High-performance self-cascade nanoreactors for combined ferroptosis, photothermal therapy, and starving therapy.

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO2 shell would deplete glutathione (GSH) and produce Mn2+, while a large amount of H2O2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn2+, producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.

Micro-encapsulation of garlic oil using esterified-wheat porous starch and whey protein isolate: Physicochemical properties, release behavior during in vitro digestion.

The study aimed to inhibit the stimulating impact of garlic oil (GO) on the stomach and attain high release in the intestine during digestion. So, wheat porous starch (WPS) was modified with octenyl succinic acid (OSA) and malic acid (MA) to obtain esterified WPS, OWPS and MWPS, respectively. The differences in physicochemical, encapsulation, and digestive properties of two GO microcapsules, WPI/OWPS/GO and WPI/MWPS/GO microcapsules produced by using OWPS and MWPS as variant carrier materials and whey protein isolate (WPI) as the same coating agent, were compared. The results found that OWPS had greater amphiphilicity, while MWPS had better hydrophobicity and anti-digestive ability than WPS. Encapsulation efficiency of WPI/OWPS/GO (94.67 %) was significantly greater than WPI/MWPS/GO (91.44 %). The digestion inhibition and low GO release (approximately 23 %) of WPI/OWPS/GO and WPI/MWPS/GO microcapsules in the gastric phase resulted from the protective effect of WPI combined with the good adsorption and lipophilicity of OWPS and MWPS. Especially, WPI/OWPS/GO microcapsule was relatively stable in the gastric phase and had sufficient GO release (67.24 %) in the intestinal phase, which was significantly higher than WPI/MWPS/GO microcapsule (56.03 %), benefiting from the adsorption and digestive properties of OWPS, and resulting in a total cumulative GO release rate of 90.86 %.

2-week prevalence and associated factors of fever, diarrhea, and coexisting fever and diarrhea among children aged 6-23 months in rural Hunan Province.

Fever and diarrhea are key causes of malnutrition, growth and development disorders, and death among children. At present, most studies on the associated factors of fever and diarrhea in children are concentrated in African and South Asian countries, but relevant research in China is very limited. This study was aimed to analyze the two-week prevalence of fever, diarrhea, and coexisting fever and diarrhea among children aged 6-23 months in rural areas of Hunan Province and to explore the associated factors. The survey data of the Nutrition Improvement Program for Children in Poor Areas (NIPCPA) from 2016 to 2023 was used here. NIPCPA is a cross-sectional survey completed annually in Hunan to collect children's nutrition and health indicators. The two-week prevalence rates of fever, diarrhea, and coexisting fever and diarrhea among children aged 6-23 months were 12.2% (2066/16,985), 9.6% (1634/16,985), and 3.2% (542/16,985), respectively. Multivariate logistic regression analysis showed the risks of fever, diarrhea, and coexisting fever and diarrhea were higher among younger children. The high educational level of caregivers, effective consumption of Yingyangbao (a complementary food supplement containing iron, zinc, calcium, vitamins A, D, B1, B2, B12, folic acid, and other micronutrients), and complementary feeding meeting minimum dietary diversity and meeting minimum acceptable diet were protective factors against fever in children, with adjusted odds ratios (aORs) of 0.87 (95%CI: 0.78-0.98), 0.78 (0.69-0.87), 0.73 (0.65-0.82), and 0.74 (0.66-0.84), respectively. Effective consumption of Yingyangbao, and complementary feeding meeting the minimum dietary diversity and meeting minimum acceptable diet were protective factors against diarrhea in children, with aORs of 0.72 (95%CI: 0.63-0.83), 0.79 (0.70-0.91), and 0.80 (0.70-0.92), respectively. Effective consumption of Yingyangbao, and complementary feeding meeting the minimum dietary diversity and meeting minimum acceptable diet were protective factors against coexisting fever and diarrhea among children, with aORs of 0.53 (95%CI: 0.43-0.66), 0.71 (0.58-0.89), and 0.70 (0.56-0.88), respectively. Fever, diarrhea, and the coexisting fever and diarrhea affect one in eight, one in ten, and one in thirty children respectively in rural areas of Hunan. Effective interventions should be actively taken, such as improving the education level of caregivers, enhancing their scientific feeding skills for children, and promoting children's compliance with Yingyangbao consumption, to further reduce the prevalence of fever and diarrhea in children.

