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PURPOSE OF REVIEW: Traditional Chinese Medicine has a unique system to diagnose and treat bone diseases with symptoms similar to those of osteoporosis. Sambucus williamsii Hance (SWH), a folk medicine in northern part of China for fractures healing and pain alleviation, has been demonstrated to exert bone anabolic effects in ovariectomized (OVX) rat and mice models in our previous studies. Lignans were identified to be the main bioactive fractions of SWH. However, pharmacokinetics study showed that the levels of lignan were too low to be detected in rat serum even upon taking 15 times of the effective dose of lignan-rich fraction from SWH. We hypothesize that lignans from SWH might exert its bone protective effect via the gut microbiome. RECENT FINDINGS: Our study revealed that the lignan-rich fraction of SWH did not influence the diversity of gut microbiota in OVX rats, but significantly increased the abundance of a few phyla, in particular, the restoration of the abundance of several genera that was directly correlated with bone mineral density (BMD). In addition, a subsequent metabolomic study indicated that serotonin, a neurotransmitter synthesized in the intestine and influenced by gut microbiota, may be involved in mediating the bone protective action of the lignans. Gut-derived serotonin is thought to inhibit bone growth. Based on this finding, several inhibitors that suppressed the synthesis of serotonin were identified from the lignans of SWH. Our studies suggested that microbiome is an indispensable factor for lignans derived from S. willimasii to exert bone beneficial effects.

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The immune responses play a profound role in the progression of lung lesions in both infectious and non-infectious diseases. Dendritic cells, as the "frontline" immune cells responsible for antigen presentation, set up a bridge between innate and adaptive immunity in the course of these diseases. Among the receptors equipped in dendritic cells, Toll-like receptors are a group of specialized receptors as one type of pattern recognition receptors, capable of sensing environmental signals including invading pathogens and self-antigens. Toll-like receptor 4, a pivotal member of the Toll-like receptor family, was formerly recognized as a receptor sensitive to the outer membrane component lipopolysaccharide derived from Gram-negative bacteria, triggering the subsequent response. Moreover, its other essential roles in immune responses have drawn significant attention in the past decade. A better understanding of the implication of Toll-like receptor 4 in dendritic cells could contribute to the management of pulmonary diseases including pneumonia, pulmonary tuberculosis, asthma, acute lung injury, and lung cancer.

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OBJECTIVE: The aim of the present study was to assess the therapeutic impact of diosgenin derivative ML5 on Parkinson's disease (PD) and explore the mechanism underlying mitochondrial biogenesis and fusion/fission. METHODS: We established 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models and N-methyl-4-phenylpyridinium iodide (MPP+)-induced cell models of PD. The pole test and forced swimming test were used to detect the motor coordination and depressive symptoms in mice. The influence of ML5 on dopaminergic neuronal injury was investigated. Meanwhile, adenosine triphosphate (ATP) content, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) production were measured to evaluate mitochondrial function. Confocal and transmission electron microscopy were used to detect mitochondrial morphology of cell. The expression of mitochondrial biogenesis-related proteins was measured by Western blotting. RESULTS: The administration of ML5 showed the neuroprotection against MPTP-induced damage in vivo and in vitro. The levels of ATP, MMP, and ROS were restored after ML5 administration. In addition, we observed that ML5 preserved the mitochondrial network morphology and inhibited mitochondrial fission. Furthermore, the amelioration of mitochondrial dysfunction was mediated by enhancing 5'-monophosphate-activated protein kinase (AMPK) and peroxisome proliferators-activated receptor γ coactivator-l alpha (PGC-1α) expression, which activated its downstream modulators leading to the enhancing of mitochondrial biogenesis and the balance of mitochondrial fusion/fission. CONCLUSION: ML5 can protect the PD models against MPTP/MPP+-induced mitochondrial dysfunction and neuronal injury via promoting AMPK/PGC-1α signaling activation and be used as a therapeutic drug for PD treatment.

