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Our case demonstrated unique cytomegalovirus (CMV) encephalitis post-haploidentical donor hematopoietic stem cell transplantation (HID-HSCT), with early findings on diffusion-weighted brain magnetic resonance imaging (MRI) in the absence of any neurologic symptoms. A 54-year-old Chinese man with acute lymphoblastic leukemia (Philadelphia chromosome-negative) underwent HID-HSCT. After HSCT, the patient developed CMV viremia and severe acute graft-versus-host disease. Recurrence of CMV viremia was observed. On day 129, brain MRI was performed to determine the cause for the intermittent fever. Diffusion-weighted imaging (DWI) revealed several bright spots in the cortex of the frontal lobes and anterior angle of the left lateral ventricle. Subsequently, he developed transplant-associated thrombotic microangiopathy, posterior reversible encephalopathy syndrome, and enlargement of lesions alongside the ventricular wall on a brain MRI series. Metagenomic next-generation sequencing (NGS) of the cerebrospinal fluid (CSF) led to the final diagnosis of CMV encephalitis. Although ganciclovir combined with foscarnet was administered, the patient's consciousness deteriorated, followed by respiratory failure. The patient died on day 198. Additionally, we performed a systematic review to comprehensively analyze this disease. Regarding treatment, immunological therapies, including virus-specific T cells from a third donor and CMV-cytotoxic T lymphocytes, may be more effective. This case report and systematic review underscores the complexities of managing CMV ventriculoencephalitis in HSCT recipients and emphasizes the importance of early diagnosis by brain MRI and CSF polymerase chain reaction or NGS and ongoing research in improving outcomes.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Imageamento por Ressonância Magnética , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Infecções por Citomegalovirus/diagnóstico por imagem , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/virologia , Citomegalovirus/genética , Encefalite Viral/etiologia , Encefalite Viral/diagnóstico por imagem , Transplante Haploidêntico , Antivirais/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Ventriculite Cerebral/diagnóstico por imagem , Ventriculite Cerebral/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Evolução FatalRESUMO
BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a serious fungal infection. However, current diagnostic methods have limitations. The purpose of this study was to use artificial intelligence to achieve a more accurate diagnosis of IPA. METHODS: Totally 263 patients (148 cases of IPA, 115 cases of non-IPA) were retrospectively enrolled from a single institution and randomly divided into training and test sets at a ratio of 7:3. Clinic-radiological independent risk factors for IPA were screened using univariate analysis and multivariate logistic regression analysis, after which a clinic-radiological model was constructed. The optimal radiomics features were extracted and screened based on CT images to construct the radiomics label score (Rad-score) and radiomics model. The optimal DL features were extracted and screened using four pre-trained convolutional neural networks, respectively, followed by the construction of the DL label score (DL-score) and DL model. Then, the radiomics-DL model was constructed. Finally, the combined model was constructed based on clinic-radiological independent risk factors, the Rad-score, and the DL-score. LR was adopted as the classifier. Receiver operating characteristic (ROC) curves were drawn, and the areas under the curve (AUC) were calculated to evaluate the efficacy of each model in predicting IPA. Additionally, based on the best-performing model on the LR classifier, four other machine learning (ML) classifiers were constructed to evaluate the predictive value for IPA. RESULTS: The AUC of the clinic-radiological model for predicting IPA in the training and test sets was 0.845 and 0.765, respectively. The AUC of the radiomics-DL and combined models in the training set was 0.871 and 0.932, while in the test set was 0.851 and 0.881, respectively. The combined model showed better predictive performance than all other models. DCA showed that taking 0.00-1.00 as the threshold, the clinical benefit of the combined model was higher than that of all other models. Then, the combined model was trained on four other machine learning classifiers, all of which achieved AUC values above 0.80 in the test set, showing good performance in predicting IPA. CONCLUSION: Clinic, CT radiomics, and DL combined model could be used to predict IPA effectively.
