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ABSTRACT Importance Nutrition is associated with neurodevelopment. Infants at high risk of cerebral palsy (CP) usually suffer from undernutrition, yet the relationship between nutritional status and neurodevelopmental levels is unclear. Objective To describe the nutritional status characteristics of infants at high risk of CP, and to explore the relationship between neurodevelopmental levels and nutritional status. Methods This single‐center cross‐sectional study enrolled infants at high risk of CP, with corrected age from 0 days to 12 months. Weight and height were measured and calculated into z‐scores, which were used to classify the nutritional status based on the World Health Organization growth charts and American Society for Parenteral and Enteral Nutrition standards. The Bayley Scales of Infant and Toddler Development were used to evaluate the developmental levels of gross motor, fine motor, cognition, receptive communication, and expressive communication. Results A total of 479 infants at high risk of CP were recruited, with 43.4% classified as undernutrition. Compared to those with normal neurodevelopment, the odds of moderate and severe undernutrition were about 1.8 and 3.9 times higher in gross motor delay, 2.2 and 3.1 times higher in fine motor delay, 2.5 and 9.4 times higher in cognition delay, 2.2 and 3.9 times higher in receptive communication delay, and 3.0 and 5.6 times higher in expressive communication delay. There were significant positive correlations between nutritional status and neurodevelopmental levels (P < 0.001). Interpretation Undernutrition and neurodevelopmental delays are prevalent among infants at high risk of CP. Worse nutritional status was correlated with lower neurodevelopmental levels.

Abstract The first-order second-moment checking point method was introduced to judge the instability probability and evaluate the stability of the TCURM. The frequency–response stability calculation and the reliability results were compared, and a frequency–response stability and reliability analysis method was proposed. Taking the Zengziyan W12# unstable rock mass in Nanchuan, Chongqing, China, as an example, the calculation shows that the dynamic indexes and geological indexes decrease as the stiffness of the deterioration area decreases. According to the statistical data of the laboratory test and the field investigation, reliability theory is used to evaluate the stability of the TCURM, and the failure probabilities are 80.3% and 96.27% under natural and saturated conditions, which correspond to states of poor stability and instability, respectively. The reliability evaluation results are consistent with the conclusion of the frequency–response stability analysis. The new method can provide a theoretical basis for developing the dynamic monitoring and early warning indicators of the TCURM and disaster prevention and mitigation in mountainous areas.

AbstractContext The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use.Objective The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases.Methods We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence.Results Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment.Conclusions Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.

Changji'an Formula (CJAF) is a Chinese herbal compound, which is effective against irritable bowel syndrome with predominant diarrhea (IBS-D) in clinic. However, the molecular mechanism has not been well defined. In the current study, the potential targets and signaling pathways of CJAF against IBS-D were predicted using network pharmacology analysis. The pharmacological mechanisms of CJAF against IBS-D and the potential mechanism were validated by using an IBS-D mouse model induced by enema with trinitrobenzene-sulfonic acid (TNBS) plus with restraint stress and further intervened with CJAF. A total of 232 active compounds of CJAF were obtained, a total of 397 potential targets for the active ingredients were retrieved and a total of 219 common targets were obtained as the potential targets of CJAF against IBS-D. GO and KEGG enrichment analyses showed that multiple targets were enriched and could be experimentally validated in a mouse model of IBS-D. The mechanisms were mainly converged on the immune and inflammatory pathways, especially the NF-κB, TNF and IL-17 signaling pathway, which were closely involved in the treatment of CJAF against IBS-D. Animal experiment showed that CJAF alleviated visceral hypersensitivity and diarrhea symptom of IBS-D. CJAF also restored the histological and ultrastructure damage of IBS-D. The result of Western blot showed that CJAF upregulated colonic tight junction proteins of ZO-1, Occludin and Claudin-1. Further results demonstrated that CJAF inhibited the protein expression of NF-κB/NLRP3 inflammasome pathway targets and downregulated proinflammatory mediators of IL-1β, IL-18, TNF-α. In conclusion, CJAF could effectively reduce inflammatory response and alleviate visceral hypersensitivity as well as diarrhea symptom of IBS-D by inhibiting the NF-κB/NLRP3 signaling pathway. This study not only reveals the mechanism of CJAF against IBS-D, but also provides a novel therapeutic strategy for IBS-D.

