Search

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.

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.

Abstract Tumor necrosis factor receptors (TNFRs) are promising targets for cancer therapy. However, activating their downstream signaling requires cross‐linking of TNFRs. Herein, to devise strong agonists of TNFRs, ligands targeting TNFRs, such as OX40L and tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), were fused with a multivalent protein scaffold (MV) to prepare multivalent agonists for cross‐linking TNFRs. The nano‐clustered multivalent‐OX40L (MV‐OX40L) and MV‐TRAIL could promote T cell activation and directly induce tumor cell apoptosis. Moreover, to develop a universal nano‐adaptor for the rapid preparation of multivalent agonists of different TNFRs, the Fc receptor that could immobilize antibodies was fused with MV to prepare MV‐FcR, which could multimerize commercial agonist antibodies targeting TNFRs, such as anti‐OX40 antibody (αOX40). Simply incubating αOX40 with MV‐FcR could prepare MV‐αOX40 to enhance its antitumor efficacy. In addition, MV‐FcR could multimerize with other therapeutic antibodies, such as anti‐PD‐L1 antibody, to enhance their valency. This study provides a promising strategy for engineering multivalent antitumor protein drugs.

Abstract Herein, the first diversity‐oriented catalytic asymmetric dearomatization of indoles with o‐quinone diimides (o‐QDIs) is reported. The catalytic asymmetric dearomatization (CADA) of indoles is one of the research focuses in terms of the structural and biological importance of dearomatized indole derivatives. Although great achievements have been made in target‐oriented CADA reactions, diversity‐oriented CADA reactions are regarded as more challenging and remain elusive due to the lack of synthons featuring multiple reaction sites and the difficulty in precise control of chemo‐, regio‐, and enantio‐selectivity. In this work, o‐QDIs are employed as a versatile building block, enabling the chemo‐divergent dearomative arylation and [4 + 2] cycloaddition reactions of indoles. Under the catalysis of chiral phosphoric acid and mild conditions, various indolenines, furoindolines/pyrroloindolines, and six‐membered‐ring fused indolines are collectively prepared in good yields with excellent enantioselectivities. This diversity‐oriented synthesis protocol enriches the o‐quinone chemistry and offers new opportunities for CADA reactions.

Maternal exposure to inflammation may represent a major risk factor for neuropsychiatric disorders with associated cognitive dysfunction in offspring in later life. Growing evidence has suggested that resveratrol exerts a beneficial effect on cognitive impairment via its anti-inflammatory and antioxidant properties and by ameliorating synaptic dysfunction. However, how resveratrol affects maternal immune activation-induced cognitive dysfunction and the underlying mechanisms are unclear. In the present study, pregnant dams were given an intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) on gestational day 15. Subsequently, the offspring mice were treated or not with resveratrol (40 mg/kg) from postnatal day (PND) 60 to PND 88. Male offspring were selected for the evaluation of cognitive function using the Morris water maze test. The hippocampal levels of pro-inflammatory cytokines were examined by ELISA. The mRNA and protein levels of sirtuin-1 (SIRT1), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYP) were determined by RT-qPCR and western blot, respectively. The results showed that male offspring mice exposed to LPS in utero exhibited learning and memory impairment. Additionally, the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were increased while those of SIRT1, BDNF, PSD-95, and SYP were decreased in male offspring of LPS-treated mothers. Treatment with resveratrol reversed cognitive impairment and attenuated the increase in the levels of pro-inflammatory cytokines induced by maternal immune activation in the offspring mice. Furthermore, resveratrol reversed the deleterious effects of maternal immune activation on SIRT1, BDNF, PSD-95, and SYP levels in the hippocampus. Collectively, our results suggested that resveratrol can effectively improve learning and memory impairment induced by maternal immune activation via the modulation of inflammation and synaptic dysfunction.

In response to the exist problems such as the lack of accuracy in load forecasting leading to large errors in contracted power purchases, and the ambiguous market boundaries leading to duplication in assessment and settlement when load aggregators organize demand-side resources to participate in the peaking market and the electricity energy market, a load aggregator potential calculation and peaking strategy based on the longitudinal modified autoregressive integrated moving average (ARIMA) model is proposed. Firstly, the longitudinal modified ARIMA forecasting algorithm is applied to forecast the load baseline for obtaining the model of peak regulation potential of load aggregators, thus exploring the adjustable capacity of demand-sideresources to provide a database for power market trading. Secondly, the load deviation assessment method of electric energy market and peak shaving market is formulated, and the load aggregator peak shaving model considering the deviation assessment is constructed with the goal of maximizing the monthly rolling time domain comprehensive settlement income. Finally, the proposed method is analyzed based on the monthly historical load data of load aggregators in a typical region. The results show that the proposed load aggregator peak shaving strategy considering load deviation assessment can improve the peak shaving revenue of aggregators by about 23.7% and reduce the load aggregator peak-to-valley difference of about 10%, which verifies the rationality and effectiveness of the method.

Abstract Background A high prevalence of nasopharyngeal carcinoma (NPC) has been found in China, but it rarely occurs with syncope. Studies have demonstrated that syncope due to NPC may be related to carotid sinus syndrome, glossopharyngeal irritation, and parapharyngeal and retropharyngeal space lesions. Such patients require evaluation by nasopharyngoscopy and head magnetic resonance imaging/computed tomography. There is no known single effective treatment for these patients. Various interventions may be considered in an effort to relieve syncope, including vasoconstrictive drugs, cardiac pacemaker implantation, radiotherapy and chemotherapy, and surgical resection. Case presentation This case report describes a 56-year-old man who developed recurrent syncope with atrial fibrillation, a long RR interval, and hypotension. A single chamber pacemaker was fitted, but it failed to relieve the symptom. Cranial magnetic resonance imaging and pathological tests led to a final diagnosis of NPC. After six courses of chemotherapy and 35 sessions of radiotherapy, the patient became asymptomatic. However, he died from a massive uncontrolled hemorrhage in the nasopharynx two years later. Conclusions This case brings attention to the fact that syncope can be a symptom of NPC. Due to the insidiously malignant nature of this cancer, when a patient presents with syncope, clinicians should bear in mind this connection, albeit a rare one. There are at least two ways of treating NPC-associated syncope, but there is disagreement about which is the most effective.

