Synergistically Engineering Grains and Grain Boundaries toward Li Dendrite-Free Li7La3Zr2O12.

Cation-doped cubic Li7La3Zr2O12 is regarded as a promising solid electrolyte for safe and energy-dense solid-state lithium batteries. However, it suffers from the formation of Li2CO3 and high electronic conductivity, which give rise to an unconformable Li/Li7La3Zr2O12 interface and lithium dendrites. Herein, composite AlF3-Li6.4La3Zr1.4Ta0.6O12 solid electrolytes were created based on thermal AlF3 decomposition and F/O displacement reactions under a high-temperature sintering process. When the AlF3 is thermally decomposed, it leaves Al2O3/AlF3 meliorating the grain boundaries and F- ions partially displacing O2- ions in the grains. Due to the higher electronegativity of F- in the grains and the grain-boundary modification, these AlF3-Li6.4La3Zr1.4Ta0.6O12 deliver optimized electronic conduction and chemical stability against the formation of Li2CO3. The Li/AlF3-Li6.4La3Zr1.4Ta0.6O12/Li cell exhibits a low interfacial resistance of ∼16 Ω cm2 and an ultrastable long-term cycling behavior for 800 h under a current density of 200 µA/cm2, leading to Li//LiCoO2 solid-state batteries with good rate performance and cycling stability.

Discovery of potential components characteristic by conjugated enone from the branches and leaves of Croton lauioides with anti-neuroinflammatory activity via regulating the NF-κB pathway.

In this study, the chemical composition and pharmacological activity of Croton lauioides were investigated for the first time. The bioactive and HPLC-UV guided isolation led to the discovery of twenty-three conjugated enone-type components (1-23), including nine previously unknown sesquiterpenoid derivatives (1-4, 9-10, 12-14). Notably, compounds 1 and 12 are epoxides containing an endoperoxide bridge (1) or a unique dioxaspiro core (12), respectively. Compounds 2-7 are non-benzenoid aromatics featuring a tropone function, while 9-11 possess a rare rearranged scaffold with tropone shift into benzene. Extensive characterization was performed using NMR spectra, HRESIMS data, and electronic circular dichroism (ECD) calculations. Furthermore, we evaluated the bioactivities of all isolated compounds against neuroinflammation in LPS-stimulated BV-2 microglial cells. Remarkably, most sesquiterpenoid derivatives exhibited significant NO inhibit activities, and compound 5 showed the most potent effect with an IC50 value of 0.14 ± 0.04 µM. Structure-activity relationship (SAR) analysis revealed that sesquiterpenoids modified with endocyclic enone conjugation may serve as a key pharmacophore for NO inhibition, particularly involving aromatic tropone moiety. The qPCR and Western blot results demonstrated that 5 exerted an inhibitory effect on the mRNA levels of iNOS, TNF-α and COX-2 in a time-dependent manner, as well as suppressed the protein expression of iNOS, TNF-α, COX-2. In mechanism, 5 could prevented activation of NF-κB pathway by suppressing phosphorylation of p65 and IκB-α. These findings revealed C. lauioides might be a promising resource for drug candidate development targeting neuroinflammation.

A new cassane diterpenoid from the seed of Caesalpinia sappan.

In this study, a previously undescribed cassane diterpenoid, named caesalpinin JF (1), along with two known cassane diterpenoids caesanine C (2) and tomocinol B (3), was isolated from 95% EtOH extract of the seeds of Caesalpinia sappan Linn. Additionally, three known compounds including pulcherrin R (4), syringaresinol-4'-O-ß-D-glucopyranoside (5) and kaempferol (6) were also identified. The structures of the isolated compounds were elucidated by comprehensive 1D and 2D NMR spectroscopic analyses. Additionally, electronic circular dichroism (ECD) calculation was used to identify the absolute structure of compound 1. Among the isolated compounds, compound 1 displayed a potent anti-neuroinflammation with an IC50 value of 9.87 ± 1.71 µM.

Associations between Social Adversities and Chronic Medical Conditions in a Statewide Sample of Individuals in Treatment for Mental Illnesses.

