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Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.
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Calcium oxalate (CaOx) crystals are the main constituents of renal crystals in humans and induce tubular lumen damage in renal tubules, leading to renal calcium deposition and kidney stone formation. Oxidative stress and inflammation play important roles in regulating calcium oxalate-induced injury. Here, we evaluated the efficacy in inhibiting oxidation and inflammation of pectinolinarigenin, a biologically active natural metabolite, in CaOx nephrocalcinosis and further explored its targets of action. First, we developed cellular and mouse models of calcium oxalate renal nephrocalcinosis and identified the onset of oxidative stress and inflammation according to experimental data. We found that pectolinarigenin inhibited this onset while reducing renal crystal deposition. Network pharmacology was subsequently utilized to screen for hypoxia-inducible factor-1α (HIF-1α), a regulator involved in the body's release and over-oxidation of inflammatory factors. Finally, molecular docking, cellular thermal shift assay, and other experiments to detect HIF-1α expression showed that pectolinarigenin directly combined with HIF-1α and prevented downstream reactive oxygen species activation and release. Our results indicate that pectolinarigenin can target and inhibit HIF-1α-mediated inflammatory responses and oxidative stress damage and be a novel drug for CaOx nephrocalcinosis treatment.
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Aims: We sought to reveal the landscape of epithelial cell subpopulations in the human esophageal squamous cell carcinoma microenvironment and investigate their parts on esophageal squamous carcinoma (ESCC) development. Background: Epithelial cells play an important role in the occurrence and development of ESCC through multiple mechanisms. While the landscape of epithelial cell subpopulations in ESCC, remains unclear. Objective: Exploring the role of epithelial cell subpopulations in ESCC progression. Methods: Seurat R package was used for single-cell RNA sequencing (scRNA-seq) data filtering, dimensionality reduction, clustering and differentially expressed genes analysis. Cellmarker database was adopted for cell cluster annotation. Functional enrichment analysis was carried out by Gene Ontology (GO) analysis. InferCNV package was conducted for copy number variation (CNV) of epithelial cell subpopulations in all chromosomal regions. Pseudotime trajectory analysis was implemented for exploring differentiation trajectory of epithelial cells subgroups during the cancer progression. CellChat analysis was used for probing the interactions between epithelial cells and NK/T cells. cellular experiments were performed using Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR), Wound-Healing Assay and transwell. Results: 11 major cell subpopulations were identified in ESCC and adjunct tissues. Further reclassification of epithelial cells uncovered 4 subpopulations. Enrichment analysis revealed that highly expressed genes in 4 epithelial cell subpopulations were related to cell proliferation, immune response and angiogenesis. CNV analysis found that UBD + epithelial cells and GAS2L3+ epithelial cells had a higher proportion of CNV. Cell differentiation trajectories disclosed that KRT6C+ and GSTA1+ epithelial cells were in an intermediate state of differentiation, while UBD+ and GAS2L3+ epithelial cells are in an end state of differentiation during ESCC progression. Finally, we found that four epithelial cell subpopulations all inhibited NK/T cells through NECTIN2-TIGIT and CLEC2B-KLRB1. Low ATF3 and DDIT3 mRNA expression inhibited ESCC cell migration and invasion. Conclusion: Here, we obtained a through epithelial cell atlas of ESCC at single-cell resolution, explored the role of epithelial cell in ESCC progression, and unveiled immunosuppressive signals to NK/T cells in promoting ESCC. Our findings expand the comprehension of epithelial cells and offer a theoretical guidance for future anti-epithelial cell treatment of ESCC.