Metal- and oxidant-free alkenyl C–H thiolation enabled by the azo group had been established for the modular synthesis of tetrasubstituted acyclic olefins. The reaction was performed under mild reaction conditions with a broad substrate scope. The intramolecular 6-membered hydrogen-bonding network accounts for the observed excellent stereo-control.

BackgroundSpontaneous echo contrast (SEC) observed in transesophageal echocardiography (TEE) is a reliable predictor of the risk of future ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Left atrial strain globally reflects atrial function, remodeling and distensibility. The left atrial appendage (LAA) is a myogenic remnant of the left atrium, which can actively relax and contract. The left atrial appendage (LAA) is an important part of releasing the pressure of the left atrium. The key role of the left atrium is to regulate the left ventricular filling pressure, act as a reservoir for pulmonary venous return during ventricular contraction, and act as a conduit, transferring blood to the Left ventricle during early ventricular diastole. The purpose of this study was to explore the relationship between left atrial function and left atrial appendage spontaneous echo contrast (LAASEC).MethodsA retrospective study of 338 patients with non-valvular AF was conducted. Two-dimensional speckle-tracking echocardiography provided the following metrics of LA strain: LA strain during the reservoir phase (LASr), LA strain during the conduit phase (LAScd). LA or LAA has the dense SEC of more than grade 3, which is defined as mud like change or pre thrombosis.ResultsPatients with level 3 SEC (n = 81) has lower LASr than those with lower grades of SEC (n = 257) (7.20 ± 3.70 vs. 17.48 ± 8.67, P 2 scores with sensitivity and specificity were 79% and 85%.ConclusionLower LASr is independently associated with the dense LAASEC in NVAF and has incremental values superior to clinical scores. The decrease of LASr may be a potential non-invasive parameter for evaluating the higher risk of LAA thrombosis.

Blockchain technology could effectively solve the problems of lack of trust,malicious tampering and false transactions.However,the open and transparent characteristics of the blockchain make the distributed energy trading model based on the blockchain extremely vulnerable to be attacked,leading to the disclosure of user’s privacy.Therefore,a privacy-preserving scheme BLDP-AM based on differential privacy algorithm and account mapping technology is proposed to protect the privacy information of trading data.Our scheme redesigns the data perturbation mechanism of the local differential privacy algorithm to make it applicable to blockchain technology,and constructs the BLDP algorithm based on this perturbation mechanism to protect the privacy of transaction data.At the same time,in order to ensure the correctness of trading and hide the characteristics of the trading curve,our scheme first associates users with multiple accounts through account mapping technology,then uses the exponential smoo-thing prediction algorithm to calculate the trading prediction value of each account,and finally uses the BLDP algorithm to perturb the trading prediction value to obtain the real trading value and conduct trading.Our scheme not only guarantee the correctness of transactions but also achieve the purpose of protecting the privacy of trading data.The privacy analysis proves the feasibility of the scheme in protecting user privacy,and the experimental analysis shows that the scheme has better performance.

Objective: The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk. Methods: All eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software. Results: In overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR = 1.316, 95% CI: 1.213–1.427, P = 0.000; DD versus ID + II: OR = 1.414, 95% CI: 1.253–1.595, P = 0.000; II versus DD + ID: OR = 0.750, 95% CI: 0.647–0.869, P = 0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR = 1.361, 95% CI: 1.243–1.490, P = 0.000; DD versus ID + II: OR = 1.503, 95% CI: 1.310–1.726, P = 0.000; II versus DD + ID: OR = 0.738, 95% CI: 0.626 –0.870, P = 0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients. Conclusion: ACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD. Resumen: Objetivo: El objetivo de este estudio fue evaluar la influencia de los polimorfismos del gen I/D de la ECA en el riesgo de enfermedad renal diabética (ERD). Métodos: Se identificaron todas las investigaciones elegibles, se revisó el número de varios genotipos en el grupo de casos y controles. El análisis combinado se realizó con el software Stata. Resultados: En el conjunto de los sujetos, se incluyeron 24.321 participantes con 12.961 casos y 11.360 controles. El análisis combinado mostró una relación significativa entre el alelo D, el genotipo DD o II y el riesgo de DKD (D frente a I: OR = 1,316, IC del 95%: 1,213–1,427, P = 0,000; DD frente a ID + II: OR = 1,414, IC del 95%: 1,253-1,595, P = 0,000; II frente a DD + ID: OR = 0,750, 95% CI: 0,647-0,869, P = 0,000). El análisis de subgrupos mostró que el polimorfismo del gen I/D de la ECA se correlacionaba con la DMD tanto en la población asiática como en la china. Además, el polimorfismo del gen I/D de la ECA se correlacionó con la DKD de tipo 2 (D frente a I: OR = 1,361, IC del 95%: 1,243-1,490, P = 0,000; DD frente a ID + II: OR = 1,503, IC del 95%: 1,310-1,726, P = 0,000; II frente a DD + ID: OR = 0,738, 95% CI: 0,626 -0,870, P = 0,000). Sin embargo, no hubo una correlación evidente en los sujetos caucásicos y en los pacientes diabéticos de tipo 1. Conclusión: Los polimorfismos I/D de la ECA se correlacionaron con la DKD en poblaciones asiáticas y diabéticas de tipo 2. El alelo D de la ECA/genotipo DD podría ser un factor de riesgo, mientras que el genotipo II de la ECA podría ser un factor de protección para la DKD.

