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1.
J Nat Med ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103726

RESUMEN

Fungi, such as Trichophyton rubrum (T. rubrum) and Microsporum canis Bodin Anamorph (M. canis Bodin Anamorph) are the main pathogens of dermatophysis. According to ancient books records, Rumex japonicus Houtt. (RJH) has a miraculous effect on the treatment of dermatophysis. To reveal the anti-fungi (T. rubrum and M. canis Bodin Anamorph) components and its mechanism of the Rumex japonicus Houtt. The vinegar extraction and alcohol precipitation, HPLC and nuclear magnetic resonance spectroscopy (NMR) were employed for analyzing the chemical compositions of RJH; in vitro anti-fungal experiment was investigated including test the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC), spore germination rate, nucleic acid, protein leakage rate, biofilm structure, and the mechanism of anti-fungal and anti-fungal biofilms in RJH. Seven anthraquinones and their glycoside compounds were obtained in this study respectively, such as chrysophanol, physcion, aloe-emodin, emodin, rhein, emodin-8-O-ß-D-glucoside and chrysophanol-8-O-ß-D-glucoside. In vitro anti-fungal experiment results showed that RJH extracts have good anti-fungal activity for dermatophytic fungi. Among them, the MIC of the rhein, emodin and aloe-emodin against T. rubrum are 1.9 µg/ml, 3.9 µg/ml and 15.6 µg/ml, respectively; the MIC of emodin and aloe-emodin against M. canis Bodin Anamorph are 7.8 µg/ml and 62.5 µg/ml, respectively. In addition, its active components can inhibit fungal spore germination and the formation of bud tube, change cell membrane permeability, prevent hyphal growth, destroy biofilm structure, and down-regulate the expression of agglutinin-like sequence family 1 of the adhesion phase of biofilm growth. The study shows that RJH play a fungicidal role.

2.
Eur J Pharmacol ; : 176894, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39147013

RESUMEN

Sepsis is a systemic inflammatory response syndrome triggered by infection, presenting with symptoms such as fever, increased heart rate, and low blood pressure. In severe cases, it can lead to multiple organ dysfunction, posing a life-threatening risk. Sepsis-induced cardiomyopathy (SIC) is a critical factor in the poor prognosis of septic patients, leading to myocardial dysfunction characterized by cell death, inflammation, and diminished cardiac function. Ferroptosis, an iron-dependent form of programmed cell death, is a key mechanism causing cardiomyocyte damage in SIC. Growth differentiation factor 15 (GDF15), a member of the TGF-ß superfamily, is associated with various cardiovascular diseases and can inhibit oxidative stress, reduce reactive oxygen species (ROS), and suppress ferroptosis. Elevated serum GDF15 levels in sepsis are correlated with organ injuries, suggesting its potential as a therapeutic target. However, its role and mechanisms in SIC remain unclear. Glutathione peroxidase 4 (GPX4), the only enzyme capable of reducing lipid peroxides within cells, protects cells by reducing lipid peroxidation levels and inhibiting ferroptosis. Investigating the regulatory factors of GPX4 may provide a theoretical basis for SIC treatment. In this study, a mouse SIC model revealed that elevated GDF15 exerts a protective effect. Antagonizing GDF15 exacerbates myocardial damage. Through transcriptomic analysis and other methods, we confirmed that GDF15 inhibits the expression of SOCS1 by activating the ALK5-SMAD2/3 pathway, thereby activates the JAK2/STAT3 pathway, promotes the transcription of GPX4, inhibits ferroptosis in cardiomyocytes, and plays a myocardial protective role in SIC.