Emulsification properties of ovalbumin-fucoidan (OVA-FUC) binary complexes.

The poor thermal stability and emulsifying properties of ovalbumin (OVA) limit its functional performance, but these limitations may be overcome by forming binary complexes. We prepared binary complexes of OVA and fucoidan (FUC) through electrostatic self-assembly and investigated the emulsifying properties of the complex by measuring the particle size, interfacial membrane thickness, zeta potential, and stability of the emulsion prepared with camellia oil and the complex. The OVA-FUC emulsions have a thicker interfacial membrane, lower mobility, higher viscosity, and better stability compared with the OVA emulsions. The emulsion prepared with 1.5 % OVA-FUC remained stable and homogeneous during storage. They tended to become unstable with freeze-thaw, but the oil encapsulated did not leak after coalescence occurred. With the addition of Ca2+, the OVA-FUC emulsion will be converted into a gel state. These findings indicate that OVA-FUC binary complexes can be used to prepare high-performance emulsions with great potential for development.

Identification of osteogenic differentiation-related miRNA-mRNA regulatory network of human periodontal ligament stem cells.

This study aimed to investigate the hub genes and miRNA-mRNA regulatory network around periodontal ligament stem cells (PDLSC) for osteogenic differentiation through bioinformatic analysis. The dataset with osteogenic differentiation of human PDLSC was downloaded from the GEO database. The Weighted gene coexpression network analysis (WGCNA) was performed to identify key modules and hub genes. In addition, differentially expressed genes (DEGs) analysis was conducted with limma. The functional enrichment of differentially expressed hub genes was implemented with KEGG and GSEA analysis. The targeted genes of differentially expressed miRNA were predicted based on miRWalk database. The miRNA-mRNA interaction network of osteogenic differentiation of PDLSC was constructed and visualized. The WGNCA results showed that the light-cyan module was positively correlated with osteogenic differentiation (r=0.98, P<0.05). A total of 3125 hub genes and 1426 differentially expressed hub genes were detected in OG group. Innate immune-related signaling pathways and metabolic pathways were involved in the osteogenic differentiation. In addition, total of 2 upregulated miRNAs with 63 targeted DEGs and 6 downregulated miRNAs with 214 targeted DEGs were detected, which contributed to osteogenic differentiation by regulating amino acid metabolism signaling pathway. We identified hub genes and miRNA-mRNA regulatory network contributing to osteogenic differentiation of human PDLSC, which will provide novel strategy for periodontal disease therapy.

Divalent metal ions under low concentration environment improved the thermal gel properties of egg yolk.

To improve the thermal gel properties of egg yolk, the effect of several valence metal ions (K+, Ca2+, Mg2+ and Fe3+) with different concentrations (0-0.72%) on the rheological, gel, and structural properties of egg yolk were investigated. Results showed that monovalent and divalent ions were beneficial to the formation of uniform and dense gel network, especially with the addition of 0.72% magnesium ion, which further improved gel hardness, water holding capacity (WHC) and viscoelastic properties, the properties of egg yolk gel increased with the increase of the concentration of mono-bivalent metal ions. Adding ferric ion remarkably increased the average particle size (d4,3) and apparent viscosity of egg yolk, destroying the disulfide bonds and the hydrophobic interactions in gel. Fourier transform infrared spectroscopy (FT-IR) and fluorescence spectra analysis revealed that metal ions promoted the hydrophobic aggregation among egg yolk proteins and induced the transition of protein secondary structure from ordered to disordered. This work will provide a theoretical reference for the development of low salt and nutrient fortified egg yolk products.

