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Epilepsy is a common brain disorder characterized by recurrent epileptic seizures with neuronal hyperexcitability. Apart from the classical imbalance between excitatory glutamatergic transmission and inhibitory γ-aminobutyric acidergic transmission, cumulative evidence suggest that cholinergic signaling is crucially involved in the modulation of neural excitability and epilepsy. In this review, we briefly describe the distribution of cholinergic neurons, muscarinic, and nicotinic receptors in the central nervous system and their relationship with neural excitability. Then, we summarize the findings from experimental and clinical research on the role of cholinergic signaling in epilepsy. Furthermore, we provide some perspectives on future investigation to reveal the precise role of the cholinergic system in epilepsy.

Neuropathic pain is a chronic pain caused by tissue injury or disease involving the somatosensory nervous system, which seriously affects the patient’s body function and quality of life. At present, most clinical medications for the treatment of neuropathic pain, including antidepressants, antiepileptic drugs, or analgesics, often have limited efficacy and non-negligible side effects. As a bioactive and therapeutic component extracted from Chinese herbal medicine, the role of the effective compounds in the prevention and treatment of neuropathic pain have gradually become a research focus to explore new analgesics. Notably, saponins have shown analgesic effects in a large number of animal models. In this review, we summarized the most updated information of saponins, related to their analgesic effects in neuropathic pain, and the recent progress on the research of therapeutic targets and the potential mechanisms. Furthermore, we put up with some perspectives on future investigation to reveal the precise role of saponins in neuropathic pain.

Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid‐gestational age—the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case–control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis. Synopsis Mass spectrometry‐based proteomics for plasma proteome profiling were performed on early gestational pregnant women with or without congenital heart disease (CHD) offspring. In‐depth analysis revealed a potential pathogenic mechanism and identified a set of biomarkers in early gestational plasma predicting fetal CHD. A total of 104 early gestational pregnant women with CHD offspring and 103 controls with healthy offspring were included. A total of 264 proteins were found significantly upregulated and 358 proteins downregulated in the plasma of early gestational pregnant women with CHD offspring. Dyslipidemia and CD4 + might be involved in the occurrence of CHD. Nine CHD‐related biomarkers had been identified. Graphical Abstract Mass spectrometry‐based proteomics for plasma proteome profiling was performed on early gestational pregnant women with or without congenital heart disease (CHD) offspring. In‐depth analysis revealed a potential pathogenic mechanism and identified a set of biomarkers in early gestational plasma predicting fetal CHD.

In oncology, the conventional reliance on the maximum tolerated dose (MTD) strategy for chemotherapy may not optimize treatment outcomes for individual patients. CURATE.AI is an AI-derived platform that utilizes a patient’s own, small dataset to dynamically personalize only their own dose recommendations. The primary objective of this feasibility trial was to assess the logistical and scientific feasibility of providing dynamically personalized AI-derived chemotherapy dose recommendations for patients with advanced solid tumors at/for treatment with single-agent capecitabine, capecitabine in combination with oxaliplatin (XELOX), or capecitabine in combination with irinotecan (XELIRI). CURATE.AI demonstrated adaptability to clinically relevant situations encountered by patients often treated with palliative intent of care. High rates of user adherence were demonstrated, which could be in part due to the high engagement of the physicians in selecting data and boundaries for CURATE.AI operations.

Background Standard‐of‐care for warfarin dose titration is conventionally based on physician‐guided drug dosing. This may lead to frequent deviations from target international normalized ratio (INR) due to inter‐ and intra‐patient variability and may potentially result in adverse events including recurrent thromboembolism and life‐threatening hemorrhage. Objectives We aim to employ CURATE.AI, a small‐data, artificial intelligence‐derived platform that has been clinically validated in a range of indications, to optimize and guide warfarin dosing. Patients/methods A personalized CURATE.AI response profile was generated using warfarin dose (inputs) and corresponding change in INR between two consecutive days (phenotypic outputs) and used to identify and recommend an optimal dose to achieve target treatment outcomes. CURATE.AI's predictive performance was then evaluated with a set of metrics that assessed both technical performance and clinical relevance. Results and conclusions In this retrospective study of 127 patients, CURATE.AI fared better in terms of Percentage Absolute Prediction Error and Percentage Prediction Error of 20% compared to other models in the literature. It also had negligible underprediction bias, potentially translating into lower bleeding risk. Modeled potential time in therapeutic range with CURATE.AI was not significantly different from physician‐guided dosing, so it is on‐par yet provides a systematic approach to warfarin dosing, easing the mental‐burden on guesswork by physicians. This study lays the groundwork for the prospective study of CURATE.AI as a clinical decision support system. CURATE.AI may facilitate the effective use of affordable warfarin with a well‐established safety profile, without the need for costly, new oral anticoagulants. This can have significant impact both on the individual and public health.