3.
J Chromatogr A ; 1732: 465233, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39142171

RESUMEN

Metabolites identification is crucial to develop functional foods or perform quality control. Prunella vulgaris (Xia-Ku-Cao) is a medicinal and edible plant used as the herbal medicine or main additive in functional beverage. However, current analytical strategies can only on-line characterize tens of compounds, restricted by insufficient chromatographic resolution and low coverage of the mass spectrometric scan methods. This work was designed to characterize the wide-polarity components from the ear of P. vulgaris. The total extract was fractionated by semi-preparative high-performance liquid chromatography into the retained medium-polarity fraction and unretained polar fraction, which were further analyzed by offline two-dimensional liquid chromatography (2D-LC) and hydrophilic interaction chromatography, respectively. Data-independent high-definition MSE of the Vion™ ion mobility time-of-flight mass spectrometer was utilized enabling the high-coverage acquisition of collision-induced dissociation-MS2 data. The offline 2D-LC, configuring the XBridge Amide and HSS T3 columns, gave high orthogonality (0.81) and effective peak capacity (1555). Automatic peak annotation facilitated by the UNIFI™ bioinformatics platform and comparison with 62 reference compounds achieved the efficient and more reliable structural elucidation. We could characterize 255 compounds from P. vulgaris, with numerous phenylpropanoid phenolic acids and triterpenoid O-glycosides newly reported. Especially, collision cross section (CCS) prediction and targeted isolation of three compounds assisted in the identification of 39 groups of isomers. Additionally, 17 hydrophilic compounds, involving oligosaccharides and organic acids, were characterized from the unretained polar fraction. Conclusively, the in-depth metabolites identification of P. vulgaris was accomplished, and the results can benefit the development and better quality control of this valuable plant.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39038795

RESUMEN

OBJECTIVE: The recent surge in large language models (LLMs) across various fields has yet to be fully realized in traditional Chinese medicine (TCM). This study aims to bridge this gap by developing a large language model tailored to TCM knowledge, enhancing its performance and accuracy in clinical reasoning tasks such as diagnosis, treatment, and prescription recommendations. MATERIALS AND METHODS: This study harnessed a wide array of TCM data resources, including TCM ancient books, textbooks, and clinical data, to create 3 key datasets: the TCM Pre-trained Dataset, the Traditional Chinese Patent Medicine (TCPM) Question Answering Dataset, and the Spleen and Stomach Herbal Prescription Recommendation Dataset. These datasets underpinned the development of the Lingdan Pre-trained LLM and 2 specialized models: the Lingdan-TCPM-Chat Model, which uses a Chain-of-Thought process for symptom analysis and TCPM recommendation, and a Lingdan Prescription Recommendation model (Lingdan-PR) that proposes herbal prescriptions based on electronic medical records. RESULTS: The Lingdan-TCPM-Chat and the Lingdan-PR Model, fine-tuned on the Lingdan Pre-trained LLM, demonstrated state-of-the art performances for the tasks of TCM clinical knowledge answering and herbal prescription recommendation. Notably, Lingdan-PR outperformed all state-of-the-art baseline models, achieving an improvement of 18.39% in the Top@20 F1-score compared with the best baseline. CONCLUSION: This study marks a pivotal step in merging advanced LLMs with TCM, showcasing the potential of artificial intelligence to help improve clinical decision-making of medical diagnostics and treatment strategies. The success of the Lingdan Pre-trained LLM and its derivative models, Lingdan-TCPM-Chat and Lingdan-PR, not only revolutionizes TCM practices but also opens new avenues for the application of artificial intelligence in other specialized medical fields. Our project is available at https://github.com/TCMAI-BJTU/LingdanLLM.

5.
Nature ; 631(8021): 635-644, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38961291

RESUMEN

Innate immune pattern recognition receptors, such as the Toll-like receptors (TLRs), are key mediators of the immune response to infection and central to our understanding of health and disease1. After microbial detection, these receptors activate inflammatory signal transduction pathways that involve IκB kinases, mitogen-activated protein kinases, ubiquitin ligases and other adaptor proteins. The mechanisms that connect the proteins in the TLR pathways are poorly defined. To delineate TLR pathway activities, we engineered macrophages to enable microscopy and proteomic analysis of the endogenous myddosome constituent MyD88. We found that myddosomes form transient contacts with activated TLRs and that TLR-free myddosomes are dynamic in size, number and composition over the course of 24 h. Analysis using super-resolution microscopy revealed that, within most myddosomes, MyD88 forms barrel-like structures that function as scaffolds for effector protein recruitment. Proteomic analysis demonstrated that myddosomes contain proteins that act at all stages and regulate all effector responses of the TLR pathways, and genetic analysis defined the epistatic relationship between these effector modules. Myddosome assembly was evident in cells infected with Listeria monocytogenes, but these bacteria evaded myddosome assembly and TLR signalling during cell-to-cell spread. On the basis of these findings, we propose that the entire TLR signalling pathway is executed from within the myddosome.