Nitric oxide mediates red light-induced perylenequinone production in Shiraia mycelium culture.

Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627 nm, 200 lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation. Red light exposure induced NO generation, peaking to 81.7 µmol/g FW on day 8 of the culture, with the involvement of nitric oxide synthase (NOS)- or nitrate reductase (NR)-dependent pathways. The application of a NO donor sodium nitroprusside (SNP) restored conidiation of Shiraia sp. S9 under red light and stimulated PQ production, which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028. These results showed that red light-induced NO, as a signaling molecule, was involved in the regulation of growth and PQ production in Shiraia sp. S9 through the NO-cGMP-PKG signaling pathway. While mycelial H2O2 content exhibited no significant alternations, a transient increase of intracellular Ca2+ and extracellular ATP (eATP) content was detected upon exposure to red light. The generation of NO was found to be interdependent on cytosolic Ca2+ and eATP concentration. These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp. S9. Notably, the combined treatment of red light with 5 µM SNP yielded a synergistic effect, resulting in a substantially higher level of hypocrellin A (HA, 254 mg/L), about 3.0-fold over the dark control. Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi.

A new insight into the key matrix components for aftertaste in Ampelopsis grossedentata (vine tea) infusion: From the intensity and duration of taste profiles using non-targeted metabolomics and molecular simulation.

The aftertaste with a prolonged duration in ampelopsis grossedentata infusion (AGTI) is easily perceived, however, its formation mechanism is unclear. Therefore, aftertaste-A and richness were confirmed as the characteristic aftertaste of AGTI through sensory evaluation and electronic tongue. Moreover, 5-KETE, theobromine, etc., metabolites were identified as the differential components between AGTI and green tea infusion. Among them, p-coumaroyl quinic acid, xanthine etc., and proline, dihydromyricetin, etc., components contributed more to the formation of aftertaste-A and richness, respectively. Further, the bonding between characteristic metabolites for aftertaste in AGTI with their receptors were shown to be more stable using molecular docking, compared to metabolites related to typical taste profiles. The aftertaste in AGTI was more easily perceived by saltiness components or in NaCl system by molecular simulation. This study offers novel insight into the interaction mechanism of aftertaste in tea infusion and will contribute to further study on aftertaste for other foods.

Influence mechanisms of linoleic acid and oleic acid on the gel properties of egg yolk protein.

BACKGROUND: Gel property is among the crucial functional properties of egg yolk (EY), which determines the texture and flavor of EY products. In the present study, the effects of two unsaturated fatty acids [monounsaturated fatty acid oleic acid (OA) and diunsaturated fatty acid linoleic acid (LA)] on the gel properties of EY protein were investigated. RESULTS: Compared with the blank group, the addition of LA and OA (10-50 g kg-1) improved the gel hardness (from 270.54 g to 385.85 g and 414.38 g, respectively) and viscosity coefficient (from 0.015 Pa.sn to 11.892 Pa.sn and 1.812 Pa.sn, respectively). The surface hydrophobicity of EY protein increased to a maximum value of 40 g kg-1 with the addition of both fatty acids (39.06 µg and 41.58 µg, respectively). However, excess unsaturated fatty acids (≥ 50 g kg-1) disrupted the completeness of the gel matrix and weakened the structural properties of the EY gel. CONCLUSION: Both fatty acids improved the gel properties of EY protein. At the same addition level, OA was superior to LA in improving gel properties. The present study provides a theoretical underpinning for the sensible application of unsaturated fatty acids in improving EY gel properties. © 2024 Society of Chemical Industry.

Press Needle: A Traditional Chinese Medicine Therapy for Myopia Patients with Dry Eye.