Objective: The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk. Methods: All eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software. Results: In overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR = 1.316, 95% CI: 1.213–1.427, P = 0.000; DD versus ID + II: OR = 1.414, 95% CI: 1.253–1.595, P = 0.000; II versus DD + ID: OR = 0.750, 95% CI: 0.647–0.869, P = 0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR = 1.361, 95% CI: 1.243–1.490, P = 0.000; DD versus ID + II: OR = 1.503, 95% CI: 1.310–1.726, P = 0.000; II versus DD + ID: OR = 0.738, 95% CI: 0.626 –0.870, P = 0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients. Conclusion: ACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD. Resumen: Objetivo: El objetivo de este estudio fue evaluar la influencia de los polimorfismos del gen I/D de la ECA en el riesgo de enfermedad renal diabética (ERD). Métodos: Se identificaron todas las investigaciones elegibles, se revisó el número de varios genotipos en el grupo de casos y controles. El análisis combinado se realizó con el software Stata. Resultados: En el conjunto de los sujetos, se incluyeron 24.321 participantes con 12.961 casos y 11.360 controles. El análisis combinado mostró una relación significativa entre el alelo D, el genotipo DD o II y el riesgo de DKD (D frente a I: OR = 1,316, IC del 95%: 1,213–1,427, P = 0,000; DD frente a ID + II: OR = 1,414, IC del 95%: 1,253-1,595, P = 0,000; II frente a DD + ID: OR = 0,750, 95% CI: 0,647-0,869, P = 0,000). El análisis de subgrupos mostró que el polimorfismo del gen I/D de la ECA se correlacionaba con la DMD tanto en la población asiática como en la china. Además, el polimorfismo del gen I/D de la ECA se correlacionó con la DKD de tipo 2 (D frente a I: OR = 1,361, IC del 95%: 1,243-1,490, P = 0,000; DD frente a ID + II: OR = 1,503, IC del 95%: 1,310-1,726, P = 0,000; II frente a DD + ID: OR = 0,738, 95% CI: 0,626 -0,870, P = 0,000). Sin embargo, no hubo una correlación evidente en los sujetos caucásicos y en los pacientes diabéticos de tipo 1. Conclusión: Los polimorfismos I/D de la ECA se correlacionaron con la DKD en poblaciones asiáticas y diabéticas de tipo 2. El alelo D de la ECA/genotipo DD podría ser un factor de riesgo, mientras que el genotipo II de la ECA podría ser un factor de protección para la DKD.

ObjectiveIn the present systematic review and meta-analysis, we aimed to evaluate and update the effects of aquatic exercise on physical fitness and quality of life (QoL) in postmenopausal women.MethodsThe databases Cochrane Library, PubMed, Web of Science, and MEDLINE were searched for randomized controlled trials (RCTs) on the topic from inception to July 2022. The GetData software was used to extract data from the published images. RevMan5.4 software was used for statistical analysis. Data are expressed as standardized mean difference (SMD) with 95% confidence intervals (CI). I2 index was employed for heterogeneity. Egger's test was used to assess publication bias. We evaluated the methodological quality of included studies using the Physiotherapy Evidence Database scale.ResultsWe included 594 participants in 16 RCTs (19 comparison groups). The results indicated that aquatic exercise can significantly improve lower limb strength (LLS), upper limb strength (ULS), agility, flexibility, and overall QoL. No significant effects were found on aerobic capacity. Subgroup-analysis results indicated that aquatic exercise only significantly improved LLS, ULS, agility, and flexibility in postmenopausal women < 65 years of age. However, aquatic exercise improves the overall QoL both in postmenopausal women < 65 years and ≥ 65 years. Aquatic resistance exercise significantly improves LLS, ULS, agility and flexibility. In addition, aquatic aerobic exercise can effectively increase LLS, and combined aquatic aerobic and resistance exercise can enhance the overall QoL.ConclusionsAquatic exercise can effectively improve physical fitness and overall QoL in postmenopausal women, but has limited effects on aerobic capacity; thus, it is highly recommended in postmenopausal women.

BackgroundCardiac surgery–associated acute kidney injury (CSA-AKI) is a major complication following pediatric cardiac surgery, which is associated with increased morbidity and mortality. The early prediction of CSA-AKI before and immediately after surgery could significantly improve the implementation of preventive and therapeutic strategies during the perioperative periods. However, there is limited clinical information on how to identify pediatric patients at high risk of CSA-AKI. ObjectiveThe study aims to develop and validate machine learning models to predict the development of CSA-AKI in the pediatric population. MethodsThis retrospective cohort study enrolled patients aged 1 month to 18 years who underwent cardiac surgery with cardiopulmonary bypass at 3 medical centers of Central South University in China. CSA-AKI was defined according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Feature selection was applied separately to 2 data sets: the preoperative data set and the combined preoperative and intraoperative data set. Multiple machine learning algorithms were tested, including K-nearest neighbor, naive Bayes, support vector machines, random forest, extreme gradient boosting (XGBoost), and neural networks. The best performing model was identified in cross-validation by using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using the Shapley additive explanations (SHAP) method. ResultsA total of 3278 patients from one of the centers were used for model derivation, while 585 patients from another 2 centers served as the external validation cohort. CSA-AKI occurred in 564 (17.2%) patients in the derivation cohort and 51 (8.7%) patients in the external validation cohort. Among the considered machine learning models, the XGBoost models achieved the best predictive performance in cross-validation. The AUROC of the XGBoost model using only the preoperative variables was 0.890 (95% CI 0.876-0.906) in the derivation cohort and 0.857 (95% CI 0.800-0.903) in the external validation cohort. When the intraoperative variables were included, the AUROC increased to 0.912 (95% CI 0.899-0.924) and 0.889 (95% CI 0.844-0.920) in the 2 cohorts, respectively. The SHAP method revealed that baseline serum creatinine level, perfusion time, body length, operation time, and intraoperative blood loss were the top 5 predictors of CSA-AKI. ConclusionsThe interpretable XGBoost models provide practical tools for the early prediction of CSA-AKI, which are valuable for risk stratification and perioperative management of pediatric patients undergoing cardiac surgery.

