Quantifying attention in children with intellectual and developmental disabilities through multicenter electrooculogram signal analysis.

In a multicenter case-control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA's capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

Cationic Curcumin Nanocrystals Liposomes for Improved Oral Bioavailability: Formulation Development, Optimization, In Vitro and In Vivo Evaluation.

Curcumin, a naturally occurring poorly water-soluble polyphenol with a broad spectrum, is a typical BCS IV drug. The objective of this study was to develop curcumin nanocrystals liposomes with the aim of improving bioavailability. In this study, we prepared cationic curcumin nanocrystals with a particle size of only 29.42 nm; such a phenomenal range of particle sizes is very rare. Moreover, we summarized and evaluated the parameters of the nanocrystal preparation process, including methods, formulations, etc., and the rules we concluded can be generalized to other nanocrystal preparation processes. To counteract the instability of the nanocrystals in the digestive tract, cationic curcumin nanocrystals were loaded into negatively charged liposomes through gravitational force between different charges. Unexpectedly, chitosan oligosaccharide was found to promote the self-assembly process of curcumin nanocrystal liposomes. In vitro and in vivo experiments demonstrated that chitosan-modified curcumin nanocrystal liposomes exhibited enhanced resistance to enzyme barriers, mucus barriers, and cellular barriers, resulting in a 5.4-fold increase in bioavailability compared to crude powder formulations. It can be concluded that cationic nanocrystals liposomes represent an appropriate novel strategy for improving the dissolution rate and bioavailability of poorly soluble natural products such as curcumin.

Relationship of dietary natural folate and synthetic folic acid co-exposure patterns with biological aging: findings from NHANES 2003-2018.

Background: The mandatory folic acid fortification program in the United States has inevitably exposed most Americans to both natural folate and synthetic folic acid. We aim to examine the association of dietary folate co-exposure patterns with biological aging indicators. Methods: A total of 18 889 participants were enrolled from 2003 to 2018. Dietary intake of folate from diverse sources was evaluated by 24-hour dietary recall. Biological aging indicators were developed based on age-related clinical indicators, including the phenotypic age (PA), Klemera-Doubal method (KDM), homeostatic dysregulation (HD), and allostatic load (AL). The unsupervised K-means clustering method, logistic regression model, and restricted cubic spline (RCS) regression model were used to explore the relationship of natural folate and synthetic folic acid co-exposure with biological aging indicators. Results: The results indicated that higher intake of total folate, dietary folate, and food natural folate was associated with lower PA [OR = 0.75 (0.64, 0.88); OR = 0.79 (0.70, 0.90); OR = 0.65 (0.57, 0.75)], KDM [OR = 0.63 (0.53, 0.75); OR = 0.80 (0.65, 0.98); OR = 0.62 (0.49, 0.77)], HD [OR = 0.69 (0.56, 0.84); OR = 0.78 (0.67, 0.92); OR = 0.78 (0.68, 0.90)], and AL [OR = 0.69 (0.58, 0.82); OR = 0.73 (0.63, 0.85); OR = 0.74 (0.62, 0.90)], consistently. Four co-exposure patterns were generated based on the intake of folate from diverse sources, as follows: "low folate exposure group" to cluster 1, "dietary folate exposure group" to cluster 2, "mixed source high folate exposure group" to cluster 3, and "mixed source excessive folate exposure group" to cluster 4. Compared with cluster 1, participants in cluster 2 are associated with lower biological age indicators (ORPA = 0.82 [0.72, 0.93]; ORKDM = 0.58 [0.47, 0.70]; ORHD = 0.85 [0.75, 0.97]; ORAL = 0.87 [0.77, 0.98]), while participants in cluster 3 and cluster 4 are not. Conclusion: For individuals subjected to folic acid fortification programs, a higher intake of dietary folate, especially natural folate, coupled with a lower consumption of folic acid supplements, was found to be associated with lower biological age indicators.

