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Abstract Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein–protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

Abstract Background The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS‐31), a novel mitochondrion‐targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS‐31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. Methods Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS‐31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus‐dependent cognitive function. Western blotting and reverse transcription‐quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS‐31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme‐linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. Results SS‐31 could improve the cognitive impairment induced by CSD. In particular, SS‐31 treatment restored the CSD‐induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator‐activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa‐B and inflammatory cytokines, including interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐alpha. Furthermore, SS‐31 significantly increased the levels of brain‐derived neurotrophic factor, postsynaptic density protein‐95, and synaptophysin in CSD mice. Conclusion Taken together, these results suggest that SS‐31 could improve CSD‐induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.

PurposeDevelop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis.Patients & methodsChildren with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model.ResultsA total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834–0.908).ConclusionWe developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.

Objective To explore changes of brain structure in patients with functional movement disorder (FMD) and their correlation with disease severity. Methods Nine patients with FMD (FMD group) as well as 10 gender⁃ and age⁃matched healthy volunteers (control group) were recruited in Ruijin Hospital, Shanghai Jiaotong University School of Medicine, from May to October 2023, and then they underwent MRI. Simplified Functional Movement Disorder Rating Scale (S ⁃FMDRS) was used to assess movement disorder symptoms and severity. Clinical Global Impression ⁃ Severity (CGI ⁃ S) was used to evaluate disease severity. Somatoform Dissociation Questionnaire ⁃ 20 (SDQ ⁃20) was used to assess body dissociation. Chinese version of Maltreatment and Abuse Chronology of Exposure (MACE) was used to assess childhood abuse situation. 36⁃Item Short Form of Health Survey (SF⁃36) was used to assess health status. Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale 17 (HAMD⁃17) were used to evaluate anxiety and depression. Results Compared with the control group, the FMD group exhibited higher scores on SDQ⁃20 (Z = 2.259, P = 0.028) and Chinese version of MACE (t = ⁃ 3.570, P = 0.002) as well as HAMA (t = ⁃ 3.999, P = 0.001), while SF⁃36 scores for vitality (t = 3.091, P = 0.009) and social functioning (t = 2.275, P = 0.046) were lower in the FMD group. Cortical thickness was greater in the FMD group in the right inferior occipital gyrus and sulcus cortex (t = ⁃ 2.924, P = 0.009), right anterior cingulate gyrus and sulcus cortex (t = ⁃ 3.286, P = 0.004), right orbitofrontal cortex (t = ⁃ 2.381, P = 0.029), while thickness in the left subcallosal area (t = 2.492, P = 0.023) and left paracentral lobule gyrus and sulcus (t = 2.139, P = 0.047), as well as volume of the right cerebellar white matter (t = 2.685, P = 0.016), left cerebellar white matter (t = 2.121, P = 0.049), and the middle posterior region of the corpus callosum (t = 2.550, P = 0.021) were smaller than those of the control group. Correlation analysis revealed left cerebellar white matter were positively correlated with disease duration (r = 0.837, P = 0.038), while cortical thickness in the left subcallosal area were negatively correlated with disease duration (r = ⁃ 0.831, P = 0.040). Conclusions There are structural changes in the limbic system, sensorimotor area, visual cortex, and certain white matter regions in the brains of FMD patients, and several regions were correlated with the disease duration.

High Fischer ratio oligopeptides (HFOs) have a variety of biological activities, but their mechanisms of action for anti-fatigue are less systematically studied at present. This study aimed to systematically evaluate the anti-fatigue efficacy of HFOs from Antarctic krill (HFOs-AK) and explore its mechanism of action through establishing the fatigue model of endurance swimming in mice. Therefore, according to the comparison with the endurance swimming model group, HFOs-AK were able to dose-dependently prolong the endurance swimming time, reduce the levels of the metabolites (lactic acid, blood urea nitrogen, and blood ammonia), increase the content of blood glucose, muscle glycogen, and liver glycogen, reduce lactate dehydrogenase and creatine kinase extravasation, and protect muscle tissue from damage in the endurance swimming mice. HFOs-AK were shown to enhance Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities and increase ATP content in muscle tissue. Meanwhile, HFOs-AK also showed significantly antioxidant ability by increasing the activities of superoxide dismutase and glutathione peroxidase in the liver and decreasing the level of malondialdehyde. Further studies showed that HFOs-AK could regulate the body’s energy metabolism and thus exert its anti-fatigue effects by activating the AMPK signaling pathway and up-regulating the expression of p-AMPK and PGC-α proteins. Therefore, HFOs-AK can be used as an auxiliary functional dietary molecules to exert its good anti-fatigue activity and be applied to anti-fatigue functional foods.