The present study aimed to compare the efficacy of different exercises on systolic blood pressure (SBP), diastolic blood pressure (DBP), and aortic pulse wave velocity (PWV) in postmenopausal women. We searched the China National Knowledge Infrastructure (CNKI), Wanfang database, Web of Science, PubMed, and Cochrane library databases, up to July 2022. The randomized controlled trials (RCTs) were selected following the inclusion criteria. We assessed study quality with the PEDro scale. The Stata software was used for statistical analysis. Twenty-three papers (26 RCTs) and 729 participants were included. Meta-analysis demonstrated that exercise decreased SBP (WMD = −6.74 mmHg, 95%CI: −9.08, −4.41, p = 0.000), DBP (WMD = −4.13 mmHg, 95%CI: −5.78, −2.48, p = 0.000) and aortic PWV (WMD = −0.79 m/s, 95%CI: −1.02, −0.56, p = 0.000). Aerobic exercise can significantly decrease SBP (WMD = −7.97 mmHg, 95%CI: −12.99, −2.60, p = 0.003) and DBP (WMD = −5.97 mmHg, 95%CI: −8.55, −3.39, p = 0.000). Resistance exercise can significantly decrease SBP (WMD = −5.62 mmHg, 95%CI: −9.00, −2.23, p = 0.001), DBP (WMD = −1.87 mmHg, 95%CI: −2.75, −0.99, p = 0.000) and aortic PWV (WMD = −0.67 m/s，95%CI: −0.98, −0.36, p = 0.000). Combined aerobic and resistance exercise can significantly decrease SBP (WMD = −5.42 mmHg, 95%CI: −10.17, −0.68, p = 0.025). The efficacy of mind-body exercise (Tai Chi/Yoga) on SBP, DBP, and aortic PWV were not obvious (p > 0.05). Exercise significantly improved SBP, DBP, and aortic PWV in postmenopausal women. Aerobic exercise decreased SBP and DBP. Resistance exercise decreased SBP, DBP, and aortic PWV. Additionally, further research is required to confirm the efficacy of mind-body exercise (Tai Chi/Yoga) on blood pressure and arterial stiffness.

Abstract Gastric cancer (GC) is one of the most common digestive system tumors in the world. Many circular RNAs (circRNAs) are involved in the progression of GC. The purpose of this study was to delve into the expression characteristics and biological functions of circ_0000064 in GC, and further study its mechanisms. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to detect circ_0000064 expression in 61 GC tissues and cell lines. Circ_0000064 knockdown was successfully modeled with siRNA. The effects of circ_0000064 on the biological functions of GC cells were analyzed by CCK‐8, BrdU, and Transwell assays. Bioinformatics and dual‐luciferase reporter gene assay were adopted to explore the relations between circ_0000064 and microRNA‐621 (miR‐621). Western blot was used to examine the regulatory function of circ_0000064 and miR‐621 on SYF2 pre‐mRNA splicing factor 2. Cric_0000064 expression was elevated in GC tissues and cell lines. Knocking down cric_0000064 could inhibit the viability, migration, and invasion of GC cells. Dual‐luciferase reporter gene assay showed that miR‐621 could bind circ_0000064 and SYF2 3'UTR; in addition, miR‐621 overexpression or SYF2 knockdown could partially weaken the cancer‐promoting effect of circ_0000064 on GC cells. Circ_0000064 expression was negatively correlated with miR‐621 expression in GC tissues while positively with SYF2 expression. Circ_0000064 can participate in the GC progression via modulating miR‐621/SYF2 axis. This implies that circ_0000064 may be a new diagnosed biomarker or a new therapeutic target of GC.

To prepare peptides with high angiotensin-converting enzyme (ACE) inhibitory (ACEi) activity, Alcalase was screened from five proteases and employed to prepare protein hydrolysate (TMH) of skipjack tuna (Katsuwonus pelamis) milts. Subsequently, 10 novel ACEi peptides were isolated from the high-ACEi activity TMH and identified as Tyr-Asp-Asp (YDD), Thr-Arg-Glu (TRE), Arg-Asp-Tyr (RDY), Thr-Glu-Arg-Met (TERM), Asp-Arg-Arg-Tyr-Gly (DRRYG), Ile-Cys-Tyr (ICY), Leu-Ser-Phe-Arg (LSFR), Gly-Val-Arg-Phe (GVRF), Lys-Leu-Tyr-Ala-Leu-Phe (KLYALF), and Ile-Tyr-Ser-Pro (IYSP) with molecular weights of 411.35, 404.41, 452.45, 535.60, 665.69, 397.48, 521.61, 477.55, 753.91, and 478.53 Da, respectively. Among them, the IC50 values of ICY, LSFR, and IYSP on ACE were 0.48, 0.59, and 0.76 mg/mL, respectively. The significant ACEi activity of ICY, LSFR, and IYSP with affinities of −7.0, −8.5, and −8.3 kcal/mol mainly attributed to effectively combining with the ACEi active sites through hydrogen bonding, electrostatic force, and hydrophobic interaction. Moreover, ICY, LSFR, and IYSP could positively influence the production of nitric oxide (NO) and endothelin-1 (ET-1) secretion in human umbilical vein endothelial cells (HUVECs) and weaken the adverse impact of norepinephrine (NE) on the production of NO and ET-1. In addition, ICY, LSFR, and IYSP could provide significant protection to HUVECs against H2O2 damage by increasing antioxidase levels to decrease the contents of reactive oxide species and malondialdehyde. Therefore, the ACEi peptides of ICY, LSFR, and IYSP are beneficial functional molecules for healthy foods against hypertension and cardiovascular diseases.