[Research progress in coatings with active compounds and extracts of traditional Chinese medicines for coronary intervention devices].

In recent years, the incidence and mortality rates of cardiovascular diseases in China have kept rising, with no significant reduction in disease burden observed. Percutaneous coronary intervention(PCI) is an effective approach for treating coronary artery disease. Drug-eluting stents and drug-coated balloons are currently the most common PCI devices used in clinical practice. However, challenges with restenosis and late-stage thrombotic events persist. Inhibiting the proliferation of vascular smooth muscle cells while enhancing endothelial cell activity is crucial for reducing restenosis and preventing thrombosis, and it remains a challenge in research. The active compounds and extracts of traditional Chinese medicine(TCM), particularly the combinations of active compounds in coatings, possess multi-target potential and serve as a supplement to coatings prepared from synthetic compounds. This review elucidates the application of TCM active compounds(such as arsenic trioxide, paclitaxel, hirudin, tetramethylpyrazine, emodin, oxymatrine, and curcumin), combinations of TCM active compounds(paclitaxel/hirudin, geniposide/baicalin), and TCM extracts(such as Curcumae Rhizoma extract and Tripterygium hypoglaucum extract) in the coatings for PCI devices in recent years. Furthermore, this review expounds the current challenges and future prospects in this field, giving insights into the innovation of PCI devices.

A drug delivery system of HIF-1α siRNA nanoparticles loaded by mesenchymal stem cells on choroidal neovascularization.

Aim: To assess mesenchymal stem cells (MSCs) as carriers for HIF-1α siRNA-loaded nanoparticles (NPs) for targeted therapy of experimental choroidal neovascularization (CNV).Materials & methods: A poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid NP was designed. The transfection efficacy of MSCs with the hybrid NPs was assessed. Mice were intravenously injected with MSCs after laser photocoagulation and CNV was assessed at 7 days post-injection.Results & conclusion: The transfection efficiency of hybrid NPs into MSCs was 72.7%. HIF-1α mRNA expression in 661w cells co-cultured with MSC-hybrid-siRNA NPs was significantly lower. Intravenous delivery of MSC-hybrid-siRNA NPs greatly reduced CNV area and length. Intravenous injection of MSC-hybrid-siRNA NPs achieved therapeutic efficacy in reducing CNV area. The MSC-mediated homing enabled targeted inhibition of ocular angiogenesis.

[Box: see text].

Artificial intelligence in the anterior segment of eye diseases.

Ophthalmology is a subject that highly depends on imaging examination. Artificial intelligence (AI) technology has great potential in medical imaging analysis, including image diagnosis, classification, grading, guiding treatment and evaluating prognosis. The combination of the two can realize mass screening of grass-roots eye health, making it possible to seek medical treatment in the mode of "first treatment at the grass-roots level, two-way referral, emergency and slow treatment, and linkage between the upper and lower levels". On the basis of summarizing the AI technology carried out by scholars and their teams all over the world in the field of ophthalmology, quite a lot of studies have confirmed that machine learning can assist in diagnosis, grading, providing optimal treatment plans and evaluating prognosis in corneal and conjunctival diseases, ametropia, lens diseases, glaucoma, iris diseases, etc. This paper systematically shows the application and progress of AI technology in common anterior segment ocular diseases, the current limitations, and prospects for the future.

The association between weight loss behaviors and body weight perception in Chinese adolescents: 2007-2022.

