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The high incidence, low healing rate and huge economic burden of wounds (especially chronic wounds) worldwide remain a great challenge for clinical staff and patients. The various stages of wound healing are regulated by paracrine or autocrine cytokines and growth factors, and the study of their intrinsic mechanisms is a prerequisite for better wound treatment. Lactate, the end product of glycolysis, plays a role in all stages of wound healing, and recent studies have identified lactate as an epigenetic regulator that regulates gene expression through histone lysine lactylation and stimulates posttranslational modifications to regulate related gene expression, thereby causing a series of biological functional changes. This article reviews the progress of research on lactate and lactylation during wound healing or in related diseases, including its involvement in immune regulation, inflammation control, and proliferative remodeling, and finally describes the prospects for lactate therapy regarding wound healing.
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BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent autoimmune encephalitis and is closely related to catatonia. This study aimed to investigate the clinical features and disease outcomes of adult catatonic anti-NMDAR encephalitis patients. METHODS: Adult patients diagnosed with anti-NMDAR encephalitis between January 2013 and October 2021 were retrospectively enrolled in this study. According to the Bush Francis Catatonia screening instrument (BFCSI), patients were divided into two groups: those with catatonia and those without catatonia. The modified Rankin scale (mRS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), Neuropsychiatric Inventory (NPI), Patient Health Questionnaire-9 (PHQ-9) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7) scores were assessed at follow-up. The Mann-Whitney U test (nonparametric), Student's t test (parametric), and chi-squared test were used to analyse the differences between the two groups. RESULTS: Eighty-four patients were recruited, including twenty-five catatonic patients and fifty-nine noncatatonic patients. Among them, 28 had positive antibody only in cerebrospinal fluid (CSF), 4 had positive antibody only in serum and 52 had positive antibody both in CSF and serum. Catatonic patients experienced more disturbance of consciousness (p = 0.01), aggression (p = 0.046) and affective disorders (p = 0.043) than noncatatonic patients. The mRS scores of the catatonia group assessed at admission (p = 0.045) were worse than those of the non-catatonia group. Catatonic patients were more inclined to develop deep vein thrombosis (p = 0.003), decubitus (p = 0.046), pneumonia (p = 0.025), and to be admitted to the intensive care unit (ICU) (p = 0.011) than noncatatonic patients. All patients in the catatonia group received first-line immunotherapy. At the 24-month follow-up, 2 patients in the catatonia group did not achieve good outcomes. At the last follow-up, the catatonia group had more relapses (p = 0.014) and more neuropsychiatric problems (p = 0.035). CONCLUSIONS: Adult anti-NMDAR encephalitis patients with catatonia present distinct clinical features in disease course and are prone to experience more relapses and long-term neuropsychiatric problems than those without catatonia.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Catatonia , Humanos , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Catatonia/tratamiento farmacológico , Estudios de CohortesRESUMEN
Organoids are 3D structures generated from stem cells. Their functions and physiological characteristics are similar to those of normal organs. They are used in disease mechanism research, new drug development, organ transplantation and other fields. In recent years, the application of 3D materials in plastic surgery for repairing injuries, filling, tissue reconstruction and regeneration has also been investigated. The PubMed/MEDLINE database was queried to search for animal and human studies published through July of 2022 with search terms related to Organoids, Plastic Surgery, Pluripotent Stem Cells, Bioscaffold, Skin Reconstruction, Bone and Cartilage Regeneration. This review presents stem cells, scaffold materials and methods for the construction of organoids for plastic surgery, and it summarizes their research progress in plastic surgery in recent years.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Procedimientos de Cirugía Plástica , Cirugía Plástica , Animales , Humanos , Cirugía Plástica/métodos , OrganoidesRESUMEN
BACKGROUND: Intelligent monitoring of fixation quality is a prerequisite for automated green tea processing. To meet the requirements of intelligent monitoring of fixation quality in large-scale production, fast and non-destructive detection means are urgently needed. Here, smartphone-coupled micro near-infrared spectroscopy and a self-built computer vision system were used to perform rapid detection of the fixation quality in green tea processing lines. RESULTS: Spectral and image information from green tea samples with different fixation degrees were collected at-line by two intelligent monitoring sensors. Competitive adaptive reweighted sampling and correlation analysis were employed to select feature variables from spectral and color information as the target data for modeling, respectively. The developed least squares support vector machine (LS-SVM) model by spectral information and the LS-SVM model by image information achieved the best discriminations of sample fixation degree, with both prediction set accuracies of 100%. Compared to the spectral information, the image information-based support vector regression model performed better in moisture prediction, with a correlation coefficient of prediction of 0.9884 and residual predictive deviation of 6.46. CONCLUSION: The present study provided a rapid and low-cost means of monitoring fixation quality, and also provided theoretical support and technical guidance for the automation of the green tea fixation process. © 2022 Society of Chemical Industry.