Asunto(s)
Macrófagos , Transducción de Señal , Receptores Toll-Like , Animales , Humanos , Ratones , Listeria monocytogenes/inmunología , Listeriosis/inmunología , Listeriosis/microbiología , Listeriosis/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/microbiología , Factor 88 de Diferenciación Mieloide/metabolismo , Proteómica , Receptores Toll-Like/metabolismo , Microscopía , Inmunidad Innata
6.
Front Physiol ; 15: 1386788, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39027901

RESUMEN

Objective: This study aims to analyze the effects of plyometric training (PT) on physical fitness and skill-related performance in female basketball players. Method: Five databases, including Web of Science, Scopus, PubMed, EBSCOhost, and Google Scholar, were used to select articles published up to 20 December 2023, using a combination of keywords related to PT and female basketball players. The risk of bias and the certainty of evidence in included articles were assessed using the Cochrane risk of bias (RoB2) tool and "The Grading of Recommendations Assessment, Development, and Evaluation" (GRADE). Results: Ten studies were included for the systematic review, and eight for the meta-analysis, totalling 246 female basketball players aged 14.5-22.5 years. Most of these players were highly trained. Most of the included studies exhibited concerns regarding the risk of bias. The PT programs lasted 4-8 weeks, conducted 2-3 sessions per week, with sessions lasting 20-90 min and including 29-190 jumps. In the systematic review, most studies showed that PT significantly improved performance in countermovement jump (CMJ), squat jump (SJ), Sargent jump, standing long jump, lateral hop, medicine ball throw, t-Test, Illinois agility, lane agility drill, linear 20-m sprint, stable and dynamic leg balance, dribbling, passing, shooting, and various basketball-specific tests, as well as increased muscle volume and thigh cross-sectional area. However, some studies showed PT to induce no significant changes in performance during CMJ, t-Test, Illinois agility, knee extensor/flexor strength, linear sprint, and single leg balance tests. In the meta-analysis, CMJ height (ES = 0.37; p = 0.036), vertical jump (VJ) peak power (ES = 0.57; p = 0.015), VJ peak velocity (ES = 0.26; p = 0.004), and t-Test performance time (ES = 0.32; p = 0.004) were significantly improved with small effects following PT. Conclusion: The effect of PT on performance in female basketball players was mixed. Most studies indicated that PT could improve various measures of physical fitness and skill-related performance, but performance remained unchanged in some tests. More studies with established tests are needed to investigate the effect of PT on female basketball players in the future. Systematic Review Registration: https://inplasy.com/, Identifier INPLASY2023120078.

7.
J Vis Exp ; (209)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39072623

RESUMEN

Pulmonary macrophages exhibit a dose-dependent pattern in phagocytizing particles. Following engulfment, these macrophages are subsequently excreted with sputum, rendering macrophages and particles visible and quantifiable under light microscopy. Notably, elemental carbon within the mammalian body originates exclusively from external contaminants. Consequently, the carbon content in airway macrophages (CCAM) serves as a valid exposure biomarker, accurately estimating individual exposure to carbon-containing particulate matter (PM). This article delineates a protocol involving sputum collection, preservation, processing, slide preparation, and staining, as well as macrophage photo acquisition and analysis. After removing the macrophage nuclei, the proportion of cytoplasm area occupied by carbon particles (PCOC) was calculated to quantify carbon content in each macrophage. The results indicate an elevation in CCAM levels after exposure to carbon-containing PM. In summary, this non-invasive, precise, reliable, and standardized method enables the direct measurement of carbon particles within target cells and is utilized for large-scale quantification of individual CCAM through induced sputum.