Bruce llosis is a bacterial disease caused by various Brucella species, which infect primarily cattle, swine, goats, sheep, and dogs. The disease is typically transmitted to humans through direct contact with diseased animals, consumption of contaminated animal products, or inhalation of airborne pollutants. The majority of cases are caused by consuming unpasteurized goat or sheep milk or cheese. Based on observed Brucellosis occurrence data and ecogeographic variables, a MaxEnt algorithm was used to model the current and future distribution of Brucellosis in Qinghai Lake basin, P.R. China. Our model showed the Brucellosis current distribution and predicts suitable habitat shifts under future climate scenarios. In the new representatives; SSP 2.6 and SSP 4.5 for the year 2050s and 2070s, our model predicts an expansion in the current suitable areas. This indicates that under the possible climate changes in the future, the living space of Brucellosis in Qinghai Lake basin China will expand significantly. Ecogeographic variables that contributed significantly to the distribution of Brucellosis in Qinghai Lake basin are revealed by our model. The results of our study will promote comparisons with future research and provide a new perspective to inform decision-making in the field of public health in Qinghai province.

Abstract The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.

The first diastereodivergent formal [4 ​+ ​1] cycloaddition reactions of azoalkenes with p-quinone methides (p-QMs) have been accomplished. The reported reaction occurred via a domino oxa-1,4-addition/1,6-addition process, allowing the use of common azoalkenes as C1 synthons. A broad range of 2,3-dihydrobenzofurans was smoothly prepared in good yields and with reversible diastereoselectivities. The steric hindrance and hydrogen-bonding interaction were proposed to account for the two different modes of diastereo-control. The projected reaction features the employment of azoalkene as carbene-like C1 synthon, mild conditions, broad substrate scope and tunable diastereoselectivity.

Abstract Background Exercise is an effective treatment in chronic low back pain (CLBP), but there are few studies on CLBP in the elderly, and the intervention effect is controversial. We aimed to compare the efficacy of different exercises therapy on CLBP, dysfunction, quality of life, and mobility in the elderly. Methods We searched Web of Science, MEDLINE, Cochrane Library, Chinese National Knowledge Infrastructure, EMBASE, and PubMed from the database inception till December 31, 2022. The publication languages were Chinese and English. Randomized controlled trials (RCTs) of exercise intervention in the elderly (≥ 60 years) with CLBP were included. Two reviewers independently extracted the data and evaluated them using the Revised Cochrane Risk of Bias Tool for Randomized Trials 2 (RoB2). The pooled effect sizes on different aspects of outcome measures were calculated. Results Sixteen articles (18 RCTs) were included, comprising a total of 989 participants. The quality of included studies was relatively high. Meta-analysis results indicated that exercise therapy could improve visual analog scale (VAS) (WMD = − 1.75, 95% CI − 2.59, − 0.92, p