Abstract Soil roadbed along the river suffers from water erosion at the bottom and collapse at the top under flood scouring, which leads to the suspension of upper pavement slab. In order to ensure the safety of soil roadbed along the river, this study explored the development mechanism of soil roadbed damage by flood in actual cases, and proposed the evolution process of instability under roadbed scouring. The stability law of roadbed along the river under flood scouring was analyzed, and the stability safety factor was corrected to analyze the sensitivity of water depth, flow rate, river bending angle and stability safety factor K in working conditions. The sensitivity of width and height of soil roadbed after flood scouring to water depth, flow velocity, river bending angle was investigated. Moreover, numerical simulation was carried out to determine the displacement nephogram and maximum shear stress nephogram of soil roadbed along the river under the conditions of road surface and roadbed load, vehicle loading or constant change of water depth. By comparing the above theories and engineering cases, the water damage mechanism of soil roadbed along the river was further verified.

Background: The prevalence of breast cancer (BRCA), which is common among women, is on the rise. This study applied network pharmacology to explore the potential mechanism of action of herba sarcandrae in BRCA and construct a prognostic signature composed of inflammation-related genes. Methods: The active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The “drug-active compound-potential target” network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses. Results: Forty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells. Conclusions: Herba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.

The aim of this study was to investigate the anti-Eimeria tenella mechanism of Qingchang Compound (QCC) and provide a basis for its clinical application. The active ingredients, active ingredient-disease intersection targets, and possible pathways of QCC for the treatment of chicken coccidiosis were analyzed, the binding ability of pharmacodynamic components and target proteins was determined by network pharmacology and the molecular docking, and a model of infection with coccidiosis was constructed to verify and analyze the mechanism of action of QCC against coccidiosis. Among the 57 components that met the screening conditions, the main bioactive components were quercetin, dichroine, and artemisinin, with IL-1β, IL-6, IL-10, IFN-γ, and IL-8 as the core targets. Simultaneously, the KEGG signaling pathway of QCC anti-coccidiosis in chickens was enriched, including cytokine-cytokine receptor interactions. The results showed that the main pharmacodynamic components of QCC and the core targets could bind well; artemisinin and alpine possessed the largest negative binding energies and presented the most stable binding states. In addition, in vivo studies showed that QCC reduced blood stool in chickens with coccidiosis, restored cecal injury, and significantly reduced the mRNA and protein expression levels of IL-1β, IL-10, and IFN-γ in ceca (p

BackgroundThe prevalence of malnutrition in older adults is high. Early use of appropriate screening scales for malnutrition risk and early intervention can effectively improve life quality of the elderly in communities. ObjectiveTo evaluate the risk of malnutrition among the community-dwelling elderly in a district of Shanghai and explore its influencing factors. MethodsFrom October to December 2021, a total of 960 seniors aged 65 years and above in community committees (villages) of Minhang District were selected by stratified random sampling. Trained investigators conducted one-to-one interviews with included seniors using questionnaires. The questionnaires included the Geriatric Depression Scale (GDS), the Activity of Daily Living Scale (ADL), and the malnutrition risk assessment for elderly adults. Height, weight, waist circumference, and calf circumference were measured. Chi-square test and logistic regression were used to analyze potential influencing factors of malnutrition in the elderly. ResultsAmong the 960 community-dwelling seniors of Minhang District, 13 (1.35%) were malnourished and 311 (32.40%) were at the risk of malnutrition. There were statistically significant differences in nutritional status across different categories of age, sex, monthly family income, education level, marital status, waist circumference, dental health status, activity of daily living, nutrition knowledge, suffering from chronic diseases, having > 3 chronic diseases, taking > 3 long-term prescriptions, depression symptoms, sleeping duration, daily outdoor activity time, number of daily food species (milk/soy products/fish/meat/poultry/eggs), daily intake of vegetables and fruits, daily consumption of cooking oil, frequency of physical exercise, frequency of smoking, and living alone (P < 0.05). The logistic regression analysis results showed that poor dental conditions, insufficient daily intake of milk/soy products/fish/meat/poultry/eggs (25 g), insufficient daily outdoor activities ( 3 chronic diseases, taking > 3 long-term prescriptions, and being single/widowed/divorced were the main risk factors for nutritional abnormalities in the elderly (P< 0.05). ConclusionThe elderly in Minhang District of Shanghai have a high malnutrition risk, and their nutritional status is affected by multiple factors, including poor dental status, irrational dietary structure, insufficient time for outdoor activities, suffering from chronic diseases, having > 3 chronic diseases, taking > 3 long-term prescriptions, low educational level, living alone, and being single/widowed/divorced.

Relationship Extraction (RE) is a central task in information extraction. The use of entity mapping to address complex scenarios with overlapping triples, such as CasRel, is gaining traction, yet faces challenges such as inadequate consideration of sentence continuity, sample imbalance and data noise. This research introduces an entity mapping-based method CasRelBLCF building on CasRel. The main contributions include: A joint decoder for the head entity, utilizing Bi-LSTM and CRF, integration of the Focal Loss function to tackle sample imbalance and a reinforcement learning-based noise reduction method for handling dataset noise. Experiments on relation extraction datasets indicate the superiority of the CasRelBLCF model and the enhancement on model's performance of the noise reduction method.