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OBJECTIVES: This study aimed to investigate the prevalence of diabetes using structural equation modelling (SEM) to examine the pathways and associations of socioeconomic and lifestyle factors on diabetes in rural southwest China. DESIGN: Data were collected from a cross-sectional health interview and examination survey among individuals aged ≥35 years in rural southwest China. Fasting blood glucose, blood pressure, height, weight and waist circumference (WC) were measured for each participant. SEM was employed to assess the relationships between demographic characteristics (sex, age and ethnicity), socioeconomic position (SEP; annual household income, education level and access to medical services), lifestyle factors (obesity status (body mass index and WC) and physical inactivity), hypertension, hyperlipidaemia and family history of diabetes. SETTING: This study was conducted in rural Yunnan Province of China. PARTICIPANTS: 7536 individuals aged ≥35 years consented to participate in the study. RESULTS: The overall prevalence of diabetes in the present study was 8.3%. Prevalence did not differ by gender (prevalence for both men and women was 8.3% (p>0.05)). The results of SEM indicated that SEP, age, ethnicity, obesity status and physical inactivity had both significant direct and indirect effects on diabetes, with total effect size of 0.091, 0.149, -0.094, 0.212 and 0.089, respectively (p<0.01). Family history of diabetes (0.128, p<0.01), hypertension (0.135, p<0.01) and hyperlipidaemia (0.137, p<0.01) were directly associated with diabetes. CONCLUSIONS: Socioeconomic and lifestyle factors have both direct and indirect effects on prevalence of diabetes in rural southwest China. Future efforts to implement comprehensive interventions to promote the prevention and control of diabetes should in particular focus on obese individuals.
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Diabetes Mellitus , Estilo de Vida , População Rural , Fatores Socioeconômicos , Humanos , Masculino , China/epidemiologia , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Prevalência , População Rural/estatística & dados numéricos , Diabetes Mellitus/epidemiologia , Adulto , Idoso , Obesidade/epidemiologia , Fatores de Risco , Hipertensão/epidemiologia , Análise de Classes Latentes , Índice de Massa CorporalRESUMO
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical images shown in Fig. 2B and C on p. 896 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published before this paper was received at International Journal of Molecular Medicine (several of which have been retracted). Moreover, the flow-cytometric data shown in Fig. 2A appeared to be potentially anomalous. In view of the fact that the abovementioned data had already apparently been published prior to the submission of this paper to International Journal of Molecular Medicine, the Editor has decided that the article should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 890-900, 2019; DOI: 10.3892/ijmm.2018.4006].
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INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.
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Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole-brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD-FOG) and 8 without FOG (PD-nFOG), and 10 healthy controls were enrolled. High-resolution 3D T1-weighted and resting-state functional MRI (rs-fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs-fMRI FC using seed-based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs-fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = -0.82, P < .001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD-nFOG group. PD-FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD-nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD-FOG and distinguishing between PD subtypes.
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MOTIVATION: Target discovery is a crucial step in drug development, as it directly affects the success rate of clinical trials. Knowledge graphs (KGs) offer unique advantages in processing complex biological data and inferring new relationships. Existing biomedical KGs primarily focus on tasks such as drug repositioning and drug-target interactions, leaving a gap in the construction of KGs tailored for target discovery. RESULTS: We established a comprehensive biomedical KG focusing on target discovery, termed TarKG, by integrating seven existing biomedical KGs, nine public databases, and traditional Chinese medicine knowledge databases. TarKG consists of 1,143,313 entities and 32,806,467 relations across 15 entity categories and 171 relation types, all centered around three core entity types: Disease, Gene, Compound. TarKG provides specialized knowledges for the core entities including chemical structures, protein sequences or text descriptions. By using different KG embedding algorithms, we assessed the knowledge completion capabilities of TarKG, particularly for disease-target link prediction. In case studies, we further examined TarKG's ability to predict potential protein targets for Alzheimer's disease (AD) and to identify diseases potentially associated with the metallo-deubiquitinase CSN5, using literature analysis for validation. Furthermore, we provided a user-friendly web server (https://tarkg.ddtmlab.org) that enables users to perform knowledge retrieval and relation inference using TarKG. AVAILABILITY: TarKG is accessible at https://tarkg.ddtmlab.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Hydrophobic antifouling polymers capable of self-healing performance are highly desirable for industrial applications. However, the construction of self-healing, hydrophobic antifouling polymers is challenging considering their complex fouling environments, which are humid in aqueous environment. In this work, a self-healing hydrophobic polymer containing Fe3+-catechol coordination applicable to antifouling is synthesized. The hydrophobic fluoroalkyl segments in the polymers formed unique domains dispersed in a polydimethylsiloxane matrix. The as-synthesized polymers can completely restore their tensile strength, and their self-healing efficiency is above 90% in both artificial seawater and pure water because of the dynamic Fe3+-catechol coordination interactions. The as-synthesized polymer exhibited self-healing and antifouling properties against common marine bacteria. The colony adhesion and self-healing processes of the damaged coating in artificial seawater containing marine bacteria are characterized by laser confocal microscopy. This strategy may be useful for the development of future polymeric antifouling materials.
