the degree of influence and interactions of clinical indicators of PSCI. Methods: Information from 270 patients with PSCI and their Wechsler Adult Intelligence Scale (WAIS-RC) scores, totaling 18 indicators, were retrospectively collected. Correlations between the indicators and WAIS scores were calculated. Multiple linear regression model(MLR), genetic algorithm modified Back-Propagation neural network(GA-BP), logistic regression model (LR), XGBoost model (XGB), and structural equation model were used to analyze the degree of influence of factors on the WAIS and their mediating effects. Results: Seven indicators were significantly correlated with the WAIS scores: education, lesion side, aphasia, frontal lobe, temporal lobe, diffuse lesions, and disease course. The MLR showed significant effect of education, lesion side, aphasia, diffuse lesions, and frontal lobe on the WAIS. The GA-BP included five factors: education, aphasia, frontal lobe, temporal lobe, and diffuse lesions. LR predicted that the lesion side contributed more to mild cognitive impairment, while education, lesion side, aphasia, and course of the disease contributed more to severe cognitive impairment. XGB showed that education, side of the lesion, aphasia, and diffuse lesions contributed the most to PSCI. Aphasia plays a significant mediating role in patients with severe PSCI. Conclusions: Education, lesion side, aphasia, frontal lobe, and diffuse lesions significantly affected PSCI. Aphasia is a mediating variable between clinical information and the WAIS in patients with severe PSCI.

The effects of rTMS on motor recovery after stroke: a systematic review of fMRI studies.

Repetitive transcranial magnetic stimulation (rTMS) has been widely used in motor rehabilitation after stroke, and functional magnetic resonance imaging (fMRI) has been used to investigate the neural mechanisms of motor recovery during stroke therapy. However, there is no review on the mechanism of rTMS intervention for motor recovery after stroke based on fMRI explicitly. We aim to reveal and summarize the neural mechanism of the effects of rTMS on motor function after stroke as measured by fMRI. We carefully performed a literature search using PubMed, EMBASE, Web of Science, and Cochrane Library databases from their respective inceptions to November 2022 to identify any relevant randomized controlled trials. Researchers independently screened the literature, extracted data, and qualitatively described the included studies. Eleven studies with a total of 420 poststroke patients were finally included in this systematic review. A total of 338 of those participants received fMRI examinations before and after rTMS intervention. Five studies reported the effects of rTMS on activation of brain regions, and four studies reported results related to brain functional connectivity (FC). Additionally, five studies analyzed the correlation between fMRI and motor evaluation. The neural mechanism of rTMS in improving motor function after stroke may be the activation and FCs of motor-related brain areas, including enhancement of the activation of motor-related brain areas in the affected hemisphere, inhibition of the activation of motor-related brain areas in the unaffected hemisphere, and changing the FCs of intra-hemispheric and inter-hemispheric motor networks.

Advances in the investigation of the role of autophagy in the etiology of chronic obstructive pulmonary disease: A review.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory illness. It arises from emphysema and chronic bronchitis and is characterized by progressive and irreversible airflow limitation and chronic inflammation of the lungs, which eventually progresses to pulmonary hypertension, chronic pulmonary heart disease and respiratory failure. Autophagy is a highly conserved cellular homeostasis maintenance mechanism that involves the transport of damaged organelles and proteins to lysosomes for destruction. Dysregulation of autophagy is one of the pathogenic mechanisms of many diseases and is strongly associated with the development of COPD, although the precise mechanisms are unknown. In this paper, we focus on macroautophagy, a type of autophagy that has been thoroughly studied, and describe the characteristics, processes, regulatory pathways, and functions of autophagy, and discuss its relationship with COPD from the perspectives of inflammation, emphysema, mucus hypersecretion, cilia structure and function, airway remodeling, vascular remodeling, and bacterial infections, with a view to searching for the therapeutic targets of COPD from the perspective of autophagy, which is hoped to be helpful for the clinical treatment.

Different doses of intermittent theta burst stimulation for upper limb motor dysfunction after stroke: a study protocol for a randomized controlled trial.