For efficiently utilizing the processing byproducts of miiuy croaker to prepare novel angiotensin I-converting enzyme (ACE) inhibitory (ACEi) peptides, in vitro gastrointestinal (GI) digestion method was screened and employed to prepare swim bladder hydrolysate with the highest ACEi activity. Subsequently, seven novel ACEi peptides were isolated from the hydrolysate and identified as DEGPE, EVGIQ, SHGEY, GPWGPA, GPFGTD, SPYGF, and VIGPF with molecular weights of 545.49, 544.58, 591.55, 583.63, 592.59, 569.60, and 531.63 Da, respectively. SHGEY and SPYGF exhibited remarkable ACEi activity with IC50 values of 0.86 ± 0.12 and 0.37 ± 0.06 mg/mL. Molecular docking experiment illustrated that the significant ACEi activity of SHGEY and SPYGF with the affinity of -8.7 and -9.7 kcal/mol mainly attributed to effectively combining with the ACEi active sites by hydrophobic interaction, electrostatic force and hydrogen bonding. Moreover, SHGEY and SPYGF could significantly up-regulate the nitric oxide (NO) production and decrease the endothelin-1 (ET-1) secretion in human umbilical vein endothelial cells (HUVECs), but also abolished the negative impacting of norepinephrine to the levels of NO and ET-1. Furthermore, SHGEY and SPYGF showed significant protection to HUVECs against H2O2 damage by increasing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity to lower the contents of reactive oxide species and malondialdehyde. Consequently, ACEi peptides derived from miiuy croaker swim bladders, especially SHGEY and SPYGF, are health-promoting ingredients for functional products as a supplementary treatment to hypertension and cardiovascular diseases.

In this study, N-(2,4,6-tribromophenyl)maleimide (TBPMI) was synthesized using three different catalysts, including stannous chloride, anhydrous acetic acid, and phosphoric acid, respectively. Comparative analysis was carried out on the synthesis conditions and the yields of TBPMI synthesized using different catalysts. Infrared spectroscopy and nuclear magnetic resonance spectroscopy were employed to characterize TBPMI. Results showed that the use of phosphoric acid as the catalyst required harsh reaction conditions and also the catalytic efficiency was poor. On the other hand, under similar conditions, the catalytic efficiency of anhydrous acetic acid was higher than that of stannous chloride, along with the reduction in problems associated with erosion and pollution.

To effectively utilize skipjack tuna (Katsuwonus pelamis) processing by-products to prepare peptides with high angiotensin-I-converting enzyme (ACE) inhibitory (ACEi) activity, Neutrase was selected from five kinds of protease for hydrolyzing skipjack tuna dark muscle, and its best hydrolysis conditions were optimized as enzyme dose of 1.6%, pH 6.7, and temperature of 50°C using single factor and response surface experiments. Subsequently, 14 novel ACEi peptides were prepared from the high ACEi protein hydrolysate and identified as TE, AG, MWN, MEKS, VK, MQR, MKKS, VKRT, IPK, YNY, LPRS, FEK, IRR, and WERGE. MWN, MEKS, MKKS, and LPRS displayed significantly ACEi activity with IC50 values of 0.328 ± 0.035, 0.527 ± 0.030, 0.269 ± 0.006, and 0.495 ± 0.024 mg/mL, respectively. Furthermore, LPRS showed the highest increasing ability on nitric oxide (NO) production among four ACEi peptides combining the direct increase and reversing the negative influence of norepinephrine (NE), and MKKS showed the highest ability on directly decreasing and reversing the side effects of NE on the secretion level of endothelin-1 (ET-1) among four ACEi peptides. These findings demonstrate that seafood by-product proteins are potential ACEi peptide sources and prepared ACEi peptides from skipjack tuna dark muscle, which are beneficial components for functional food against hypertension and cardiovascular diseases.

Supersymmetric quantum mechanics provides a powerful method for solving the Schrödinger equation in quantum mechanics problems. In this paper, a hyperbolic tangent superpotential is generalized according to a new hyperbolic tangent superpotential. Shape invariances of partner potentials of the generalized superpotential with additive partner potential are derived based on supersymmetric quantum mechanics. Their coefficient-dependent eigenfunctions and eigenvalues have been calculated according to those potentials. It is found that only the ground state exists when one of the two parameters satisfies additivity. But if the two parameters meet additivity, the number of excited states has an upper limit, then the energy levels are finite. These potentials increase the number of exactly solvable potentials and could be used as good models in quantum physics, atomic physics, mathematical physics, etc. Moreover, the consistent eigenvalues are obtained through the potential algebra method.

Field monitoring of water quality during the autumn flood season in the middle and lower reaches of the Yellow River in 2021 was carried out. During this period, a host of methods, including the single-factor evaluation method, index evaluation method, and fuzzy mathematics method, were utilized to evaluate the water quality status. The relevant findings indicate that the water quality of the mainstream and tributaries in the middle and lower reaches of the Yellow River in the autumn flood season is excellent, which meets the water function zoning and water quality goals. In particular, the single-factor evaluation method emphasizes the use of the single index with the most serious pollution to represent the comprehensive water quality category, whereas the fuzzy mathematics method uses the multi-factor contribution rate to calculate the membership degree of water quality. Therefore, it is superior to the single-factor evaluation method in determining the water quality of the water functional zones within the evaluation scope. Meanwhile, the Nemerow index of the water quality of the tributaries of Yiluo River and Qinhe River at the section entering the Yellow River is lower than that of the mainstream, indicating that the water quality of tributaries is better than that of the mainstream during the monitoring period. Overall, the results of this research are conducive to the objective evaluation of the water quality of the Yellow River during the autumn flood season, thus providing more scientific technical support for the ecological conservation and restoration of the Yellow River basin.

With a dinuclear zinc-ProPhenol complex as a catalyst, an efficient and novel [3 + 3] annulation of indoline-2-thiones and isatylidene malononitriles has been successfully developed via the Brønsted base and Lewis acid cooperative activation model. This practical methodology gives access to a broad range of chiral spiro[indoline-3,4′-thiopyrano[2,3-b]indole] derivatives in good yields with excellent levels of enantioselectivities (up to 88% yield and 99% ee).