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Aprendizado Profundo , Aspergilose Pulmonar Invasiva , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Masculino , Estudos Retrospectivos , Feminino , Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Curva ROC , Adulto , Fatores de Risco , Redes Neurais de Computação , RadiômicaRESUMO
The distribution characteristics and risk levels of PAHs in surface sediment in the Honghai Bay of China are studied in this paper. The results showed that the concentration of total PAHs in this area ranged from 100.65 ng·g-1 to 241.31 ng·g-1, with an average concentration of 158.83 ng·g-1. The tricyclic PAHs were the main components in the detected PAHs. PAH pollution levels in this region were low and moderate as compared with adjacent areas. Traceability results showed that the sediment PAHs mainly originate from coal and biomass combustion. PAHs concentrations at some stations were above the Environmental Quality Reference Level. The PAHs toxicity and ecological risk level in surface sediments in the area was determined to be low to moderate by toxicity equivalence testing and risk entropy value assessment.
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Baías , Monitoramento Ambiental , Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Hidrocarbonetos Policíclicos Aromáticos/análise , Sedimentos Geológicos/química , China , Medição de Risco , Poluentes Químicos da Água/análise , Baías/químicaRESUMO
Many studies have indicated an alarming prevalence of anxiety among Chinese adolescents, highlighting the critical need for prevention protocols. DNA-V (Discoverer, Noticer, Advisor-Values model) is an adapted version of Acceptance and Commitment Therapy designed to prevent mental health problems in adolescents. This study investigated the effects and underlying mechanisms of DNA-V. The DNA-V prevention program was culturally adapted and optimized in both content and form specifically for Chinese adolescents, with the aim of reducing anxiety levels. A total of 139 participants (59 females) from six eighth-grade classes at an average middle school in Beijing were randomly assigned to one of three groups consisting of the DNA-V face-to-face group (two classes), the DNA-V web-based group (two classes), or the active control group (two classes). Adolescents' anxiety and cognitive fusion were measured before (Time 1), immediately after (Time 2), and 2 months after (Time 3) the program using the Chinese Secondary School Students Anxiety Scale (CSSSAS) and Cognitive Fusion Questionnaire (CFQ). Results showed that in the DNA-V face-to-face group, the anxiety score at Time 3 was significantly lower than the scores at Time 1 (p < .001, Cohen's drm = 0.56) and Time 2 (p = .043, Cohen's drm = 0.24). The cognitive fusion score at Time 3 was significantly lower than the scores at Time 1 (p = .001, Cohen's drm = 0.51) and Time 2 (p = .003, Cohen's drm = 0.37). The results of the study suggest that the DNA-V prevention program could serve as an effective tool for reducing anxiety in adolescents.
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Ansiedade , Humanos , Adolescente , Feminino , Masculino , Ansiedade/psicologia , China , Estudantes/psicologia , Terapia Cognitivo-Comportamental/métodos , População do Leste AsiáticoRESUMO
The purpose of this study was to improve the efficacy of olopatadine hydrochloride (OT) in treating allergic conjunctivitis (AC). To achieve this goal, we developed an eye formulation without antimicrobial agents using a temperature-pH dual-sensitive in situ gel technology combined with heat sterilization. Various types of carbomers were evaluated and their optimal doses determined. The prescription containing poloxamer 407 (P407) and poloxamer 188 (P188) was optimized using central composite design for response surface methodology (CCD-RSM). The final optimized dual-sensitive in situ gel (TP-gel) consisted of 0.1% olopatadine hydrochloride, 18.80% P407, 0.40% P188, 0.30% Pemulen™TR-1(TR-1), 4.0% mannitol, and 0.08% Tri(hydroxymethyl)aminomethane(Tris).Sterilization was performed at a temperature of 121â for a duration of 20 min. Experimental results showed that TP-gel had good safety profile and remained on the ocular surface for approximately (65.83 ± 8.79) minutes, which is four times longer than eye drops. The expression levels of IL-13, IL-17, and OVA-IgE in mouse ocular tissues with allergic conjunctivitis treated with TP-gel were significantly reduced. This suggests that TP-gel has the potential to be an effective treatment method for allergic conjunctivitis.