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Espectroscopía Infrarroja Corta , Té , Té/química , Espectroscopía Infrarroja Corta/métodos , Análisis de los Mínimos Cuadrados , Máquina de Vectores de SoporteRESUMEN
Trace water in organic solvents can play a crucial role in the construction of supramolecular assemblies, which has not gained enough attention until very recent years. Herein, we demonstrate that residual water in organic solvents plays a decisive role in the regulation of the evolution of assembled structures and their functionality. By adding Mg(ClO4)2 into a multi-component organic solution containing terpyridine-based ligand 3Tpy and monodentate imidazole-based ligand M2, the system underwent an unexpected kinetic evolution. Metallo-supramolecular polymers (MSP) formed first by the coordination of 3Tpy and Mg2+, but they subsequently decomposed due to the interference of M2, resulting in a transient MSP system. Further investigation revealed that this occurred because residual water in the solvent and M2 cooperatively coordinated with Mg2+. This allowed M2 to capture Mg2+ from MSP, which led to depolymerization. However, owing to the slow reaction between trace water/M2/Mg2+, the formation of MSP still occurred first. Therefore, water regulated both the thermodynamics and kinetics of the system and was the key factor for constructing the transient MSP. Fine-tuning the water content and other assembly motifs regulated the assembly evolution pathway, tuned the MSP lifetime, and made the luminescent color of the system undergo intriguing transition processes over time.
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Imidazoles , Agua , Agua/química , Ligandos , Solventes/química , Polímeros/químicaRESUMEN
Biofilm formation in drinking water distribution systems (DWDS) has many adverse consequences. Knowledge of microbial community structure of DWDS biofilm can aid in the design of an effective control strategy. However, biofilm bacterial community in real DWDS and the impact of drinking water purification strategy remain unclear. The present study investigated the composition and diversity of biofilm bacterial community in real DWDSs transporting waters with different purification strategies (conventional treatment and integrated treatment). High-throughput Illumina MiSeq sequencing analysis illustrated a large shift in the diversity and structure of biofilm bacterial community in real DWDS. Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Nitrospirae, and Cyanobacteria were the major components of biofilm bacterial community. Proteobacteria (mainly Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria) predominated in each DWDS biofilm, but the compositions of the dominant proteobacterial classes and genera and their proportions varied among biofilm samples. Drinking water purification strategy could shape DWDS biofilm bacterial community. Moreover, Pearson's correlation analysis indicated that Actinobacteria was positively correlated with the levels of total alkalinity and dissolved organic carbon in tap water, while Firmicutes had a significant positive correlation with nitrite nitrogen.
