Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring.

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a Traditional Chinese Medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.

Ketogenic therapy towards precision medicine for brain diseases.

Precision nutrition and nutrigenomics are emerging in the development of therapies for multiple diseases. The ketogenic diet (KD) is the most widely used clinical diet, providing high fat, low carbohydrate, and adequate protein. KD produces ketones and alters the metabolism of patients. Growing evidence suggests that KD has therapeutic effects in a wide range of neuronal diseases including epilepsy, neurodegeneration, cancer, and metabolic disorders. Although KD is considered to be a low-side-effect diet treatment, its therapeutic mechanism has not yet been fully elucidated. Also, its induced keto-response among different populations has not been elucidated. Understanding the ketone metabolism in health and disease is critical for the development of KD-associated therapeutics and synergistic therapy under any physiological background. Here, we review the current advances and known heterogeneity of the KD response and discuss the prospects for KD therapy from a precision nutrition perspective.

Influence of Aging on Outcomes of Sacubitril/Valsartan in Hypertensive Patients with Heart Failure: A Multicenter Retrospective Study.

BACKGROUND: The aim of this study was to investigate the influence of aging on the effectiveness and tolerance of sacubitril/valsartan (sac/val) among hypertensive patients complicated with heart failure in a real-world setting. METHODS: This multicenter, retrospective study included patients (≥18 years old) admitted with a diagnosis of hypertension and heart failure, starting sac/val therapy between January 2020 and December 2021 from 3 medical centers. Patients were grouped by the cutoff age of 65 years. Outcomes were collected 31-365 days after the initiation of sac/val and were compared in a matched cohort after 1: 1 propensity score matching (PSM). RESULTS: A total of 794 patients were finally analyzed. Blood pressure and cardiac functions improved significantly compared with values at baseline. There were 269 patients in each cohort (<65 years and ≥65 years) after PSM. After PSM, the incidence of hyperuricemia and hypotension in the elderly patients (≥65 years) was significantly higher than in those <65 years of age. Kaplan-Meier estimate suggested that the cumulative incidence of new or recurrent cardiovascular events increased significantly at the age of ≥65 years after the point of 3 months (log-rank P =.00087). CONCLUSION: Sac/val benefited patients in both cohorts by improving blood pressure and cardiac function. Elderly patients (≥65 years) were susceptible to hypotension, low diastolic blood pressure, hyperuricemia, and underwent cardiac-related readmissions more frequently.

Promoting the process of determining brain death through standardized training.

Objective: This study aims to explore the training mode for brain death determination to ensure the quality of subsequent brain death determination. Methods: A four-skill and four-step (FFT) training model was adopted, which included a clinical neurological examination, an electroencephalogram (EEG) examination, a short-latency somatosensory evoked potential (SLSEP) examination, and a transcranial Doppler (TCD) examination. Each skill is divided into four steps: multimedia theory teaching, bedside demonstration, one-on-one real or dummy simulation training, and assessment. The authors analyzed the training results of 1,577 professional and technical personnel who participated in the FFT training model from 2013 to 2020 (25 sessions), including error rate analysis of the written examination, knowledge gap analysis, and influencing factors analysis. Results: The total error rates for all four written examination topics were < 5%, at 4.13% for SLSEP, 4.11% for EEG, 3.71% for TCD, and 3.65% for clinical evaluation. The knowledge gap analysis of the four-skill test papers suggested that the trainees had different knowledge gaps. Based on the univariate analysis and the multiple linear regression analysis, among the six factors, specialty categories, professional and technical titles, and hospital level were the independent influencing factors of answer errors (p < 0.01). Conclusion: The FFT model is suitable for brain death (BD) determination training in China; however, the authors should pay attention to the professional characteristics of participants, strengthen the knowledge gap training, and strive to narrow the difference in training quality.

Comparison of kinematics and joint moments calculations for lower limbs during gait using markerless and marker-based motion capture.