BACKGROUND: Weight misperceptions are common in children and adolescents, which is related to the engagement of weight loss behaviors. The aim of this study was to investigate the association between body weight perception and weight loss behaviors of lower-calorie diets and increased levels of physical activity (PA). METHODS: The Ningbo Youth Risk Behavior Survey was conducted from 2007 to 2022. A multistage, stratified cluster sampling procedure was utilized to draw target adolescents aged 12 to 18 years participating in each survey wave (2007, 2012, 2017, 2022). Data of anthropometry, weight perception, and weight loss behaviors were collected through self-administered questionnaires. A binary generalized linear model was used to examine associations between body weight perception and weight loss behaviors of lower calorie diets and increased levels of PA. RESULTS: The sample sizes for each survey wave were 777, 885, 1588 and 2638. The prevalence of overweight (OW)/obesity (OB), self-perception of OW/OB and overestimated perception increased from 7.6%, 27.0% and 29.1% in 2007 to 16.3%, 39.9% and 41.4% in 2022, respectively. Adolescents that perceived themselves as OW/OB had higher odds of lower-calorie diets (OR: 4.2, 3.3-5.4) and increased level of PA (OR: 3.8, 2.9-5.0), whereas adolescents that perceived themselves as underweight had lower odds of lower-calorie diets (OR: 0.371, 0.253-0.542) and increased levels of PA (OR: 0.381, 0.295-0.559). CONCLUSION: OW, self-perception of OW/OB and overestimated perception were prevalent in Chinese adolescents. Self-perception of OW/OB was positively associated with lower-calorie diets and increased levels of PA. The results can support public health specialists to promote health education of body perception and improve self-esteem in Chinese children and adolescents.

Using cerebral regional oxygen saturation and amplitude-integrated electroencephalography in neonates on extracorporeal membrane oxygenation: preliminary experience from a single center.

OBJECTIVE: This study aims to evaluate the application value in neurological outcome of cerebral regional oxygen saturation (CrSO2) and amplitude-integrated electroencephalography (aEEG) monitoring during neonatal extracorporeal membrane oxygenation (ECMO) courses. METHODS: We retrospectively analyzed 18 neonates receiving veno-arterial ECMO (V-A ECMO) support at our hospital from July 2021 to December 2022. Continuous monitoring of CrSO2 and brain electrical activity was conducted using near-infrared spectroscopy (NIRS) and aEEG throughout the ECMO treatment. We collected and analyzed related clinical data. RESULTS: Among the 11 survivors, 5 were categorized as the normal group (N group) and 6 as the abnormal group (AN group) based on post-ECMO brain MRI outcomes. The N group exhibited shorter time percentage of significant CrSO2 reduction (> 25% from baseline or absolute value < 40%), better fractional tissue oxygen extraction (FTOE) rates, and more stable mean percentage changes in CrSO2 compared to the AN group. Neonates in the N group predominantly showed mildly abnormal aEEG readings, with one patient displaying disrupted sleep-wake cycles. This particular patient also had more significant CrSO2 reduction and poorer FTOE compared to others in the N group. Additionally, the Test of Infant Motor Performance (TIMP) scores indicated hypoevolutism in this patient before discharge, while others in the N group had normal TIMP scores. In the AN group, 4 exhibited moderate and 2 severe aEEG abnormalities; 5 had hypoevolutism TIMP scores, and 1 with moderate aEEG abnormalities maintained a normal TIMP score, exhibiting lesser CrSO2 reduction and improved FTOE. CONCLUSION: CrSO2 and aEEG monitoring show potential as routine assessments for neurological outcomes during neonatal ECMO. In our cohort, a tendency was observed where neonates with greater reductions in CrSO2 and more severe aEEG abnormalities experienced poorer neurological outcomes.

