Multiple processes of vocal sensory-motor interaction in primate auditory cortex.

Sensory-motor interactions in the auditory system play an important role in vocal self-monitoring and control. These result from top-down corollary discharges, relaying predictions about vocal timing and acoustics. Recent evidence suggests such signals may be two distinct processes, one suppressing neural activity during vocalization and another enhancing sensitivity to sensory feedback, rather than a single mechanism. Single-neuron recordings have been unable to disambiguate due to overlap of motor signals with sensory inputs. Here, we sought to disentangle these processes in marmoset auditory cortex during production of multi-phrased 'twitter' vocalizations. Temporal responses revealed two timescales of vocal suppression: temporally-precise phasic suppression during phrases and sustained tonic suppression. Both components were present within individual neurons, however, phasic suppression presented broadly regardless of frequency tuning (gating), while tonic was selective for vocal frequencies and feedback (prediction). This suggests that auditory cortex is modulated by concurrent corollary discharges during vocalization, with different computational mechanisms.

Synergistic effect of chitosan and ß-carotene in inhibiting MNU-induced retinitis pigmentosa.

In this study, N-Methyl-N-nitrosourea (MNU) was intraperitoneally injected to construct a mouse retinitis pigmentosa (RP) model to evaluate the protective effect of chitosan and ß-carotene on RP. The results demonstrated that chitosan synergized with ß-carotene significantly reduced retinal histopathological structural damage in RP mice. The co-treatment group of ß-carotene and chitosan restored the retinal thickness and outer nuclear layer thickness better than the group treated with the two alone, and the thickness reached the normal level. The content of ß-carotene and retinoids in the liver of chitosan and ß-carotene co-treated group increased by 46.75 % and 20.69 %, respectively, compared to the ß-carotene group. Chitosan and ß-carotene supplement suppressed the expressions of Bax, Calpain2, Caspase3, NF-κB, TNF-α, IL-6, and IL-1ß, and promoted the up-regulation of Bcl2. Chitosan and ß-carotene interventions remarkably contributed to the content of SCFAs and enhanced the abundance of Ruminococcaceae, Rikenellaceae, Odoribacteraceae and Helicobacteraceae. Correlation analysis demonstrated a strong association between gut microbiota and improvement in retinitis pigmentosa. This study will provide a reference for the study of the gut-eye axis.

Sex differences in anhedonia in bipolar depression: a resting-state fMRI study.

Previous studies about anhedonia symptoms in bipolar depression (BD) ignored the unique role of gender on brain function. This study aims to explore the regional brain neuroimaging features of BD with anhedonia and the sex differences in these patients. The resting-fMRI by applying fractional amplitude of low-frequency fluctuation (fALFF) method was estimated in 263 patients with BD (174 high anhedonia [HA], 89 low anhedonia [LA]) and 213 healthy controls. The effects of two different factors in patients with BD were analyzed using a 3 (group: HA, LA, HC) × 2 (sex: male, female) ANOVA. The fALFF values were higher in the HA group than in the LA group in the right medial cingulate gyrus and supplementary motor area. For the sex-by-group interaction, the fALFF values of the right hippocampus, left medial occipital gyrus, right insula, and bilateral medial cingulate gyrus were significantly higher in HA males than in LA males but not females. These results suggested that the pattern of high activation could be a marker of anhedonia symptoms in BD males, and the sex differences should be considered in future studies of BD with anhedonia symptoms.

Simple and sensitive sandwich-like electrochemical immunosensing strategy for D-dimer based on cyclodextrin-carbon nanotube and nanogold-ferrocene.