Asunto(s)
Carbono , Material Particulado , Esputo , Material Particulado/análisis , Material Particulado/toxicidad , Humanos , Carbono/química , Carbono/toxicidad , Esputo/química , Esputo/citología , Esputo/metabolismo , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/química , Macrófagos Alveolares/citología
8.
Pharmacol Res ; 207: 107306, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39002871

RESUMEN

Many inflammatory disorders, including diabetic kidney disease (DKD), are associated with pyroptosis, a type of inflammation-regulated cell death. The purpose of this work was to ascertain the effects of apabetalone, which targets BRD4, a specific inhibitor of the bromodomain (BRD) and extra-terminal (BET) proteins that target bromodomain 2, on kidney injury in DKD. This study utilized pharmacological and genetic approaches to investigate the effects of apabetalone on pyroptosis in db/db mice and human tubular epithelial cells (HK-2). BRD4 levels were elevated in HK-2 cells exposed to high glucose and in db/db mice. Modulating BRD4 levels led to changes in the generation of inflammatory cytokines and cell pyroptosis linked to NLRP3 inflammasome in HK-2 cells and db/db mice. Likewise, these cellular processes were mitigated by apabetalone through inhibition BRD4. Apabetalone or BRD4 siRNA suppressed PLK1 expression in HK-2 cells under high glucose by P300-dependent H3K27 acetylation on the PLK1 gene promoter, as demonstrated through chromatin immunoprecipitation and immunoprecipitation assays. To summarize, apabetalone relieves renal proptosis and fibrosis in DKD. BRD4 regulates the P300/H3K27ac/PLK1 axis, leading to the activation of the NLRP3 inflammasome and subsequent cell pyroptosis, inflammation, and fibrosis. These results may provide new perspectives on DKD treatment.

9.
Int J Mol Sci ; 25(14)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39062952

RESUMEN

Gastrodin (GAS) is the main chemical component of the traditional Chinese herb Gastrodia elata (called "Tianma" in Chinese), which has been used to treat neurological conditions, including headaches, epilepsy, stroke, and memory loss. To our knowledge, it is unclear whether GAS has a therapeutic effect on Huntington's disease (HD). In the present study, we evaluated the effect of GAS on the degradation of mutant huntingtin protein (mHtt) by using PC12 cells transfected with N-terminal mHtt Q74. We found that 0.1-100 µM GAS had no effect on the survival rate of Q23 and Q74 PC12 cells after 24-48 h of incubation. The ubiquitin-proteasome system (UPS) is the main system that clears misfolded proteins in eukaryotic cells. Mutated Htt significantly upregulated total ubiquitinated protein (Ub) expression, decreased chymotrypsin-like, trypsin-like and caspase-like peptidase activity, and reduced the colocalization of the 20S proteasome with mHtt. GAS (25 µM) attenuated all of the abovementioned pathological changes, and the regulatory effect of GAS on mHtt was found to be abolished by MG132, a proteasome inhibitor. The autophagy-lysosome pathway (ALP) is another system for misfolded protein degradation. Although GAS downregulated the expression of autophagy markers (LC3II and P62), it increased the colocalization of LC3II with lysosomal associated membrane protein 1 (LAMP1), which indicates that ALP was activated. Moreover, GAS prevented mHtt-induced neuronal damage in PC12 cells. GAS has a selective effect on mHtt in Q74 PC12 cells and has no effect on Q23 and proteins encoded by other genes containing long CAGs, such as Rbm33 (10 CAG repeats) and Hcn1 (>30 CAG repeats). Furthermore, oral administration of 100 mg/kg GAS increased grip strength and attenuated mHtt aggregates in B6-hHTT130-N transgenic mice. This is a high dose (100 mg/kg GAS) when compared with experiments on HD mice with other small molecules. We will design more doses to evaluate the dose-response relationship of the inhibition effect of GAS on mHtt in our next study. In summary, GAS can promote the degradation of mHtt by activating the UPS and ALP, making it a potential therapeutic agent for HD.