Background: Upper limb motor recovery is one of the important goals of stroke rehabilitation. Intermittent theta burst stimulation (iTBS), a new type of repetitive transcranial magnetic stimulation (rTMS), is considered a potential therapy. However, there is still no consensus on the efficacy of iTBS for upper limb motor dysfunction after stroke. Stimulus dose may be an important factor affecting the efficacy of iTBS. Therefore, we aim to investigate and compare the effects and neural mechanisms of three doses of iTBS on upper limb motor recovery in stroke patients, and our hypothesis is that the higher the dose of iTBS, the greater the improvement in upper limb motor function. Methods: This prospective, randomized, controlled trial will recruit 56 stroke patients with upper limb motor dysfunction. All participants will be randomized in a 1:1:1:1 ratio to receive 21 sessions of 600 pulses active iTBS, 1,200 pulses active iTBS, 1,800 pulses active iTBS, or 1,800 pulses sham iTBS in addition to conventional rehabilitation training. The primary outcome is the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score from baseline to end of intervention, and the secondary outcomes are the Wolf Motor Function Test (WMFT), Grip Strength (GS), Modified Barthel Index (MBI), and Stroke Impact Scale (SIS). The FMA-UE, MBI, and SIS are assessed pre-treatment, post-treatment, and at the 3-weeks follow-up. The WMFT, GS, and resting-state functional magnetic resonance imaging (rs-fMRI) data will be obtained pre- and post-treatment. Discussion: The iTBS intervention in this study protocol is expected to be a potential method to promote upper limb motor recovery after stroke, and the results may provide supportive evidence for the optimal dose of iTBS intervention.

Brassinosteroids affect wood development and properties of Fraxinus mandshurica.

Introduction: Xylem development plays a crucial role in wood formation in woody plants. In recent years, there has been growing attention towards the impact of brassinosteroids (BRs) on this xylem development. In the present study, we evaluated the dynamic variation of xylem development in Fraxinus mandshurica (female parent, M8) and a novel interspecific hybrid F. mandshurica × Fraxinus sogdiana (1601) from May to August 2020. Methods: We obtained RNA-Seq transcriptomes of three tissue types (xylem, phloem, and leaf) to identify the differences in xylem-differentially expressed genes (X-DEGs) and xylem-specifically expressed genes (X-SEGs) in M8 and 1601 variants. We then further evaluated these genes via weighted gene co-expression network analysis (WGCNA) alongside overexpressing FmCPD, a BR biosynthesis enzyme gene, in transient transgenic F. mandshurica. Results: Our results indicated that the xylem development cycle of 1601 was extended by 2 weeks compared to that of M8. In addition, during the later wood development stages (secondary wall thickening) of 1601, an increased cellulose content (14%) and a reduced lignin content (11%) was observed. Furthermore, vessel length and width increased by 67% and 37%, respectively, in 1601 compared with those of M8. A total of 4589 X-DEGs were identified, including enzymes related to phenylpropane metabolism, galactose metabolism, BR synthesis, and signal transduction pathways. WGCNA identified hub X-SEGs involved in cellulose synthesis and BR signaling in the 1601 wood formation-related module (CESA8, COR1, C3H14, and C3H15); in contrast, genes involved in phenylpropane metabolism were significantly enriched in the M8 wood formation-related module (CCoAOMT and CCR). Moreover, overexpression of FmCPD in transient transgenic F. mandshurica affected the expression of genes associated with lignin and cellulose biosynthesis signal transduction. Finally, BR content was determined to be approximately 20% lower in the M8 xylem than in the 1601 xylem, and the exogenous application of BRs (24-epi brassinolide) significantly increased the number of xylem cell layers and altered the composition of the secondary cell walls in F. mandshurica. Discussion: Our findings suggest that BR biosynthesis and signaling play a critical role in the differing wood development and properties observed between M8 and 1601 F. mandshurica.

Effects of excitatory transcranial magnetic stimulation over the different cerebral hemispheres dorsolateral prefrontal cortex for post-stroke cognitive impairment: a systematic review and meta-analysis.