Repetitive transcranial magnetic stimulation for major depression and obsessive-compulsive disorders in Singapore.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is used for treatment-resistant major depressive disorder (MDD) and obsessive-compulsive disorder (OCD), but there are few studies on patient outcomes in Southeast Asia. In this study, we describe the clinical profile and outcome of patients with MDD and OCD treated with rTMS in Singapore. Method: A naturalistic retrospective study of 71 patients (inpatient and outpatient) who received rTMS treatment between June 2018 and April 2023 was conducted. The depressive and obsessive outcome rating scales used were clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS), Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Clinical Global Impressions-Severity (CGI-S) and self-rated Depression Anxiety and Stress Scale-21 (DASS-21). Results: Clinician-rated and self-rated mood and general condition improved significantly. MADRS mean score improved from 28.1 (standard deviation [SD] 7.3) to 20.7 (SD 10.1) (P<0.0001) (20.8% response rate/17% remission rate). CGI-S mean 4.6 (SD 0.8) improved to 3.3 (SD 1.2) (P<0.0001). DASS-21 total mean improved from 67.3 (SD 24.6) to 49.6 (SD 28.0) (P<0.0001). Y-BOCS mean score displayed a trend towards improvement from 30.1 (SD 7.5) to 27.2 (SD 6.9) (P=0.799). However, 44.4% of patients with OCD responded with a minimal 20% reduction in baseline Y-BOCS. Moreover, the subgroup of 35.8% of patients with less than 30 rTMS sessions had contributed disproportionately to nonresponse (85.7%). Patients who received rTMS treatment (>30 sessions) had a trend of larger improvement of MADRS score when compared to patients with (≤30 sessions) (9.4 [SD 9.7] versus 3.8 [SD 12.3] [P=0.078]). Conclusion: Response and remission rates for MDD and OCD suggest patients have a good response to rTMS treatment. Dosing longer rTMS sessions after an acute course helps to maximise effectiveness. Further research to determine predictors of outcome and characterise clinical features of late responders to target treatment more effectively is recommended.

IL-27/Blimp-1 axis regulates the differentiation and function of Tim-3+ Tregs during early pregnancy.

Decidual regulatory T cells (Tregs) are essential for successful pregnancy outcome. A subset of Tregs, T cell immunoglobulin and mucin domain-containing protein 3-positive regulatory T cells (TregsTim-3+), plays a central role in the acceptance of the fetus during early stages of normal pregnancy. The molecular mechanism regulating the differentiation and function of TregsTim-3+ is unknown. Here, we investigated the role of the transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) on decidual TregTim-3+ differentiation. We demonstrated that Blimp-1 enhanced the coexpression of negative costimulatory molecules (Tim-3, T cell immunoreceptor with Ig and ITIM domains, and programmed cell death protein 1) on Tregs and improved their immunosuppressive functions, including increased IL-10 secretion, suppression of effector T cell proliferation, and promotion of macrophage polarization toward the M2 phenotype. Furthermore, we showed that IL-27 regulated the expression of Tim-3 and Blimp-1 through the STAT1 signaling pathway and that transfer of TregsBlimp-1+ into an abortion-prone mouse model effectively reduced embryo absorption rate. We postulated that abnormalities in the IL-27/Blimp-1 axis might be associated with recurrent pregnancy loss (RPL). These findings provided insights for developing more efficient immunotherapies for women with RPL.

Improved Measurement of the Differential Polarizability Using Co-Trapped Ions.

We present a novel approach for measuring the differential static scalar polarizability of a target ion utilizing a "polarizability scale" scheme with a reference ion co-trapped in a linear Paul trap. The differential static scalar polarizability of the target ion can be precisely extracted by measuring the ratio of the ac Stark shifts induced by an add-on infrared laser shed on both ions. This method circumvents the need for the calibration of the intensity of the add-on laser, which is usually the bottleneck for measurements of the polarizability of trapped ions. As a demonstration, ^{27}Al^{+} (the target ion) and ^{40}Ca^{+} (the reference ion) are used in this work, with an add-on laser at 1068 nm injected into the ion trap along the trap axis. The differential static scalar polarizability of ^{27}Al^{+} is extracted to be 0.416(14) a.u. by measuring the ratio of the ac Stark shifts of both ions. Compared to the most recent result [Phys. Rev. Lett. 123, 033201 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.033201], the relative uncertainty of the differential static scalar polarizability of ^{27}Al^{+} is reduced by approximately a factor of 4, to 3.4%. This improvement is expected to be further enhanced by using an add-on laser with a longer wavelength.