Asunto(s)
Autofagia , Alcoholes Bencílicos , Glucósidos , Proteína Huntingtina , Lisosomas , Complejo de la Endopetidasa Proteasomal , Ubiquitina , Animales , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Ratas , Complejo de la Endopetidasa Proteasomal/metabolismo , Células PC12 , Autofagia/efectos de los fármacos , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Ubiquitina/metabolismo , Alcoholes Bencílicos/farmacología , Glucósidos/farmacología , Ratones , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/genética , Proteolisis/efectos de los fármacos , Mutación
10.
J Infect Dis ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995029

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden. METHODS: We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at two hospitals during two respiratory seasons (2018-2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n=1558), acute and convalescent sera (n=568), and expectorated sputum (n=153) from participants, and recorded standard-of-care (SOC) NP results (n=805). We measured RSV antibodies by two immunoassays and performed BioFire testing on respiratory specimens. RESULTS: Of 1,558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP PCR yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to Study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab RT-PCR results increased RSV detection by 25.9% (47 vs 59). CONCLUSIONS: The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults.

12.
Mikrochim Acta ; 191(8): 453, 2024 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970675

RESUMEN

An electrochemical biosensor has been developed for detection of Escherichia coli O157 by integrating lateral flow with screen-printed electrodes. The screen-printed electrodes were attached under the lateral flow detection line, and organic-inorganic nanoflowers prepared from E. coli O157-specific antibodies as an organic component were attached to the lateral flow detection line. In the presence of E. coli O157, an organic-inorganic nanoflower-E. coli O157-antimicrobial peptide-labelled ferrocene sandwich structure is formed on the lateral flow detection line. Differential pulse voltammetry is applied using a smartphone-based device to monitor ferrocene on the detection line. The resulting electrochemical biosensor could specifically detect E. coli O157 with a limit of detection of 25 colony-forming units mL-1. Through substitution of antibodies of organic components in organic-inorganic nanoflowers, biosensors have great potential for the detection of other pathogens in biomedical research and clinical diagnosis.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Escherichia coli O157 , Escherichia coli O157/aislamiento & purificación , Escherichia coli O157/inmunología , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Límite de Detección , Nanoestructuras/química , Electrodos , Compuestos Ferrosos/química , Anticuerpos Inmovilizados/inmunología , Metalocenos/química , Anticuerpos Antibacterianos/química , Anticuerpos Antibacterianos/inmunología , Péptidos Antimicrobianos/química
13.
Sci Total Environ ; 949: 175023, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39067599

RESUMEN

The environmental impact of the discharge of lithium (Li) by anthropogenic activity has been overlooked. By analyzing Li concentrations and isotope compositions (δ7Li) of water and sediment samples, this study evaluates the influence of anthropogenic Li discharge on the Xiaoqing River and Laizhou Bay, which are heavily polluted areas in China. High Li concentrations of the river water (up to 7.8 µmol/L) should be linked to anthropogenic Li discharge. However, no profound δ7Li anomalies were observed, preventing identification of the exact discharge sources. In the river sediments, Li concentrations (19.0-45.0 µg/g) were weakly correlated with Zn, Cu, and Cr concentrations, whereas δ7Li values ranged from 0.6 ‰ to 13.9 ‰ with high values being accompanied by high contents of total organic carbon and heavy Cr isotope compositions (δ53Cr). All these point to significant influence of anthropogenic activity on the Li budget of river sediments. A simple mass balance calculation indicates that smelters, Li-bearing therapeutic drugs, and secondary Li-ion batteries are the main anthropogenic Li sources. In contrast to river sediments, marine sediments in the Laizhou Bay were broadly homogeneous at both spatial and temporal scales, indicating no significant influence of anthropogenic Li discharge. Overall, our data indicate that Li isotope systematics in river sediments, especially sediments near intense anthropogenic activity, are effective at tracing potential Li pollution and can help obtain accurate results for environmental inspection.