In atomic and molecular physics, the Pöschl-Teller potential and its modified form (hyperbolic Pöschl-Teller potential) are particularly significant potentials. It is of great importance to study the Schrödinger equation with those potentials. In this paper, we further extend the hyperbolic Pöschl-Teller potential through generalizing the superpotential of that potential of the form Atanh (αx)-Bcoth (αx) to the more general form -Atanh (npx)-Bcoth (mpx). First, we introduce briefly the shape invariance and the potential algebra in supersymmetric quantum mechanics. Second, we derive three additive shape invariances, which are related to parameters A and B of the partner potentials with the generalized superpotential, and discuss the eigenfunctions and eigenvalues in detail. Although the superpotential has two parameters, those shape invariances still belong to the one-parameter form. The reason is that there is always a constraint relationship between A and B in the additive shape invariance of the partner potentials. Third, through the potential algebra approach, we obtain the relevant shape invariance and calculate the corresponding eigenvalue of the Schrödinger equation with the potential of the generalized superpotential. The calculation shows that the algebraic form shape invariance of the partner potentials with that superpotential is anastomotic to the above. Last, we make a summary and outlook.

Abstract Background Flurbiprofen axetil (FA) is a commonly prescribed agent to relieve perioperative pain, but the relationship between FA and postoperative acute kidney injury (AKI) remains unclear. This study attempted to evaluate the effects of different dose of perioperative FA on postoperative AKI. Methods A total of 9915 patients were enrolled for this retrospective study. The clinical characteristics and the prevalence of postoperative AKI among patients non-using, using low dose (50-100 mg), middle dose (100-250 mg) and large dose (≧250 mg) of FA were analyzed respectively. The impact of different dose of FA on postoperative AKI was analyzed using univariable and multivariate logistic regression analysis. Results The prevalence of postoperative AKI was 6.7% in the overall subjects and 5.1% in 2446 cases who used FA. The incidence of AKI in low dose group was significantly less than that of non use group (4.5% vs 7.2%, P

Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3′UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

This article discussed how to train standardized pediatric residents during the COVID-19 pandemic, which included the knowledge and capacity building for infection prevention and control, standardized residents training and psychological intervention and so on. It ought to be useful to improve the professional competence of pediatric residents.

Abstract Background Contrast-induced acute kidney injury (CI-AKI) is a major adverse effect caused by intravascular administration of iodinated contrast medium. Whether there is a difference in CI-AKI incidence between iso-osmolar (IOCM) and low-osmolar contrast media (LOCM) among diabetic patients is controversial. Methods Randomized controlled trials comparing the nephrotoxic effects between IOCM and LOCM in diabetic patients with or without CKD (eGFR

Abstract Background Oxymatrine (OM), a quinolizidine alkaloid extracted from a herb Sophorae Flavescentis Radix, has been used to treat liver fibrotic diseases. However, the mechanism of its anti-fibrosis effects is still unclear. TGF-β/Smad signaling and miR-195 have been proved to paly an important role in hepatic stellate cells (HSCs) activation and liver fibrosis. In this study, we investigated whether OM could inhibit HSCs activation through TGF-β1/miR-195/Smads signaling or not. Methods First, the effects of OM on HSC-T6 in different concentrations and time points were tested by MTT assay. We choose three appropriate concentrations of OM as treatment concentrations in following experiment. By Quantitative Real-time PCR and Western Blot, then we investigated the effect of OM on miR-195, Smad7 and α-SMA’s expressions to prove the correlation between OM and the TGF-β1/miR-195/Smads signaling. Last, miR-195 mimic and INF-γ were used to investigate the relation between miR-195 and OM in HSC activation. Results Our results showed that the proliferation of HSC was significantly inhibited when OM concentration was higher than 200 μg/mL after 24 h, 100 μg/mL after 48 h and 10 μg/mL after 72 h. The IC50 of OM after 24, 48 and 72 h were 539, 454, 387 μg/mL respectively. OM could down-regulate miR-195 and α-SMA (P

A new type of unsaturated poly ester-amide was prepared by melt polycondensation and characterized completely. Influence of heat treatment conditions and cross-linking content on mechanical and degradation properties of unsaturated polyester-amide were studied. Results suggested that the newly synthesized unsaturated poly(ester-amide) possessed good heat stabilization properties. Mechanical and degradation properties of cross-linked poly (ester-amide) were determined by heat treatment conditions and cross-linker content. Different initiation-accelerating agent systems and their content differences have an insignificant influence on the cross-linking time at Room Temperature (RT). Increasing heat treatment time increased the retention rate of mechanical properties during the degradation process and decreased hydrolysis rate in alkaline solution.

Background. The connection between angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphisms and IgA nephropathy (IgAN) was conflicting. This pooled analysis was performed to explore this issue. Methods. All eligible investigations were identified from various electronic databases, and the pooled analysis was evaluated using Stata software. Results. 27 studies with 2538 IgAN cases and 3592 controls were included. In overall subjects, ACE D allele, DD, and II genotype were associated with IgAN susceptibility (D vs. I: OR = 1.21, 95% CI: 1.10–1.32, P

Objective: This study aimed to assess the effect and mechanism of SS31 on cisplatin-induced acute kidney injury (CP-AKI) both in vivo and in vitro. Method: Male mices and HK-2 cells were treated using cisplatin to establish models of CP-AKI. 32 C57BL/6 mices were randomly divided into four groups (control group, CP group, CP + normal saline group, CP + SS-31 group). Cisplatin was intraperitoneally injected once to the mice (25 mg/kg). SS31 was administrated for 10 days at dosages of 10 mg/kg per day. Kidney histological changes and level of reactive oxygen species(ROS) were detected. In vitro studies, HK-2 cells were incubated with cisplatin (50 u M) or combimed with SS-31(100 u M), the level of mitochondrial ROS, apoptosis rate and the the expression of NLRP3, Caspase-1 and IL-1β were tested. Results: Renal tubulointerstitial apoptosis and oxidative stress were significantly increased in CP-AKI mice. Cisplatin caused elevation of serum creatinine (Scr), blood urea nitrogen (BUN) levels and enhanced IL-1β, caspase1 and NLRP3 expression, the electron microscopy examination showed mitochondria cristae swelling, mitochondrial spheres and partial ridge breakdown in renal tubular cell of CP-AKI mice. SS31 treatment could effectively suppress mitochondrial ROS, ameliorate these lesions and decrease the expression of NLRP3, IL-1β and Caspase1. In vitro studies, SS31 could restored the level of mitochondrial ROS and downregulate apoptosis rate in HK-2 cells, moreover, the elevated expression of NLRP3, IL-1β and Caspase-1were restored. Conclusion: SS31 could protect CP-AKI in mices, which might be due to an anti-oxidative and anti-apoptotic action via regulating mitochondrial ROS-NLRP3 pathway. NLRP3 inflammasome might be considered as a novel therapeutic target of CP-AKI.