Individuals with mental illnesses experience disproportionately high rates of social adversities, chronic medical conditions, and early mortality. We analyzed a large, statewide dataset to explore associations between four social adversities and the presence of one or more, and then two or more, chronic medical conditions among individuals in treatment for mental illnesses in New York State. In Poisson regression models adjusting for multiple covariates (e.g., gender, age, smoking status, alcohol use), the presence of one or more adversities was associated with the presence of at least one medical condition (prevalence ratio (PR) = 1.21) or two or more medical conditions (PR = 1.46), and two or more adversities was associated with at least one medical condition (PR = 1.25) or two or more medical conditions (PR = 1.52) (all significant at p < .0001). Greater attention to primary, secondary, and tertiary prevention of chronic medical conditions is needed in mental health treatment settings, especially among those experiencing social adversities.

Selective Covalent Targeting of Anti-apoptotic BFL-1 by a Sulfonium-Tethered Peptide.

Anti-apoptotic B cell lymphoma 2 (BCL-2) family proteins are proven targets for human cancers. Targeting the BH3-binding pockets of these anti-apoptotic proteins could reactivate apoptosis in BCL-2-depedent cancers. BFL-1 is a BCL-2 family protein overexpressed in various chemoresistant cancers. A unique cysteine at the binding interface of the BH3 and BFL-1 was previously proven to be an intriguing targeting site to irreversibly inhibit BFL-1 functions with stabilized cyclic peptide bearing a covalent warhead. Recently, we developed a sulfonium-tethered peptide cyclization strategy to construct peptide ligands that could selectively and efficiently react with the cysteine(s) of target proteins near the interacting interface. Using this method, we constructed a BFL-1 peptide inhibitor, B4-MC, that could selectively conjugate with BFL-1 both in vitro and in cell. B4-MC showed good cellular uptake, colocalized with BFL-1 on mitochondria, and showed obvious growth inhibition of BFL-1 over-expressed cancer cell lines.

Computer Simulations on a pH-Responsive Anticancer Drug Delivery System Using Zwitterion-Grafted Polyamidoamine Dendrimer Unimolecular Micelles.

Unimolecular micelles have attracted wide attention in the field of drug delivery because of their thermodynamic stability and uniform size distribution. However, their drug loading/release mechanisms at the molecular level have been poorly understood. In this work, the stability and drug loading/release behaviors of unimolecular micelles formed using generation-5 polyamidoamine-graft-poly(carboxybetaine methacrylate) (PAMAM(G5)-PCBMA) were studied by dissipative particle dynamics simulations. In addition, the unimolecular micelles formed using generation-5 polyamidoamine-graft-poly(ethyleneglycol methacrylate) (PAMAM(G5)-PEGMA) were used as a comparison. The simulation results showed that PAMAM(G5)-PCBMA can spontaneously form core-shell unimolecular micelles. The PAMAM(G5) dendrimer constitutes a hydrophobic core to load the doxorubicin (DOX), while the zwitterionic PCBMA serves as a protective shell to improve the stability of the unimolecular micelle. The DOX can be encapsulated into the cavity of PAMAM(G5) at the physiological pH 7.4. The drug loading efficiency and drug loading content showed some regularities with the increase in the drug concentration. At the acidic pH 5.0, the loaded DOX can be released gradually from the hydrophobic core. The comparison of DOX-loaded morphologies between the PAMAM(G5)-PCBMA system and PAMAM(G5)-PEGMA system showed that the former has better monodisperse stability. This work could offer theoretical guidance for the design and development of promising unimolecular micelles for drug delivery.

Design, synthesis and antitumour and anti-angiogenesis evaluation of 22 moscatilin derivatives.