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Conjuntivite Alérgica , Géis , Cloridrato de Olopatadina , Temperatura , Conjuntivite Alérgica/tratamento farmacológico , Animais , Camundongos , Concentração de Íons de Hidrogênio , Cloridrato de Olopatadina/administração & dosagem , Poloxâmero/química , Soluções Oftálmicas/administração & dosagem , Feminino , Antialérgicos/administração & dosagem , Antialérgicos/farmacologia , Resinas AcrílicasRESUMO
Ice, water, and sediment represent three interconnected habitats in lake ecosystems, and bacteria are crucial for maintaining ecosystem equilibrium and elemental cycling across these habitats. However, the differential characteristics and driving mechanisms of bacterial community structures in the ice, water, and sediments of seasonally frozen lakes remain unclear. In this study, high-throughput sequencing technology was used to analyze and compare the structure, function, network characteristics, and assembly mechanisms of bacterial communities in the ice, water, and sediment of Wuliangsuhai, a typical cold region in Inner Mongolia. The results showed that the bacterial communities in the ice and water phases had similar diversity and composition, with Proteobacteria, Bacteroidota, Actinobacteria, Campilobacterota, and Cyanobacteria as dominant phyla. The bacterial communities in sediments displayed significant differences from ice and water, with Chloroflexi, Proteobacteria, Firmicutes, Desulfobacterota, and Acidobacteriota being the dominant phyla. Notably, the bacterial communities in water exhibited higher spatial variability in their distribution than those in ice and sediment. This study also revealed that during the frozen period, the bacterial community species in the ice, water, and sediment media were dominated by cooperative relationships. Community assembly was primarily influenced by stochastic processes, with dispersal limitation and drift identified as the two most significant factors within this process. However, heterogeneous selection also played a significant role in the community composition. Furthermore, functions related to nitrogen, phosphorus, sulfur, carbon, and hydrogen cycling vary among bacterial communities in ice, water, and sediment. These findings elucidate the intrinsic mechanisms driving variability in bacterial community structure and changes in water quality across different media phases (ice, water, and sediment) in cold-zone lakes during the freezing period, offering new insights for water environmental protection and ecological restoration efforts in such environments.
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Bactérias , Ecossistema , Congelamento , Sedimentos Geológicos , Lagos , Lagos/microbiologia , Lagos/química , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Bactérias/classificação , Bactérias/genética , China , Microbiologia da Água , Gelo , Microbiota , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Mercury and arsenic are two highly toxic pollutants, and many researchers have explored the effects of the two substances on the environment. However, the research content of toxic substances in frozen periods is relatively small. To explore the spatial and vertical distribution of mercury and arsenic in the ice, water, and sediments of Wuliangsuhai Lake under ice conditions, and to assess the harm degree of the two toxic substances to human beings. We collected the ice, water, and sediments of the lake in December 2020, and tested the contents of Hg and As. The single-factor pollution index method, the local cumulative index method, and the ecological risk coding method were used to assess the pollution status in these three environmental media, and the Monte Carlo simulation combined with the quantitative model recommended by USEPA was used to assess the population health risk. The results showed that (1) The average single-factor pollution values of Hg and As in water were 0.367 and 0.114, both pollutants were at clean levels during the frozen period. (2) The mean Igeo values of Hg and As were 0.657 and -0.948. The bioavailability of Hg in the sediments of Wuliangsuhai Lake during the frozen period was high, and its average value was 7.8%, which belonged to the low-risk grade. The bioavailability of As ranged from 0.2% to 3.7%, with an average value of 1.3%. (3) Monte Carlo simulation results indicate acceptable levels of health risks in both water and ice. This study preliminarily investigated the distribution characteristics of toxic substances and their potential effects on human health in lakes in cold and arid regions during the frozen period. It not only clarified the pollution characteristics of lakes in cold and arid regions during the frozen period, but also provided beneficial supplements for the ecological protection of lake basins. This study lays a foundation for further environmental science research in the region in the future.