Most patients with myopia have dry eye, which has been shown to adversely affect ocular symptoms, myopia progression, and quality of life in patients with myopia. Needle prickling has been shown to be effective in providing symptom relief in patients with myopia and dry eye. Press needle is a long-lasting, easy-to-operate, and inexpensive traditional Chinese medicine treatment. The standard practice of needle insertion is very important for the treatment of myopia and dry eye. The specific steps include selecting the appropriate acupoints, piercing them with appropriate needles, and fixing them in the skin or subcutaneously at the acupoints, burying them for 2 days, resting for 1 day; the course of treatment lasts for 2 weeks. Specifically, the following indicators were assessed: uncorrected visual acuity and the ocular surface disease index. This article will explain how to standardize the operation of a press needle in the treatment of myopia and dry eye.

Relationship between arginine methylation and vascular calcification.

In patients on maintenance hemodialysis (MHD), vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD), which is the primary cause of death in chronic kidney disease (CKD). The main component of VC in CKD is the vascular smooth muscle cells (VSMCs). VC is an ordered, dynamic activity. Under the stresses of oxidative stress and calcium-­phosphorus imbalance, VSMCs undergo osteogenic phenotypic transdifferentiation, which promotes the formation of VC. In addition to traditional epigenetics like RNA and DNA control, post-translational modifications have been discovered to be involved in the regulation of VC in recent years. It has been reported that the process of osteoblast differentiation is impacted by catalytic histone or non-histone arginine methylation. Its function in the osteogenic process is comparable to that of VC. Thus, we propose that arginine methylation regulates VC via many signaling pathways, including as NF-B, WNT, AKT/PI3K, TGF-/BMP/SMAD, and IL-6/STAT3. It might also regulate the VC-related calcification regulatory factors, oxidative stress, and endoplasmic reticulum stress. Consequently, we propose that arginine methylation regulates the calcification of the arteries and outline the regulatory mechanisms involved.

Preparation and characterization of zein-caseinate-pectin complex nanoparticles for encapsulation of curcumin: pectin extracted by high-speed shearing from passion fruit (Passiflora edulis f. flavicarpa) peel.

BACKGROUND: Pectin extracted by high-speed shearing from passion fruit peel (HSSP) is a potentially excellent wall material for encapsulating curcumin, which has multiple advantages over pectin prepared by heated water extraction. HSSP was used to fabricate complex nanoparticles of zein-sodium caseinate-pectin for encapsulation of curcumin in this study. The influence of heating on the physicochemical properties of the composite nanoparticles was also investigated, as well as the effect of composite nanoparticles on the encapsulation efficiency, antioxidant activity and release characteristics of curcumin. RESULTS: The nanoparticles were formed through electrostatic interactions, hydrogen bonds and hydrophobic interactions between the proteins and HSSP. A temperature of 50 °C was more favorable for generating compact and small-sized nanoparticles, which could effectively improve the encapsulation efficiency and functional properties. Moreover, compared to other pectin used in the study, the nanoparticles prepared with HSSP showed the best functionality with a particle size of 234.28 ± 0.85 nm, encapsulation rate of 90.22 ± 0.54%, free radical scavenging rate of 78.97% and strongest protective capacity in simulated gastric fluid and intestinal release effect. CONCLUSION: Zein-sodium caseinate-HSSP is effective for encapsulating and delivering hydrophobic bioactive substances such as curcumin, which has potential applications in the functional food and pharmaceutical industries. © 2024 Society of Chemical Industry.

Electrochemical Conversion of CO2 into Formate Boosted by In Situ Reconstruction of Bi-MOF to Bi2O2CO3 Ultrathin Nanosheets.