To prepare bioactive peptides with high angiotensin-I-converting enzyme (ACE)-inhibitory (ACEi) activity, Alcalase was selected from five kinds of protease for hydrolyzing Skipjack tuna (Katsuwonus pelamis) muscle, and its best hydrolysis conditions were optimized using single factor and response surface experiments. Then, the high ACEi protein hydrolysate (TMPH) of skipjack tuna muscle was prepared using Alcalase under the optimum conditions of enzyme dose 2.3%, enzymolysis temperature 56.2 °C, and pH 9.4, and its ACEi activity reached 72.71% at 1.0 mg/mL. Subsequently, six novel ACEi peptides were prepared from TMPH using ultrafiltration and chromatography methods and were identified as Ser-Pro (SP), Val-Asp-Arg-Tyr-Phe (VDRYF), Val-His-Gly-Val-Val (VHGVV), Tyr-Glu (YE), Phe-Glu-Met (FEM), and Phe-Trp-Arg-Val (FWRV), with molecular weights of 202.3, 698.9, 509.7, 310.4, 425.6, and 606.8 Da, respectively. SP and VDRYF displayed noticeable ACEi activity, with IC50 values of 0.06 ± 0.01 and 0.28 ± 0.03 mg/mL, respectively. Molecular docking analysis illustrated that the high ACEi activity of SP and VDRYF was attributed to effective interaction with the active sites/pockets of ACE by hydrogen bonding, electrostatic force, and hydrophobic interaction. Furthermore, SP and VDRYF could significantly up-regulate nitric oxide (NO) production and down-regulate endothelin-1 (ET-1) secretion in HUVECs after 24 h treatment, but also abolish the negative effect of 0.5 μM norepinephrine (NE) on the generation of NO and ET-1. Therefore, ACEi peptides derived from skipjack tuna (K. pelamis) muscle, especially SP and VDRYF, are beneficial components for functional food against hypertension and cardiovascular diseases.

Hepatic ischemia reperfusion (I/R) injury (HIRI) HIRI is a complex, multifactorial pathophysiological process and in liver surgery has been known to significantly affect disease prognosis, surgical success rates, and patient survival. Ginsenoside Rgl (Rgl) monomer is one of the main active ingredients of ginseng. Previous studies have demonstrated that Rgl exerts various pharmacological effects through several mechanisms including suppression of apoptosis-related proteins levels, downregulation of inflammatory mediators and as well as antioxidant, which effectively exerts an organ protective effect I/R-induced damage. However, the exact mechanisms of Rg1 on HIRI remain to be elucidated. In the present study, we investigated the protective effect of Rg1 on hepatic ischemia-reperfusion (I/R) injury (HIRI) and explored its underlying molecular mechanism. A rat warm I/R injury model in vivo and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated BRL-3A cell model in vitro were established after pretreating with Rg1(20 mg/kg). The results showed that Rg1 reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TUNEL staining showed that pretreated with Rg1 inhibited the apoptosis rate compared with the I/R group. Moreover, pretreated with Rg1 significantly reduced the expression of Cyt-C, Caspase-9 and Caspase-3 to inhibit the cell apoptosis. Flow cytometry analysis showed the MMP in the I/R group was significantly increased, whereas pretreated with Rg1 effectively stabilized the MMP compared with the I/R group. in vitro, the proliferation of BRL-3A cells was significantly decreased by the OGD/R treatment, while Rg1 effectively reversed this phenomenon. In addition, western blotting showed that the increase of Cyt-C, Caspase-9 and Caspase-3 was inhibited by H2O2. These observations suggest that Rg1 exerts the protective effect by inhibiting the CypD protein-mediated mitochondrial apoptotic pathway.

Background/Aims: Transforming growth factor beta-induced protein (TGFBI) is an extracellular matrix protein induced by TGF-β. Previous studies have reported that the abnormal expression of TGFBI is related to the occurrence and development of some types of cancers, while the role of TGFBI in glioma is uncertain. Methods: The association between TGFBI expression and the prognosis of patients with glioma was analyzed based on data obtained from The Cancer Genome Atlas database. TGFBI expression was analyzed in 3 normal human brains and 57 cases of human gliomas by immunohistochemistry followed by an evaluation of the relationships between TGFBI expression and clinic-pathological features. Furthermore, the RNA interference plasmid pSUPER-shTGFBI was constructed and transfected into U87 and U251 cells to explore the effect of short hairpin RNA against TGFBI (shTGFBI) on cell proliferation, migration, invasion and apoptosis. Western blot analysis was performed to examine the expression of proteins related to apoptosis and proteins in the PI3K/Akt signaling pathway. Results: High TGFBI expression was found to be associated with poor prognosis in patients with glioblastoma multiforme. Immunohistochemistry showed that TGFBI expression was significantly higher in glioma tissue than in normal human brain tissues. The expression level of TGFBI showed no significant correlation with age, sex, lymph-node metastasis, or pathological grade. sh-TGFBI could inhibit proliferation, invasion and migration and induce apoptosis in U87 and U251 cells in vitro. Furthermore, the phosphorylation levels of AKT and mTOR declined significantly in sh-TGFBI transfected U81 and U251 cells when compared with control. Conclusion: TGFBI was up-regulated in glioma cells and played a promoting role in the growth and motility of U87 and U251 cells. These results suggested that TGFBI has the potential to be a diagnostic marker and to serve as a target for the treatment of gliomas.