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In this paper, an improved CKF (Cubature Kalman Filter) target tracking method is adopted to solve the tracking and pointing problem in the field of the Active Denial System. The math model of the system is built and the precision requirement is analyzed. The improved CKF method is input as the feedforward compensation for system control to improve the system tracking performance. In the process of the iterative CKF algorithm, nonlinear means are used. The method makes full use of measurement information and estimates the target velocity acceleration model parameters through the neural network, which is used as the input of the CKF to modify the process parameters of CKF and improve the state estimation accuracy. At the same time, the limited lower bound method is used to ensure that the gain reaches the lower bound bottom line of the precision demand, so that it does not tend to zero with time, so as to avoid affecting its rapid response ability during maneuvering and so that the prediction error is also controlled within the range of the precision demand. The simulation and experimental results show the superiority of the method and make the system fully meet the design requirements.
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Synaptotagmin-1 (Syt1) is a calcium sensor that regulates synaptic vesicle fusion in synchronous neurotransmitter release. Syt1 interacts with negatively charged lipids and the SNARE complex to control the fusion event. However, it remains incompletely understood how Syt1 mediates Ca2+-trigged synaptic vesicle fusion. Here, we discovered that Syt1 undergoes liquid-liquid phase separation (LLPS) to form condensates both in vitro and in living cells. Syt1 condensates play a role in vesicle attachment to the PM and efficiently recruit SNAREs and complexin, which may facilitate the downstream synaptic vesicle fusion. We observed that Syt1 condensates undergo a liquid-to-gel-like phase transition, reflecting the formation of Syt1 oligomers. The phase transition can be blocked or reversed by Ca2+, confirming the essential role of Ca2+ in Syt1 oligomer disassembly. Finally, we showed that the Syt1 mutations causing Syt1-associated neurodevelopmental disorder impair the Ca2+-driven phase transition. These findings reveal that Syt1 undergoes LLPS and a Ca2+-sensitive phase transition, providing new insights into Syt1-mediated vesicle fusion.
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Cálcio , Vesículas Sinápticas , Sinaptotagmina I , Sinaptotagmina I/metabolismo , Sinaptotagmina I/genética , Cálcio/metabolismo , Humanos , Animais , Vesículas Sinápticas/metabolismo , Multimerização Proteica , Proteínas SNARE/metabolismo , Proteínas SNARE/genética , Transição de Fase , Mutação/genética , Células HEK293 , Fusão de Membrana , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Separação de FasesRESUMO
Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed thatï¼ fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundanceï¼ the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances ï¼PET, PBTï¼, cellulose, and polypropylene ï¼PPï¼ were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was ï¼73 ±5ï¼ n·L-1, the effluent abundance was ï¼14 ±2ï¼ n·L-1, and the overall removal rate was ï¼80.8 ±12.1ï¼%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids ï¼49.2 ±7.4ï¼% and secondary sedimentation tanks ï¼92.4 ±13.9ï¼%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.
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Cidades , Microplásticos , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Microplásticos/análise , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , China , Esgotos/química , Plásticos , Tamanho da Partícula , Polipropilenos , Monitoramento AmbientalRESUMO
Metabolic-associated steatohepatitis (MASH) and ulcerative colitis (UC) exhibit a complex interconnection with immune dysfunction, dysbiosis of the gut microbiota, and activation of inflammatory pathways. This study aims to identify and validate critical butyrate metabolism-related shared genes between both UC and MASH. Clinical information and gene expression profiles were sourced from the Gene Expression Omnibus (GEO) database. Shared butyrate metabolism-related differentially expressed genes (sBM-DEGs) between UC and MASH were identified via various bioinformatics methods. Functional enrichment analysis was performed, and UC patients were categorized into subtypes using the consensus clustering algorithm based on sBM-DEGs. Key genes within sBM-DEGs were screened through Random Forest, Support Vector Machines-Recursive Feature Elimination, and Light Gradient Boosting. The diagnostic efficacy of these genes was evaluated using receiver operating characteristic (ROC) analysis on independent datasets. Additionally, the expression levels of characteristic genes were validated across multiple independent datasets and human specimens. Forty-nine shared DEGs between UC and MASH were identified, with enrichment analysis highlighting significant involvement in immune, inflammatory, and metabolic pathways. The intersection of butyrate metabolism-related genes with these DEGs produced 10 sBM-DEGs. These genes facilitated the identification of molecular subtypes of UC patients using an unsupervised clustering approach. ANXA5, CD44, and SLC16A1 were pinpointed as hub genes through machine learning algorithms and feature importance rankings. ROC analysis confirmed their diagnostic efficacy in UC and MASH across various datasets. Additionally, the expression levels of these three hub genes showed significant correlations with immune cells. These findings were validated across independent datasets and human specimens, corroborating the bioinformatics analysis results. Integrated bioinformatics identified three significant biomarkers, ANXA5, CD44, and SLC16A1, as DEGs linked to butyrate metabolism. These findings offer new insights into the role of butyrate metabolism in the pathogenesis of UC and MASH, suggesting its potential as a valuable diagnostic biomarker.