Substantial emissions of CO2 have presented formidable challenges for global climate dynamics. Electrochemical reduction of CO2 to produce formic acid (HCOOH) is considered to be a promising approach for achieving carbon neutrality. Nevertheless, the development of a catalyst exhibiting both high catalytic activity and selectivity toward desired products remains an arduous task. Herein, we report the synthesis of a unique porous bismuth-based MOF (Bi-BTC) through microwave-assisted agitation. The Bi-BTC MOF has a good catalytic performance in electrochemical CO2RR to formate products. At -0.9 V (vs RHE) potential, the Faradaic efficiency of formate can reach 96%, and the current density of the CO2RR is 25 mA/cm2. Bi-BTC also exhibits good electrochemical stability. FEformate and current density were maintained for 24 h with almost no attenuation. It was found that Bi-BTC was reconstructed in the CO2RR process. The shape of nanocolumn before electrolysis is transformed into an ultrathin nanosheet. The soft and hard acid-base theory (HSAB) proves that the reason for the reconfiguration is that the hard base ions (HCO3-) and the intermediate acid (Bi3+) break in the Bi-O bond in Bi-MOF, resulting in the transition of the original column structure of Bi-BTC to Bi2O2CO3 ultrathin nanosheeets. The DFT calculation shows that the restructured Bi2O2CO3 nanosheet exposes a crystal surface structure, which is conducive to lower the activation energy barrier of the electrochemical CO2RR intermediate *OCHO and stabilizing the reaction intermediate. Therefore, it is more beneficial to improve the selectivity of the electrochemical CO2RR to formate formation. This result proves that irreversible reconfiguration of catalyst is beneficial to electrochemical CO2RR. In addition, coupling a Bi-BTC cathode with a stable anode (IrO2) enables battery-driven high-activity CO2RR and an OER with good activity and efficiency.

Interaction mechanisms of edible film ingredients and their effects on food quality.

Traditional food packaging has problems such as nondegradable and poor food safety. Edible films play an important role in food packaging, transportation and storage, having become a focus of research due to their low cost, renewable, degradable, safe and non-toxic characteristics. According to the different materials of edible films substrate, edible films are usually categorized into proteins, polysaccharides and composite edible films. Functional properties of edible films prepared from different substrate materials also vary, single substrate edible films are defective in some aspects. Functional ingredients such as proteins, polysaccharides, essential oils, natural products, nanomaterials, emulsifiers, and so on are commonly added to edible films to improve their functional properties, extend the shelf life of foods, improve the preservation of sensory properties of foods, and make them widely used in the field of food preservation. This paper introduced the classification, characteristics, and modification methods of common edible films, discussed the interactions among the substrate ingredients of composite edible films, the influence of functional ingredients on the properties of edible films, and the effects of modified edible films on the quality of food, aiming to provide new research ideas for the wide application and further study of edible films.

HDAC2 counteracts vascular calcification by activating autophagy in chronic kidney disease.

Vascular calcification is a major risk factor for cardiovascular disease mortality, with a significant prevalence in chronic kidney disease (CKD). Pharmacological inhibition of histone acetyltransferase has been proven to protect against from vascular calcification. However, the role of Histone Deacetylase 2 (HDAC2) and molecular mechanisms in vascular calcification of CKD remains unknown. An in vivo model of CKD was established using mouse fed with a high adenine and phosphate diet, and an in vitro model was produced using human aortic vascular smooth muscle cells (VSMCs) stimulated with ß-glycerophosphate (ß-GP). HDAC2 expression was found to be reduced in medial artery of CKD mice and ß-GP-induced VSMCs. Overexpression of HDAC2 attenuated OPN and OCN upregulation, α-SMA and SM22α downregulation, and calcium deposition in aortas of CKD. The in vitro results also demonstrated that ß-GP-induced osteogenic differentiation was inhibited by HDAC2. Furthermore, we found that HDAC2 overexpression caused an increase in LC3II/I, a decrease in p62, and an induction of autophagic flux. Inhibition of autophagy using its specific inhibitor 3-MA blocked HDAC2's protective effect on osteogenic differentiation in ß-GP-treated VSMCs. Taken together, these results suggest that HDAC2 may protect against vascular calcification by the activation of autophagy, laying out a novel insight for the molecular mechanism in vascular calcification of CKD.