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Gesture sensors are essential to collect human movements for human-computer interfaces, but their application is normally hampered by the difficulties in achieving high sensitivity and an ultrawide response range simultaneously. In this article, inspired by the spider silk structure in nature, a novel gesture sensor with a core-shell structure is proposed. The sensor offers a high gauge factor of up to 340 and a wide response range of 60%. Moreover, the sensor combining with a deep learning technique creates a system for precise gesture recognition. The system demonstrated an impressive 99% accuracy in single gesture recognition tests. Meanwhile, by using the sliding window technology and large language model, a high performance of 97% accuracy is achieved in continuous sentence recognition. In summary, the proposed high-performance sensor significantly improves the sensitivity and response range of the gesture recognition sensor. Meanwhile, the neural network technology is combined to further improve the way of daily communication by sign language users.
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Gestos , Grafite , Aprendizado de Máquina , Nanotubos de Carbono , Língua de Sinais , Grafite/química , Humanos , Nanotubos de Carbono/química , Redes Neurais de Computação , Aprendizado ProfundoRESUMO
The description and analysis of chemical bonds have been difficult following the popularization of electronic structure calculations. Although many attempts have been made from the perspective of electronic structure, the sheer volume of information in the electronic structure has left contemporary chemical bond analysis methods grappling with an inescapable "Trilemma" where the model briefness, generality, and descriptiveness (descriptive power) cannot be obtained simultaneously. To push the generality and descriptiveness to their extremes, herein a general machine learning-based framework is introduced to compact chemical bonds into a detailed residue-by-residue "genome" with matched encoding/decoding tools. The framework fuses the quantum mechanical aspects, auto feature extraction, nanostructures and/or simulations, and generative models. The encoded genomes are information-dense and decodable, where 100% generality is guaranteed. The descriptiveness of genomes appears to be broader than most known models. As a proof of concept, the realization presented in this work compacts the complete information regarding two critical chemical bonds in thiolate-protected gold nanoclusters, the S-Au and Au-Au bonds, from a Bosonic-Fermionic character perspective into 8-valued genomes. The machine learning component is trained based on 26,528 density functional theory simulated electron localization function images. With an exploration of the space span for the genome, bond polarization, hybridization, intrusion of other atoms, alignments, crystal orientation, atomic motions, and more details are observed. Furthermore, it has emerged from extensive generation tests that molecules and solids can be integrated in such a concise manner than is typically achieved with purely geometric representations. To showcase the intraclass complexity of S-Au and Au-Au bonds visually, a roadmap is plotted by summarizing and correlating the similarities of 8-value-genomes. Furthermore, genomes can be associated with realistic indices easily with a simple multilayer perception architecture as a simple calculating tool. Besides, there are 3 sets of applications, including a set of chemisorption, a set of molecular dynamical analysis, and a set of ultrafast processes, showcasing the interpretability potentials of interatomic genomes in the geometric structures, kinetic properties, and vibration characteristics of molecular systems. As the framework rose to the challenge of nanoclusters from a complicated mesoscopic family of material, the displayed generality and comprehensiveness indicate that the model may "understand" chemical bonds in a machine's way.