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Cymbidium (Orchidaceae: Epidendroideae), with around 60 species, is widely-distributed across Southeast Asia, providing a nice system for studying the processes that underlie patterns of biodiversity in the region. However, phylogenetic relationships of Cymbidium have not been well resolved, hampering investigations of species diversification and the biogeographical history of this genus. In this study, we construct a plastome phylogeny of 56 Cymbidium species, with four well-resolved major clades, which provides a framework for biogeographical and diversification rate analyses. Molecular dating and biogeographical analyses show that Cymbidium likely originated in the region spanning northern Indo-Burma to the eastern Himalayas during the early Miocene (∼21.10 Ma). It then rapidly diversified into four major clades in East Asia within approximately a million years during the middle Miocene. Cymbidium spp. migration to the adjacent regions (Borneo, Philippines, and Sulawesi) primarily occurred during the Pliocene-Pleistocene period. Our analyses indicate that the net diversification rate of Cymbidium has decreased since its origin, and is positively associated with changes in temperature and monsoon intensity. Favorable hydrothermal conditions brought by monsoon intensification in the early Miocene possibly contributed to the initial rapid diversification, after which the net diversification rate was reduced with the cooling climate after the middle Miocene. The transition from epiphytic to terrestrial habits may have enabled adaptation to cooler environments and colonization of northern niches, yet without a significant effect on diversification rates. This study provides new insights into how monsoon activity and temperature changes affected the diversification dynamics of plants in Southeast Asia.

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Tartary buckwheat (Fagopyrum tataricum) field weeds are rich in species, with many weeds causing reduced quality, yield, and crop failure. The selection of herbicide-resistant Tartary buckwheat varieties, while applying low-toxicity and efficient herbicides as a complementary weed control system, is one way to improve Tartary buckwheat yield and quality. Therefore, the development of herbicide-resistant varieties is important for the breeding of Tartary buckwheat. In this experiment, 50 mM ethyl methyl sulfonate solution was used to treat Tartary buckwheat seeds (M1) and then planted in the field. Harvested seeds (M2) were planted in the experiment field of Guizhou University, and when seedlings had 5-7 leaves, the seedlings were sprayed with 166 mg/L tribenuron-methyl (TBM). A total of 15 resistant plants were obtained, of which three were highly resistant. Using the homologous cloning method, an acetolactate synthase (ALS) gene encoding 547 amino acids was identified in Tartary buckwheat. A GTG (valine) to GGA (glycine) mutation (V409G) occurred at position 409 of the ALS gene in the high tribenuron-methyl resistant mutant sm113. The dm36 mutant harbored a double mutation, a deletion mutation at position 405, and a GTG (valine) to GGA (glycine) mutation (V411G) at position 411. The dm110 mutant underwent a double mutation: an ATG (methionine) to AGG (arginine) mutation (M333R) at position 333 and an insertion mutation at position 372. The synthesis of Chl a, Chl b, total Chl, and Car was significantly inhibited by TBM treatment. TBM was more efficient at suppressing the growth of wild-type plants than that of mutant plants. Antioxidant enzyme activities such as ascorbate peroxidase, peroxidase, and superoxide dismutase were significantly higher in resistant plants than in wild-type after spraying with TBM; malondialdehyde content was significantly lower than in wild-type plants after spraying with TBM. Plants with a single-site mutation in the ALS gene could survive, but their growth was affected by herbicide application. In contrast, plants with dual-site mutations in the ALS gene were not affected, indicating that plants with dual-site mutations in the ALS gene showed higher levels of resistance than plants with a single-site mutation in the ALS gene.