Chronic obstructive pulmonary disease (COPD) is a lung inflammatory disease that is associated with environmental allergic component exposure. Cigarette smoke is an environmental toxicant that induces lung malfunction leading to various pulmonary diseases. Astaxanthin (AST) is a carotenoid that shows antioxidant and anti-inflammatory activities which might be a promising candidate for COPD therapy. In this study, we released that AST could attenuate cigarette smoke-induced DNA damage and apoptosis in vivo and in vitro. AST administration ameliorated cigarette smoke extract (CSE)-induced activation of Caspase-3 and apoptosis. Pretreated mice with AST significantly decrease CSE-induced DNA damage which shows lower nuclear γ-H2AX level. AST treatment also dramatically reduces the production of intracellular reactive oxygen species (ROS) by suppressing the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme 4 (NOX4) and dual oxidase 1 (DUOX1). Taken together, this study suggested that AST can decrease CSE-induced DNA damage and apoptosis by inhibiting NOX4/DUOX1 expression that promotes ROS generation. AST may be a potential protective agent against CSE-associated lung disease that is worth in-depth investigation.

Irritable bowel syndrome with predominant diarrhea (IBS-D) is characterized by increased intestinal permeability. Previous studies have shown that the microRNA-29 gene is involved in the regulation of intestinal permeability in patients with IBS-D. NF-κB was proved to play a key role in inflammatory response of intestine and resultant disruption of tight junction integrity, whose activity could be inhibited by TNF Receptor-Associated Factor 3 (TRAF3). However, the exact mechanism that induces increased intestinal permeability in IBS-D patients has not been clarified. In this study, we found that microRNA-29b‑3p (miR-29b-3p) was significantly upregulated, while TRAF3 was decreased and the NF-κB-MLCK pathway was activated within the colonic tissue of IBS-D patients. Subsequently, we confirmed the targeting relationship between miR-29b-3p and TRAF3 through a double-luciferase reporter assay. Lentivirus transfection of NCM460 cells with miR-29b-3p-overexpressing and -silencing vectors demonstrated that the expression of TRAF3 was negatively correlated with the level of miR-29b-3p. The NF-κB/MLCK pathway was activated in the miR-29b-3p-overexpressing group and inhibited to some extent in the miR-29b-3p-silencing group. Results in WT and miR-29 knockout mice showed that miR-29b-3p levels were increased, TRAF3 levels were decreased, and the NF-κB/MLCK signaling was activated in the WT IBS-D group as compared with the WT control group. The protein levels of TRAF3 and TJs in the miR-29b-/- IBS-D group were partially recovered and NF-κB/MLCK pathway indicators were, to a certain extent, decreased as compared with the WT IBS-D group. These results suggested that miR-29b-3p deletion enhances the TRAF3 level in IBS-D mice and alleviates the high intestinal permeability. In brief, through the analysis of intestinal tissue samples from IBS-D patients and miR-29b-/- IBS-D mice, we showed that miR-29b-3p is involved in the pathogenesis of intestinal hyperpermeability in IBS-D via targeting TRAF3 to regulate the NF-κB-MLCK signaling pathway.

Background: Nutritional problems are common in children with cerebral palsy (CP), yet the relationship between nutritional status and the severity of CP is unclear. Objective: To describe the nutritional status and characteristics of children with CP, and to explore the relationship between severity of CP and nutritional status in children. Methods: This multicentre cross-sectional study included children with CP in China. Weight and height were measured and converted to z-scores. Gross Motor Function Classification System (GMFCS), Eating and Drinking Ability Classification System (EDACS), Subjective Global Nutritional Assessment (SGNA), social life ability, and blood indicators were tested. Results: All 1,151 participants were given oral-feeding and 50.8% of them demonstrated undernutrition. Compared with those in GMFCS or EDACS levels I–III, the odds of moderate and severe undernutrition were 2.6 and 8.9 times higher in GMFCS levels IV and V, and 4.3 and 12.6 times higher in EDACS levels IV and V, respectively. Except for serum 25-hydroxyvitamin D, no significant differences were found in blood indicators among normal, undernourished and overnourished groups. Conclusion: Degrees of undernutrition in children with CP are correlated with the severity of eating and drinking dysfunction and with gross motor impairment. Blood indicators may not reflect nutritional status in children with CP. LAY ABSTRACT Cerebral palsy is the most common physical disability in children in the world. Children with cerebral palsy may have a high risk of having malnutrition as a result of the high energy consumption and/or low energy intake. The former is mainly caused by the abnormal muscular tone, and the latter may emerge from the dysphagia and gastrointestinal problems. As for the optimization of nutritional status is integral to the overall health and clinical management of children with cerebral palsy, the nutritional status stands out for its clinical importance in this group. Children with cerebral palsy are affected by different degrees of motor dysfunction, and may also be faced with eating and drinking problems or limited daily life ability, it is not clear whether nutritional status and function are interrelated. What's more, it is believed that the blood tests may indicate the nutritional status, but it is not well understood. In this project we will look at the nutritional status of children with cerebral palsy in China and investigate the relationship between nutritional status and function and blood indicators. This will then allow clinicians and caregivers to formulate future policies to improve nutritional status for this group of children.