Copper-catalysed asymmetric annulation of yne-allylic esters with amines to access axially chiral arylpyrroles.

The construction of atropisomers with 1,2-diaxes, while maintaining high enantiocontrol, presents a significant challenge due to the dynamic nature of steric hindrance at ortho-aryl substituents. Although various catalytic asymmetric methods have been developed for accessing axially chiral arylpyrroles, the synthesis of axially chiral arylpyrroles with 1,2-diaxes in a catalytic asymmetric manner has remained rare. Herein, the authors report the synthesis of diverse axially chiral arylpyrroles with 1,2-diaxes, and C-C and C-N axes through copper-catalysed asymmetirc [4 + 1] annulation of yne-allylic esters with arylamines via a remote stereocontrol strategy. This approach provides facile access to a broad range of heterobiaryl atropisomers (67 examples) in excellent enantioselectivities, each bearing one or two C-C/C-N axes, demonstrating its versatility and efficiency. The utility of this methodology is further highlighted by the transformation of the product into chiral phosphine ligand, and chiral thioureas for the use in asymmetric catalysis.

Genetic evidence supporting potential causal roles of EIF4 family in breast cancer: a two-sample randomized Mendelian study.

Translational control plays a crucial role in the regulation of apoptosis, with the EIF4 family serving as one of the mRNA translation factors that modulate the process of mRNA translation based on mRNA characteristics. To address this potential causal role of EIF4 family proteins and breast cancer, Mendelian randomization was employed. The study incorporated four sets of genetics instrumental variables, namely EIF4E, EIF4B, EIF4A, and EIF4EBP2. The outcome variables selected for analysis were the BCAC consortium, which included estrogen receptor positive (ER+) and estrogen receptor negative (ER-) samples. To assess the potential violations of the MR assumption, the primary MR analysis employed inverse variance weighted (IVW), and several sensitivity analyses were conducted. The findings of the two-sample MR analysis indicate that EIF4E has an adverse effect on breast cancer risk (p = 0.028). However, the evidence for the relationship between EIF4E and ER status of breast cancer suggests a weak association with ER+ breast cancer (p = 0.054), but not with ER- breast cancer (p > 0.05). The study findings indicate that EIF4A is not causally linked to the risk of ER+ breast cancer, but is significantly associated with an elevated risk of ER- breast cancer (p = 0.028). However, the evidence is inadequate to support the effects of EIF4B and EIF4EBP2 on breast cancer (p > 0.05). Our results suggest that EIF4 may be a potential factor in the occurrence and development of breast cancer, which may lead to a better understanding of its causes and prevention.

Momordica charantia L.-derived exosome-like nanovesicles stabilize p62 expression to ameliorate doxorubicin cardiotoxicity.

BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.

Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation.

Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

First-principle calculations of the electronic, vibrational, and thermodynamic properties of nitrogen-rich salt of 3,6-dinitramino-1,2,4,5-tetrazine [(NH4)2(DNAT)].

CONTEXT: Energy-containing materials such as explosives have attracted considerable interest recently. In the field of high-energy materials, tetrazine and its derivatives can largely meet the requirements of high nitrogen content and oxygen balance. Nitrogen-rich energetic salts are important research subjects. Nitrogen-rich salt of 3,6-dinitramino-1,2,4,5-tetrazine is a high-energy nitrogen-rich material, but there are few related studies. This paper systematically studies the crystal structure and electronic, vibrational, and thermodynamic properties of (NH4)2(DNAT). The lattice parameters of (NH4)2(DNAT) are observed to align well with the experimental values. The properties of electrons are analyzed by band structure and density of states (DOS). The phonon dispersion curves indicate that the compound is dynamically stable. The vibrational modes of bonds and chemical groups are described in detail, and the peaks in the Raman and infrared spectra are assigned to different vibration modes. Based on the vibration characteristics, thermodynamic properties such as enthalpy (H), Helmholtz free energy (F), entropy (S), Gibbs free energy (G), constant volume heat capacity (CV), and Debye temperature (Θ) are analyzed. This article can pave the way for subsequent work or provide data support to other researchers, promoting further research. METHODS: In this study, we utilized the density functional theory (DFT) for our calculations. The exchange-correlation potential and van der Waals interactions were characterized based on the GGA-PBE + G function calculation. We obtained Brillouin zone integrals using Monkhorst-Pack k-point grids, with the k-point of the Brillouin zone set to a 2 × 2 × 2 grid. During the self-consistent field operation, we set the total energy convergence tolerance to 5 × 10-6 eV per atom. The cut-off energy for the calculation was established at 830 eV. Additionally, the states of H (1s1), C (2s2 2p2), N (2s2 2p3), and O (2s2 2p4) were treated as valence electrons in our study.