Background: The associated factors of peritoneal small solute transport was not fully understood. This research aimed to investigate the connection between dialysate inflammatory markers (e.g. macrophage migration inhibitory factor, MIF) in peritoneal dialysis (PD) effluent and peritoneal solute transport rate (PSTR) properties. Subjects and design: A total of 80 stable PD patients in the First ShaoYang Hospital were enrolled in present study. Overnight PD effluent and serum inflammatory markers including MIF, MCP-1, VEGF, IL-6, TNFα and TGFβ were detected. Pearson correlation analysis and Logistic regression was performed to determine the risk factors for the increased PSTR. Results: A trend toward increased values of MIF, MCP-1 and IL-6 in PD effluent was observed in subjects with high PSTR when compared with those with low PSTR. The Pearson correlation test showed that D/P Cr exhibited positive correlations with dialysis effluent MIF (r = 0.32, p = 0.01), MCP-1 (r = 0.47, p = 0.01), IL-6 (r = 0.48, p = 0.01). Conversely, no significant correlation was found between D/P Cr and TGF-β (r = 0.04, p = 0.70), TNF-ɑ (r = 0.22, p = 0.05), VEGF (r = 0.02, p = 0.86) and serum inflammatory markers. In the unadjusted regression analysis, dialysis effluent MIF (OR 2.41), MCP-1 (OR 1.72), IL-6 (OR 1.55) were associated with high PSTR condition. Multivariate logistic regression analysis showed that the adjusted odds ratios (OR) of dialysis effluent MIF for high PSTR were 2.47 in all subjects (p = 0.03). Conclusion: Elevated MIF, MCP-1 and IL-6 levels in PD effluent were associated with increased PSTR. Elevated dialysis effluent MIF levels was an independent risk factor for high PSTR in subjects with PD treatment. Resumen: Antecedentes: Los factores asociados del transporte peritoneal de pequeños solutos no se conocen completamente. Esta investigación tuvo como objetivo investigar la conexión entre los marcadores inflamatorios del dializado (por ejemplo, el factor inhibidor de la migración de macrófagos [MIF]) en el efluente de diálisis peritoneal (DP) y las propiedades de la tasa de transporte de solutos peritoneal (PSTR). Sujetos y diseño: Se incluyó un total de 80 pacientes con DP estable en el primer Hospital de Shaoyang. Se detectaron efluentes de DP nocturnos y marcadores inflamatorios séricos, incluyendo MIF, MCP-1, VEGF, IL-6, TNF -ɑ, TGF -β. Se realizó un análisis de correlación de Pearson y regresión logística para determinar los factores de riesgo para la PSTR aumentada. Resultados: Se observó una tendencia hacia valores incrementados de MIF, MCP-1 e IL-6 en el efluente de DP en sujetos con PSTR alta, en comparación con aquellos con PSTR baja. La prueba de correlación de Pearson mostró que D/Pcr exhibe correlaciones positivas con el MIF del efluente diálisis (r = 0,32, p = 0,01), MCP-1 (r = 0,47, p = 0,01), IL-6 (r = 0,48, p = 0,01). Por el contrario, no se encontró una correlación significativa entre D/Pcr y TGF-β (r = 0,04, p = 0,70), TNF-ɑ (r = 0,22, p = 0,05), VEGF (r = 0,02, p = 0,86) y marcadores séricos de inflamación. En el análisis de regresión no ajustado, el MIF del efluente diálisis (OR 2,41), la MCP-1 (OR 1,72), la IL-6 (OR 1,55) se asociaron con una PSTR elevada. El análisis de regresión logística multivariante mostró que las odds ratios (OR) ajustadas del MIF del efluente diálisis para PSTR alta fueron de 2,47 en todos los sujetos (p = 0,03). Conclusión: Los niveles elevados de MIF, MCP-1 y IL-6 en el efluente de DP se asociaron con un aumento de la PSTR. Los niveles elevados del MIF del efluente diálisis fueron un factor de riesgo independiente para PSTR elevada en sujetos tratados con DP.

Intratumoral abundance of chemokines, such as CXCL9, is an important driver of T cell infiltration in tumors. Here the authors describe the design of a tumor-specific expression strategy to drive secretion of CXCL9 and an anti-PD-L1 scFv (αPD-L1) in the tumor microenvironment, promoting T cell recruitment and anti-tumor immune response in preclinical cancer models.

Introduction: Bacterial pneumonia poses a significant global public health challenge, where unaddressed pathogens and inflammation can exacerbate acute lung injury and prompt cytokine storms, increasing mortality rates. Alveolar macrophages are pivotal in preserving lung equilibrium. Excessive inflammation can trigger necrosis in these cells, disrupting the delicate interplay between inflammation and tissue repair.Methods: We obtained extracellular vesicle from aloe and tested the biosafety by cell viability and hemolysis assays. Confocal microscopy and flow cytometry were used to detect the uptake and internalization of extracellular vesicle by macrophages and the ability of extracellular vesicle to affect the phenotypic reprogramming of macrophages in vitro. Finally, we conducted a clinical feasibility study employing clinical bronchoalveolar lavage fluid as a representative model to assess the effective repolarization of macrophages influenced by extracellular vesicle.Results: In our study, we discovered the potential of extracellular vesicle nanovesicles derived from aloe in reprograming macrophage phenotypes. Pro-inflammatory macrophages undergo a transition toward an anti-inflammatory immune phenotype through phagocytosing and internalizing these aloe vera-derived extracellular vesicle nanovesicles. This transition results in the release of anti-inflammatory IL-10, effectively curbing inflammation and fostering lung tissue repair.Discussion: These findings firmly establish the immunomodulatory impact of aloe-derived extracellular vesicle nanovesicles on macrophages, proposing their potential as a therapeutic strategy to modulate macrophage immunity in bacterial pneumonia.