Elevated platelet count is associated with decreased mortality from hemorrhagic stroke in hospital: a multi-center retrospective cohort study.

This study aimed to investigate the relationship between platelet count (PC) and mortality in patients with hemorrhagic stroke (HS). The research reviewed data from 10,466 patients hospitalized in 208 hospitals in the United States from January 1, 2014, to December 31, 2015. Of these, 3262 HS patients were included in the primary analysis for those admitted to the intensive care unit (ICU). The average age of these patients was 67.05 years, with 52.79% being male. The median PC was (221.67 ± 73.78) × 109/L. Multivariate logistic regression analysis revealed that PC was a protective factor for mortality in HS patients (OR = 0.98, 95% CI 0.97-1.00, P < 0.05). Additionally, a non-linear association between PC and mortality in HS patients was found using a generalized additive model (GAM) and smooth curve fitting (penalty spline method). For the first time, a recursive algorithm identified the inflection point of platelet count as 194 × 109/L. On the left side of the inflection point, for every increase of 10 units in platelet count, the mortality rate of HS patients decreases by 10%. The study demonstrates a non-linear relationship between PC and the risk of mortality in HS patients. A platelet counts higher than the inflection point (194 × 109/L) may be a significant intervention to reduce mortality in HS patients.

Improved detection of aortic dissection in non-contrast-enhanced chest CT using an attention-based deep learning model.

Rationale and objectives: This study investigated the effects of implementing an attention-based deep learning model for the detection of aortic dissection (AD) using non-contrast-enhanced chest computed tomography (CT). Materials and methods: We analysed the records of 1300 patients who underwent contrast-enhanced chest CT at 2 medical centres between January 2015 and February 2023. We considered an internal cohort of 200 patients with AD and 200 patients without AD and an external test cohort of 40 patients with AD and 40 patients without AD. The internal cohort was divided into training and test sets, and a deep learning model was trained using 9600 CT images. A convolutional block attention module (CBAM) and a traditional deep learning architecture (namely, You Only Look Once version 5 [YOLOv5]) were combined into an attention-based model (i.e., YOLOv5-CBAM). Its performance was measured against the unmodified YOLOv5 model, and the accuracy, sensitivity, and specificity of the algorithm were evaluated by two independent radiologists. Results: The CBAM-based model outperformed the traditional deep learning model. In the external testing set, YOLOv5-CBAM achieved an area under the curve (AUC) of 0.938, accuracy of 91.5 %, sensitivity of 90.0 %, and specificity of 92.9 %, whereas the unmodified model achieved an AUC of 0.844, accuracy of 83.6 %, sensitivity of 71.2 %, and specificity of 96.0 %. The sensitivity results of the unmodified algorithms were not significantly different from those of the radiologists; however, the proposed YOLOv5-CBAM algorithm outperformed the unmodified algorithms in terms of detection. Conclusions: Incorporating the CBAM attention mechanism into a deep learning model can significantly improve AD detection in non-contrast-enhanced chest CT. This approach may aid radiologists in the timely and accurate diagnosis of AD, which is important for improving patient outcomes.

Empathy with nature promotes pro-environmental attitudes in preschool children.

This study aimed to explore whether empathy with nature (i.e., the tendency to understand and share the emotional experience of the natural world) contributes to pro-environmental attitudes in early childhood. In a correlational investigation (Study 1), 138 (Mage = 57.78 months) preschool children completed a battery of tasks to measure their pro-environmental attitudes, empathy with nature, and empathy with humans. We found that empathy with nature positively predicts pro-environmental attitudes, even beyond the predictive power of empathy with humans. In a quasi-experimental investigation (Study 2), 46 children from two parallel classes in the same preschool were recruited as the intervention (n = 23, Mage = 66.74 months) and control (n = 23, Mage = 67.61 months) groups. An intervention session that aimed to induce empathy with nature was applied to the intervention group, whereas an active control teaching session was applied to the control group. After the intervention, the intervention group demonstrated greater pro-environmental attitudes than did the control group. Together, our studies provide converging evidence that empathy with nature promotes pro-environmental attitudes in early childhood, further implying the value of integrating empathy with nature in early childhood environmental education.