D-dimer is a very important biomarker about sepsis, pulmonary thromboembolism and atherosclerosis, thus designing effective and sensitive method for its detection is of great significance. Herein, by synthesizing ß-cyclodextrin-carbon nanotube nanohybrid (CNTs-CD) as the carrier to assemble the initial antibody (Ab1) of D-dimer, immobilizing secondary antibody (Ab2) and sulfydryl ferrocene (Fc) on the nanogold (Au) particles surface as the signaling amplifier (Ab2-Au-Fc), a low cost, simple, sensitive and effective sandwich-like electrochemical immunosensing (SEI) platform of D-dimer was proposed in this work for the first time. Briefly, CNTs shows large specific area and superior electroconductivity, and CD provides high host guest recognition ability that could bound with Ab1; meanwhile, the Fc probe offers stable current response which are proportionable positively to the level of D-dimer. Under the best conditions, the designed SEI platform exhibits prominent analytical performances for D-dimer: low detection limit of 3.0 ng mL-1 and large linearity of 10.0-800.0 ng mL-1. In addition, the selectivity, stability and reproducibility as well as real applications of the proposed SEI assay were evaluated and the obtained results are satisfactory.

Ghrelin alleviates placental dysfunction by down-regulating NF-κB phosphorylation in LPS-induced rat model of preeclampsia.

In our previous study, we uncovered that ghrelin promotes angiogenesis in human umbilical vein endothelial cells (HUVECs) in vitro by activating the Jagged1/Notch2/VEGF pathway in preeclampsia (PE). However, the regulatory effects of ghrelin on placental dysfunction in PE are unclear. Therefore, we applied Normal pregnant Sprague-Dawley (SD) rats, treated with lipopolysaccharide (LPS), to establish a PE-like rat model. The hematoxylin-eosin (HE) staining method and immunohistochemistry (IHC) technology were used to detect morphological features of the placenta. IHC and Western blot were applied to examine Bax and Bcl-2 expression levels. The concentrations of serum soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PIGF) were assessed by enzyme-linked immunosorbent assay (ELISA) kit. In addition, the apoptosis rates of JEG-3 and HTR-8/SVneo trophoblast cells were determined by Annexin V-FITC/PI apoptosis detection kit. Cell migratory capacities were assessed by scratch-wound assay, and RNA-sequencing assay was used to determine the mechanism of ghrelin in regulating trophoblast apoptosis. It has been found that ghrelin significantly reduced blood pressure, urinary protein, and urine creatinine in rats with PE, at the meanwhile, ameliorated placental and fetal injuries. Second, ghrelin clearly inhibited placental Bax expression and circulating sFlt-1 as well as elevated placental Bcl-2 expression and circulating PIGF, restored apoptosis and invasion deficiency of trophoblast cells caused by LPS in vitro. Finally, transcriptomics indicated that nuclear factor kappa B (NF-κB) was the potential downstream pathway of ghrelin. Our findings illustrated that ghrelin supplementation significantly improved LPS-induced PE-like symptoms and adverse pregnancy outcomes in rats by alleviating placental apoptosis and promoting trophoblast migration.

Unlocking PD-1 antibody resistance: The MUC1 DNA vaccine augments CD8+ T cell infiltration and attenuates tumour suppression.

In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in-depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra-tumoural T-cell ratios or in the functionality of T-cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8+ T cells by elevating IFN-γ and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single-agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro-immunogenic conditions. This assertion is backed by a raised CD8+/CD4+ T-cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T-cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T-cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti-tumour immunity through the application of innovative therapeutic strategies.

Robust reactive oxygen species modulator hitchhiking yeast microcapsules for colitis alleviation by trilogically intestinal microenvironment renovation.

Ulcerative colitis (UC) is characterized by chronic inflammatory processes of the intestinal tract of unknown origin. Current treatments lack understanding on how to effectively alleviate oxidative stress, relieve inflammation, as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously. In this study, a novel drug delivery system based on a metal polyphenol network (MPN) was constructed via metal coordination between epigallocatechin gallate (EGCG) and Fe3+. Curcumin (Cur), an active polyphenolic compound, with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN. The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical (O2•-) as well as hydroxyl radical (·OH). By hitchhiking yeast microcapsule (YM), Cur-MPN was then encapsulated into YM to obtain CM@YM. Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon. When administered orally, CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS, reducing pro-inflammatory cytokines, and regulating the polarization of macrophages to M1, thus restoring barrier function and maintaining intestinal homeostasis. Importantly, CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids (SCFA) (such as acetic acid, propionic acid, and butyric acid). Collectively, with excellent biocompatibility, our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.