Objective: This study aimed at quantifying the difference in kinematic and joint moments calculation for lower limbs during gait utilizing a markerless motion system (TsingVA Technology, Beijing, China) in comparison to values estimated using a marker-based motion capture system (Nokov Motion Capture System, Beijing, China). Methods: Sixteen healthy participants were recruited for the study. The kinematic data of the lower limb during walking were acquired simultaneously based on the markerless motion capture system (120 Hz) and the marker-based motion capture system (120 Hz). The ground reaction force was recorded synchronously using a force platform (1,200 Hz). The kinematic and force data were input into Visual3D for inverse dynamics calculations. Results: The difference in the lower limb joint center position between the two systems was the least at the ankle joint in the posterior/anterior direction, with the mean absolute deviation (MAD) of 0.74 cm. The least difference in measuring lower limb angles between the two systems was found in flexion/extension movement, and the greatest difference was found in internal/external rotation movement. The coefficient of multiple correlations (CMC) of the lower limb three joint moments for both systems exceeded or equaled 0.75, except for the ad/abduction of the knee and ankle. All the Root Mean Squared Deviation (RMSD) of the lower limb joint moment are below 18 N·m. Conclusion: The markerless motion capture system and marker-based motion capture system showed a high similarity in kinematics and inverse dynamic calculation for lower limbs during gait in the sagittal plane. However, it should be noted that there is a notable deviation in ad/abduction moments at the knee and ankle.

Yigansan ameliorates maternal immune activation-induced autism-like behaviours by regulating the IL-17A/TRAF6/MMP9 pathway: Network analysis and experimental validation.

BACKGROUND: Maternal immune activation (MIA) is a significant factor inducing to autism spectrum disorder (ASD) in offspring. The fundamental principle underlying MIA is that inflammation during pregnancy impedes fetal brain development and triggers behavioural alterations in offspring. The intricate pathogenesis of ASD renders drug treatment effects unsatisfactory. Traditional Chinese medicine has strong potential due to its multiple therapeutic targets. Yigansan, composed of seven herbs, is one of the few that has been proven to be effective in treating neuro-psychiatric disorders among numerous traditional Chinese medicine compounds, but its therapeutic effect on ASD remains unknown. HYPOTHESIS: Yigansan improves MIA-induced ASD-like behaviours in offspring by regulating the IL-17 signalling pathway. METHODS: Pregnant C57BL/6J mice were intraperitoneally injected with poly(I:C) to construct MIA models and offspring ASD models. Network analysis identified that the IL-17A/TRAF6/MMP9 pathway is a crucial pathway, and molecular docking confirmed the binding affinity between the monomer of Yigansan and target proteins. qRT-PCR and Western blot were used to detect the expression levels of inflammatory factors and pathway proteins, immunofluorescence was used to detect the distribution of IL-17A, and behavioural tests were used to evaluate the ASD-like behaviours of offspring. RESULTS: We demonstrated that Yigansan can effectively alleviate MIA-induced neuroinflammation of adult offspring by regulating the IL-17A/TRAF6/MMP9 pathway, and the expression of IL-17A was reduced in the prefrontal cortex. Importantly, ASD-like behaviours have been significantly improved. Moreover, we identified that quercetin is the effective monomer for Yigansan to exert therapeutic effects. CONCLUSION: Overall, this study was firstly to corroborate the positive therapeutic effect of Yigansan in the treatment of ASD. We elucidated the relevant molecular mechanism and regulatory pathway involved, determined the optimal therapeutic dose and effective monomer, providing new solutions for the challenges of drug therapy for ASD.

Comparative analysis of the diversity of symbionts in fat body of long- and short-winged brown planthoppers.

The microbial community structure plays an important role in the internal environment of brown planthopper (BPH), Nilaparvata lugens (Hemiptera: Delphacidae), which is an indispensable part to reflect the internal environment of BPH. Wing dimorphism is a strategy for balancing flight and reproduction of insects. Here, quantitative fluorescence PCR was used to analyse the number and changes of the symbionts in the fat body of long- and short-winged BPHs at different developmental stages. A metagenomic library was constructed based on the 16 S rRNA sequence and internal transcribed spacer sequence for high-throughput sequencing, to analyze the community structure and population number of the symbionts of long- and short-winged BPHs, and to make functional prediction. This study enriches the connotation of BPH symbionts, and laid a theoretical foundation for the subsequent study of BPH-symbionts interaction and the function of symbionts in the host.