Asunto(s)

Acetolactato Sintasa , Arilsulfonatos , Fagopyrum , Resistencia a los Herbicidas , Herbicidas , Mutación , Acetolactato Sintasa/genética , Acetolactato Sintasa/metabolismo , Fagopyrum/genética , Fagopyrum/efectos de los fármacos , Resistencia a los Herbicidas/genética , Herbicidas/farmacología , Arilsulfonatos/farmacología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo

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Reactive oxygen species (ROS) play crucial roles in the pathogenesis of inflammatory bowel disease (IBD) by disrupting the mucosal barrier and subsequently leading to the dysregulation of the gut microbiome. Therefore, ROS scavengers present a promising and comprehensive strategy for the effective IBD treatment. In the current work, we explored the therapeutic potential of cerium dioxide (CeO2) nano-enzyme, which is well-known for their potent antioxidant properties and capability to mimic natural antioxidant enzymes in the regulation of oxidative stress. We developed a novel enteric-coated nanomedicine (CeO2@S100) aiming at improving the oral delivery efficacy of CeO2 in the complex gastrointestinal environment. CeO2@S100 is composed of a CeO2 nanoparticle core and a protective polyacrylic acid resin shell (Eudragit S100), ensuring targeted delivery of the core specifically at inflamed intestinal sites due to the negative surface charge. In vivo experiments revealed CeO2@S100 significantly alleviates the IBD by balancing oxidative stress and regulating gut microbiota in a dextran sulfate sodium-induced mouse colitis model. The uncomplicated synthesis of CeO2@S100 highlights its promise for clinical use, presenting an effective and safe approach to managing IBD.

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Aim: RADA16-PLGA composite scaffolds constructed with simultaneous loading of BMSCs and TGF-ß3 and explored their ability for chondrogenic differentiation in vitro.Methods: The performance of the composite scaffolds is assessed by rheometer assay, electron microscopic structural observation and ELISA release assay. The biosafety of the composite scaffolds is assessed by cytocompatibility assay and cell migration ability. The chondrogenic differentiation ability of composite scaffolds is evaluated by Alisin blue staining, PCR and immunofluorescence staining.Results: The composite scaffold has a good ECM-like structure, the ability to control the release of TGF-ß3 and good biocompatibility. More importantly, the composite scaffolds can induce the differentiation of BMSCs to chondrocytes.Conclusion: Composite scaffolds are expected to enhance the endogenous NP repair process.

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Diferenciación Celular , Condrocitos , Condrogénesis , Células Madre Mesenquimatosas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Andamios del Tejido , Factor de Crecimiento Transformador beta3 , Factor de Crecimiento Transformador beta3/farmacología , Factor de Crecimiento Transformador beta3/metabolismo , Diferenciación Celular/efectos de los fármacos , Condrogénesis/efectos de los fármacos , Andamios del Tejido/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Condrocitos/citología , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Animales , Humanos , Ingeniería de Tejidos/métodos , Células Cultivadas , Concentración de Iones de Hidrógeno , Ácido Poliglicólico/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Nanopartículas/química

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BACKGROUND: Squamosa promoter-binding protein-like (SPL) is a plant-specific transcription factor that is widely involved in the regulation of plant growth and development, including flower and grain development, stress responses, and secondary metabolite synthesis. However, this gene family has not been comprehensively evaluated in barley, the most adaptable cereal crop with a high nutritional value. RESULTS: In this study, a total of 15 HvSPL genes were identified based on the Hordeum vulgare genome. These genes were named HvSPL1 to HvSPL15 based on the chromosomal distribution of the HvSPL genes and were divided into seven groups (I, II, III, V, VI, VII, and VIII) based on the phylogenetic tree analysis. Chromosomal localization revealed one pair of tandem duplicated genes and one pair of segmental duplicated genes. The HvSPL genes exhibited the highest collinearity with the monocotyledonous plant, Zea mays (27 pairs), followed by Oryza sativa (18 pairs), Sorghum bicolor (16 pairs), and Arabidopsis thaliana (3 pairs), and the fewest homologous genes with Solanum lycopersicum (1 pair). The distribution of the HvSPL genes in the evolutionary tree was relatively scattered, and HvSPL proteins tended to cluster with SPL proteins from Z. mays and O. sativa, indicating a close relationship between HvSPL and SPL proteins from monocotyledonous plants. Finally, the spatial and temporal expression patterns of the 14 HvSPL genes from different subfamilies were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Based on the results, the HvSPL gene family exhibited tissue-specific expression and played a regulatory role in grain development and abiotic stress. HvSPL genes are highly expressed in various tissues during seed development. The expression levels of HvSPL genes under the six abiotic stress conditions indicated that many genes responded to stress, especially HvSPL8, which exhibited high expression under multiple stress conditions, thereby warranting further attention. CONCLUSION: In this study, 15 SPL gene family members were identified in the genome of Hordeum vulgare, and the phylogenetic relationships, gene structure, replication events, gene expression, and potential roles of these genes in millet development were studied. Our findings lay the foundation for exploring the HvSPL genes and performing molecular breeding of barley.