14.
Acta Pharmacol Sin ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862818

RESUMEN

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

15.
J Agric Food Chem ; 72(25): 14402-14410, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38875520

RESUMEN

Tripyrasulfone is currently the only HPPD-inhibiting herbicide that possesses outstanding selectivity even for direct-seeded rice (Oryza sativa) when applied POST to control grass weeds; however, the underlying mechanisms remain unclear. In this study, the inhibitory effects of the real active HDT of tripyrasulfone on recombinant 4-hydroxyphenylpyruvate dioxygenase (HPPDs) from rice and barnyard grass (Echinochloa crus-galli) were similar, with consistent structural interactions and similar binding energies predicted by molecular docking. However, the HPPD expression level in rice was significantly greater than that in barnyard grass after tripyrasulfone treatment. Tripyrasulfone was rapidly taken up and hydrolyzed into HDT, which was similarly distributed within the whole plants of rice and barnyard grass at 24 h after treatment. Compared with barnyard grass, rice has more uniform epicuticular wax in the cuticle of its leaves, absorbing less tripyrasulfone and metabolizing much more tripyrasulfone. Overall, to a greater extent, the different sensitivities to tripyrasulfone between barnyard grass and rice resulted from metabolic variations.


Asunto(s)
4-Hidroxifenilpiruvato Dioxigenasa , Echinochloa , Herbicidas , Simulación del Acoplamiento Molecular , Oryza , Proteínas de Plantas , Oryza/metabolismo , Oryza/química , Echinochloa/efectos de los fármacos , Echinochloa/genética , Echinochloa/metabolismo , Echinochloa/crecimiento & desarrollo , Echinochloa/química , Herbicidas/farmacología , Herbicidas/química , Herbicidas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/química , 4-Hidroxifenilpiruvato Dioxigenasa/metabolismo , 4-Hidroxifenilpiruvato Dioxigenasa/antagonistas & inhibidores , 4-Hidroxifenilpiruvato Dioxigenasa/genética , 4-Hidroxifenilpiruvato Dioxigenasa/química , Malezas/efectos de los fármacos , Malezas/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química
16.
Adv Mater ; 36(28): e2401537, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38768481

RESUMEN

In the fabrication of inverted perovskite solar cells (PSCs), the wettability, adsorbability, and compactness of self-assembled monolayers (SAMs) on conductive substrates have critical impacts on the quality of the perovskite films and the defects at the buried perovskite-substrate interface, which control the efficiency and stability of the devices. Herein, three bisphosphonate-anchored indolocarbazole (IDCz)-derived SAMs, IDCz-1, IDCz-2, and IDCz-3, are designed and synthesized by modulating the position of the two nitrogen atoms of the IDCz unit to improve the molecular dipole moments and strengthen the π-π interactions. Regulating the work functions (WF) of FTO electrodes through molecular dipole moments and energy levels, the perovskite band bends upwards with a small offset for ITO/IDCz-3/perovskite, thereby promoting hole extraction and blocking electrons. As a result, the inverted PSC employing IDCz-3 as hole-collecting layer exhibits a champion PCE of 25.15%, which is a record efficiency for the multipodal SAMs-based PSCs. Moreover, the unencapsulated device with IDCz-3 can be stored for at least 1800 h with little degradation in performance.

17.
Transl Psychiatry ; 14(1): 227, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816419

RESUMEN

Psychiatric syndromes are common following recovery from Coronavirus Disease 2019 (COVID-19) infection. This study investigated the prevalence and the network structure of depression, insomnia, and suicidality among mental health professionals (MHPs) who recovered from COVID-19. Depression and insomnia were assessed with the Patient Health Questionnaire (PHQ-9) and Insomnia Severity Index questionnaire (ISI7) respectively. Suicidality items comprising suicidal ideation, suicidal plan and suicidal attempt were evaluated with binary response (no/yes) items. Network analyses with Ising model were conducted to identify the central symptoms of the network and their links to suicidality. A total of 9858 COVID-19 survivors were enrolled in a survey of MHPs. The prevalence of depression and insomnia were 47.10% (95% confidence interval (CI) = 46.09-48.06%) and 36.2% (95%CI = 35.35-37.21%), respectively, while the overall prevalence of suicidality was 7.8% (95%CI = 7.31-8.37%). The key central nodes included "Distress caused by the sleep difficulties" (ISI7) (EI = 1.34), "Interference with daytime functioning" (ISI5) (EI = 1.08), and "Sleep dissatisfaction" (ISI4) (EI = 0.74). "Fatigue" (PHQ4) (Bridge EI = 1.98), "Distress caused by sleep difficulties" (ISI7) (Bridge EI = 1.71), and "Motor Disturbances" (PHQ8) (Bridge EI = 1.67) were important bridge symptoms. The flow network indicated that the edge between the nodes of "Suicidality" (SU) and "Guilt" (PHQ6) showed the strongest connection (Edge Weight= 1.17, followed by "Suicidality" (SU) - "Sad mood" (PHQ2) (Edge Weight = 0.68)). The network analysis results suggest that insomnia symptoms play a critical role in the activation of the insomnia-depression-suicidality network model of COVID-19 survivors, while suicidality is more susceptible to the influence of depressive symptoms. These findings may have implications for developing prevention and intervention strategies for mental health conditions following recovery from COVID-19.