Reduced production of Ethyl Carbamate in wine by regulating the accumulation of arginine in Saccharomyces cerevisiae.

Ethyl carbamate (EC), a multisite carcinogenic compound, is naturally produced from urea and ethanol in alcoholic beverages. In order to reduce the content of EC in wine, the accumulation of arginine in Saccharomyces cerevisiae was regulated by genetic modifying genes involved in arginine transport and synthesis pathways to reduce the production of urea. Knockout of genes encoding arginine permease (Can1p) and amino acid permease (Gap1p) on the cell membrane as well as argininosuccinate synthase (Arg1) respectively resulted in a maximum reduction of 66.88% (9.40 µg/L) in EC, while overexpressing the gene encoding amino acid transporter (Vba2) reduced EC by 52.94% (24.13 µg/L). Simultaneously overexpressing Vba2 and deleting Arg1 showed the lowest EC production with a decrease of 68% (7.72 µg/L). The yield of total higher alcohols of the mutants all decreased compared with that of the original strain. Comprehensive consideration of flavor compound contents and sensory evaluation results indicated that mutant YG21 obtained by deleting two allele coding Gap1p performed best in must fermentation of Cabernet Sauvignon with the EC content low to 9.40 µg/L and the contents of total higher alcohols and esters of 245.61 mg/L and 41.71 mg/L respectively. This study has provided an effective strategy for reducing the EC in wine.

Retrograde endocannabinoid signaling at inhibitory synapses in vivo.

Endocannabinoid (eCB)-mediated suppression of inhibitory synapses has been hypothesized, but this has not yet been demonstrated to occur in vivo because of the difficulty in tracking eCB dynamics and synaptic plasticity during behavior. In mice navigating a linear track, we observed location-specific eCB signaling in hippocampal CA1 place cells, and this was detected both in the postsynaptic membrane and the presynaptic inhibitory axons. All-optical in vivo investigation of synaptic responses revealed that postsynaptic depolarization was followed by a suppression of inhibitory synaptic potentials. Furthermore, interneuron-specific cannabinoid receptor deletion altered place cell tuning. Therefore, rapid, postsynaptic, activity-dependent eCB signaling modulates inhibitory synapses on a timescale of seconds during behavior.

Self-assembly of sophorolipid and eugenol into stable nanoemulsions for synergetic antibacterial properties through alerting membrane integrity.

Exploring the natural, safe, and effective antimicrobial is one of the preferable ways to control foodborne bacteria. In this work, novel oil-in-water nanoemulsions were formulated with sophorolipids and eugenol without any co-surfactant using a self-assembling strategy. These nanoemulsions showed high stability with sizes less than 200 nm when exposure to low concentrations of salt ions, various pH values (5.0, 7.0, 10.0), storage temperature and time. The synergistic antibacterial effects against both Gram-negative Escherichia coli and Gram-positive Bacillus cereus were determined with a minimum inhibitory concentration (MIC) value of 0.5 mg/mL and 0.125 mg/mL, respectively. Further microscopy (SEM, TEM, LCSM) examination and ATP/Na+-K+-ATPase assay results showed that the morphological changes, intensive cell membrane permeability, leakage of ATP, and decreased Na+-K+-ATPase contributed to the antibacterial effects. Moreover, the bonding mechanism between nanoemulsions and cell membranes were further evaluated by FTIR and ITC using a DPPC vesicle model, which demonstrated that the nanoemulsions adsorbed on the surface of bilayer, interacted with the hydrophobic chains of DPPC membrane mainly through the hydrophobic interaction, and altered the structural integrity of the lipid bilayer. These results not only provide a facile green strategy for fabricating stable nanoemulsions, but also highlight a new perspective for stabilizing essential oils for their widely application in food industry.