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Regulación de la Expresión Génica de las Plantas , Hordeum , Familia de Multigenes , Filogenia , Proteínas de Plantas , Estrés Fisiológico , Hordeum/genética , Hordeum/metabolismo , Hordeum/crecimiento & desarrollo , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Genoma de Planta , Cromosomas de las Plantas/genética , Mapeo Cromosómico , Duplicación de Gen

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Cooked note is an undesired flavor in green tea, while the key odorants and inhibition mechanisms were unknown. Here, volatiles of four green tea samples and two thermal reaction models of methionine-glucose and methional were assessed using gas chromatography­sulfur chemiluminescence detector and two dimensional gas chromatography-time-of-flight mass spectrometry. Nonvolatiles of reaction models were determined using ultra performance liquid chromatography-Q-Exactive orbitrap mass spectrometry. Four cooked smelling sulfur-containing odorants including dimethyl trisulfide, dimethyl sulfide, diethyl disulfide, and methanethiol having odor activity values > 1 were characterized in tea samples. Aroma addition tests confirmed dimethyl trisulfide (> 0.4 µg/L) as a reliable predictor of the cooked note. Seven sulfur-containing odorants were detected in reaction models. The addition of (-)-epigallocatechin gallate depleted glucose and interrupted the reaction, thus reduced sulfur-containing odorants' amounts. The study provides a novel insight on targeted strategic guidance for mitigating cooked off-flavor during the thermal processing of green tea production.

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Cyclometalated iridium(III) compounds have been widely explored due to their outstanding photo-physical properties and multiple anticancer activities. In this paper, three cyclometalated iridium(III) compounds [Ir(ppy)2(DBDIP)]PF6 (5a), [Ir(bzq)2(DBDIP)]PF6 (5b), and [Ir(piq)2(DBDIP)]PF6 (5c) (ppy: 2-phenylpyridine; bzq: benzo[h]quinoline; piq: 1-phenylisoquinoline, and DBDIP: 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and the mechanism of antitumor activity was investigated. Compounds photoactivated by visible light show strong cytotoxicity against tumor cells, especially toward A549 cells. Biological experiments such as migration, cellular localization, mitochondrial membrane potential and permeability, reactive oxygen species (ROS) and calcium ion level detection were performed, and they demonstrated that the compounds induced the apoptosis of A549 cells through a mitochondrial pathway. At the same time, oxidative stress caused by ROS production increases the release of damage-related molecules and the expression of porogen gasdermin D (GSDMD), and the content of LDH released from damaged cell membranes also increased. Besides, the content of the lipid peroxidation product, malondialdehyde (MDA), increased and the expression of GPX4 decreased. These indicate that the compounds promote cell death by combining ferroptosis and pyroptosis. The results reveal that cyclometalated iridium(III) compounds 5a-5c may be a potential chemotherapeutic agent for photodynamic therapy of cancers.