Two series of moscatilin derivatives were designed, synthesized and evaluated as anti-tumor and anti-angiogenesis agents. Most of these compounds showed moderate-to-obvious cytotoxicity against five cancer cell lines (A549, HepG2, MDA-MB-231, MKN-45, HCT116). Among these cell lines, compounds had obvious effects on HCT116. Especially for 8Ae, the IC50 was low to 0.25 µM. 8Ae can inhibit the viability and induce the apoptosis of HCT116 cells but exhibit no cytotoxic activity in noncancerous NCM460 colon cells. 8Ae can also arrest the G2/M cell cycle in HCT116 cells by inhibiting the α-tubulin expression. Zebrafish bioassay-guided screen showed the 22 moscatilin derivatives had potent anti-angiogenic activities and compound 8Ae had better activities than positive compound. Molecular docking indicated 8Ae interacted with tubulin at the affinity of -7.2 Kcal/mol. In conclusion, compound 8Ae was a potential antitumor and anti-angiogenesis candidate for further development.

Effects of Picrasma quassioides and its active constituents on Alzheimer's disease in vitro and in vivo.

Alzheimer disease (AD), a prevalent neurodegenerative disorder, is one of the leading causes of dementia. However, there is no effective drug for this disease to date. Picrasma quassioides (D.Don) Benn, a Chinese traditional medicine, was used mainly for the treatment of inflammation, fever, microbial infection and dysentery. In this paper, we reported that the EtOAc extract of Picrasma quassioides stems showed potential neuroprotective activities in l-glutamate-stimulated PC12 and Aß25-35-stimulated SH-SY5Y cell models, as well as improved memory and cognitive abilities in AD mice induced by amyloid-ß peptide. Moreover, it was revealed that the anti-AD mechanism was related to suppressing neuroinflammatory and reducing Aß1-42 deposition using ELISA assay kits. To clarify the active components of the EtOAc extract of Picrasma quassioides stems, a systematic phytochemistry study led to isolate and identify six ß-carboline alkaloids (1-6), seven canthin-6-one alkaloids (7-13), and five quassinoids (14-18). Among them, four ß-carbolines (1-3, and 6) and six canthin-6-ones (7-11, and 13) exhibited potential neuroprotective activities in vitro. Based on these date, the structure-activity relationships of alkaloids were discussed. Furthermore, molecular docking experiments showed that compounds 2 and 3 have high affinity for both of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYPKIA) and butyrylcholinesterase (BuChE).

Sesquiterpenoids from Chloranthus anhuiensis with Neuroprotective Effects in PC12 Cells.

Glutamate-induced excitotoxicity plays a vital role in neurodegenerative diseases. Neuroprotection against excitotoxicity has been considered as an effective experimental approach for preventing and/or treating excitotoxicity-mediated diseases. In the present study, six new sesquiterpenoids (1-6) and 26 known compounds of this type (7-32) were isolated and characterized from the whole plants of Chloranthus anhuiensis. Chlorantolide A (1) is the first example of a 5,6- seco-germacrane-type sesquiterpenoid, while phacadinane E (2) is a rare 4,5- seco-cadinane-type sesquiterpenoid. The structures of the new compounds were determined by spectroscopic analysis and by calculations of electronic circular dichroism (ECD) spectra. Their neuroprotective effects in mediating glutamate-induced PC12 cell apoptosis were evaluated. Compound 26 exhibited potent neuroprotective activity with an EC50 value of 3.3 ± 0.9 µM. Using Hoechst 33258 staining, a caspase-3 activity assay, and Western blot analysis it was demonstrated that this compound reduces the apoptosis of PC12 cells through inhibition of caspase-3 activity, while activating the Akt signaling pathway.

Chemical Constituents from Chloranthus anhuiensis and Their Cytotoxic Activities.

Three hiherto unknown phenylpropanoid compounds, namely (7S,8R)-1-(1-ethoxy-2-hydroxypropyl)-2-methoxy-3,4-(methylenedioxy)benzene (1), (7S,8S)-1-(1-ethoxy-2-hydroxypropyl)-2-methoxy-3,4-(methylenedioxy)benzene (2), and (7S,8R)-1-(1-methoxy-2-hydroxypropyl)-2-methoxy-3,4-(methylenedioxy)benzene (3), along with 12 known compounds (4 - 15) were obtained from the extract of whole plant of Chloranthus anhuiensis. Among them, 7 and 13 were obtained from nature for the first time. The structures of these natural compounds were characterized by extensive spectroscopic analysis and calculated electronic circular dichroism (ECD) data. Furthermore, their cytotoxic and neuroprotective activities were evaluated using MDA-MB-231, 4T1, HepG2, and PC12 cell lines. Compounds 8 and 13 exhibited moderate cytotoxic activities against MDA-MB-231 cell line with the IC50 values of 39.7 and 25.8 µm, respectively. And all the isolated compounds have no neuroprotective activities.