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Midline lumbar interbody fusion (MIDLIF) and minimally invasive transforaminal interbody fusion (MIS-TLIF) are two minimally invasive lumbar fusion methods that have gained popularity in the past two decades. MIDLIF involves the use of cortical bone trajectory screws, whereas MIS-TLIF uses traditional pedicle screws. However, there is a significant lack of research directly examining the clinical efficacy of these two methods in treating single-segment lumbar degenerative diseases. Hence, the objective of our retrospective study is to assess and contrast the surgical and clinical results of MIDLIF and MIS-TLIF. The study population comprised 133 patients diagnosed with single-segment lumbar degenerative disease that received treatment using either MIDLIF (n = 65) or MIS-TLIF (n = 68) in our department from January 2017 to January 2019. The fusion rates for MIDLIF were consistently lower than MID-TLIF at all post-operative time periods of follow-up, however, the differences between the two groups were not statistically significant. The 1-year fusion rates were 81.5% (MIDLIF) and 83.8% (MIS-TLIF) (P = 0.728), and the 2-year fusion rates were 87.7% (MIDLIF) and 91.2% (MIS-TLIF) (P = 0.513). The final follow-up fusion rates were 93.8% (MIDLIF) and 95.6% (MIS-TLIF) (P = 0.653). MIDLIF had several advantages over MIS-TLIF, including a shorter operative time (135.2 ± 15.70 vs. 160.1 ± 17.2 min, P < 0.001), decreased intraoperative blood loss (147.9 ± 36.4 vs. 169.5 ± 24.7 mL, P < 0.001), and a shorter length of hospital stay (10.8 ± 3.1 vs. 12.4 ± 4.1d; P = 0.014). No significant differences were seen between the groups in terms of the postoperative day of ambulation, Oswestry dysfunction index (ODI) scores, and visual analog scale (VAS) scores for leg and lower back pain (P > 0.05). Although not significant (P = 0.707), MIDLIF (13.8%) had fewer overall complications than MIS-TLIF (16.2%). Therefore, compared to MIS-TLIF, MIDLIF provides perioperative benefits while achieving the same outcomes as MIS-TLIF in terms of fusion rate, pain relief, functional improvement, and complication rate.
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Degeneração do Disco Intervertebral , Vértebras Lombares , Procedimentos Cirúrgicos Minimamente Invasivos , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Masculino , Feminino , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Degeneração do Disco Intervertebral/cirurgia , Idoso , Resultado do Tratamento , Parafusos PedicularesRESUMO
(1) Background: With the increasing aesthetic pursuit of facial features, the clinical use of Botulinum Toxin Type A (BoNT-A) injections for masseter hypertrophy has been on the rise. However, due to variations in masseter muscle structure and differences in clinicians' injection techniques, blind injections may lack precision, potentially compromising treatment accuracy and increasing the risk of complications. (2) Objectives: The study aims to use ultrasonography to detail the deep inferior tendon (DIT) within the masseter muscle in a young Chinese cohort, refine its classification, analyze muscle belly thickness and variations across groups, and propose a customized ultrasound-guided BoNT-A injection protocol. (3) Methods: Ultrasound imaging was used to observe the bilateral masseter muscles at rest and during clenching. The features of the DIT were classified from these images, and the thickness of the masseter's distinct bellies associated with the DIT types was measured in both states. (4) Results: The study cohort included 103 participants (27 male, 76 female), with 30 muscles in the normal masseter group and 176 muscles in the hypertrophy group. The DIT was categorized as Type A, B (subtypes B1, B2), and C. The distribution of these types was consistent across normal, hypertrophic, and gender groups, all following the same trend (B > A > C). In hypertrophy, Type B1 showed uniform thickness across masseter bellies, B2 presented with a thinner intermediate belly, and Type C had mainly superficial muscle enlargement. Changes in muscle thickness during clenching were noted but not statistically significant among different bellies. (5) Conclusions: The study evidences individual variation in the DIT, highlighting the importance of precise DIT classification for effective BoNT-A injections. A tailored ultrasound-guided BoNT-A injection strategy based on this classification may enhance safety and efficacy of the therapy.