The characterization of products produced from hydrothermal liquefaction of algal biomass is helpful to better understand the effect of different kinds of raw materials on the properties of the product fractions. The data presented in this article are related to the research article entitled “Integration of hydrothermal liquefaction and supercritical water gasification for the improvement of energy recovery from algal biomass” (Duan et al., 2018) [1]. In this data article, the compositions of gaseous products produced from hydrothermal liquefaction of eight different algae feedstocks at 350 °C for 60 min were analyzed by gas chromatography. The molecular and elemental compositions of the crude bio-oils produced from hydrothermal liquefaction of eight different algae feedstocks at 350 °C for 60 min were analyzed by comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry and organic elemental analyzer. The color of aqueous phases before and after they were subjected to supercritical water gasification was recorded by a high-resolution camera.

Background/Aims: Contrast induced-acute kidney injury (CI-AKI) is one of the most common causes of acute kidney injury (AKI) in hospitalized patients. Mitophagy, the selective elimination of mitochondria via autophagy, is an important mechanism of mitochondrial quality control in physiological and pathological conditions. In this study, we aimed to determine effects of iohexol and iodixanol on mitochondrial reactive oxygen species (ROS), mitophagy and the potential role of mitophagy in CI-AKI cell models. Methods: Cell viability was measured by cell counting kit-8. Cell apoptosis, mitochondrial ROS and mitochondrial membrane potential were detected by western blot, MitoSOX fluorescence and TMRE staining respectively. Mitophagy was detected by the colocalization of LC3-FITC with MitoTracker Red, western blot and electronic microscope. Results: The results showed that mitophagy was induced in human renal tubular cells (HK-2 cells) under different concentrations of iodinated contrast media. Mitochondrial ROS displayed increased expression after the treatment. Rapamycin (Rap) enhanced mitophagy and alleviated contrast media induced HK-2 cells injury. In contrast, autophagy inhibitor 3-methyladenine (3-MA) down-regulated mitophagy and aggravated cells injury. Conclusions: Together, our finding indicates that iohexol and iodixanol contribute to the generation of mitochondrial ROS and mitophagy. The enhancement of mitophagy can effectively protect the kidney from iodinated contrast (iohexol)-induced renal tubular epithelial cells injury.

A novel single step green-synthesis route has been developed for the synthesis of gold nanoparticles using aqueous extract of de-oiled jatropha waste (DJW). DJW, a second stage waste, was adopted as a reducing agent to reduce HAuCl4. Different optimal parameters such as ratio of HAuCl4(aq)/DJW(aq), reaction temperature and pH effects were also studied to fine-tune the shape of the gold nanoparticles (AuNPs). The resultant AuNPs were characterized by UV–visible spectrometry, Transmission electron microscopy, Selected area electron diffraction, Powder X-ray diffraction and Fourier transform infrared spectroscopy. Triangle, hexagonal and spherical shaped AuNPs were obtained with the average particle size of ∼14 nm. Furthermore, the AuNPs were capped and efficiently stabilized by protein molecules present in the DJW. In short, this novel synthesis route provides an environmental friendly and low cost option, as compared to currently available expensive chemical and/or physical methods.

For utilizing the largest source of marine proteins, Antarctic krill (Euphausia superba) proteins were defatted and hydrolyzed separately using pepsin, alcalase, papain, trypsin, and netrase, and alcalase hydrolysate (EPAH) showed the highest DPPH radical (DPPH·) and hydroxyl radical (HO·) scavenging activity among five hydrolysates. Using ultrafiltration and chromatography methods, fifteen antioxidant peptides were purified from EPAH and identified as Asn-Gln-Met (NQM), Trp-Phe-Pro-Met (WFPM), Gln-Asn-Pro-Thr (QNPT), Tyr-Met-Asn-Phe (YMNF), Ser-Gly-Pro-Ala (SGPA), Ser-Leu-Pro-Tyr (SLPY), Gln-Tyr-Pro-Pro-Met-Gln-Tyr (QYPPMQY), Glu-Tyr-Glu-Ala (EYEA), Asn-Trp-Asp-Asp-Met-Arg-Ile-Val-Ala-Val (NWDDMRIVAV), Trp-Asp-Asp-Met-Glu-Arg-Leu-Val-Met-Ile (WDDMERLVMI), Asn-Trp-Asp-Asp-Met-Glu-Pro-Ser-Phe (NWD-DMEPSF), Asn-Gly-Pro-Asp-Pro-Arg-Pro-Ser-Gln-Gln (NGPDPRPSQQ), Ala-Phe-Leu-Trp-Asn (AFLWA), Asn-Val-Pro-Asp-Met (NVPDM), and Thr-Phe-Pro-Ile-Tyr-Asp-Tyr-Pro-Gln (TFPIYDPQ), respectively, using a protein sequencer and ESI/MS. Among fifteen antioxidant peptides, SLPY, QYPPMQY and EYEA showed the highest scavenging activities on DPPH· (EC50 values of 1.18 ± 0.036, 1.547 ± 0.150, and 1.372 ± 0.274 mg/mL, respectively), HO· (EC50 values of 0.826 ± 0.027, 1.022 ± 0.058, and 0.946 ± 0.011 mg/mL, respectively), and superoxide anion radical (EC50 values of 0.789 ± 0.079, 0.913 ± 0.007, and 0.793 ± 0.056 mg/mL, respectively). Moreover, SLPY, QYPPMQY and EYEA showed strong reducing power, protective capability against H2O2-damaged plasmid DNA, and lipid peroxidation inhibition ability. Furthermore, SLPY, QYPPMQY, and EYEA had high stability under temperatures lower than 80 °C, pH values ranged from 6–8, and simulated GI digestion for 180 min. The results showed that fifteen antioxidant peptides from alcalase hydrolysate of Antarctic krill proteins, especially SLPY, QYPPMQY and EYEA, might serve as effective antioxidant agents applied in food and health products.