Background: Post-stroke cognitive impairment (PSCI) is a significant health concern. Transcranial magnetic stimulation (TMS) is considered a promising rehabilitation therapy for improving cognition, and the effects of excitatory TMS on PSCI have received much attention in recent years. However, the effects of different cerebral hemispheres on excitatory TMS treatment of cognitive impairment have not been studied. This review aimed to study the effects of excitatory TMS over the dorsolateral prefrontal cortex (DLPFC) of different cerebral hemispheres on the cognitive function of patients with PSCI. Methods: Literature published in PubMed, Web of Science, Embase, Cochrane Library, Scopus, and Wiley from inception to September 30, 2022, were searched. Two researchers independently performed literature screening, data extraction, and quality assessment. Furthermore, we conducted a meta-analysis using RevMan software (version 5.4) and rated the strength of evidence using GRADEpro. Results: A total of 19 studies were included in this meta-analysis. The results showed that excitatory TMS over the left hemisphere DLPFC was significantly better in improving global cognition (SMD = 2.26, 95% CI 1.67-2.86, P < 0.00001; vs. SMD = 2.53, 95% CI 1.86-3.20, P < 0.00001), memory (SMD = 1.29, 95% CI 0.72-1.87, P < 0.0001), attention (SMD = 2.32, 95% CI 1.64-3.01, P < 0.00001), executive (SMD = 0.64, 95% CI 0.21-1.07, P = 0.004), P300 latency (SMD = 2.69, 95% CI 2.13-3.25, P < 0.00001), and depression (SMD = 0.95, 95% CI 0.26-1.63, P = 0.007) than that of the control group, but the effect on improving activities of daily living (ADL) was unclear (P = 0.03 vs. P = 0.17). Subgroup analysis further showed that excitatory TMS over the right hemisphere DLPFC was effective in improving the global cognition of PSCI patients (P < 0.00001), but the stimulation effect over the ipsilateral hemisphere DLPFC was unclear (P = 0.11 vs. P = 0.003). Additionally, excitatory TMS over the ipsilateral hemisphere DLPFC showed no statistical difference in improving ADL between the two groups (P = 0.25). Conclusions: Compared to other hemispheric sides, excitatory TMS over the left hemisphere DLPFC was a more effective stimulation area, which can significantly improved the global cognitive function, memory, attention, executive, P300 latency, and depression in patients with PSCI. There was no apparent therapeutic effect on improving activities of daily living (ADL). In the future, more randomized controlled trials with large-sample, high quality, and follow-up are necessary to explore a usable protocol further. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022369096.

Characteristics of cognition impairment in patients after stroke based on the Wechsler Adult Intelligence Scale-Revised in China.

We aimed to explore the cognitive characteristics of patients with post-stroke cognition impairment (PSCI) on the basis of the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC) and the individual contribution of the subtests to WAIS score. We included 227 patients with PSCI who were assessed using the WAIS-RC. We described the characteristics and score distribution of the scale and subtests individually and compared them with those of the normal group to measure the damage degree of these patients. We performed item response theory analysis to explore the best criterion score for all dimensions that allowed ideal discrimination and difficulty for reflecting cognitive level. Finally, we analyzed the contribution of each dimension to the overall cognitive function. Patients with PSCI showed worse cognition levels than healthy individuals in terms of overall intelligence quotient (73.26-100, -1.78 SD), with a difference of 4.54-7.96 points in each dimension (-0.68 to -1.82 SD), and a range of 5-7 points is the appropriate range for reflecting cognitive ability in patients with PSCI. The average cognitive level of patients with PSCI was significantly inferior to normal people (-1.78 SD, 96.25%). Vocabulary contributes most to WAIS score.

Corrigendum: Prediction of motor function in patients with traumatic brain injury using genetic algorithms modified back propagation neural network: a data-based study.

[This corrects the article DOI: 10.3389/fnins.2022.1031712.].

The anticancer mechanism of Terpenoid-based drug candi-dates: focus on tumor microenvironment.

Cancer is considered to be the most lethal threat to human life globally. Although, versatile strategies have been established in the field of surgery, chemotherapy, radiotherapy and im-munotherapy against cancer, discovery of new therapeutic drugs from natural products still un-derlays anticancer remedy due to their unique functional mechanisms and potential low side ef-fects. Terpenoids are among the most diversified and enormous natural products which have been proved promising in cancer treatment. Some terpenoids have been through multiple stages of clinical trials and some even approved as anticancer agent, but most of these studies empha-sized the direct effects on tumor cells while paying less attention to their systemic effects on tu-mor microenvironment (TME) Therefore, we recruited the patent drugs and investigated drug candidates of terpenoids in this review and summarized their general anti-tumor mechanisms among which the regulation on TME was highlighted. Finally, the prospect on the drug ability of terpenoids and their potential benefits in immunotherapy were discussed to illuminate fur-ther researches on these natural products. Keywords.

Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis.