Comprehensive analysis of the aldehyde dehydrogenase gene family in Phaseolus vulgaris L. and their response to saline-alkali stress.

Background: Aldehyde dehydrogenase (ALDH) scavenges toxic aldehyde molecules by catalyzing the oxidation of aldehydes to carboxylic acids. Although ALDH gene family members in various plants have been extensively studied and were found to regulate plant response to abiotic stress, reports on ALDH genes in the common bean (Phaseolus vulgaris L.) are limited. In this study, we aimed to investigate the effects of neutral (NS) and basic alkaline (AS) stresses on growth, physiological and biochemical indices, and ALDH activity, ALDH gene expression of common bean. In addition, We used bioinformatics techniques to analyze the physical and chemical properties, phylogenetic relationships, gene replication, collinearity, cis-acting elements, gene structure, motifs, and protein structural characteristics of PvALDH family members. Results: We found that both NS and AS stresses weakened the photosynthetic performance of the leaves, induced oxidative stress, inhibited common bean growth, and enhanced the antioxidative system to scavenge reactive oxygen species. Furthermore, we our findings revealed that ALDH in the common bean actively responds to NS or AS stress by inducing the expression of PvALDH genes. In addition, using the established classification criteria and phylogenetic analysis, 27 PvALDHs were identified in the common bean genome, belonging to 10 ALDH families. The primary expansion mode of PvALDH genes was segmental duplication. Cis-acting elemental analysis showed that PvALDHs were associated with abiotic stress and phytohormonal responses. Gene expression analysis revealed that the PvALDH gene expression was tissue-specific. For instance, PvALDH3F1 and PvALDH3H1 were highly expressed in flower buds and flowers, respectively, whereas PvALDH3H2 and PvALDH2B4 were highly expressed in green mature pods and young pods, respectively. PvALDH22A1 and PvALDH11A2 were highly expressed in leaves and young trifoliates, respectively; PvALDH18B2 and PvALDH18B3 were highly expressed in stems and nodules, respectively; and PvALDH2C2 and PvALDH2C3 were highly expressed in the roots. PvALDHs expression in the roots responded positively to NS-AS stress, and PvALDH2C3, PvALDH5F1, and PvALDH10A1 were significantly (P < 0.05) upregulated in the roots. Conclusion: These results indicate that AS stress causes higher levels of oxidative damage than NS stress, resulting in weaker photosynthetic performance and more significant inhibition of common bean growth. The influence of PvALDHs potentially modulates abiotic stress response, particularly in the context of saline-alkali stress. These findings establish a basis for future research into the potential roles of ALDHs in the common bean.

Diversely regio-oxidative degradation of konjac glucomannan by lytic polysaccharide monooxygenase AA10 and generating antibacterial hydrolysate.

Konjac glucomannan (KGM) hydrolysate exhibit various biological activities and health-promoting effects. Lytic polysaccharide monooxygenases (LPMOs) play an important role on enzymatic degradation of recalcitrant polysaccharides to obtain fermentable sugars. It is generally accepted that LPMOs exhibits high substrate specificity and oxidation regioselectivity. Here, a bacteria-derived SmAA10A, with chitin-active with strict C1 oxidation, was used to catalyse KGM degradation. Through ethanol precipitation, two hydrolysed KGM components (4 kDa (KGM-1) and 5 kDa (KGM-2)) were obtained that exhibited antibacterial activity against Staphylococcus aureus. In natural KGM, KGM-1, and KGM-2, the molar ratios of mannose to glucose were 1:2.19, 1:3.05, and 1:2.87, respectively, indicating that SmAA10A preferentially degrades mannose in KGM. Fourier-transform infrared spectroscopy and scanning electron microscopy imaging revealed the breakage of glycosylic bonds during enzymatic catalysis. The regioselectivity of SmAA10A for KGM degradation was determined based on the fragmentation behaviour of the KGM-1 and KGM-2 oligosaccharides and their NaBD4-reduced forms. SmAA10A exhibited diverse oxidation degradation of KGM and generated single C1-, single C4-, and C1/C4-double oxidised oligosaccharide forms. This study provides an alternative method for obtaining KGM degradation components with antibacterial functions and expands the substrate specificity and oxidation regioselectivity of bacterial LPMOs.