Asunto(s)
COVID-19 , Depresión , Personal de Salud , Trastornos del Inicio y del Mantenimiento del Sueño , Ideación Suicida , Humanos , COVID-19/psicología , COVID-19/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Femenino , Masculino , China/epidemiología , Adulto , Prevalencia , Depresión/epidemiología , Depresión/psicología , Persona de Mediana Edad , Personal de Salud/psicología , Encuestas y Cuestionarios , SARS-CoV-2 , Intento de Suicidio/estadística & datos numéricos , Intento de Suicidio/psicología
18.
Phytomedicine ; 129: 155686, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759346

RESUMEN

BACKGROUND: Tourette syndrome (TS) represents a neurodevelopmental disorder characterized by an uncertain etiology and influencing factors. Frequently, it co-occurs with conditions such as attention deficit hyperactivity disorder, obsessive-compulsive disorder, and sleep disturbances, which have garnered substantial attention from the research community in recent years. Clinical trials have demonstrated that Shaoma Zhijing Granules (SMZJG, 5-ling granule, also known as TSupport or T92 under U.S. development), a traditional Chinese medicine compound, is an effective treatment for TS. PURPOSE: To conduct scientometric analysis on developing trends, research countries and institutions, current status, hot spots of TS and discuss the underlying mechanisms of SMZJG and its main components on TS. The aim is to provide valuable reference for ongoing clinical and basic research on TS and SMZJG. STUDY DESIGN & METHODS: Using Tourette syndrome, SMZJG and its main components along with their synonyms as keywords, we conducted a comprehensive search across major scientific databases including the Web of Science Core Collection, PubMed and China National Knowledge Infrastructure (CNKI) databases. A total of 5952 references and 99 patents were obtained. Among these, 5039 articles and reviews, as well as 54 patents were analyzed by Citespace and VOSviewer software. RESULTS: The available evidence indicates that the SMZJG's components likely exert their mechanisms in treating TS by regulating the dopaminergic pathway system, neurotransmitter imbalances, reducing neuroinflammation, promoting the repair of nerve damage and improving sleep disorders. CONCLUSION: This comprehensive analysis lays the foundation for an extensive exploration of the feasibility and clinical applications of SMZJG in TS treatment.


Asunto(s)
Medicamentos Herbarios Chinos , Síndrome de Tourette , Síndrome de Tourette/tratamiento farmacológico , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China/métodos , Animales
19.
Sci Total Environ ; 934: 172983, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744389

RESUMEN

Microbial communities assemble stochastically and deterministically, but how different assembly processes shape diatom community structure across riverine habitats is unclear, especially in sediment-laden environments. In this study, we deciphered the mechanisms of riverine diatom community assembly in the water column and riverbed substrate with varying sediment concentrations. Water and sediment samples were collected from 44 sampling sites along the Yellow River mainstream during two seasons. Diatom communities were characterized based on high-throughput sequencing of the 18S ribosomal RNA genes coupled with multivariate statistical analyses. A total of 198 diatom species were taxonomically assigned, including 182 free-living and particle-attached species and 184 surface-sediment species. Planktonic communities were structurally different from benthic communities, with Cyclotella being dominant mainly in the middle and lower reaches of the river with higher sediment concentrations. Both stochastic and deterministic processes affected diatom community assembly in different habitats. Species dispersal was more important in the water than in the substrate, and this process was strengthened by increased sediment concentration across habitats. Diatom communities exhibited lower network complexity and enhanced antagonistic or competitive interactions between species in response to higher sediment concentrations compared with lower sediment concentrations mainly in the source region of the river. Differences in the species composition and community diversity of planktonic diatoms were closely correlated with the proportion of bare land area, nitrogen nutrients, precipitation, and sediment concentration. In particular, particle-attached diatoms responded sensitively to environmental factors. These findings provide strong evidence for sediment-mediated assembly and interactions of riverine diatom communities.