Objective: An analysis of the relationship between rheumatoid arthritis (RA) and copper death-related genes (CRG) was explored based on the GEO dataset. Methods: Based on the differential gene expression profiles in the GSE93272 dataset, their relationship to CRG and immune signature were analysed. Using 232 RA samples, molecular clusters with CRG were delineated and analysed for expression and immune infiltration. Genes specific to the CRGcluster were identified by the WGCNA algorithm. Four machine learning models were then built and validated after selecting the optimal model to obtain the significant predicted genes, and validated by constructing RA rat models. Results: The location of the 13 CRGs on the chromosome was determined and, except for GCSH. LIPT1, FDX1, DLD, DBT, LIAS and ATP7A were expressed at significantly higher levels in RA samples than in non-RA, and DLST was significantly lower. RA samples were significantly expressed in immune cells such as B cells memory and differentially expressed genes such as LIPT1 were also strongly associated with the presence of immune infiltration. Two copper death-related molecular clusters were identified in RA samples. A higher level of immune infiltration and expression of CRGcluster C2 was found in the RA population. There were 314 crossover genes between the 2 molecular clusters, which were further divided into two molecular clusters. A significant difference in immune infiltration and expression levels was found between the two. Based on the five genes obtained from the RF model (AUC = 0.843), the Nomogram model, calibration curve and DCA also demonstrated their accuracy in predicting RA subtypes. The expression levels of the five genes were significantly higher in RA samples than in non-RA, and the ROC curves demonstrated their better predictive effect. Identification of predictive genes by RA animal model experiments was also confirmed. Conclusion: This study provides some insight into the correlation between rheumatoid arthritis and copper mortality, as well as a predictive model that is expected to support the development of targeted treatment options in the future.

Artificial oocyte activation with ionomycin compared with A23187 among patients at risk of failed or impaired fertilization.

RESEARCH QUESTION: Do fertilization rates differ between intracytoplasmic sperm injection (ICSI) cycles treated with artificial oocyte activation (AOA) using 10 µmol/l ionomycin or commercial A23187 in women at risk of failed or impaired fertilization? DESIGN: This single-centre, 7-year retrospective cohort study included 157 couples with a history of total fertilization failure (TFF, 0%) or low fertilization (<30%) after ICSI, or with severe oligo-astheno-teratozoospermia (OAT) in the male partner. Couples and underwent 171 ICSI-AOA cycles using either 10 µmol/l ionomycin or commercial A23187. The embryological and clinical outcomes were compared. RESULTS: Fertilization rates in the ionomycin group were significantly higher than those in the A23187 group for all three subgroups (TFF, 46.9% versus 28.4%, P = 0.002; low fertilization, 67.7% versus 49.2%, P < 0.001; severe OAT, 66.4% versus 31.6%, P < 0.001). AOA with ionomycin significantly increased the day 3 cleavage rate (P = 0.009) when compared with A23187 in the low fertilization group, but not in the TFF or severe OAT group (both P > 0.05). The rates of day 3 good-quality embryos, clinical pregnancy, implantation and live birth, and the cumulative live birth, did not differ between the two groups (all P > 0.05). A total of 64 live births resulted in 72 healthy babies born. CONCLUSIONS: AOA with 10 µmol/l ionomycin may be more effective than commercial A23187 in improving oocyte activation in patients at risk of failed or impaired fertilization, especially in cases of sperm-related defects.

Effects of combined cognitive and physical intervention on enhancing cognition in older adults with and without mild cognitive impairment: A systematic review and meta-analysis.

Background: Combined cognitive and physical intervention is commonly used as a non-pharmacological therapy to improve cognitive function in older adults, but it is uncertain whether combined intervention can produce stronger cognitive gains than either single cognitive or sham intervention. To address this uncertainty, we performed a systematic review and meta-analysis to evaluate the effects of combined intervention on cognition in older adults with and without mild cognitive impairment (MCI). Methods: We systematically searched eight databases for relevant articles published from inception to November 1, 2021. Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) were used to compare the effects of the combined intervention with a single cognitive or sham intervention on cognition in older adults with and without MCI aged ≥ 50 years. We also searched Google Scholar, references of the included articles, and relevant reviews. Two independent reviewers performed the article screening, data extraction, and bias assessment. GRADEpro was used to rate the strength of evidence, and RevMan software was used to perform the meta-analysis. Results: Seventeen studies were included in the analysis, comprising eight studies of cognitively healthy older adults and nine studies of older adults with MCI. The meta-analysis showed that the combined intervention significantly improved most cognitive functions and depression (SMD = 0.99, 95% CI 0.54-1.43, p < 0.0001) in older adults compared to the control groups, but the intervention effects varied by cognition domains. However, there was no statistically significant difference in the maintenance between the combined and sham interventions (SMD = 1.34, 95% CI -0.58-3.27, p = 0.17). The subgroup analysis also showed that there was no statistical difference in the combined intervention to improve global cognition, memory, attention, and executive function between cognitive healthy older adults and older adults with MCI. Conclusions: Combined intervention improves cognitive functions in older adults with and without MCI, especially in global cognition, memory, and executive function. However, there was no statistical difference in the efficacy of the combined intervention to improve cognition between cognitive healthy older adults and older adults with MCI. Moreover, the maintenance of the combined intervention remains unclear due to the limited follow-up data and high heterogeneity. In the future, more stringent study designs with more follow-ups are needed further to explore the effects of combined intervention in older adults. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42021292490.