Reciprocal effects between negative affect and emotion regulation in daily life.

The extended process model of emotion regulation provides a framework for understanding how emotional experiences and emotion regulation (ER) mutually influence each other over time. To investigate this reciprocal relationship, 202 adults completed a ten-day experience-sampling survey capturing levels of negative affect (NA) experience and use of ten ER strategies in daily life. Residual dynamic structural equation models (DSEMs) were used to examine within-person cross-lagged and autoregressive effects of NA and ER (strategy use and between-strategy variability). Results showed that NA predicted lower between-strategy variability, lower subsequent use of acceptance and problem-solving, but higher subsequent use of rumination and worry. Moreover, reappraisal and between-strategy variability predicted lower subsequent NA levels, while expressive suppression and worry predicted higher subsequent NA levels. Stable autoregressive effects were found for NA and for maladaptive ER strategies (e.g., rumination and worry). Exploratory correlation analyses revealed positive associations between NA inertia and maladaptive ER strategies. Together, these findings provide evidence of a dynamic interplay between NA and ER. This work deepens how we understand the challenges of applying ER strategies in daily life. Future clinical and translational research should consider these dynamic perspectives on ER and affect.

Recent advances in harnessing biological macromolecules for wound management: A review.

Wound dressings (WDs) are an essential component of wound management and serve as an artificial barrier to isolate the injured site from the external environment, thereby helping to prevent exogenous infections and supporting healing. However, maintaining a moist wound environment, providing protection from infection, good biocompatibility, and allowing for gas exchange, remain a challenge in device design. Functional wound dressings (FWDs) prepared from hybrid biological macromolecule-based materials can enhance efficacy of these systems for skin wound management. This review aims to provide an overview of the state-of-the-art FWDs within the field of wound management, with a specific focus on hybrid biomaterials, techniques, and applications developed over the past five years. In addition, we highlight the incorporation of biological macromolecules in WDs, the emergence of smart WDs, and discuss the existing challenges and future prospects for the development of advanced WDs.

Characterization of nanozyme kinetics for highly sensitive detection.

Nanozymes have been widely used as enzyme substitutes. Based on a comprehensive literature survey of 261 publications, we report the significant differences in the Michaelis-Menten constants (Km) between peroxidase-mimicking nanozymes and horseradish peroxidase (HRP). Further, these differences were not considered in more than 60% of the publications for analytical developments. As a result, nanozymes' catalytic activity is limited, resulting in a potentially higher limit of detection (LOD). We used a peroxidase-mimicking Au@Pt nanozyme, which has Km for TMB comparable with HRP and three orders of magnitude higher Km for H2O2. Using the Au@Pt nanozyme as a label for immunoassays, non-optimized nanozyme substrate concentrations led to 30 times higher LOD compared to optimized conditions. The results confirm the necessity of measuring nanozymes' kinetic parameters and the corresponding adjustment of substrate concentrations for highly sensitive detection.

Reporting of equity in observational epidemiology: A methodological review.

Background: Observational studies can inform how we understand and address persisting health inequities through the collection, reporting and analysis of health equity factors. However, the extent to which the analysis and reporting of equity-relevant aspects in observational research are generally unknown. Thus, we aimed to systematically evaluate how equity-relevant observational studies reported equity considerations in the study design and analyses. Methods: We searched MEDLINE for health equity-relevant observational studies from January 2020 to March 2022, resulting in 16 828 articles. We randomly selected 320 studies, ensuring a balance in focus on populations experiencing inequities, country income settings, and coronavirus disease 2019 (COVID-19) topic. We extracted information on study design and analysis methods. Results: The bulk of the studies were conducted in North America (n = 95, 30%), followed by Europe and Central Asia (n = 55, 17%). Half of the studies (n = 171, 53%) addressed general health and well-being, while 49 (15%) focused on mental health conditions. Two-thirds of the studies (n = 220, 69%) were cross-sectional. Eight (3%) engaged with populations experiencing inequities, while 22 (29%) adapted recruitment methods to reach these populations. Further, 67 studies (21%) examined interaction effects primarily related to race or ethnicity (48%). Two-thirds of the studies (72%) adjusted for characteristics associated with inequities, and 18 studies (6%) used flow diagrams to depict how populations experiencing inequities progressed throughout the studies. Conclusions: Despite over 80% of the equity-focused observational studies providing a rationale for a focus on health equity, reporting of study design features relevant to health equity ranged from 0-95%, with over half of the items reported by less than one-quarter of studies. This methodological study is a baseline assessment to inform the development of an equity-focussed reporting guideline for observational studies as an extension of the well-known Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guideline.