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Bacterias/clasificación , Bacterias/aislamiento & purificación , Biopelículas/crecimiento & desarrollo , Biota , Agua Potable/química , Microbiología Ambiental , Purificación del Agua/métodos , Carbono/análisis , Concentración de Iones de Hidrógeno , Nitritos/análisis , Compuestos Orgánicos/análisisRESUMEN
Lenticulostriate arteries (LSA) are potentially valuable for studying vascular cognitive impairment. This study aims to investigate correlations between cognitive impairment and LSA through clinical and radiomics features analysis. We retrospectively included 102 patients (mean age 62.5±10.3 years, 60 males), including 58 with mild cognitive impairment (MCI) and 44 with moderate or severe cognitive impairment (MSCI). The MRI images of these patients were subjected to z-score preprocessing, manual regions of interest (ROI) outlining, feature extraction (pyradiomics), feature selection [max-relevance and min-redundancy (mRMR), least absolute shrinkage and selection operator (LASSO), and univariate analysis], model construction (multivariate logistic regression), and evaluation [receiver operating characteristic curve (ROC), decision curve analysis (DCA), and calibration curves (CC)]. In the training dataset (71 patients, 44 MCI) and the test dataset (31 patients, 17 MCI), the area under curve (AUC) of the combined model (training 0.88 [95% CI 0.78, 0.97], test 0.76 [95% CI 0.6, 0.93]) was better than that of the clinical model and the radiomics model. The DCA results demonstrated the highest net yield of the combined model relative to the clinical and radiomics models. In addition, we found that LSA total vessel count (0.79 [95% CI 0.08, 1.59], P = 0.038) and wavelet.HLH_glcm_MCC (-1.2 [95% CI -2.2, -0.4], P = 0.008) were independent predictors of MCI. The model that combines clinical and radiomics features of LSA can predict MCI. Besides, LSA vascular parameters may serve as imaging biomarkers of cognitive impairment.
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Disfunción Cognitiva , Imagen por Resonancia Magnética , Humanos , Masculino , Disfunción Cognitiva/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Curva ROC , RadiómicaRESUMEN
BACKGROUND: Cerebrovascular diseases have emerged as significant threats to human life and health. Effectively segmenting brain blood vessels has become a crucial scientific challenge. We aimed to develop a fully automated deep learning workflow that achieves accurate 3D segmentation of cerebral blood vessels by incorporating classic convolutional neural networks (CNNs) and transformer models. METHODS: We used a public cerebrovascular segmentation dataset (CSD) containing 45 volumes of 1.5 T time-of-flight magnetic resonance angiography images. We collected data from another private middle cerebral artery (MCA) with lenticulostriate artery (LSA) segmentation dataset (MLD), which encompassed 3.0 T three-dimensional T1-weighted sequences of volumetric isotropic turbo spin echo acquisition MRI images of 107 patients aged 62 ± 11 years (42 females). The workflow includes data analysis, preprocessing, augmentation, model training with validation, and postprocessing techniques. Brain vessels were segmented using the U-Net, V-Net, UNETR, and SwinUNETR models. The model performances were evaluated using the dice similarity coefficient (DSC), average surface distance (ASD), precision (PRE), sensitivity (SEN), and specificity (SPE). RESULTS: During 4-fold cross-validation, SwinUNETR obtained the highest DSC in each fold. On the CSD test set, SwinUNETR achieved the best DSC (0.853), PRE (0.848), SEN (0.860), and SPE (0.9996), while V-Net achieved the best ASD (0.99). On the MLD test set, SwinUNETR demonstrated good MCA segmentation performance and had the best DSC, ASD, PRE, and SPE for segmenting the LSA. CONCLUSIONS: The workflow demonstrated excellent performance on different sequences of MRI images for vessels of varying sizes. This method allows doctors to visualize cerebrovascular structures. CRITICAL RELEVANCE STATEMENT: A deep learning-based 3D cerebrovascular segmentation workflow is feasible and promising for visualizing cerebrovascular structures and monitoring cerebral small vessels, such as lenticulostriate arteries. KEY POINTS: ⢠The proposed deep learning-based workflow performs well in cerebrovascular segmentation tasks. ⢠Among comparison models, SwinUNETR achieved the best DSC, ASD, PRE, and SPE values in lenticulostriate artery segmentation. ⢠The proposed workflow can be used for different MR sequences, such as bright and black blood imaging.