Exercise Training for Mild Cognitive Impairment Adults Older Than 60: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of mild cognitive impairment (MCI) continues to increase due to population aging. Exercise has been a supporting health strategy that may elicit beneficial effects on cognitive function and prevent dementia. OBJECTIVE: This study aimed to examine the effects of aerobic, resistance, and multimodal exercise training on cognition in adults aged > 60 years with MCI. METHODS: We searched the Cochrane Library, PubMed, and Embase databases and ClinicalTrials.gov (https://clinicaltrials.gov) up to November 2021, with no language restrictions. We included all published randomized controlled trials (RCTs) comparing the effect of exercise programs on cognitive function with any other active intervention or no intervention in participants with MCI aged > 60 years. RESULTS: Twelve RCTs were included in this review. Meta-analysis results revealed significant improvements in resistance training on measures of executive function (p < 0.05) and attention (p < 0.05); no significant differences were observed between aerobic exercise and controls on any of the cognitive comparisons. CONCLUSION: Exercise training had a small beneficial effect on executive function and attention in older adults with MCI. Larger studies are required to examine the effects of exercise and the possible moderators.

Prediction of motor function in patients with traumatic brain injury using genetic algorithms modified back propagation neural network: A data-based study.

Objective: Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. In this study, the characteristics of the patients, who were admitted to the China Rehabilitation Research Center, were elucidated in the TBI database, and a prediction model based on the Fugl-Meyer assessment scale (FMA) was established using this database. Methods: A retrospective analysis of 463 TBI patients, who were hospitalized from June 2016 to June 2020, was performed. The data of the patients used for this study included the age and gender of the patients, course of TBI, complications, and concurrent dysfunctions, which were assessed using FMA and other measures. The information was collected at the time of admission to the hospital and 1 month after hospitalization. After 1 month, a prediction model, based on the correlation analyses and a 1-layer genetic algorithms modified back propagation (GA-BP) neural network with 175 patients, was established to predict the FMA. The correlations between the predicted and actual values of 58 patients (prediction set) were described. Results: Most of the TBI patients, included in this study, had severe conditions (70%). The main causes of the TBI were car accidents (56.59%), while the most common complication and dysfunctions were hydrocephalus (46.44%) and cognitive and motor dysfunction (65.23 and 63.50%), respectively. A total of 233 patients were used in the prediction model, studying the 11 prognostic factors, such as gender, course of the disease, epilepsy, and hydrocephalus. The correlation between the predicted and the actual value of 58 patients was R 2 = 0.95. Conclusion: The genetic algorithms modified back propagation neural network can predict motor function in patients with traumatic brain injury, which can be used as a reference for risk and prognosis assessment and guide clinical decision-making.

Diagnostic efficiency of blastocyst culture medium in noninvasive preimplantation genetic testing.

OBJECTIVE: To evaluate the diagnostic efficiency of spent blastocyst culture medium (BCM) in noninvasive preimplantation genetic testing (niPGT) by comparing the karyotype concordance with corresponding inner cell mass (ICM) among initial trophectoderm (TE) biopsy, TE re-biopsy, and BCM sampling. DESIGN: Re-analysis aneuploid/mosaic blastocysts donated for research by couples. SETTING: Institutional in vitro fertilization center. PATIENTS: A total of 12 couples donated their blastocysts, which had previously been diagnosed as aneuploid or mosaic by initial TE-biopsy preimplantation genetic testing for aneuploidy (PGT-A) for research. INTERVENTIONS: A total of 26 frozen-thawed blastocysts were re-analyzed by TE re-biopsy, ICM biopsy, and the collection of spent BCM. MAIN OUTCOME MEASURES: Karyotype concordance rates. RESULTS: For 23 embryos diagnosed as aneuploid by initial TE biopsy, 78.3% of initial TE samples, 87.0% of TE re-biopsies samples, and 78.3% of BCM samples were concordant with corresponding ICM samples, and for three mosaic embryos, the concordance rates with ICM of these three groups were 0%, 100%, and 100%, respectively. With the corresponding ICM result as the true result, sensitivity of both niPGT-A and initial TE were 100%; however, the false-positive rate (FPR) of initial TE was higher than that of niPGT-A (100% vs. 0). CONCLUSIONS: niPGT-A using BCM had diagnostic efficiency similar to that of TE-biopsy PGT-A. In the case of mosaic embryos, niPGT-A using BCM may be more reliable for predicting karyotypes of ICM than initial TE biopsy.