Bimetallic PtPd Atomic Clusters as Apoptosis/Ferroptosis Inducers for Antineoplastic Therapy through Heterogeneous Catalytic Processes.

Active polymetallic atomic clusters can initiate heterogeneous catalytic reactions in the tumor microenvironment, and the products tend to cause manifold damage to cell metabolic functions. Herein, bimetallic PtPd atomic clusters (BAC) are constructed by the stripping of Pt and Pd nanoparticles on nitrogen-doped carbon and follow-up surface PEGylation, aiming at efficacious antineoplastic therapy through heterogeneous catalytic processes. After endocytosed by tumor cells, BAC with catalase-mimic activity can facilitate the decomposition of endogenous H2O2 into O2. The local oxygenation not only alleviates hypoxia to reduce the invasion ability of cancer cells but also enhances the yield of •O2- from O2 catalyzed by BAC. Meanwhile, BAC also exhibit peroxidase-mimic activity for •OH production from H2O2. The enrichment of reactive oxygen species (ROS), including the radicals of •OH and •O2-, causes significant oxidative cellular damage and triggers severe apoptosis. In another aspect, intrinsic glutathione (GSH) peroxidase-like activity of BAC can indirectly upregulate the level of lipid peroxides and promote ferroptosis. Such deleterious redox dyshomeostasis caused by ROS accumulation and GSH consumption also results in immunogenic cell death to stimulate antitumor immunity for metastasis suppression. Collectively, this paradigm is expected to inspire more facile designs of polymetallic atomic clusters in disease therapy.

Machine learning-based nomogram to predict poor response to overnight orthokeratology in Chinese myopic children: A multicentre, retrospective study.

PURPOSE: To develop and validate an effective nomogram for predicting poor response to orthokeratology. METHODS: Myopic children (aged 8-15 years) treated with orthokeratology between February 2018 and January 2022 were screened in four hospitals of different tiers (i.e. municipal and provincial) in China. Potential predictors included 32 baseline clinical variables. Nomogram for the outcome (1-year axial elongation ≥0.20 mm: poor response; <0.20 mm: good response) was computed from a logistic regression model with the least absolute shrinkage and selection operator. The data from the First Affiliated Hospital of Chengdu Medical College were randomly assigned (7:3) to the training and validation cohorts. An external cohort from three independent multicentre was used for the model test. Model performance was assessed by discrimination (the area under curve, AUC), calibration (calibration plots) and utility (decision curve analysis). RESULTS: Between January 2022 and March 2023, 1183 eligible subjects were screened from the First Affiliated Hospital of Chengdu Medical College, then randomly divided into training (n = 831) and validation (n = 352) cohorts. A total of 405 eligible subjects were screened in the external cohort. Predictors included in the nomogram were baseline age, spherical equivalent, axial length, pupil diameter, surface asymmetry index and parental myopia (p < 0.05). This nomogram demonstrated excellent calibration, clinical net benefit and discrimination, with the AUC of 0.871 (95% CI 0.847-0.894), 0.863 (0.826-0.901) and 0.817 (0.777-0.857) in the training, validation and external cohorts, respectively. An online calculator was generated for free access (http://39.96.75.172:8182/#/nomogram). CONCLUSION: The nomogram provides accurate individual prediction of poor response to overnight orthokeratology in Chinese myopic children.