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Selecting appropriate antiseizure medications (ASMs) for combination therapy in patients with drug-resistant epilepsy (DRE) is a complex task that requires an empirical approach, especially in patients receiving polytherapy. We aimed to analyze the effectiveness of various three-drug combinations in a group of patients with DRE under real-world conditions. This single-center, longitudinal observational study investigated patients with drug-resistant focal epilepsy who received three-drug regimens in the outpatient clinic of Tongji Hospital from September 2019 to December 2022. The effectiveness of each triple regimen was evaluated by the seizure-free rate and within-patient ratio of the seizure frequency (a seizure frequency ratio [SFR]<1 indicated superior efficacy). The independent t-test or Mann-Whitney U test was used for effectiveness analysis, and P values were adjusted by the Benjamini-Hochberg method for multiple comparisons. A total of 511 triple trials comprising 76 different regimens were conducted among 323 enrolled patients. Among these triple regimens, lamotrigine (LTG)/valproic acid (VPA)/topiramate (TPM) was the most frequently prescribed (29.4%, n â= â95). At the last clinical visit, 14.9% (n â= â48) of patients achieved seizure freedom after receiving triple therapy. LTG/VPA/TPM and LTG/VPA/levetiracetam (LEV) exhibited the highest seizure-free rates at 17.9% and 12.8%, respectively. These two regimens also had significantly lower median SFRs of 0.48 (interquartile range [IQR], 0.17-0.85; adjusted P â< â0.001) and 0.63 (IQR, 0.21-1.04; adjusted P â< â0.01), respectively. LTG/VPA/perampanel (PER) was another promising regimen that showed marginal effectiveness (median SFR â= â0.67; adjusted P â= â0.053). LTG/VPA/phenobarbital had the highest incidence of regimen-specific side effects (40.0%, 4/10), while the incidence of side effects from LTG/VPA/LEV was minimal (5.1%, 2/39). In conclusion, LTG/VPA/TPM and LTG/VPA/LEV exhibited superior efficacy and good tolerability in treating patients with DRE. Our results provide preliminary insights into the selection of ASMs for three-drug combination therapies in this clinically challenging population.
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Anticonvulsivantes , Epilepsia Refractaria , Quimioterapia Combinada , Epilepsias Parciales , Lamotrigina , Humanos , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Masculino , Femenino , Quimioterapia Combinada/métodos , Adulto , Epilepsias Parciales/tratamiento farmacológico , Lamotrigina/administración & dosificación , Lamotrigina/uso terapéutico , Persona de Mediana Edad , Epilepsia Refractaria/tratamiento farmacológico , Estudios Longitudinales , Resultado del Tratamiento , Topiramato/administración & dosificación , Topiramato/uso terapéutico , Ácido Valproico/administración & dosificación , Ácido Valproico/uso terapéutico , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Autologous fat transplantation is limited by the uncertainty of graft retention, impeding its application. Among the current strategies for processing lipoaspirates, high-density fat (HDF) is recommended owing to the enrichment of stem cells and washing before cotton concentration for simplicity of operation. Poloxamer 188 (P188) washing has been shown to repair the membranes of damaged cells. This study aimed to investigate the effect of P188-washing on fat graft survival and identify the best technique for processing lipoaspirates. METHODS: Lipoaspirates were prepared using centrifugation to obtain HDF, which was then washed with saline or P188 followed by cotton concentration. Tissue integrity, adipocytic activity, and viability of stromal vascular fraction (SVF) in the samples from the 3 groups were assessed. Samples were sequenced in vitro using high-throughput RNA-seq, and differentially expressed genes were validated using qPCR and western blotting (WB). After transplantation under the dorsum of nude mice for 8 weeks, the grafts were extracted and examined for residual volume, histologic characteristics, and vascularization. RESULTS: The HDF and P188 groups showed a higher survival rate of SVF, more Ki67-positive cells, intact tissue structure, and lesser fibrosis than the saline group. There were no significant differences in the density of SVF and residual volume of grafts. HDF showed significantly improved vascularization during 8 weeks. Through RNA-seq and bioinformatic analysis, notable changes in several related genes after transplantation were observed. CONCLUSIONS: P188 treatment can prevent cells from apoptosis and preserve tissue viability, thereby improving graft quality. HDF contains large amounts of SVF and can be regarded as an excellent grafting material.
