ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

This article aims to study the processing methods by exploring the main chemical constituents of Aconiti Lateralis Radix Praeparata and the toxicity-attenuating mechanisms. The relevant articles were retrieved from multiple databases with the time interval of 1960-2024, and the chemical constituents of Aconiti Lateralis Radix Praeparata and the toxicity-attenuating mechanisms of its processing methods were summarized. The review revealed that the chemical constituents of Aconiti Lateralis Radix Praeparata included 32 diester-type alkaloids, 36 monoester-type alkaloids, 43 alkanolamine-type alkaloids, and 8 lipid-type alkaloids. At the same time, other chemical constituents such as water-soluble alkaloids were also studied, and their pharmacological activities were summarized. The toxicity-attenuating mechanisms of the processing methods included constituent loss, hydrolysis, ester exchange, and ion-pair action. The processing methods of Aconiti Lateralis Radix Praeparata have developed from being traditional to modern, with simplified operation and increased retention amounts of active constituents, which have improved the efficacy of processed Aconiti Lateralis Radix Praeparata products and have facilitated the industrial production. However, the existing processing methods of Aconiti Lateralis Radix Praeparata cannot completely solve the problem of possible reduction in efficacy during toxicity attenuation. More toxicity-attenuating mechanisms and lipid-type alkaloids of Aconiti Lateralis Radix Praeparata should be explored, which is expected to reduce its toxicity while retaining its efficacy.
Aconitum/toxicity* ; Drugs, Chinese Herbal/isolation & purification* ; Alkaloids/chemistry* ; Animals ; Humans

OBJECTIVES: To explore the manifestations of sensory hypersensitivity in children with autism spectrum disorder (ASD) and individuals with subclinical autistic traits. METHODS: From September 2021 to April 2023, interviews were conducted on 18 college students with high levels of autistic traits and sensory hypersensitivity selected using the Adolescent/Adult Sensory Profile and the Autism Spectrum Quotient (as subclinical group). Interviews were also conducted on the parents of 11 children with ASD aged 6-13 years selected using the intensity sampling method (as clinical group). Qualitative content analysis and thematic analysis were performed on the interview texts to investigate the scenarios and impact of sensory hypersensitivity and coping strategies in the two groups. RESULTS: The Autism Spectrum Quotient score was significantly positively correlated with sensory hypersensitivity (r=0.504, P<0.001; n=225). Sensory modalities that triggered sensitive reactions were similar in the subclinical and clinical groups, with auditory hypersensitivity being the most prominent. Sensory hypersensitivity had significant negative impact on emotional wellbeing, cognitive ability, physical health, interpersonal relationships, and general adaptive functioning. These dimensions were interconnected, culminating in a holistic experience. Avoidance was the most commonly used coping mechanism for both groups (16 subclinical participants mentioned it 44 times; 8 clinical participants mentioned it 40 times). The clinical group required more support and help from their caregivers (18 times), while the subclinical group used more proactive coping strategies (e.g., facing sensitive scenarios, distracting attention) to alleviate the negative impact (51 times). CONCLUSIONS Sensory hypersensitivity is a common manifestation across the broad ASD phenotype, posing negative effects on multiple aspects of their lives. There is an urgent need for social tolerance and acceptance as well as the development of effective intervention measures.
Humans ; Child ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Adolescent ; Adaptation, Psychological ; Autistic Disorder/psychology* ; Sensation Disorders/etiology* ; Qualitative Research

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

Objective In order to shorten the transparency time of clear,unobstructed brain imaging cocktails and computational analysis(CUBIC),improve the transparency efficiency,and explore the possibility of applying hydrophilic tissue transparency technique,this study was conducted to optimize the perfusion of CUBIC technique and compare it with four hydrophilic tissue clearing method in terms of tissue transparency effect,transparency time,area change,volume change and adeno-associated virus(AAV)fluorescence retention.Methods Brain,liver,spleen and kidney of 6 adult Institute of Cancer Research(ICR)mice were subjected to clearing treatment by SeeDB,FRUIT,ScaleS and CUBIC method,respectively.The area and gray value of the samples were measured by Image J 1.8.0,and the volume before and after transparency was measured by drainage method to compare the transparency effect,time and size deformation of each group.Perfusion optimization of the CUBIC was performed by improving the perfusion rate with the optimal perfusion dose,each group of the experimental sample size was 6.Fluorescence preservation by different techniques was evaluated by injecting AAV in the motor cortex of 16 adult mice and taking the cervical spinal segments for transparency treatment after four weeks,and the fluorescence photographs were measured by Image J 1.8.0 to measure the mean fluorescent intensity.Results The optimal perfusion rate and dose of CUBIC was 15 ml/min and 200 ml respectively.For transparency ability and speed,the perfusion CUBIC had the lowest mean gray value and took the shortest time,while CUBIC consumed the longest time,and SeeDB,FRUIT,and ScaleS did not show good transparency ability.In terms of area and volume changes,several techniques showed different degrees of expansion after transparency of tissues or organs.In terms of fluorescence retention,perfusion CUBIC showed the best retention of green fluorescent protein(GFP)fluorescence signal,followed by CUBIC,ScaleS,FRUIT,and SeeDB.Conclusion Perfusion CUBIC technique shows the best tissue transparency,the shortest transparency time,and the most AAV fluorescence retention compared with other techniques.

A new alkaloid (1) and six known compounds (2-7) were isolated from the solid fermentation extract of the endophytic fungus Alternaria tenuissima Pas85 of Phragmites australis by silica gel column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and other chromatographic techniques. The structures of these compounds were determined by HREIMS, NMR, IR spectroscopy, and literature comparison, and the anti MRSA (methicillin-resistant Staphylococcus aureus) activity of 1-5 were tested. Compounds 1, 2, 3 and 4 exhibited certain inhibitory activity with MIC values of 64, 4, 32 and 32 μg·mL^-1, respectively, and compound 5 showed no significant inhibitory activity.