Evolutionary continuity and divergence of auditory dorsal and ventral pathways in primates revealed by ultra-high field diffusion MRI.

Auditory dorsal and ventral pathways in the human brain play important roles in supporting speech and language processing. However, the evolutionary root of the dual auditory pathways in the primate brain is unclear. By parcellating the auditory cortex of marmosets (a New World monkey species), macaques (an Old World monkey species), and humans using the same individual-based analysis method and tracking the pathways from the auditory cortex based on multi-shell diffusion-weighted MRI (dMRI), homologous auditory dorsal and ventral fiber tracks were identified in these primate species. The ventral pathway was found to be well conserved in all three primate species analyzed but extend to more anterior temporal regions in humans. In contrast, the dorsal pathway showed a divergence between monkey and human brains. First, frontal regions in the human brain have stronger connections to the higher-level auditory regions than to the lower-level auditory regions along the dorsal pathway, while frontal regions in the monkey brain show opposite connection patterns along the dorsal pathway. Second, the left lateralization of the dorsal pathway is only found in humans. Moreover, the connectivity strength of the dorsal pathway in marmosets is more similar to that of humans than macaques. These results demonstrate the continuity and divergence of the dual auditory pathways in the primate brains along the evolutionary path, suggesting that the putative neural networks supporting human speech and language processing might have emerged early in primate evolution.

Klotho stabilizes the podocyte actin cytoskeleton in idiopathic membranous nephropathy through regulating the TRPC6/CatL pathway.

INTRODUCTION: To explore the renoprotective effects of Klotho on podocyte injury mediated by complement activation and autoantibodies in idiopathic membranous nephropathy (IMN). METHODS: Rat passive Heymann nephritis (PHN) was induced as an IMN model. Urine protein levels, serum biochemistry, kidney histology, and podocyte marker levels were assessed. In vitro, sublytic podocyte injury was induced by C5b-9. The expression of Klotho, transient receptor potential channel 6 (TRPC6), and cathepsin L (CatL); its substrate synaptopodin; and the intracellular Ca2+ concentration were detected via immunofluorescence. RhoA/ROCK pathway activity was measured by an activity quantitative detection kit, and the protein expression of phosphorylated-LIMK1 (p-LIMK1) and p-cofilin in podocytes was detected via Western blotting. Klotho knockdown and overexpression were performed to evaluate its role in regulating the TRPC6-CatL pathway. RESULTS: PHN rats exhibited proteinuria, podocyte foot process effacement, decreased Klotho and Synaptopodin levels, and increased TRPC6 and CatL expression. The RhoA/ROCK pathway was activated by the increased phosphorylation of LIMK1 and cofilin. Similar changes were observed in C5b-9-injured podocytes. Klotho knockdown exacerbated podocyte injury, while Klotho overexpression partially ameliorated podocyte injury. CONCLUSION: Klotho may protect against podocyte injury in IMN patients by inhibiting the TRPC6/CatL pathway. Klotho is a potential target for reducing proteinuria in IMN patients.

Comparative efficacy of non-invasive brain stimulation for post-stroke cognitive impairment: a network meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a burgeoning approach with the potential to significantly enhance cognition and functional abilities in individuals who have undergone a stroke. However, the current evidence lacks robust comparisons and rankings of various NIBS methods concerning the specific stimulation sites and parameters used. To address this knowledge gap, this systematic review and meta-analysis seek to offer conclusive evidence on the efficacy and safety of NIBS in treating post-stroke cognitive impairment. METHODS: A systematic review of randomized control trials (RCT) was performed using Bayesian network meta-analysis. We searched RCT in the following databases until June 2022: Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and EMBASE. We compared any active NIBS to control in terms of improving cognition function and activities of daily living (ADL) capacity following stroke. RESULTS: After reviewing 1577 retrieved citations, a total of 26 RCTs were included. High-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (mean difference 2.25 [95% credible interval 0.77, 3.66]) was identified as a recommended approach for alleviating the global severity of cognition. Dual-rTMS (27.61 [25.66, 29.57]) emerged as a favorable technique for enhancing ADL function. In terms of stimulation targets, the dorsolateral prefrontal cortex exhibited a higher ranking in relation to the global severity of cognition. CONCLUSIONS: Among various NIBS techniques, HF-rTMS stands out as the most promising intervention for enhancing cognitive function. Meanwhile, Dual-rTMS is highly recommended for improving ADL capacity.