Integrative multi-omics analyses reveal vesicle transport as a potential target for thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysm (TAA) refers to dilation and enlargement of the thoracic aorta caused by various reasons. Most patients have no apparent symptoms in the early stage and are subject to a poor prognosis once the aneurysm ruptures. It is crucial to identify individuals who are predisposed to TAA and to discover effective therapeutic targets for early intervention. METHODS: We conducted a label-free quantitative proteomic analysis among aorta tissue samples from TAA patients to screen differentially expressed proteins (DEPs) and key co-expression modules. Two datasets from Gene Expression Omnibus (GEO) database were included for integrative analysis, and the identified genes were subjected to immunohistochemistry (IHC) validation. Detailed vesicle transport related enrichment analysis was conducted and two FDA-approved drugs, chlorpromazine (CPZ) and chloroquine (CQ), were selected for in vivo inhibition of vesicle transport in mice TAA model. The diameter of thoracic aorta, mortality and histological differences after interventions were evaluated. RESULTS: We found significant enrichments in functions involved with vesicle transport, extracellular matrix organizing, and infection diseases in TAA. Endocytosis was the most essential vesicle transport process in TAA formation. Interventions with CPZ and CQ significantly reduced the aneurysm diameter and elastin degradation in vivo and enhanced the survival rates of TAA mice. CONCLUSIONS: We systematically screened the aberrantly regulated bioprocesses in TAA based on integrative multi-omics analyses, identified and demonstrated the importance of vesicle transport in the TAA formation. Our study provided pilot evidence that vesicular transport was a potential and promising target for the treatment of TAA.

Bushenhuoluo Decoction improves polycystic ovary syndrome by regulating exosomal miR-30a-5p/ SOCS3/mTOR/NLRP3 signaling-mediated autophagy and pyroptosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a frequent and complicated endocrine disease that remains a major reason for infertility. Bushenhuoluo Decotion (BSHLD) has been validated to exhibit curative effects on PCOS. This study was aimed to explore the potential mechanism underlying the therapeutic action of BSHLD. METHODS: PCOS rat model was induced by dehydroepiandrosterone (DHEA). Serum hormone and cytokines levels and ovarian pathological alterations were measured to assess ovarian function. Exosomes (Exos) were identified by Transmission electron microscopy and Nanoparticle Tracking Analysis. RT-qPCR, Western blotting, immunohistochemical staining, and immunofluorescence staining were performed to detect molecule expressions. Proliferation and pyroptosis of granulosa cells (GCs) were evaluated by CCK-8 and flow cytometry, respectively. The binding relationship between miR-30a-5p and suppressor of cytokine signaling 3 (SOCS3) was verified by dual luciferase reporter and RIP assays. RESULTS: BSHLD treatment improved serum hormone abnormality, insulin sensitivity, and ovarian morphologic changes of PCOS rats. Moreover, BSHLD treatment restrained the excessive autophagy and pyroptosis in ovarian tissues of PCOS rats. Moreover, BSHLD reduced the expression of miR-30a-5p in serum, serum-derived Exos, and ovarian tissues, thus inhibiting autophagy and NLRP3-mediated pyroptosis in GCs. Mechanistically, SOCS3 was proved as a target of miR-30a-5p and could activate mTOR/P70S6K pathway to repress autophagy. The inhibitory effect of miR-30a-5p deficiency on autophagy and pyroptosis of GCs was attenuated by rapamycin. CONCLUSION: Collectively, BSHLD suppressed autophagy and pyroptosis to improve POCS by regulating exosomal miR-30a-5p/SOCS3/mTOR signaling.