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ortho-Quinone methides (o-QMs) are a class of highly reactive intermediates that serve as important nonisolable building blocks (NBBs) in organic synthesis and small-molecule library construction. Because of their instability and nonisolability, most reported o-QMs are generated through in situ chemical synthesis, and only a few natural o-QMs have been reported due to the lack of directed discovery strategies. Herein, a new natural o-QM precursor (trichophenol A, 2) was identified from the fungal strain of Trichoderma sp. AT0167 through genome mining, which was generated by trilA (nonreducing polyketide synthase) and trilB (2-oxoglutarate dependent dioxygenase). Combinatorial biosynthesis via two other known NRPKS genes with trilA and trilB was performed, leading to the generation of five new trichophenol o-QM oligomers (trichophenols D-H, 5-9). The strategy combining genome mining with combinatorial biosynthesis not only targetedly uncovered a new natural o-QM precursor but also produced various new molecules through oligomerization of the new o-QM and its designated o-QM acceptors without chemical synthesis and isolation of intermediates, which was named NBB genome mining-combinatorial biosynthesis strategy for o-QM molecule library construction. This study provides a new strategy for the targeted discovery of natural o-QMs and small-molecule library construction with natural o-QMs.

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Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.

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Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Proteómica , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Animales , Ratones , Metabolismo de los Lípidos/fisiología , Femenino , Lipidómica , Transcriptoma , Multiómica

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Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Animales , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Femenino , Ratones , Mutación , Masculino , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Ácidos Aristolóquicos/farmacología , Persona de Mediana Edad , Línea Celular Tumoral , Secuenciación del Exoma , Anciano , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico

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OBJECTIVE: Bibliometrics was employed in this study to determine the research trends in the worldwide application of 3D printing technology to treat bone tumors over the previous 10 years. METHODS: Published from 2013 to 2022, the papers related to bone tumors treated with 3D printing were located in Web of Science Core Collection (WoSCC), PubMed, and Scopus. The screened articles were included in this bibliometric study. From these papers in WoSCC, information on annual publications, journals, keywords, countries, authors, institutions, and cited references were extracted and visualized with CiteSpace (version 6.1.R6) software to investigate the state of bone tumor treatment using 3D printing as well as research hotspots. The Carrot2 online visualization tool and Vosviewer software (version 1.6.20) were employed to visualize the publications from PubMed and Scopus, respectively, in order to ascertain the most popular research topics from both databases. RESULTS: A total of 606, 233, and 364 publications were obtained from WoSCC, PubMed, and Scopus, respectively, between the years 2013 and 2022. In WoSCC, the peak number of publications was found in 2021, with 145 publications published. Acta Biomaterialia (11 publications) and World Neurosurgery (10 publications) were the most prolific journals, and Biomaterials was the journal cited the most (244 times). Yong Zhou was the most productive author with 14 publications, while Kwok-Chuen Wong (69 citations) and William F Enneking, (69 citations) possessed the most citations. The country with the largest quantity of publications was China (207). Among all institutions, Shanghai Jiao Tong University produced the most publications (29). Rapid prototyping was the keyword with the strongest citation burst (4.73). 'Reconstruction', 'surgery', 'resection', and 'design' caught the significant attention of researchers. 3D-printed materials, pelvic reconstruction, mandibular reconstruction, computer-assisted surgical techniques, photothermal therapy, and in vitro experiments were recognized as hot subjects and trends in current research. The most frequently occurring topics in Scopus are not significantly different from those found in WoSCC. The most prevalent research areas in PubMed encompass implant, patient-specific, bioceramic, models, and pelvic.

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The COVID-19 pandemic introduced an urgent need for rapid and high-throughput testing for SARS-CoV-2. RNA extraction is a major bottleneck for RT-qPCR. We describe a semi-automated, extraction-free RT-qPCR assay for detection of SARS-CoV-2 in nasal swab and saliva samples on a single platform. With a limit of detection of 4 copies/mL, this laboratory developed test performed equivalently to established methods requiring nucleic acid extraction. Five technologists staffing two shifts per day (80 person-hours) processed more than 400,000 samples over 10 months. Patients opted to provide nasal swab samples (83.6%) more frequently than saliva (16.4%), creating the added challenge of producing swab collection kits. Real-world testing data indicated a higher frequency of SARS-CoV-2 detection in saliva (10.1%) compared to nasal swab (7.7%). This cost-effective and quickly scalable approach is suitable for pandemic preparedness planning related to surveillance and diagnostic testing.