Fermentative production of short-chain fatty acids in Escherichia coli.

Escherichia coli was engineered for the production of even- and odd-chain fatty acids (FAs) by fermentation. Co-production of thiolase, hydroxybutyryl-CoA dehydrogenase, crotonase and trans-enoyl-CoA reductase from a synthetic operon allowed the production of butyrate, hexanoate and octanoate. Elimination of native fermentation pathways by genetic deletion (ΔldhA, ΔadhE, ΔackA, Δpta, ΔfrdC) helped eliminate undesired by-products and increase product yields. Initial butyrate production rates were high (0.7 g l(-1) h(-1)) but quickly levelled off and further study suggested this was due to product toxicity and/or acidification of the growth medium. Results also showed that endogenous thioesterases significantly influenced product formation. In particular, deletion of the yciA thioesterase gene substantially increased hexanoate production while decreasing the production of butyrate. E. coli was also engineered to co-produce enzymes for even-chain FA production (described above) together with a coenzyme B12-dependent pathway for the production of propionyl-CoA, which allowed the production of odd-chain FAs (pentanoate and heptanoate). The B12-dependent pathway used here has the potential to allow the production of odd-chain FAs from a single growth substrate (glucose) in a more energy-efficient manner than the prior methods.

A finite element analysis of periodontal ligament fluid mechanics response to occlusal loading based on hydro-mechanical coupling model.

OBJECTIVE: Considering fluid stimulation is one of the essential biomechanical signals for periodontal tissues, this study aims to characterizing fluid mechanics response during occlusal loading by a hydro-mechanical coupling model for periodontal ligament. DESIGN: Models simulating periodontium with normal bone height and with intraosseous defects were built with three mechanical modules: tooth, periodontal ligament and alveolar bone. Tooth was modeled as linear elastic, and periodontal ligament and alveolar bone as a hydro-mechanical coupling model. Transient analyses under dynamic occlusal loading were performed. Fluid dynamics within periodontal ligament space was simulated and visualized by post-processing module. RESULTS: Reciprocating oscillatory flow occurred within the periodontal ligament under occlusal loading. Higher pore pressure and fluid velocity were observed in furcation and apical regions compared to mid-root and cervical regions. Intraosseous defects increased pore pressure and fluid velocity within the periodontal ligament, most significantly near the defect. CONCLUSION: Based on the results of the hydro-mechanical coupling model, significant oscillatory fluid motion is observed within the periodontal ligament under occlusal loading. Particularly, higher fluid velocity is evident in the furcation and apical areas. Additionally, Intraosseous defects significantly enhance fluid motion within the periodontal ligament.

Relationships between Sensory Processing and Executive Functions in Children with Combined ASD and ADHD Compared to Typically Developing and Single Disorder Groups.

The prevalence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasing, with a tendency for co-occurrence. Some studies indicate a connection between atypical sensory processing and executive function. This study aims to explore the distinctive etiology of executive function deficits in children with ASD+ADHD by investigating the relationship between sensory processing and executive function, comparing children with ASD, ASD+ADHD, ADHD, and typically developing children (TD). METHOD: Sensory Profile 2 (SP-2) and Behavior Rating Inventory of Executive Function 2 (BRIEF-2) were measured in 120 school-aged children. The results of the above scales were compared across these four groups, and correlation and regression analyses between BRIEF2 and SP2 were conducted. RESULTS: Our research revealed varying levels of atypical sensory processing and executive function anomalies across the three neurodevelopmental disorder groups compared to the TD group. The ASD+ADHD group showed particularly significant differences. The heightened emotional problems observed in ASD+ADHD children may be associated with more prominent atypical sensory processing. Variance analysis of inhibitory function revealed differences between ASD+ADHD and ADHD children, suggesting distinct etiological mechanisms for attention issues between ASD+ADHD and ADHD. CONCLUSIONS: ASD+ADHD represents a phenotype distinct from both ASD and ADHD. Special consideration should be given to interventions for children with ASD+ADHD. The results of this study may offer a new perspective on understanding the occurrence of ASD+ADHD and potential individualized intervention methods.