Effects of Mobile Applications on Weight-Related, Behavior and Metabolic Outcomes for Adults with Overweight and Obesity: A Systematic Review and Meta-Analysis.

The meta-analysis aimed to explore the effects of mobile phone applications on weight-related, behavior, and metabolic outcomes among adults with overweight and obesity. Six databases were searched for relevant randomized controlled trials (RCTs) published between January 1, 2010 and November 7, 2023 in English. Two independent authors conducted study selection, data extraction, quality assessment. The effect size of interventions was calculated using mean difference. A random-effects model was applied for data analysis. A total of 27 studies were included. The results indicated that mobile phone application intervention reduced weight (MD=-1.38 kg, P<0.001, 95% CI -1.97 to -0.80), BMI (MD=-0.44 kg/m2, P<0.001, 95% CI -0.57 to -0.30), WC (MD=-2.13 cm, P=0.004, 95% CI -3.57 to -0.69), fat mass, and DBP (MD=-2.04 mmHg, P=0.01, 95% CI -3.65 to 0.44) with statistical significance. Future studies could consider how to optimize app interventions through behavior change strategies to enhance their overall effectiveness.

Mechanism of action of the Banxia-Xiakucao herb pair in sleep deprivation: New comprehensive evidence from network pharmacology, transcriptomics and molecular biology experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herb pairs are the most basic and compressed examples of Chinese herbal combinations and can be used to effectively explain the fundamental concepts of traditional Chinese medicine prescriptions. These pairings have gained significant interest due to their subtle therapeutic benefits, minimal side effects, and efficacy in treating complicated chronic conditions. The Banxia-Xiakucao Chinese herb pair (BXHP) consists of Pinellia ternata (Thunb.) Breit. (Banxia) and Prunella vulgaris L. (Xiakucao). This formula was documented in The Medical Classic of the Yellow Emperor approximately 2000 years ago，and clinical research has demonstrated that BXHP effectively treats insomnia. AIM OF THE STUDY: This study aimed to evaluate the efficacy and therapeutic mechanism of the BXHP through a comprehensive strategy involving network pharmacology, molecular docking, transcriptomics, and molecular biology experimental validation. MATERIALS AND METHODS: The composition of BXHP was characterized using the UPLC-Q-TOF-MS. The active compounds were screened to find drug-likeness compounds by analyzing the ADME data. To predict the molecular mechanism of BXHP in sleep deprivation (SD) by network pharmacology and molecular docking. We established a rat model of SD and the in vivo efficacy of BXHP was verified through the pentobarbital sodium righting reflex test, behavioral assays, enzyme-linked immunosorbent assay, transmission electron microscopy, HE staining, and Nissl staining, and the underlying molecular mechanism of BXHP in SD was revealed through transcriptomic and bioinformatic analyses in conjunction with quantitative real-time PCR, Western blot, and immunofluorescence staining. RESULTS: In the present study, we showed for the first time that BXHP reduced sleep latency, prolongs sleep duration, and improves anxiety; lowered serum CORT, IL6, TNF-α and MDA levels; decreased hypothalamic Glu levels; and elevated hypothalamic GABA and 5-HT levels in SD rats. We found 16 active compounds that acted on 583 targets, 145 of which are related to SD. By modularly dissecting the PPI network, we discovered three critical targets, Akt1, CREB1, and PRKACA, all of which play important roles in the effects of BXHP on SD. Molecular docking resulted in the identification of 16 active compounds that strongly bind to key targets. The results of GO and KEGG enrichment analyses of network pharmacology and transcriptomics focused on both the regulation of circadian rhythm and the cAMP signaling pathway, which strongly demonstrated that BXHP affects SD via the cAMP-PKA-CREB-Circadian rhythm pathway. Molecular biology experiments verified this hypothesis. Following BXHP administration, PKA and CREB phosphorylation levels were elevated in SD rats, the cAMP-PKA-CREB signaling pathway was activated, the expression levels of the biological clock genes CLOCK, p-BMAL1/BMAL1, and PER3 were increased, and the rhythmicity of the biological clock was improved. CONCLUSIONS: The active compounds in BXHP can activate the cAMP-PKA-CREB-Circadian rhythm pathway, improve the rhythmicity of the biological clock, promote sleep and ameliorate anxiety, which suggests that BXHP improves SD through a multicomponent, multitarget, multipathway mechanism. This study is important for the development of herbal medicines and clinical therapies for improving sleep deprivation.