Paeoniflorin has been traditionally used to treat pain and immunologic derangement in China. However, its detailed mechanism remains to be illuminated. We investigated the mechanism by which paeoniflorin alleviates the inflammatory response in a mouse model of irritable bowel syndrome with predominant diarrhea (IBS-D). C57BL/6 wild type (WT) and miR-29a knockout (KO) mice were randomly divided into control, model, rifaximin, and paeoniflorin groups (n = 7). IBS-D model was induced by single intracolonic instillation of 0.1 mL trinitro-benzene-sulfonic acid (TNBS, 50 mg/mL) combined with restraint stress for seven consecutive days. The treatment groups received rifaximin (100 mg/kg) and paeoniflorin (50 mg/kg) via intragastric administration for seven days, respectively. The results showed that the fecal water content, fecal pellet output, visceral sensitivity, and histopathological score after paeoniflorin treatment were lower than those of the model group in both WT and miR-29a KO mice (P < 0.05). In both lineage mice, damage was observed in the colon tissues of model group, while paeoniflorin treatment partially ameliorated the tissue damage. Serum levels of DAO, DLA, IL-1β, IL-18, TNF-α, and MPO were decreased after paeoniflorin treatment (P < 0.05), with miR-29a KO mice in a lower level compared with that of WT mice. RT-PCR showed that the relative expression of miR-29a, NF-κB (p65), NLRP3, ASC, caspase-1, IL-1β, and TNF-α was downregulated while NKRF was upregulated after paeoniflorin treatment (P < 0.05). Immunohistochemistry showed that intestinal epithelial protein levels of NLRP3, ASC, and caspase-1 decreased while those of Claudin-1 and ZO-1 increased in the paeoniflorin treatment group (P < 0.05). In general, compared with WT mice, NLRP3 inflammasome pathway targets was in much lower expression level than miR-29a KO mice. In conclusion, paeoniflorin could inhibit abnormal activation of the NLRP3 inflammasome pathway by inhibiting miR-29a in IBS-D, thereby relieving the inflammatory response of the intestinal mucosa and reconstructing the intestinal epithelial barrier.

BackgroundMini-Manual Ability Classification System (Mini-MACS) was developed for children with cerebral palsy aged 1–4 years, but its validity and reliability in different cultures are unavailable yet. This study was to determine the reliability and validity of Mini-MACS in East Asian children with cerebral palsy and investigate the correlation between Mini-MACS and Gross Motor Function Classification System.MethodsOne hundred and four East Asian children with cerebral palsy aged 12–48 months were classified by one of their parents, an occupational therapist, and a physical therapist with Mini-MACS. The results were analyzed for inter-rater reliability by using intraclass correlation coefficient (ICC). The Nine-hole Peg Test was used for the criterion-related validity analysis, and parents retested their children after 2 weeks to evaluate test–retest reliability. Gross Motor Function Classification System levels were also collected to investigate the correlation with Mini-MACS.ResultsGood inter-rater reliability among the occupational therapist, physical therapist, and parents was found [ICC = 0.984 (95% confidence interval, CI, 0.976–0.989), 0.973 (95% CI 0.960–0.982), and 0.966 (95% CI 0.950–0.977), respectively; p