Notopterygium incisum roots extract (NRE) alleviates neuroinflammation pathology in Alzheimer's disease through TLR4-NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Notopterygium incisum Ting ex H. T. Chang, also called 'Qianghuo', is a distinct umbelliferae plant in China. The rhizomes and roots of Notopterygium incisum have long been used to treat headaches, colds, analgesia and rheumatoid arthritis. It is a main traditional Chinese medicine in Qianghuo Yufeng Decoction, which was used to treat diseases such as liver and kidney insufficiency, mental paralysis and dementia. AIM OF THIS STUDY: As the most common dementia, Alzheimer's disease (AD) has a complicated pathogenesis. So far, there is no effective drug to prevent its pathological process. Previous research has shown that Notopterygium incisum root extract (NRE) may inhibit the release of Aß and the activation of tau in mice with AD. However, the effect of NRE on the pathological process of neuroinflammation is still unclear. MATERIALS AND METHODS: We determined the pro-inflammatory cytokines levels in BV2 cells exposed to LPS/Aß42 after treated with NRE. APP/PS1 and LPS-induced C57BL/6 neuroinflammatory mice were given NRE for 8 weeks and 5 days respectively to detect the pathological changes of neuroinflammation. RESULTS: The findings showed that NRE had a notable inhibitory effect on the levels of TNF-α and IL-1ß in BV2 cells induced by LPS/Aß42. The results of in vivo experiments show that following NRE treatment, there was a notable decrease in the number of activated microglia in the hippocampus of APP/PS1 mice as indicated by immunofluorescence results. Sholl analysis showed that microglia branches increased in NRE group, indicating that M1 microglia activation was inhibited. In the mice model injected with LPS in the tail vein, PCR and Western Blot results confirmed the anti-inflammatory effect of NRE, Nissl staining showed the protective effect of NRE on neurons, and immunofluorescence results also indicated that the activation of M1 microglia was inhibited. CONCLUSION: These results suggest that long term oral administration of NRE may inhibit neuroinflammation in the progression of AD.

Protective effects of fermented Rosa roxburghii Tratt juice against ethanol­induced hepatocyte injury by regulating the NRF2­AMPK signaling pathway in AML­12 cells.

Alcohol­related liver disease (ALD) is a major health concern worldwide. In recent years, there has been growing interest in natural products and functional foods for preventing and treating ALD due to their potential antioxidant and hepatoprotective properties. Rosa roxburghii Tratt, known for its rich content of bioactive compounds, has demonstrated promising health benefits, including anti­inflammatory and antioxidant effects. Fermentation has been utilized as a strategy to enhance the bioavailability and efficacy of natural products. In the present study, using a mixture of Rosa roxburghii Tratt juice, lotus leaf extract and grape seed proanthocyanidins fermented by Lactobacillus plantarum HH­LP56, a novel fermented Rosa roxburghii Tratt (FRRT) juice was discovered that can prevent and regulate ethanol­induced liver cell damage. Following fermentation, the pH was significantly decreased, and the content of VC and superoxide dismutase (SOD) were significantly increased, along with a noticeable enhancement in hydroxyl and 2,2­diphenyl­1­picrylhydrazyl free radical scavenging abilities. Alpha Mouse liver 12 cells were exposed to ethanol for 24 h to establish an in vitro liver cell injury model. The present study evaluated the effects of FRRT on cell damage, lipid accumulation and oxidative stress markers. The results revealed that FRRT pretreatment (cells were pre­treated with 2.5 and 5 mg/ml FRRT for 2 h) significantly reduced lipid accumulation and oxidative stress in liver cells. Mechanistically, FRRT regulated lipid metabolism by influencing key genes and proteins, such as AMP­activated protein kinase, sterol regulatory element binding transcription factor 1 and Stearyl­CoA desaturase­1. Furthermore, FRRT enhanced antioxidant activity by increasing SOD activity, glutathione and catalase levels, while reducing reactive oxygen species and malondialdehyde levels. It also reversed the expression changes of ethanol­induced oxidative stress­related genes and proteins. In conclusion, a novel functional food ingredient may have been discovered with extensive potential applications. These findings indicated that FRRT has antioxidant properties and potential therapeutic benefits in addressing ethanol­induced liver cell damage through its effects on liver lipid metabolism and oxidative stress.