Efficient sugar utilization and high tolerance to inhibitors enable Rhodotorula toruloides C23 to robustly produce lipid and carotenoid from lignocellulosic feedstock.

The utilization of lignocellulosic substrates for microbial oil production by oleaginous yeasts has been evidenced as an economically viable process for industrial-scale biodiesel preparation. Efficient sugar utilization and tolerance to inhibitors are critical for lipid production from lignocellulosic substrates. This study investigated the lignocellulosic sugar utilization and inhibitor tolerance characteristics of Rhodotorula toruloides C23. The results demonstrated that C23 exhibited robust glucose and xylose assimilation irrespective of their ratios, yielding over 21 g/L of lipids and 11 mg/L of carotenoids. Furthermore, C23 exhibited high resistance and efficiently degradation towards toxic inhibitors commonly found in lignocellulosic hydrolysates. The potential molecular mechanism underlying xylose metabolism in C23 was explored, with several key enzymes and signal regulation pathways identified as potentially contributing to its superior lipid synthesis performance. The study highlights R. toruloides C23 as a promising candidate for robust biofuel and carotenoid production through direct utilization of non-detoxified lignocellulosic hydrolysates.

Physical activity promotes brain development through serotonin during early childhood.

Early childhood serves as a critical period for neural development and skill acquisition when children are extremely susceptible to the external environment and experience. As a crucial experiential stimulus, physical activity is believed to produce a series of positive effects on brain development, such as cognitive function, social-emotional abilities, and psychological well-being. The World Health Organization recommends that children engage in sufficient daily physical activity, which has already been strongly advocated in the practice of preschool education. However, the mechanisms by which physical activity promotes brain development are still unclear. The role of neurotransmitters, especially serotonin, in promoting brain development through physical activity has received increasing attention. Physical activity has been shown to stimulate the secretion of serotonin by increasing the bioavailability of free tryptophan and enriching the diversity of gut microbiota. Due to its important role in modulating neuronal proliferation, differentiation, synaptic morphogenesis, and synaptic transmission, serotonin can regulate children's explicit cognitive and social interaction behavior in the early stages of life. Therefore, we hypothesized that serotonin emerges as a pivotal transmitter that mediates the relationship between physical activity and brain development during early childhood. Further systematic reviews and meta-analyses are needed to specifically explore whether the type, intensity, dosage, duration, and degree of voluntariness of PA may affect the role of serotonin in the relationship between physical activity and brain function. This review not only helps us understand the impact of exercise on development but also provides a solid theoretical basis for increasing physical activity during early childhood.