Fraxinus mandshurica 4-coumarate-CoA ligase 2 enhances drought and osmotic stress tolerance of tobacco by increasing coniferyl alcohol content.

4-Coumarate-CoA ligase (4CL) is an important branch point in the phenylpropane pathway and plays important roles in plant growth and development. In this study, the 4CL2 gene from Fraxinus mandshurica (designated Fm4CL2) was identified and isolated. Sequence analysis revealed that Fm4CL2 is a type I 4CL gene involved in lignin biosynthesis. Analysis of cell wall components revealed that Fm4CL2-overexpressing (OE-Fm4CL2) tobacco showed increased lignin content (by 58.9%) and decreased hemicellulose content (by 41.2%). Detection of small-molecule metabolites in the lignin pathway revealed that coumaric acid content decreased by 48% and coniferyl alcohol content increased by 250% compared with the control values. Compared with wild type, OE-Fm4CL2 tobacco showed increased xylem cell layer number (by 120%) and cell wall thickness (by 54.5%). Under osmotic stress, transgenic tobacco showed higher growth than wild-type tobacco. The germination rate of transgenic tobacco was higher than that of wild type. Reactive oxygen species accumulation and malondialdehyde content were significantly lower in transgenic tobacco than in wild type. Under drought, the expression of stress-related genes was higher in 35S-Fm4CL2-infected Fraxinus mandshurica plants than in control plants. These results indicate that Fm4CL2 overexpression can enhance drought and osmotic stress tolerance of plants.

Zebularine significantly improves the preimplantation development of ovine somatic cell nuclear transfer embryos.

Aberrant DNA methylation reduces the developmental competence of mammalian somatic cell nuclear transfer (SCNT) embryos. Thus, hypomethylation-associated drugs are beneficial for improving reprogramming efficiency. Therefore, in the present study we investigated the effect of zebularine, a relatively novel DNA methyltransferase inhibitor, on the developmental potential of ovine SCNT embryos. First, reduced overall DNA methylation patterns and gene-specific DNA methylation levels at the promoter regions of pluripotency genes (octamer-binding transcription factor 4 (Oct4), SRY (sex determining region Y)-box 2 (Sox2) and Nanog) were found in zebularine-treated cumulus cells. In addition, the DNA methylation levels in SCNT embryos derived from zebularine-treated cumulus cells were significantly reduced at the 2-, 4-, 8-cell, and blastocyst stages compared with their corresponding controls (P<0.05). The blastocyst rate was significantly improved in SCNT embryos reconstructed by the cumulus donor cells treated with 5nM zebularine for 12h compared with the control group (25.4±1.6 vs 11.8±1.7%, P<0.05). Moreover, the abundance of Oct4 and Sox2 mRNA was significantly increased during the preimplantation stages after zebularine treatment (P<0.05). In conclusion, the results indicate that, in an ovine model, zebularine decreases overall DNA methylation levels in donor cumulus cells and reconstructed embryos, downregulates the DNA methylation profile in the promoter region of pluripotency genes in donor cells and ultimately elevates the expression of pluripotency genes in the reconstructed embryos, which can lead to improved development of SCNT embryos.

Intranasal oxytocin administration improves depression-like behaviors in adult rats that experienced neonatal maternal deprivation.

Oxytocin (OT), a hypothalamic neuropeptide, has been implicated in the regulation of social behaviors in rodents and humans. This study assessed the effects of intranasal administration of OT on depressive-like behaviors and hippocampal neurogenesis in adult rats following neonatal maternal deprivation (NMD). Here, we show that NMD resulted in significant depression-like behaviors, as indicated by decreases in physical activity and emotional reactivity in a novel environment, in 2-month-old animals. Notably, the OT levels in the plasma, hypothalamus, and hippocampus were decreased in these animals. Intranasal administration of OT reduced the depressive-like behaviors in NMD rats and rescued hippocampal long-term plasticity impaired by NMD stress in rats by promoting hippocampal neurogenesis. These results indicate that OT alleviates the depressive-like behaviors in NMD adult rats, probably mediated by improving adult hippocampal neurogenesis.