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Butiratos , Colite Ulcerativa , Biologia Computacional , Humanos , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Butiratos/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Curva ROC , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Bases de Dados Genéticas , Transcriptoma , Microbioma Gastrointestinal/genéticaRESUMO
Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.
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Mielofibrose Primária , Proteínas Recombinantes de Fusão , Humanos , Masculino , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/complicações , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos , China , Anemia Refratária/tratamento farmacológico , Receptores de Activinas Tipo II/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Resultado do Tratamento , Seguimentos , Anemia/tratamento farmacológico , Anemia/etiologiaRESUMO
The oceans are rich in diverse microorganisms, animals, and plants. This vast biological complexity is a major source of unique secondary metabolites. In particular, marine fungi are a promising source of compounds with unique structures and potent antibacterial properties. Over the last decade, substantial progress has been made to identify these valuable antibacterial agents. This review summarizes the chemical structures and antibacterial activities of 223 compounds identified between 2012 and 2023. These compounds, effective against various bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus, exhibit strong potential as antibacterial therapeutics. The review also highlights the relevant challenges in transitioning from drug discovery to product commercialization. Emerging technologies such as metagenomics and synthetic biology are proposed as viable solutions. This paper sets the stage for further research on antibacterial compounds derived from marine fungi and advocates a multidisciplinary approach to combat drug-resistant bacteria.
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Antibacterianos , Produtos Biológicos , Fungos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/química , Fungos/efeitos dos fármacos , Organismos Aquáticos/química , Animais , Humanos , Bactérias/efeitos dos fármacos , Descoberta de Drogas , Testes de Sensibilidade MicrobianaRESUMO
Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.
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Antifúngicos , Cromoblastomicose , Imiquimode , Itraconazol , Terbinafina , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/microbiologia , Imiquimode/uso terapêutico , Humanos , Antifúngicos/uso terapêutico , Itraconazol/uso terapêutico , Terbinafina/uso terapêutico , Masculino , Resultado do Tratamento , Microscopia Confocal , Pele/patologia , Pele/microbiologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. METHODS: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. RESULTS: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. CONCLUSION: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.
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Azul de Metileno , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes , Iodeto de Potássio , Iodeto de Potássio/farmacologia , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Fotoquimioterapia/métodos , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Cromoblastomicose/tratamento farmacológico , Ascomicetos/efeitos dos fármacos , Oxigênio Singlete/metabolismo , Peróxido de Hidrogênio/farmacologiaRESUMO
Background: This study aims to elucidate the role of mitochondrial autophagy in metabolic dysfunction-associated steatohepatitis (MASH) by identifying and validating key mitophagy-related genes and diagnostic models with diagnostic potential. Methods: The gene expression profiles and clinical information of MASH patients and healthy controls were obtained from the Gene Expression Omnibus database (GEO). Limma and functional enrichment analysis were used to identify the mitophagy-related differentially expressed genes (mito-DEGs) in MASH patients. Machine learning models were used to select key mito-DEGs and evaluate their efficacy in the early diagnosis of MASH. The expression levels of the key mito-DEGs were validated using datasets and cell models. A nomogram was constructed to assess the risk of MASH progression based on the expression of the key mito-DEGs. The mitophagy-related molecular subtypes of MASH were evaluated. Results: Four mito-DEGs, namely MRAS, RAB7B, RETREG1, and TIGAR were identified. Among the machine learning models employed, the Support Vector Machine demonstrated the highest AUC value of 0.935, while the Light Gradient Boosting model exhibited the highest accuracy (0.9189), kappa (0.7204), and F1-score (0.9508) values. Based on these models, MRAS, RAB7B, and RETREG1 were selected for further analysis. The logistic regression model based on these genes could accurately predict MASH diagnosis. The nomogram model based on these DEGs exhibited excellent prediction performance. The expression levels of the three mito-DEGs were validated in the independent datasets and cell models, and the results were found to be consistent with the findings obtained through bioinformatics analysis. Furthermore, our findings revealed significant differences in gene expression patterns, immune characteristics, biological functions, and enrichment pathways between the mitophagy-related molecular subtypes of MASH. Subtype-specific small-molecule drugs were identified using the CMap database. Conclusion: Our research provides novel insights into the role of mitophagy in MASH and uncovers novel targets for predictive and personalized MASH treatments.