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Toxinas Botulínicas Tipo A , Hipertrofia , Músculo Masseter , Tendões , Ultrassonografia , Músculo Masseter/diagnóstico por imagem , Músculo Masseter/efeitos dos fármacos , Músculo Masseter/anormalidades , Humanos , Masculino , Feminino , Toxinas Botulínicas Tipo A/administração & dosagem , Hipertrofia/diagnóstico por imagem , Adulto Jovem , Tendões/diagnóstico por imagem , Tendões/efeitos dos fármacos , Injeções Intramusculares , Fármacos Neuromusculares/administração & dosagem , Adulto , AdolescenteRESUMO
OBJECTIVE: Post-stroke depression (PSD) is one of the most common and severe neuropsychological sequelae after stroke. Using a prediction model composed of multiple predictors may be more beneficial than verifying the predictive performance of any single predictor. The primary objective of this study was to construct practical prediction tools for PSD at discharge utilizing a decision tree (DT) algorithm. METHODS: A multi-center prospective cohort study was conducted from May 2018 to October 2019 and stroke patients within seven days of onset were consecutively recruited. The independent predictors of PSD at discharge were identified through multivariate logistic regression with backward elimination. Classification and regression tree (CART) algorithm was employed as the DT model's splitting method. RESULTS: A total of 876 stroke patients who were discharged from the neurology departments of three large general Class A tertiary hospitals in Wuhan were eligible for analysis. Firstly, we divided these 876 patients into PSD and non-PSD groups, history of coronary heart disease (OR = 1.835; 95 % CI, 1.106-3.046; P = 0.019), length of hospital stay (OR = 1.040; 95 % CI, 1.013-1.069; P = 0.001), NIHSS score (OR = 1.124; 95 % CI, 1.052-1.201; P = 0.001), and Mini mental state examination (MMSE) score (OR = 0.935; 95 % CI, 0.893-0.978; P = 0.004) were significant predictors. The subgroup analysis results have shown that hemorrhagic stroke, history of hypertension and higher modified Rankin Scale score (mRS) score were associated with PSD at discharge in the young adult stroke patients. CONCLUSIONS: Several predictors of PSD at discharge were identified and convenient DT models were constructed to facilitate clinical decision-making.
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Cardiomyocyte loss and myocardial fibrosis are major determinants of myocardial infarction (MI) pathological changes. Mesenchymal stem cell (MSC)-derived exosomes (exos) and Danshen decoction (DSY) have been demonstrated to mediate cardiac repair following MI. BM-MSCs exos or BM-MSCsDSY exos were intramuscularly injected into post-MI rats. On the 7th, 14th and 28th days, serum CK, LDH, α-HBDH, ALT, and AST were measured and electrocardiogram changes were monitored to identify cardiac function; Triphenyltetrazolium chloride staining, Hematein&Eosin staining, Masson trichrome staining and Transmission Electron Microscope were adopted to analyze infarct area, cardiac morphology, histopathology, and fibrosis and cardiomyocyte ultrastructure; TUNEL assay, real-time PCR and western blot were performed to detect cardiomyocyte apoptosis and autophagy. As a result, BMMSCsDSY exos are superior to BM-MSCs-exos in improvement of cardiac function, morphology, histopathology and cardiomyocyte ultrastructure, as well as in reduction of infarction area and cardiac fibrosis by inhibiting apoptosis and promoting autophagy of cardiomyocytes.