Effects and mechanisms of sciadonic acid on colonic transit function through regulating 5-HT4/cAMP/PKA/AQP4 signaling pathway in STC model mice.

Torreya grandis (T. grandis) oil has been reported to alleviate symptoms of slow transit constipation (STC). However, the impact of sciadonic acid (SA), a distinctive fatty acid found in T. grandis oil, on the pathological progression of STC remains unclear. This study aimed to evaluate the effect of SA on STC and uncover the underlying mechanisms. The STC model was established by feeding Balb/c mice with loperamide. After 2 weeks of intervention, SA significantly improved weight loss and intestinal motility decline induced by STC, along with enhancing plasma indices and reducing colon pathological damage. SA effectively reversed the STC-induced decrease in the 5-HT4/cAMP/PKA/AQP4 signaling pathway genes and expression. Furthermore, 16S rRNA analysis demonstrated that SA mitigated the imbalance of the intestinal microbiota induced by STC, by reducing the ratio of Firmicutes to Bacteroidetes (F/B) and increasing the abundance of beneficial bacteria such as Akkermansia. In conclusion, SA intervention alleviated colonic dysfunction in STC mice. The activation of the SA-mediated 5-HT4/cAMP/PKA/AQP4 signaling pathway may serve as a potential target for STC treatment. These findings suggest that SA holds promise as a treatment option for STC and could potentially be extended to other related gut diseases for further investigation.

Preference for Self-Resembling Male Faces in Gay Men in China.

Self-resemblance refers to couples with similar characteristics, also known as homogamy or positive assortative mating. Previous studies have indicated that heterosexual men and women prefer partners with similar facial features. In this study, we examined whether Chinese gay men preferred self-resemblance to faces. The participants (N = 70) completed a personal information questionnaire and preference selection task involving 10 pairs of self-resembling/control male faces. Ten pairs of self-resembling/control male faces of each participant were also rated by another gay man. The results revealed that the proportion of the participants who chose self-resembling faces was significantly higher than that of the control faces. However, the preference for "self-resembling" and control faces by other-rating was not significantly different. These findings indicate homogeneity in facial preferences among gay men.

Identifying activity level related movement features of children with ASD based on ADOS videos.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects about 2% of children. Due to the shortage of clinicians, there is an urgent demand for a convenient and effective tool based on regular videos to assess the symptom. Computer-aided technologies have become widely used in clinical diagnosis, simplifying the diagnosis process while saving time and standardizing the procedure. In this study, we proposed a computer vision-based motion trajectory detection approach assisted with machine learning techniques, facilitating an objective and effective way to extract participants' movement features (MFs) to identify and evaluate children's activity levels that correspond to clinicians' professional ratings. The designed technique includes two key parts: (1) Extracting MFs of participants' different body key points in various activities segmented from autism diagnostic observation schedule (ADOS) videos, and (2) Identifying the most relevant MFs through established correlations with existing data sets of participants' activity level scores evaluated by clinicians. The research investigated two types of MFs, i.e., pixel distance (PD) and instantaneous pixel velocity (IPV), three participants' body key points, i.e., neck, right wrist, and middle hip, and five activities, including Table-play, Birthday-party, Joint-attention, Balloon-play, and Bubble-play segmented from ADOS videos. Among different combinations, the high correlations with the activity level scores evaluated by the clinicians (greater than 0.6 with p < 0.001) were found in Table-play activity for both the PD-based MFs of all three studied key points and the IPV-based MFs of the right wrist key point. These MFs were identified as the most relevant ones that could be utilized as an auxiliary means for automating the evaluation of activity levels in the ASD assessment.