AimTo investigate the efficacy and safety of high-calorie formula vs. Chinese daily food on the nutritional status and motor function of undernourished children with cerebral palsy (CP).MethodsIn this prospective, assessor-blind, and randomized controlled trial, we recruited children (1–10 years) with CP and undernutrition based on the WHO and the American Society for Parenteral and Enteral Nutrition criteria from the National Children's Medical Center. Participants were randomly allocated (1:1) to a high-calorie formula group or a Chinese daily food diet group (control group) for 6 months. Indirect calorimetry was used to estimate energy requirements. We compared the nutritional status and gross motor function of participants in both groups based on weight, height, z-scores (weight-for-age, height-for-age, weight-for-height, and BMI-for-age), and the Gross Motor Function Measure (GMFM), respectively, at baseline, 3-, and 6-months follow-up. In addition, the effective rate of nutritional intervention, and adverse events were simultaneously assessed.ResultsFrom July 2020 to December 2021, a total of 119 participants were enrolled and randomized, and 110 participants completed the study (with 54 children in the high-calorie formula group and 56 children in the control group). After 6 months of treatment, the weight, height, z-scores (weight-for-height, weight-for-age, and BMI-for-age), and GMFM of both groups were significantly improved (p < 0.05). There were significant differences in changes in weight, weight-for-age z-scores, and GMFM between the two groups (p < 0.05). During the study period, 16 children experienced at least one mild adverse event [9 (16.7%) in the formula group and 7 (12.5%) in the control group].ConclusionNutritional intervention with a high-calorie formula may be an effective and safe option in children with CP for improving undernutrition and gross motor dysfunction.Clinical trial registrationwww.chictr.org.cn, identifier: ChiCTR2000033878.

Transcranial direct current stimulation (tDCS) has shown a promising prospect in improving function and spasticity in school-aged children with cerebral palsy, but little is known in preschool children. The aim of this study was to explore the safety and effects of tDCS on hand function in preschool children (aged 3–6 years) with hemiplegic cerebral palsy (HCP). We designed a crossover, single-blind, sham-controlled study in 30 preschool children with HCP, who were recruited to receive one session of sham and one session of active anodal tDCS (1.5 mA, 20 min) on the primary motor cortex of the affected hemisphere, with a 24-h interval between the two sessions. Questionnaire was completed by each participant and their attendants immediately, 90 min, and 24 h after each session to monitor common adverse events of tDCS, such as skin irritation, skin erythema, burning sensation, headache, dizziness, etc. Box and Block Test, Selective Control of the Upper Extremity Scale, Modified Ashworth Scale, and Melbourne Assessment 2 were conducted at baseline, immediately, and 90 min after each session. No severe adverse event occurred during the study and only a few of them felt transient and slight discomfort. Results also showed that all participants performed better at Box and Block Test of the hemiplegic hand immediately after a single anodal tDCS (P < 0.05) and this improvement lasted at least 90 min and more than 24 h. However, there was no significant improvement in Selective Control of the Upper Extremity Scale of both hands, Box and Block Test of the non-hemiplegic hand, Modified Ashworth Scale, and Melbourne Assessment 2 of the hemiplegic upper limb (P > 0.05). Shortly, this study supported the safety and effects of a single anodal tDCS on improving the manual dexterity of the hemiplegic hand for preschool children with HCP. Further researches with larger samples about the optimal dose and treatment cycle of tDCS for preschool children with HCP are warranted. This study gained the approval of ethics committee of the organization and was registered at chictr.org (ChiCTR2000031141).

Rechargeable microbatteries are important power supplies for microelectronic devices. Two essential targets for rechargeable microbatteries are high output energy and minimal footprint areas. In addition to the development of new high-performance electrode materials, the device configurations of microbatteries also play an important role in enhancing the output energy and miniaturizing the footprint area. To make a clear vision on the design principle of rechargeable microbatteries, we firstly summarize the typical configurations of microbatteries. The advantages of different configurations are thoroughly discussed from the aspects of fabrication technologies and material engineering. Towards the high energy output at a minimal footprint area, a revolutionary design for microbatteries is of great importance. In this perspective, we review the progress of fabricating microbatteries based on the rolled-up nanotechnology, a derivative origami technology. Finally, we discussed the challenges and perspectives in the device design and materials optimization.

Constraint-induced movement therapy (CIMT) combined with repetitive transcranial magnetic stimulation (rTMS) have shown great potential in improving function in schoolchildren with unilateral cerebral palsy attributed to perinatal stroke. However, the prospect of application in preschool children with unilateral cerebral palsy (UCP) attributed to various brain disorders remains unclear. In this prospective, assessor-blinded, randomized controlled study, 40 preschool children with UCP (aged 2.5–6 years) were randomized to receive 10 days of CIMT combined with active or sham rTMS. Assessments were performed at baseline, 2 weeks, and 6 months post-intervention to investigate upper limb extremity, social life ability, and perceived changes by parents and motor-evoked potentials. Overall, 35 participants completed the trial. The CIMT plus active stimulation group had greater gains in the affected hand function (range of motion, accuracy, and fluency) than the CIMT plus sham stimulation group (P < 0.05), but there was no significant difference in muscular tone, social life ability, and perceived changes by parents between the two groups (P > 0.05). In addition, there was no significant difference in hand function between children with and without motor-evoked potential (P > 0.05). No participants reported severe adverse events during the study session. In short, the treatment of CIMT combined with rTMS is safe and feasible for preschool children with UCP attributed to various brain disorders. Randomized controlled studies with large samples and long-term effects are warranted.