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Strain engineering plays an important role in tuning electronic structure and improving catalytic capability of biocatalyst, but it is still challenging to modify the atomic-scale strain for specific enzyme-like reactions. Here, we systematically design Pt single atom (Pt1), several Pt atoms (Ptn) and atomically-resolved Pt clusters (Ptc) on PdAu biocatalysts to investigate the correlation between atomic strain and enzyme-like catalytic activity by experimental technology and in-depth Density Functional Theory calculations. It is found that Ptc on PdAu (Ptc-PA) with reasonable atomic strain upshifts the d-band center and exposes high potential surface, indicating the sufficient active sites to achieve superior biocatalytic performances. Besides, the Pd shell and Au core serve as storage layers providing abundant energetic charge carriers. The Ptc-PA exhibits a prominent peroxidase (POD)-like activity with the catalytic efficiency (Kcat/Km) of 1.50 × 109 mM-1 min-1, about four orders of magnitude higher than natural horseradish peroxidase (HRP), while catalase (CAT)-like and superoxide dismutase (SOD)-like activities of Ptc-PA are also comparable to those of natural enzymes. Biological experiments demonstrate that the detection limit of the Ptc-PA-based catalytic detection system exceeds that of visual inspection by 132-fold in clinical cancer diagnosis. Besides, Ptc-PA can reduce multi-organ acute inflammatory damage and mitigate oxidative stress disorder.
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Biocatálise , Catalase , Ouro , Platina , Platina/química , Ouro/química , Humanos , Catalase/química , Catalase/metabolismo , Paládio/química , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo , Catálise , Teoria da Densidade Funcional , Nanopartículas Metálicas/químicaRESUMO
Nematode-trapping (NT) fungi are a major resource for controlling parasitic nematodes. Arthrobotrys flagrans, as a typical NT fungus, can capture nematodes by producing three-dimensional nets. The APSES transcription factor Swi6 plays a vital role in fungal growth and the pathogenicity of pathogens. In this study, we characterized AfSwi6 via gene disruption using the homologous recombinant method and transcriptome sequencing. Knockout of the AfSwi6 gene caused defects in mycelial growth, trap formation and pathogenicity, chlamydospore production, and stress response. Moreover, the transcriptome data indicated that AfSwi6 was related to DNA repair, stress response, and plasma membrane fusion. The result showed that AfSwi6 has a significant effect on trap development and chlamydospore production in A. flagrans.
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The study aims to evaluate the effect of Kaixin Powder(KXP) on the behavior and brain tissue of chemotherapy-treated mice to explore its mechanism in alleviating chemotherapy-induced cognitive impairment in tumor-bearing mice. Thirty female BALB/c mice were inoculated with 4T1 breast cancer cells to establish a tumor-bearing mouse model and randomly divided into the tumor group, a doxorubicin group, and a KXP group. Behavioral tests, including open field test, elevated plus maze test, forced swimming test, tail suspension test, Morris water maze test, and novel object recognition test, were conducted. Pathological examinations, including hematoxylin-eosin staining, Nissl staining, toluidine blue staining, Fluoro-Jade B staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay, immunofluorescence staining, and transmission electron microscopy, were performed. Network pharmacology and whole transcriptome sequencing methods were used to analyze the mechanism of chemotherapy-induced cognitive impairment and the targets of KXP. The results showed that KXP prevented chemotherapy-induced behavioral changes(P<0.001), increased the total movement distance and central zone residence time in the open field test, increased exploration time in the open arm area in the elevated plus maze test, reduced immobility time in the forced swimming test and tail suspension test, reduced escape latency in the Morris water maze test and increased platform crossings, and improved cognitive index in the novel object recognition test. KXP also inhibited chemotherapy-induced neuroinflammation, apoptosis, and autophagy in the prefrontal cortex, and reshaped the RNA expression profile of the prefrontal cortex tissue during chemotherapy(P<0.05). In conclusion, KXP may alleviate chemotherapy-induced cognitive impairment in tumor-bearing mice by reshaping the RNA expression profile of prefrontal cortex tissue, thereby reducing neuronal tissue damage.