Asunto(s)
Diatomeas , Ecosistema , Sedimentos Geológicos , Ríos , Ríos/microbiología , Monitoreo del Ambiente , China , Biodiversidad , ARN Ribosómico 18S/genética
20.
Phytomedicine ; 129: 155618, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38678949

RESUMEN

BACKGROUND: Vascular calcification refers to the abnormal accumulation of calcium in the walls of blood vessels and is a risk factor often overlooked in cardiovascular disease. However, there is currently no specific drug for treating vascular calcification. Compound Danshen Dripping Pill (CDDP) is widely used to treat cardiovascular diseases, but its effect on vascular calcification has not been reported. PURPOSE: We investigated the effects of CDDP on vascular calcification in ApoE-/- mice and in vitro and elucidated its mechanism of action. STUDY DESIGN: Firstly, we found that CDDP has the potential to improve calcification based on network pharmacology analysis. Then, we performed the following experiments: in vivo, ApoE-/- mice were fed a high-fat diet randomly supplemented with CDDP for 16 weeks. Atherosclerosis and vascular calcification were determined. In vitro, human aortic smooth muscle cells (HASMCs), human umbilical vein endothelial cells (HUVECs), and human aortic endothelial cells (HAECs) were used to determine the mechanisms for CDDP-inhibited vascular calcification. RESULTS: In this study, we observed that CDDP reduced intimal calcification in atherosclerotic lesions of ApoE-deficient mice fed a high-fat diet, as well as the calcification in cultured SMCs and ECs. Mechanistically, CDDP inhibited the Wnt/ß-catenin pathway by up-regulating the expression of DKK1 and LRP6, which are upstream inhibitors of Wnt, leading to a reduction in the expression of osteoblastic transition markers (ALP, OPN, BMP2, and RUNX2). Furthermore, CDDP enhanced the secretion of DKK1, which plays a role in mediating EC-SMC crosstalk in calcification. Additionally, VC contributes to vascular aging by inhibiting Sirt1 and increasing senescence parameters (SA-ß-gal, p21, and p16). However, CDDP reversed these changes by activating Sirt1. CDDP also reduced the levels of pro-inflammatory cytokines and the senescence-associated secretory phenotype in vivo and in vitro. CONCLUSIONS: Our study suggests that CDDP reduces vascular calcification by regulating the DKK1/LRP6/ß-catenin signaling pathway in ECs/SMCs and interactions with the crosstalk of ECs and SMCs. It also reduces the senescence of ECs/SMCs, contributing to the Sirt1 activation, indicating CDDP's novel role in ameliorating vascular calcification.


Asunto(s)
Aterosclerosis , Dieta Alta en Grasa , Medicamentos Herbarios Chinos , Células Endoteliales de la Vena Umbilical Humana , Salvia miltiorrhiza , Calcificación Vascular , Animales , Calcificación Vascular/tratamiento farmacológico , Humanos , Medicamentos Herbarios Chinos/farmacología , Salvia miltiorrhiza/química , Masculino , Dieta Alta en Grasa/efectos adversos , Aterosclerosis/tratamiento farmacológico , Ratones , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Sirtuina 1/metabolismo , Ratones Endogámicos C57BL , Miocitos del Músculo Liso/efectos de los fármacos , Apolipoproteínas E/genética , Farmacología en Red , Vía de Señalización Wnt/efectos de los fármacos , Aorta/efectos de los fármacos , Canfanos , Péptidos y Proteínas de Señalización Intercelular , Panax notoginseng
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