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Tejido Adiposo , Supervivencia de Injerto , Lipectomía , Ratones Desnudos , Poloxámero , Animales , Poloxámero/farmacología , Ratones , Tejido Adiposo/trasplante , Lipectomía/métodos , Humanos , Femenino , Recolección de Tejidos y Órganos/métodos , Trasplante AutólogoRESUMEN
Decellularized adipose tissue (DAT) has great clinical applicability, owing to its abundant source material, natural extracellular matrix microenvironment, and nonimmunogenic attributes, rendering it a versatile resource in the realm of tissue engineering. However, practical implementations are confronted with multifarious limitations. Among these, the selection of an appropriate gelation strategy serves as the foundation for adapting to diverse clinical contexts. The cross-linking strategies under varying physical or chemical conditions exert profound influences on the ultimate morphology and therapeutic efficacy of DAT. This review sums up the processes of DAT decellularization and subsequent gelation, with a specific emphasis on the diverse gelation strategies employed in recent experimental applications of DAT. The review expounds upon methodologies, underlying principles, and clinical implications of different gelation strategies, aiming to offer insights and inspiration for the application of DAT in tissue engineering and advance research for tissue engineering scaffold development.
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With the increasing prevalence of bone tissue diseases, three-dimensional (3D) bioprinting applied to bone tissue engineering for treatment has received a lot of interests in recent years. The research and popularization of 3D bioprinting in bone tissue engineering require bioinks with good performance, which is closely related to ideal material and appropriate construction form. Hydroxyapatite (HAp) is the inorganic component of natural bone and has been widely used in bone tissue engineering and other fields due to its good biological and physicochemical properties. Previous studies have prepared different bioinks containing HAp and evaluated their properties in various aspects. Most bioinks showed significant improvement in terms of rheology and biocompatibility; however, not all of them had sufficiently favorable mechanical properties and antimicrobial activity. The deficiencies in properties of bioink and 3D bioprinting technology limited the applications of bioinks containing HAp in clinical trials. This review article summarizes the construction forms of bioinks containing HAp and its modifications in previous studies, as well as the 3D bioprinting techniques adopted to print bioink containing HAp. In addition, this article summarizes the advantages and underlying mechanisms of bioink containing HAp, as well as its limitations, and suggests possible improvement to facilitate the development of bone tissue engineering bioinks containing HAp in the future.
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Muscle tissue engineering is a promising therapeutic strategy for volumetric muscle loss (VML). Among them, decellularized extracellular matrix (dECM) biological scaffolds have shown certain effects in restoring muscle function. However, researchers have inconsistent or even contradictory results on whether dECM biological scaffolds can efficiently regenerate muscle fibers and restore muscle function. This suggests that therapeutic strategies based on dECM biological scaffolds need to be further optimized and developed. In this study, we used a recellularization method of perfusing adipose-derived stem cells (ASCs) and L6 into adipose dECM (adECM) through vascular pedicles. On one hand, this strategy ensures sufficient quantity and uniform distribution of seeded cells inside scaffold. On the other hand, auxiliary L6 cells addresses the issue of low myogenic differentiation efficiency of ASCs. Subsequently, the treatment of VML animal experiments showed that the combined recellularization strategy can improve muscle regeneration and angiogenesis than the single ASCs recellularization strategy, and the TA of former had greater muscle contraction strength. Further single-nucleus RNA sequencing (snRNA-seq) analysis found that L6 cells induced ASCs transform into a new subpopulation of cells highly expressing Mki67, CD34 and CDK1 genes, which had stronger ability of oriented myogenic differentiation. This study demonstrates that co-seeding ASCs and L6 cells through vascular pedicles is a promising recellularization strategy for adECM biological scaffolds, and the engineered muscle tissue constructed based on this has significant therapeutic effects on VML. Overall, this study provides a new paradigm for optimizing and developing dECM-based therapeutic strategies.
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Matriz Extracelular Descelularizada , Enfermedades Musculares , Animales , Matriz Extracelular , Regeneración , Ingeniería de Tejidos/métodos , Células Madre , Obesidad , Músculo Esquelético/fisiología , Andamios del TejidoRESUMEN
Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.