Apnea Testing Practice to Increase Baseline PaCO2 and Frequency of Blood Gas Analyses.

OBJECTIVE: To study the influence of the initial partial pressure of carbon dioxide (PaCO2) and frequency of blood gas analyses on the positivity rate and safety of apnea testing (AT). DESIGN: A prospective multicenter cohort study. SETTING: Seven teaching hospitals. PARTICIPANTS: A total of 55 patients who underwent AT. INTERVENTIONS: Patients were divided into 2 groups according to their initial PaCO2-the experimental group (≥40 mmHg, 27 patients) and the control group (<40 mmHg, 28 patients). Blood gas analysis was performed at 3, 5, and 8 minutes, and vital signs were taken. AT results and complications were compared between the groups. RESULTS: The initial PaCO2 of the experimental group was 42.8 ± 2.2 mmHg v 36.4 ± 2.9 mmHg in the controls. The AT positivity rate was 100%. The experimental group needed less time to reach the target PaCO2 than the control group (4.07 ± 1.27 minutes v 5.68 ± 2.06 minutes; p = 0.001). Twenty-six patients (96.3%) in the experimental group reached the target PaCO2 in 5 minutes v 17 in the control group (60.7%) (p = 0.001). Seven patients (12.7%) were unable to complete 8-minute disconnection due to hypotension. The experimental group had a slightly lower incidence of hypotension than the control group, but there was no statistical difference (7.4% v 17.9%, p = 0.245). CONCLUSION: Increasing the baseline PaCO2 and doing more blood gas analyses can significantly shorten the time needed for AT and improve the AT positivity rate.

Effects of high power pulsed microwave on the enhanced color and flavor of aged blueberry wine.

A new method of high-power pulsed microwave (HPPM) was applied to accelerate the aging of blueberry wine. The color changes of blueberry wines during aging were investigated through Chemical Wine Age and CIE-LAB measurement. Results showed that the blueberry wines treated by HPPM at low frequencies (50 and 100 Hz) exhibited improved color characteristics with L* value reaching 47.04 at 100 Hz, an increased maturity of wine body, and a shortened chemical wine age from 90 days to 75 days. Moreover, the aroma changes determined by GC-MS showed that HPPM accelerated the formation of esters in blueberry wine, which were increased by 18.44% and 56.97% respectively under the conditions of 50 and 150 Hz. The formation of acid substances was reduced compared with the original wine, with contents of acetic acid, caproic acid, and octanoic acid of 29.46 µg/mL, 15.60 µg/mL, 17.74 µg/mL, respectively, displaying an enhanced wine flavor.

To Accelerate the Process of Brain Death Determination in China Through the Strategy and Practice of Establishing Demonstration Hospitals.

BACKGROUND: Our objective was to explore whether a brain death determination (BDD) strategy with demonstration hospitals can accelerate the process of BDD in China. METHODS: We proposed the construction standards for the BDD quality control demonstration hospitals (BDDHs). The quality and quantity of BDD cases were then analyzed. RESULTS: A total of 107 BDDHs were established from 2013 to 2022 covering 29 provinces, autonomous regions, and municipalities under jurisdiction of the central government of the Chinese mainland (except Qinghai and Tibet). A total of 1,948 professional and technical personnel from these 107 BDDHs received training in BDD, 107 quality control personnel were trained in the quality control management of BDD, and 1,293 instruments for electroencephalography, short-latency somatosensory evoked potential recordings, and transcranial Doppler imaging were provided for BDD. A total of 6,735 BDD cases were submitted to the quality control center. Among the nine quality control indicators for BDD in these cases, the implementation rate, completion rate, and coincidence rate of apnea testing increased the most, reaching 99%. CONCLUSIONS: The strategy of constructing BDDHs to promote BDD is feasible and reliable. Ensuring quality and quantity is a fundamental element for the rapid and orderly popularization of BDD in China.

Magnetic and injectable Fe-doped liquid metals for controlled movement and photothermal/electromagnetic therapy.