Gut-microbiota dysbiosis links to allergic diseases. The mechanism of the exacerbation of food allergy caused by gut-microbiota dysbiosis remains unknown. Regulation of retinoic acid receptor alpha (RARα) signaling is critical for gut immune homeostasis. Here we clarified that RARα in dendritic cells (DCs) promotes Th2 cell differentiation. Antibiotics treatment stimulates retinoic acid signaling in mucosal DCs. We found microbiota metabolites short-chain fatty acids (SCFAs) maintain IGF-1 levels in serum and mesenteric lymph nodes. The IGF-1/Akt pathway is essential for regulating the transcription of genes targeted by RARα. And RARα in DCs affects type I interferon (IFN-I) responses through regulating transcription of IFN-α. Our study identifies SCFAs crosstalk with RARα in dendritic cells as a critical modulator that plays a core role in promoting Th2 cells differentiation at a state of modified/disturbed microbiome.

Alcohol aqueous solvents were prepared by individually adding n-propanol, isopropanol, 1,2-propanediol, and glycerol to deionized water for use as lubricants for the electrostatic minimum quantity lubrication (EMQL) machining of aluminum alloys. The tribological characteristics of those formulated alcohol solvents under EMQL were assessed using a four-ball configuration with an aluminum–steel contact, and their static chemisorption on the aluminum surfaces was investigated. It was found that the negatively charged alcohol lubricants (with charging voltages of −5 kV) resulted in 31% and 15% reductions in the coefficient of friction (COF) and wear scar diameter (WSD), respectively, in comparison with those generated using neutral alcohol lubricants. During the EMQL, static charges could help dissociate the alcohol molecules, generating more negative ions, which accelerated the chemisorption of those alcohol molecules on the aluminum surfaces and thereby yielded a relatively homogeneous-reacted film consisting of more carbon and oxygen. This lubricating film improved the interfacial lubrication, thus producing a better tribological performance for the aluminum alloys. The results achieved from this study will offer a new way to develop high-performance lubrication technologies for machining aluminum alloys.

Asthma has become a global health issue, suffering more than 300 million people in the world, which is a heterogeneous disease, usually characterized by chronic airway inflammation and airway hyperreactivity. Combination of inhaled corticosteroids (ICS) and long acting β-agonists (LABA) can relieve asthma symptoms and reduce the frequency of exacerbations, especially for patients with refractory asthma, but there are limited treatment options for people who do not gain control on combination ICS/LABA. The increase in ICS dose generally provides little additional benefit, and there is an increased risk of side effects. Therefore, therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. Some findings suggest autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. The chinese herbal medicine (CHM) have been demonstrated clinically as potent therapeutic interventions for asthma. Moreover some reports have found that the bioactive components isolated from CHM could modulate autophagy, and exhibit potent Anti-inflammatory activity. These findings have implied the potential for CHMs in asthma or allergic inflammation therapy via the modulation of autophagy. In this review, we discuss the basic pathomechanisms underpinning asthma, and the potential role of CHMs in treating asthma with modulating autophagy.

Knowledge graph (KG) reasoning improves the perception ability of graph structure features, improving model accuracy and enhancing model learning and reasoning capabilities. This paper proposes a new GraphDIVA model based on the variational reasoning divergent autoencoder (DIVA) model. The network structures and calculation processes of the models are analyzed. The GraphSAGE algorithm is introduced into the path reasoning module to solve the inability of the original model to perceive the features of the graph structure, which leads to a decline in the accuracy rate. Hence, GraphDIVA can achieve a higher accuracy rate with fewer learning iterations. The experiments show the efficiency and effectiveness of our model and proves that our method has a better effect on the accuracy rate and training difficulty than the baseline model on the FB15k-237 and NELL-995 benchmark datasets.

Summary: IgE and IgG1 production in the type 2 immune response is the characteristic feature of an allergic reaction. However, whether bacterial molecules modulate IgE and IgG1 production remains obscure. Here, we demonstrate that the bacterial quorum sensing molecules acyl homoserine lactones (AHLs) induce IgE and IgG1 production by activating the RARE (retinoic acid response element) response in dendritic cells (DCs) in vivo. DC-specific knockout of the retinoic acid transcriptional factor Rara diminished the AHL-stimulated type 2 immune response in vitro. AHLs altered DC phenotype, upregulated OX40L and IFN-I signature, and promoted T helper 2 cell differentiation in vitro. Finally, AHLs activated the RARE response by inhibiting AKT phosphorylation in vitro, as the AKT agonists IGF-1 and PDGF abolished the effect of AHLs on the RARE response. This study demonstrates a mechanism by which AHLs drive allergic airway inflammation through activating retinoic acid signaling in DCs.