Examine sex differences in autism spectrum disorder in school-aged children and adolescents with fluent language.

There are noteworthy sex disparities in the prevalence of autism spectrum disorders (ASD), while findings regarding the sex differences in core symptoms are inconsistent. There are few relevant studies on sex differences in mainland China. This study was dedicated to a deeper understanding of the impact of sex differences on the clinical presentation of ASD with fluent language. We retrospectively studied 301 children with ASD (58 females) and utilized raw scores from the ADI-R and ADOS and the intelligence quotient (IQ) to measure symptomatology. Based on the Full-Scale IQ (FS-IQ), a binary split of average, above-average IQ (high-IQ), and below-average IQ (low IQ) occurs at 85. Across the entire sample, males and females are comparable in the FS-IQ, while males scored higher in the Perceptual Reasoning Index (PRI) (F = 7.812, p = 0.006). ADI-R did not find any statistically significant sex differences in the diagnostic cutoff score satisfaction or the raw domain scores. While a significant effect of sex on ADOS social affect domain scores was found in the total sample [λ = 0.970, partial η2 = 0.030, F (3,295) = 3.019, p = 0.030]. Tests of between-subjects effects revealed that males scored higher than females mainly in the ADOS reciprocal social interaction subcategory (partial η2 = 0.022, F = 6.563, p = 0.011). Stratified analysis revealed that the effect of sex on ADOS reciprocal social interaction subcategory scores only significant in the low-IQ children with ASD (partial η2 = 0.092, F = 10.088, p = 0.002). In general, overall cognitive functioning is similar across males and females with ASD, while males have a higher perceptual reasoning ability. Females with ASD are more likely to have comorbid intellectual impairment than males, and they could require additional intervention support. Autistic children with low IQs are more likely to exhibit sex differences in their core symptoms than children with high IQs. Intelligence plays a key role in sex-based differences in the core symptoms of ASD.

Salvianolic acid B promotes angiogenesis and inhibits cardiomyocyte apoptosis by regulating autophagy in myocardial ischemia.

BACKGROUND: Myocardial ischemia (MI) can cause angina, myocardial infarction, and even death. Angiogenesis is beneficial for ensuring oxygen and blood supply to ischemic tissue, promoting tissue repair, and reducing cell damage. In this study, we evaluated the effects of Salvianolic acid B (Sal B) against myocardial ischemia and explored its underlying mechanism on autophagy. METHODS: The anti-apoptosis effect of Sal B was conducted by staining Annexin V-FITC/PI and Hoechst as well as evaluating apoptosis bio-markers at protein level in H9c2 cells at glucose deprivation condition. HUVECs were co-cultured with H9c2, and the tube formation assay was used to monitor Sal B's impact on angiogenesis. The MI model of mice was induced by intraperitoneal injection of isoproterenol (ISO). The effect of Sal B on MI mice was evaluated by HE, Masson, immunohistochemistry, WB and kits. In addition, Atg5 siRNA was applied to verify whether the protective effect of Sal B was regulated to autophagy. RESULTS: In H9c2, Sal B reduced the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and reactive oxygen species (ROS), improved the levels of superoxide dismutase (SOD) and mitochondrial membrane potential, downregulated the expressions of Bax and cleaved-Caspase3, upregulated the expression of Bcl-2. Therefore, Sal B could significantly inhibit the damage of H9c2 caused by glucose deprivation. In the co-culture system of H9c2 and HUVECs, vascular endothelial growth factor (VEGF) level in the supernatant was dramatically raised by Sal B. Sal B upregulated the expressions of VEGF, platelet derived growth factor (PDGF) and endothelial marker CD31. It implied that Sal B exerted a significant pro-angiogenic effect. Moreover, Sal B increased the expression of LC3, Atg5, and Beclin1, while reducing the level of P62. When the expression of Atg5 was inhibited, the protective effects of Sal B on apoptosis and angiogenesis was reversed. CONCLUSIONS: Sal B inhibited cardiomyocyte apoptosis and promoted angiogenesis by regulating autophagy, thereby improving MI.