A 10-week feeding trial was conducted to investigate the effects of dietary carbohydrate-to-lipid (CHO:L) ratios on glycogen content, hematological indices, liver, and intestinal enzyme activity of sub-adult grouper Epinephelus coioides. Five iso-nitrogenous (496.0 g kg−1 protein) and iso-energetic (21.6 KJ g−1 gross energy) diets with varying CHO: L ratios of 0.65 (D1), 1.31 (D2), 2.33 (D3), 4.24 (D4), and 8.51 (D5), respectively, were fed to triplicate groups of 20 fish (average 275.1 ± 1.86 g). Results showed that the weight gain rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER) of sub-adult grouper increased and then stable when dietary CHO:L ratios reach D4 (CHO:L = 4.24). The trend of feed conversion ratio (FCR) was opposite to PER. Along with the dietary CHO:L ratios, the liver and muscle glycogen level increased gradually. Plasma triglycerides (TG) and glucose (GLU) were all maximized at D5 (CHO:L = 8.51) group, cholesterol (CHOL) at D4 (CHO:L = 4.24) group. Digestive enzyme activities were significantly affected by dietary CHO:L ratios. Liver hexokinase (HK), alkaline phosphatase (AKP), and glucose-6-phosphate dehydrogenase (G6PDH) activity increased significantly as CHO:L ratios increased. Liver lysozyme (LYZ) and superoxide dismutase (SOD) activity of sub-adult grouper fed the D4 diet was significantly higher than that of the D2 (CHO:L = 1.31) diet. The trend of acid phosphatase (ACP) is opposite to AKP. The regression model analysis showed that the most suitable dietary CHO:L ratio to reach the highest SGR is 6.06.

The gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established. From May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs. Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs ( =0.003). , , and were less abundant and more abundant in irAE patients, while and were less abundant and more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients ( =0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9). The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.

An 8-week feeding trial was conducted to investigate the effects of dietary soy protein concentrate (SPC) levels on growth, blood biochemical indexes, non-specific immune enzyme activity, and nutrient apparent digestibility for juvenile Litopenaeus vannamei (initial weight 0.44 ± 0.002 g). They were formulated by replacing 0% (the control), 10%, 20%, 30%, 40%, 60%, and 80% of fish meal (FM) protein with SPC (designed FM, S11, S22, S33, S44, S55, and S66, respectively). With the replacement level of SPC in the diet was higher than 30%, weight gain (WG) and specific growth rate (SGR) for juvenile Litopenaeus vannamei significantly decreased (P < 0.05) with SPC increasing, but feed conversion ratio (FCR) significantly increased (P < 0.05). When the replacement level was above 40%, the protein efficiency ratio (PER), survival rate (SR), apparent digestibility of dry matter, and energy significantly decreased (P < 0.05). On the contrary, the content of triglyceride glucose (TG) in serum was increased significantly (P < 0.05). Apparent digestibility for crude protein and total lipid were significantly higher at higher fishmeal inclusion (0 and 10% SPC replacement) and significantly lower at lower fishmeal inclusion (< 70%) (P < 0.05). In conclusion, with reference to all the parameters, SPC can be used to replace up to 30% of fishmeal protein in shrimp feeds and so the total fishmeal exceeds 70% be used to cater to shrimps’ dietary needs.

IntroductionDigital game-based training interventions are scalable solutions that may improve cognitive function for many populations. This protocol for a two-part review aims to synthesise the effectiveness and key features of digital game-based interventions for cognitive training in healthy adults across the life span and adults with cognitive impairment, to update current knowledge and impact the development of future interventions for different adult subpopulations.Methods and analysisThis systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. A systematic search was performed in PubMed, Embase, CINAHL, Cochrane Library, Web of Science, PsycINFO and IEEE Explore on 31 July 2022 for relevant literature published in English from the previous 5 years. Experimental, observational, exploratory, correlational, qualitative and mixed methods studies will be eligible if they report at least one cognitive function outcome and include a digital game-based intervention intended to improve cognitive function. Reviews will be excluded but retained to search their reference lists for other relevant studies. All screening will be done by at least two independent reviewers. The appropriate Joanna Briggs Institute Critical Appraisal Tool, according to the study design, will be applied to perform the risk of bias assessment. Outcomes related to cognitive function and digital game-based intervention features will be extracted. Results will be categorised by adult life span stages in the healthy adult population for part 1 and by neurological disorder in part 2. Extracted data will be analysed quantitatively and qualitatively, according to study type. If a group of sufficiently comparable studies is identified, we will perform a meta-analysis applying the random effects model with consideration of the I2 statistic.Ethics and disseminationEthics approval is not applicable for this study since no original data will be collected. The results will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42022351265.

Aims Temporal lobe epilepsy (TLE), often associated with cognitive impairment, is one of the most common types of medically refractory epilepsy. Deep brain stimulation (DBS) shows considerable promise for the treatment of TLE. However, the optimal stimulation targets and parameters of DBS to control seizures and related cognitive impairment are still not fully illustrated. Methods In the present study, we evaluated the therapeutic potential of DBS in the medial septum (MS) on seizures and cognitive function in mouse acute and chronic epilepsy models. Results We found that DBS in the MS alleviated the severity of seizure activities in both kainic acid‐induced acute seizure model and hippocampal‐kindled epilepsy model. DBS showed antiseizure effects with a wide window of effective stimulation frequencies. The antiseizure effects of DBS were mediated by the hippocampal theta rhythm, as atropine, which reversed the DBS‐induced augmentation of the hippocampal theta oscillation, abolished the antiseizure effects of DBS. Further, in the kainic acid‐induced chronic TLE model, DBS in the MS not only reduced spontaneous seizures, but also improved behavioral performance in novel object recognition. Conclusion DBS in the MS is a promising approach to attenuate TLE probably through entrainment of the hippocampal theta rhythm, which may be therapeutically significant for refractory TLE treatment. Here, we inferred that the DBS in the MS may be therapeutically significant for the treatment of refractory TLE. DBS in the MS not only alleviated seizures activities, but also improved behavioral performance in memory tests, via the enhancement of hippocampal theta rhythm.