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Modelos Animales de Enfermedad , Exosomas , Células Madre Mesenquimatosas , Muromegalovirus , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Animales , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , FN-kappa B/metabolismo , Muromegalovirus/fisiología , Ratones Endogámicos C57BL , Macrófagos/inmunología , Infecciones por Citomegalovirus/terapia , Infecciones por Citomegalovirus/virología , Pulmón/virología , Pulmón/patología , Neumonía Viral/terapia , Neumonía Viral/virología , Infecciones por Herpesviridae/terapia , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/inmunología , Neumonía/terapia , Neumonía/virologíaRESUMEN
As one of the predominant benthic organisms in the Palaeozoic, brachiopod was largely eliminated in the Permian-Triassic boundary mass extinction, and then highly diversified in the Middle Triassic. Since fossil data from the Early Triassic are rarely reported, the recovery patterns of Early Triassic brachiopods remain unclear. This study documents a well-preserved fauna that is the most diverse Olenekian brachiopod fauna so far (age constrained by conodont biostratigraphy) from the Datuguan section of ramp facies in South China. This fauna is composed of 14 species within nine genera, including six genera (Hirsutella, Sulcatinella, Paradoxothyris, Dioristella, Neoretzia and Isocrania) found in the Early Triassic for the first time and three new species, including Paradoxothyris flatus sp. nov., Hirsutella sulcata sp. nov. and Sulcatinella elongata sp. nov. The Datuguan fauna indicates that the diversity of Olenekian brachiopod fauna has been underestimated, which can be caused by a combination of reduced habitats (in geographic size and sedimentary type) compared with the end-Permian, great bed thickness making it difficult to find fossils and most species in the fauna having low abundance. Based on the faunal change in the Datuguan section and environmental changes in South China, it can be inferred that brachiopod recovery in the studied section occurred in the latest Spathian rather than the Smithian when the environment started to ameliorate. Global brachiopod data also indicates that the initial recovery of brachiopods happened in the Spathian, and many genera that widely occurred in the Middle or Late Triassic had originated in the Olenekian.
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The aim of this study was to reveal the molecular basis of aroma changes during storage of An tea (AT). The key volatile compounds in AT were screened using SPME-GC-MS and SPE-GC-MS analytical techniques in combination with odor activity value (OAV) and flavor dilution factor (FD). The results showed that with the increase of storage time the stale and woody aromas were revealed. Esters, acids and hydrocarbons are the main types of volatile compounds in AT, and their content accounts for 52.69 %-61.29 % of the total volatile compounds. The key volatile compounds with stale and woody aromas during AT storage were obtained by OAV value and FD value, namely ketoisophorone (flavor dilution factor, FD = 64), linalool oxide C (FD = 64), 1-octen-3-ol (OAV > 1, FD = 32), 1,2-dimethoxybenzene (FD = 16), naphthalene (OAV > 1, FD = 32), 3,4-dimethoxytoluene (FD = 16), and 1,2,3-trimethoxybenzene (FD = 8). Our research provides a scientific basis and insights for the improvement of quality during the storage of dark tea.