Prediction of Anti-rheumatoid Arthritis Natural Products of Xanthocerais Lignum Based on LC-MS and Artificial Intelligence.

AIMS: Employing the technique of liquid chromatography-mass spectrometry (LCMS) in conjunction with artificial intelligence (AI) technology to predict and screen for antirheumatoid arthritis (RA) active compounds in Xanthocerais lignum. BACKGROUND: Natural products have become an important source of new drug discovery. RA is a chronic autoimmune disease characterized by joint inflammation and systemic inflammation. Although there are many drugs available for the treatment of RA, they still have many side effects and limitations. Therefore, finding more effective and safer natural products for the treatment of RA has become an important issue. METHODS: In this study, a collection of inhibitors targeting RA-related specific targets was gathered. Machine learning models and deep learning models were constructed using these inhibitors. The performance of the models was evaluated using a test set and ten-fold cross-validation, and the most optimal model was selected for integration. A total of five commonly used machine learning algorithms (logistic regression, k-nearest neighbors, support vector machines, random forest, XGBoost) and one deep learning algorithm (GCN) were employed in this research. Subsequently, a Xanthocerais lignum compound library was established through HPLC-Q-Exactive- MS analysis and relevant literature. The integrated model was utilized to predict and screen for anti-RA active compounds in Xanthocerais lignum. RESULTS: The integrated model exhibited an AUC greater than 0.94 for all target datasets, demonstrating improved stability and accuracy compared to individual models. This enhancement enables better activity prediction for unknown compounds. By employing the integrated model, the activity of 69 identified compounds in Xanthocerais lignum was predicted. The results indicated that isorhamnetin-3-O-glucoside, myricetin, rutinum, cinnamtannin B1, and dihydromyricetin exhibited inhibitory effects on multiple targets. Furthermore, myricetin and dihydromyricetin were found to have relatively higher relative abundances in Xanthocerais lignum, suggesting that they may serve as the primary active components contributing to its anti-RA effects. CONCLUSION: In this study, we utilized AI technology to learn from a large number of compounds and predict the activity of natural products from Xanthocerais lignum on specific targets. By combining AI technology and the LC-MS approach, rapid screening and prediction of the activity of natural products based on specific targets can be achieved, significantly enhancing the efficiency of discovering new bioactive molecules from medicinal plants.

A Fully Automated Mini-Mental State Examination Assessment Model Using Computer Algorithms for Cognitive Screening.

Background: Rapidly growing healthcare demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults. Objective: To develop a fully automated Mini-Mental State Examination (MMSE) assessment model and validate the model's rating consistency. Methods: The Automated Assessment Model for MMSE (AAM-MMSE) was an about 10-min computerized cognitive screening tool containing the same questions as the traditional paper-based Chinese MMSE. The validity of the AAM-MMSE was assessed in term of the consistency between the AAM-MMSE rating and physician rating. Results: A total of 427 participants were recruited for this study. The average age of these participants was 60.6 years old (ranging from 19 to 104 years old). According to the intraclass correlation coefficient (ICC), the interrater reliability between physicians and the AAM-MMSE for the full MMSE scale AAM-MMSE was high [ICC (2,1)=0.952; with its 95% CI of (0.883,0.974)]. According to the weighted kappa coefficients results the interrater agreement level for audio-related items showed high, but for items "Reading and obey", "Three-stage command", and "Writing complete sentence" were slight to fair. The AAM-MMSE rating accuracy was 87%. A Bland-Altman plot showed that the bias between the two total scores was 1.48 points with the upper and lower limits of agreement equal to 6.23 points and -3.26 points. Conclusions: Our work offers a promising fully automated MMSE assessment system for cognitive screening with pretty good accuracy.