We generated an induced human pluripotent stem cell line from a child with microcephaly carrying compound heterozygous mutations of TYW1 inherited from healthy parents. This iPS cell line showed typical embryonic stem cell-like morphology, expressed pluripotent markers that comparable to human embryonic stem cells. Moreover, these cells have the ability to differentiate into three germ layers and maintain a normal karyotype.

Mucus secretion accumulation in the airways may act as a contributing factor for the development of airflow limitation in severe fetal asthma patients. Accumulated evidences showed that transforming growth factor beta (TGF-β) plays a regulatory role in airway remodeling including mucus hyper-secretion in asthma. However, the detailed molecular mechanisms of TGF-β3 induced MUC5AC hyper-expression in airway epithelium remains unclear. Here, we demonstrated the pivotal roles of autophagy in regulation of MUC5AC hyper-production induced by TGF-β3 in airway epithelium. Our experimental data showed that inhibiting autophagy pathway in repeated ovalbumin (OVA) exposed mice exhibited decreased airway hyper-response and airway inflammation, diminishing the expression of Muc5ac and TGF-β3. Furthermore, our studies demonstrated that autophagy was induced upon exposure to TGF-β3 and then mediated MUC5AC hyper-expression by activating the activator protein-1 (AP-1) in human bronchial epithelial cells. Finally, Smad2/3 pathway was involved in TGF-β3-induced MUC5AC hyper-expressions by promoting autophagy. These data indicated that autophagy was required for TGF-β3 induced airway mucous hyper-production, and that inhibition of autophagy exerted therapeutic benefits for TGF-β3 induced airway mucus secretion. Keywords: TGF-β3, MUC5AC, Autophagy, Smad2/3

Vespa auraria (Smith) is a common wasp species which is broadly distributed in south Asia. This species was spotted in filed forensic studies and disrupted the insect succession on the decaying corpse. Complete mitochondrial genome of V. auraria was presented here for its forensically potential influence. The mitogenome was assemblied to 18613 bp in length. The nucleotide composition of present mitogenome was calculated (A: 40.1%, G: 5.5%, T: 41.7%, C: 12.7%). Gene annotation analysis found 22 tRNA, 2 rRNA, and 13 protein-coding genes (PCGs). All the tRNA sequences could be folded into the typical structure of clover-leaf with the excepstion of tRNA-Ser (AGN). Phylogenetic development was analyzed based on V. auraria with other species of Hymenoptera.

Although near-surface seawater is supersaturated with CaCO3, only a minor part of it is abiogenic (e.g., carbonate cements). The possible reason for such a phenomenon has attracted much attention in the past decades. Substrate effects on the heterogeneous nucleation and growth of CaCO3 at various Mg2+/Ca2+ ratios may contribute to the understanding of the origin of abiogenic CaCO3 cements. Here, we used in situ atomic force microscopy (AFM), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Raman spectroscopy to study the heterogeneous nucleation and growth of CaCO3 on both calcite (104) and aragonite (110) surfaces. The results show that (1) calcite spiral growth occurs on calcite (104) surfaces by monomer-by-monomer addition; (2) the aggregative growth of aragonite appears on aragonite (110) surfaces through a substrate-controlled oriented attachment (OA) along the [001] direction, followed by the formation of elongated columnar aragonite; and (3) Mg2+ inhibits the crystallization of both calcite and aragonite without impacting on crystallization pathways. These findings disclose that calcite and aragonite substrates determine the crystallization pathways, while the Mg2+/Ca2+ ratios control the growth rate of CaCO3, indicating that both types of CaCO3 substrate in shallow sediments and aqueous Mg2+/Ca2+ ratios constrain the deposition of abiogenic CaCO3 cements in the ocean.

To compare the muscle thickness, fascicle length, and pennation angle of the gastrocnemius, soleus, and tibialis anterior between Asian children with spastic cerebral palsy (CP) and typically developing (TD) peers.This cross-sectional study involved a total of 72 children with hemiplegic CP (n = 24), and diplegic CP (n = 24) and their TD peers (n = 24). Muscle architecture was measured at rest using ultrasound. Clinical measures included gross motor function and a modified Ashworth scale.The thicknesses of the tibialis anterior and medial gastrocnemius muscles were smaller in the affected calf of children with CP (p

The harmful nature of high concentrations of antibiotics to humans and animals requires the urgent development of novel materials and techniques for their absorption. In this work, CTAB (Cetyltrimethyl Ammonium Bromide)-assisted synthesis of ZIF-8 (zeolitic imidazolate framework)-derived hollow carbon (ZHC) was designed, prepared, and used as a high-performance adsorbent, and further evaluated by Langmuir and Freundlich isothermal adsorption experiments, dynamic analysis, as well as theoretical calculation. The maximum capacities of ZHC for adsorbing tetracycline (TC), norfloxacin (NFO), and levofloxacin (OFO) are 267.3, 125.6, and 227.8 mg g-1, respectively, which delivers superior adsorptive performance when compared to widely studied inorganic adsorbates. The design concept of ZIF-8-derived hollow carbon material provides guidance and insights for the efficient adsorbent of environmental antibiotics.