As a multifunctional material, gallium-based liquid metal (LM) mixtures with metal particles dispersed in the LM environment display many excellent and intriguing properties. In this study, biomaterials were prepared by mixing Fe particles with LM for easily manageable photothermal or electromagnetic therapy and evaluated. Clinically, the fabricated 5%Fe/LM sample was injectable and radiopaque, which allowed its smooth delivery through a syringe to the target tissues, where it could help achieve clear imaging under CT. Meanwhile, because of the loading of Fe particles, the 5%Fe/LM possessed a magnetic property, implying a high manipulation capability. According to the experiments, the capsule containing 5%Fe/LM when placed in an isolated pig large intestine could move as desired to the designated position through an external magnet. Further, the biosafety and low toxicity of the 5%Fe/LM were confirmed by cytotoxicity tests in vitro, and the temperature changes at the interface between the 5%Fe/LM and intestinal tissue after near-infrared (NIR) laser irradiation were determined through theoretical modeling and numerical simulation data analysis. Due to the excellent photothermal and magnetothermal effects of LM, the temperature of the 5%Fe/LM injected into the rabbit abdominal cavity could significantly increase under NIR laser or alternating magnetic field (AMF) administration. As a novel functional biomaterial, the 5%Fe/LM exhibited promising potential for designated position movement and photothermal or magnetothermal therapy in the near future.

Metallic Materials for Bone Repair.

Repair of large bone defects caused by trauma or disease poses significant clinical challenges. Extensive research has focused on metallic materials for bone repair because of their favorable mechanical properties, biocompatibility, and manufacturing processes. Traditional metallic materials, such as stainless steel and titanium alloys, are widely used in clinics. Biodegradable metallic materials, such as iron, magnesium, and zinc alloys, are promising candidates for bone repair because of their ability to degrade over time. Emerging metallic materials, such as porous tantalum and bismuth alloys, have gained attention as bone implants owing to their bone affinity and multifunctionality. However, these metallic materials encounter many practical difficulties that require urgent improvement. This article systematically reviews and analyzes the metallic materials used for bone repair, providing a comprehensive overview of their morphology, mechanical properties, biocompatibility, and in vivo implantation. Furthermore, the strategies and efforts made to address the short-comings of metallic materials are summarized. Finally, the perspectives for the development of metallic materials to guide future research and advancements in clinical practice are identified.

Potential biopsychosocial factors mediating/moderating the relationship between depressive symptoms and body size among children and adolescents: A systematic review.

The prevalence of depression and obesity in the pediatric population has increased along with multiple adverse health outcomes in later life. However, the mechanisms underlying the bidirectional relationship between obesity and depression have not yet been clarified. We aim to systematically summarize the literature reporting on mediational or moderational biopsychosocial factors in the relationship between depression and body size among children and adolescents. Four electronic databases (PubMed, Web of Science, PsycINFO, and PsychArticles) were systematically searched from inception until December 23, 2021, and subsequently updated until June 9, 2023. The study protocol was registered with PROSPERO (CRD42022301475). A total of 36 unique records reporting 152,513 children and adolescents meeting the inclusion criteria were identified. The results indicate that disparate psychological variables (e.g., body image, victimization and bullying, eating disorders, and sleep problems) may mediate the bidirectional relationship between depressive symptoms and body size. Moreover, the mediational/moderational effect of biological factors has not been well established. The moderational effect of social factors was inconsistently reported. Future research should aim to identify and characterize factors that may impact the bidirectional relationship between depression and obesity to inform prevention intervention strategies for affected children and adolescents.

How do aeration mode and influent carbon/nitrogen ratio affect pollutant removal, gas emission, functional genes and bacterial community in subsurface wastewater infiltration systems?