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Odorantes , Compuestos Orgánicos Volátiles , Odorantes/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Té , Compuestos Orgánicos Volátiles/análisis , Olfatometría/métodosRESUMEN
Immunocompromised individuals are particularly vulnerable to viral infections and reactivation, especially endogenous herpes viruses such as Epstein-Barr virus (EBV), a member of oncogenic gamma-herpesviruses, which are commonly linked to pneumonia and consequently significant morbidity and mortality. In the study of human and animal oncogenic gammaherpesviruses, the murine gamma-herpesviruses-68 (MHV-68) model has been applied, as it can induce pneumonia in immunocompromised mice. Mesenchymal stem cell (MSC) treatment has demonstrated therapeutic potential for pneumonia, as well as other forms of acute lung injury, in preclinical models. In this study, we aim to investigate the therapeutic efficacy and underlying mechanisms of human bone marrow-derived MSC (hMSC) on MHV-68-induced pneumonia. We found that intravenous administration of hMSCs significantly reduced lung damages, diminished inflammatory mediators and somehow inhibited MHV-68 replication. Furthermore, hMSCs treatment can regulate innate immune response and induce macrophage polarization from M1 to M2 phenotype, could significantly alter leukocyte infiltration and reduce pulmonary fibrosis. Our findings with co-culture system indicated that hMSCs effectively reduced the secretion of of inflammation-related factors and induced a shift in macrophage polarization, consistent with in vivo results. Further investigations revealed that hMSCs treatment suppressed the activation of macrophage ROS/NLRP3 signaling pathway in vivo and in vitro. Moreover, administration of MCC950, a selective NLRP3 inhibitor has been shown to effectively reduce ROS production and subsequently alleviate inflammation induced by MHV-68. Taken together, our work has shown that hMSCs can effectively protect mice from lethal MHV-68 pneumonia, which may throw new light on strategy for combating human EBV-associated pneumonia.
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BACKGROUND: Prolonged intermittent theta-burst stimulation (iTBS) is effective for major depressive disorder (MDD). However, whether longer piTBS treatment in a single session could have antidepressant efficacy remains elusive. Therefore, this double-blind, randomized, sham-controlled study aimed to investigate the antidepressant efficacy of 2 daily piTBS sessions for treating MDD patients with a history of poor responses to at least 1 adequate antidepressant trial in the current episode. METHODS: All patients received 2 uninterrupted sessions per day for 10 weekdays (i.e., 2 weeks; a total of 20 sessions). Seventy-two patients were recruited and 1:1:1 randomly assigned to one of three groups: piTBS (piTBSx2), 10-Hz rTMS (rTMSx2), or sham treatment (shamx2, randomly assigned to piTBS or rTMS). 10-Hz rTMS group was included as an active comparison group to enhance assay sensitivity. RESULTS: piTBSx2 group had significantly more responders at week 2 than shamx2 group, but it did not yield better antidepressant effects regarding the %depression changes. The changes of antidepressant scores were not different among the three groups at week 1 (-26.2% vs. -23.3% vs. -22.%) or at week 2 (-34.1% vs. -37.1% vs. -30.1%). Longer treatment duration did not result in stronger placebo effects [sham(piTBS)x2: - 31.7% vs. sham(rTMS)x2: - 26.7%]. CONCLUSION: The present sham-controlled study confirmed that piTBS is an effective antidepressant option, but found no evidence to support that longer piTBS treatment duration resulted in more rapid or better antidepressant effects. A high placebo effect was observed, but longer treatment duration of brain stimulation was not linearly associated with stronger placebo effects.
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Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive tract with a low 5-year survival rate due to the lack of effective treatment methods. Although therapeutic monoclonal antibodies (mAbs) now play an important role in cancer therapy, effective targeted mAbs are still lacking for ESCC. B7-H3 is highly expressed in a variety of tumors and has emerged as a promising therapeutic target. Several mAbs against B7-H3 have advanced to clinical trials, but their development has not yet been pursued for ESCC. Here, we developed a humanized and Fc-engineered anti-B7H3 mAb 24F-Hu-mut2 and systematically evaluated its anti-tumor activity in vitro and in vivo. The 24F-Hu-mut2 was humanized and modified in Fc fragment to obtain stronger antibody-dependent cell-mediated cytotoxicity(ADCC) activity and nanomolar affinity. Furthermore, both of ESCC cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice models indicated that 24F-Hu-mut2 displayed potent in vivo anti-tumor activity. In addition, a computational docking model showed that the mAb bound to IgC1 and IgC2 domain of B7-H3, which is closer to the cell membrane. Consistently, our ELISA results verified the binding of 24F-Hu-WT and IgC1 and IgC2. Our results indicate that 24F-Hu-mut2 has significant anti-ESCC activity both in vitro and in vivo, and this monoclonal antibody may be a promising antibody against ESCC and other B7-H3 overexpressing tumors.