Background TAM receptors (Tyro3, Axl and Mer) are expressed in hematopoietic tissues. The roles of the three receptors in hematopoiesis are, however, largely unknown. We investigated the role of TAM receptors in regulating erythropoiesis.Design and Methods Single and double mutant mice for Axl and Mer were used in the study. Cellularity of bone marrow and spleen, hematologic parameters, flow cytometry analysis of erythroid cell maturation, erythropoietic response to acute hemolytic anemia, bone marrow transplantation and the expression of erythropoisis were analyzed to evaluate the function of Axl and Mer in erythropoiesis.Results Axl and Mer, but not Tyro3, were constitutively expressed in developing erythroid cells. Mice lacking Axl and Mer (Axl−/−Me−/−) had impaired erythropoiesis in bone marrow and expanded splenic erythropoiesis. We found an inhibition of differentiation at the transition from erythroid progenitors to proerythroblasts in Axl−/−Mer−/− mice. These mice exhibited a low rate of erythropoietic response to acute anemia induced by phenylhydrazine. Bone marrow transplantation studies showed that the impaired erythropoiesis in Axl−/−Mer−/− mice is erythroid cell-autonomous. TAM receptors may influence erythropoiesis through the regulation of GATA-1 erythropoietin receptor and EpoR expression in erythroid progenitors. Notably, mice lacking single Axl or Mer exhibited normal erythropoiesis in steady-state conditions.Conclusions Axl and Mer play an important role in regulating erythropoiesis. This finding provides a novel insight into the mechanism of erythropoiesis.

Background and Objectives The molecular mechanisms regulating megakaryocytopoiesis and hemostasis remain largely unknown. The Tyro 3 subfamily of receptor tyrosine kinases (RTK), which is composed of three members (Tyro 3, Axl and Mer), plays important roles in various tissues, such as those in the nervous, immune and reproductive systems. Here, we investigate the roles of the Tyro 3 RTK subfamily in regulating megakaryocytopoiesis and hemostasis.Design and Methods Single, double, and triple knock-out mice for the three Tyro 3 RTK were used in the study. Bleeding time, platelet count, megakaryocyte count, megakaryocyte ploidy, rate of proplatelet formation, platelet aggregation and ATP release were used as criteria to evaluate hemostasis, megakaryocytopoiesis and platelet function.Results Mice lacking all three receptors had impaired hemostasis and mild thrombocytopenia, which may be due to platelet dysfunction and defective megakaryocytopoiesis. Mice lacking different combinations of two receptors of the Tyro 3 RTK subfamily had normal platelet counts in peripheral blood, but exhibited impaired hemostasis and platelet function. Although knock-out mice for any single receptor had normal hemostasis and megakaryocytopoiesis, they exhibited a mild platelet dysfunction.Interpretation and Conclusions The Tyro 3 RTK subfamily plays important roles in regulating hemostasis, megakaryocytopoiesis and platelet function.

Introduction: The dry ripe sarcocarp of Cornus officinalis Sieb.et Zucc (in Chinese Shanyurou) has the properties of tonifying the liver and kidney. Wine-steamed Corni Fructus, as the main processed product from Corni Fructus, is widely used in traditional Chinese clinical medicine. This article aims to study the Corni Fructus composition changes when wine-steamed processed and to discuss the optimal processing technology of Corni Fructus combined with pharmacological experiments. Methods: The differences between Corni Fructus and wine-steamed Corni fructus constituents were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The effects of Corni Fructus and wine-steamed Corni Fructus with different processing times were studied from the aspects of immune activity, liver protection, and kidney yin deficiency. Results: A total of 132 compounds were identified in the wine-steamed process of Corni Fructus. There were no significant differences in immune function, liver protection, and kidney yin deficiency of Corni Fructus with different processing times. However, the effects of Corni Fructus processed by wine-steaming were significantly enhanced in all aspects. Conclusion: The wine-steamed Corni Fructus chemical composition may be the material basis for enhancing liver and kidney function. After processing, Corni Fructus can enhance immune function, liver protection function, and liver and kidney toning function. [ABSTRACT FROM AUTHOR]