This study investigated the influences of aeration mode and influent carbon/nitrogen ratio on matrix oxygen concentration, pollutant removal, greenhouse gas emission, functional gene abundances and bacterial community in subsurface wastewater infiltration systems (SWISs). Intermittent or continuous aeration enhanced oxygen supply at 0.6 m depth in the matrix, which improved organics removal, nitrogen removal, the abundances of bacterial 16S rRNA, amoA, nxrA, narG, napA, nirK, nirS, norB, nosZ genes, bacterial community Alpha diversity, the relative abundances of Actinobacteria at 0.6 m depth, the relative abundances of Chloroflexi, Gemmatimonadetes, Bacteroidetes and Firmicutes at 0.9 and 1.2 m depth and reduced CH4 and N2O conversion efficiencies, the abundance of mcrA gene with carbon/nitrogen ratio of 12 and 16 compared with non-aeration. Increased carbon/nitrogen ratio resulted in higher TN removal efficiencies and lower CH4 and N2O conversion efficiencies in aeration SWISs than those in non-aeration SWIS. Intermittent aeration SWIS obtained high removal efficiencies of 83.2, 85.4 and 90.8% for TN, NH4+ -N and COD and low conversion efficiency of 0.21 and 0.65% for N2O and CH4 with optimal carbon/nitrogen ratio of 12. However, high TN (82.6%), NH4+ -N (84.9%) and COD (92.2%) removal efficiencies and low CH4 (0.67%) and N2O (0.23%) conversion efficiencies were achieved in continuous aeration SWIS with carbon/nitrogen ratio of 16.

Accuracy and depth evaluation of clinical low pass genome sequencing in the detection of mosaic aneuploidies and CNVs.

BACKGROUND: Low-pass genome sequencing (LP GS) has shown distinct advantages over traditional methods for the detection of mosaicism. However, no study has systematically evaluated the accuracy of LP GS in the detection of mosaic aneuploidies and copy number variants (CNVs) in prenatal diagnosis. Moreover, the influence of sequencing depth on mosaicism detection of LP GS has not been fully evaluated. METHODS: To evaluate the accuracy of LP GS in the detection of mosaic aneuploidies and mosaic CNVs, 27 samples with known aneuploidies and CNVs and 1 negative female sample were used to generate 6 simulated samples and 21 virtual samples, each sample contained 9 different mosaic levels. Mosaic levels were simulated by pooling reads or DNA from each positive sample and the negative sample according to a series of percentages (ranging from 3 to 40%). Then, the influence of sequencing depth on LP GS in the detection of mosaic aneuploidies and CNVs was evaluated by downsampling. RESULTS: To evaluate the accuracy of LP GS in the detection of mosaic aneuploidies and CNVs, a comparative analysis of mosaic levels was performed using 6 simulated samples and 21 virtual samples with 35 M million (M) uniquely aligned high-quality reads (UAHRs). For mosaic levels > 30%, the average difference (detected mosaic levels vs. theoretical mosaic levels) of 6 mosaic CNVs in simulated samples was 4.0%, and the average difference (detected mosaic levels vs. mosaic levels of Y chromosome) of 6 mosaic aneuploidies and 15 mosaic CNVs in virtual samples was 2.7%. Furthermore, LP GS had a higher detection rate and accuracy for the detection of mosaic aneuploidies and CNVs of larger sizes, especially mosaic aneuploidies. For depth evaluation, the results of LP GS in downsampling samples were compared with those of LP GS using 35 M UAHRs. The detection sensitivity of LP GS for 6 mosaic aneuploidies and 15 mosaic CNVs in virtual samples increased with UAHR. For mosaic levels > 30%, the total detection sensitivity reached a plateau at 30 M UAHRs. With 30 M UAHRs, the total detection sensitivity was 99.2% for virtual samples. CONCLUSIONS: We demonstrated the accuracy of LP GS in mosaicism detection using simulated data and virtual samples, respectively. Thirty M UAHRs (single-end 35 bp) were optimal for LP GS in the detection of mosaic aneuploidies and most mosaic CNVs larger than 1.48 Mb (Megabases) with mosaic levels > 30%. These results could provide a reference for laboratories that perform clinical LP GS in the detection of mosaic aneuploidies and CNVs.