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Four previously unreported phenylpropanoid glycosides (1-4), together with four known analogues (5-8), were isolated from the leaves of Illicium dunnianum. The structures of these new compounds were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR, IR, UV) and chemical methods. In addition, the neuroprotective activities of all the isolates were evaluated by measuring their cell viability in H2O2-induced OLN-93 cell injury model.

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Feline bocavirus (FBoV) is a globally distributed linear, single-stranded DNA virus infect cats, currently classified into three distinct genotypes. Although FBoV can lead to systemic infections, its complete pathogenic potential remains unclear. In this study, 289 blood samples were collected from healthy cats in Harbin, revealing an overall FBoV prevalence of 12.1%. Notably, genotypes 1 and 3 of FBoV were found co-circulating among the cat population in Harbin. Additionally, recombination events were detected, particularly in the newly discovered NG/104 and DL/102 strains. Furthermore, negative selection sites were predominantly observed across the protein coding genes of FBoV. These findings suggest a co-circulation of genetically diverse FBoV strains among cats in Harbin, indicate that purifying selection is the primary driving force shaping the genomic evolution of FBoV, and also underscore the importance of comprehensive surveillance efforts to enhance our understanding of the epidemiology and evolutionary characteristics of FBoV.

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Bocavirus , Enfermedades de los Gatos , Variación Genética , Genotipo , Infecciones por Parvoviridae , Filogenia , Gatos , Animales , China/epidemiología , Enfermedades de los Gatos/virología , Enfermedades de los Gatos/epidemiología , Infecciones por Parvoviridae/veterinaria , Infecciones por Parvoviridae/virología , Infecciones por Parvoviridae/epidemiología , Bocavirus/genética , Bocavirus/clasificación , Bocavirus/aislamiento & purificación , Prevalencia , Recombinación Genética , Genoma Viral , Evolución Molecular

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BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.

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Disfunción Cognitiva , Demencia Vascular , Modelos Animales de Enfermedad , Fármacos Neuroprotectores , Estrés Oxidativo , Sustancia Blanca , Animales , Demencia Vascular/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Masculino , Sustancia Blanca/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones , Gardenia/química , Ratones Endogámicos C57BL , Carotenoides/farmacología , Carotenoides/uso terapéutico , Circulación Cerebrovascular/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Extractos Vegetales/farmacología

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Sediment-derived dissolved organic matter (SDOM) is instrumental in the cycling of nutrients and heavy metals within lakes, influencing ecological balance and contaminant distribution. Given the influence of photodegradation on the alteration and breakdown of SDOM, further understanding of this process is essential. In this research, the properties of the SDOM photodegradation process and its metal-binding reactions in Nansi Lake were analyzed using the EEM-PARAFAC and 2D-SF/FTIR-COS techniques. Our study identified three sorts of humic-like components and one protein-like component in SDOM, with the humic-like material accounting for 71.3 ± 5.19% of the fluorescence intensity (Fmax). Photodegradation altered the abundance and structure of SDOM, with a 41.6 ± 5.82% decrease in a280 and a 29.1 ± 9.31% reduction in Fmax after 7 days, notably reducing the protein-like component C4 by 54.0 ± 5.17% and the humic-like component C2 by 48.5 ± 2.54%, which led to SDOM being formed with lower molecular weight and aromaticity. After photodegradation, the LogKCu values for humic-like and protein-like substances decreased (humic-like C2: LogKCu: 1.35 ± 0.10-1.11 ± 0.15, protein-like C4: 1.49 ± 0.14-1.29 ± 0.34), yet the preferential binding sequence of protein-like materials and specific functional groups with Cu2+ such as aliphatic C-OH, amide (I) C=O and polysaccharide C-O groups remained unaltered. Our results enhance the knowledge of light-induced SDOM alterations and offer insights into SDOM-metal interactions in aquatic ecosystems.

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Sedimentos Geológicos , Lagos , Fotólisis , Contaminantes Químicos del Agua , Lagos/química , China , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Sustancias Húmicas/análisis , Compuestos Orgánicos/química , Metales/química , Monitoreo del Ambiente/métodos

RESUMEN

The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.