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Aerogel fibers are good thermal insulators, suitable for weaving, and show potential as the next generation of intelligent textiles that can effectively reduce heat consumption for personal thermal management. However, the production of continuous aerogel fibers from biomass with sufficient strength and radial elasticity remains a significant challenge. Herein, continuous gel fibers were produced via wet spinning using agarose (AG) as the matrix, 2,2,2,6,6-tetramethylpiperidine-1-oxyl radical-oxidized cellulose nanofibers (TOCNs) as the reinforcing agent, and no other chemical additives by utilizing the gelling properties of AG. Supercritical drying and chemical vapor deposition (CVD) were then used to produce hydrophobic AG-TOCN aerogel fibers (HATAFs). During CVD, the HATAF gel skeleton was covered with an isostructural silica coating. Consequently, the HATAFs can recover from radial compression under 60% strain. Moreover, the HATAFs have low densities (≤0.14 g cm-3), high porosities (≥91.8%), high specific surface areas (≥188 m2 g-1), moderate tensile strengths (≤1.75 MPa), excellent hydrophobicity (water contact angles of >130°), and good thermal insulating properties at different temperatures. Thus, HATAFs are expected to become a new generation of materials for efficient personal thermal management.
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Cardiovascular diseases (CVD) are the leading cause of death worldwide, despite advances in understanding cardiovascular health. Significant barriers still exist in effectively preventing and managing these diseases. Vascular smooth muscle cells (VSMCs) are crucial for maintaining vascular integrity and can switch between contractile and synthetic functions in response to stimuli such as hypoxia and inflammation. These transformations play a pivotal role in the progression of cardiovascular diseases, facilitating vascular modifications and disease advancement. This article synthesizes the current understanding of the mechanisms and signaling pathways regulating VSMC phenotypic transitions, highlighting their potential as therapeutic targets in cardiovascular disease interventions.
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Objective: The applications of personalized abutments and abutment crown bridge products have increased year by year, but there is no clear requirement for clinical evaluation of the same variety of such products. This study mainly introduces the clinical evaluation concerns of personalized abutments and abutment crown bridge products, in order to provide reference for the declaration and registration of such products. Methods: The clinical evaluation of personalized abutments and crown bridge products are summarized, and the research content of clinical evaluation is clarified. Results: The clinical evaluation requirements that need to be considered by enterprises are introduced. Conclusion: Personalized abutment and abutment crown bridge products can refer to this study when they are launched in China, mainly using in vitro performance comparison tests for equivalence verification.
Assuntos
Prótese Parcial , ChinaRESUMO
To explore the spatial and temporal distribution characteristics of heavy metals in the surface sediments of lakes in cold regions during ice-sealing and non-ice-sealing periods, we analyzed the potential ecological risk degree and the pollution sources. A total of 20 sampling sites in Lake Ulansuhai in cold regions were collected from 2020 to 2021, and 120 surface sediment samples were collected during different periods. The contents of As, Cd, Cr, Cu, Ni, Pb, Zn, and Hg were determined. Correlation analysis, principal component analysis, and the absolute factor score-multiple linear regression (APCS-MLR) receptor model were used to trace the source of heavy metal pollution. The results showed that:â the distribution of heavy metals in lake surface sediments was different between the ice-sealing period and the non-ice-sealing period. The distribution of heavy metals during the ice-sealing period was higher in the north and lower in the south. Cd and Hg were mainly distributed in the central and southern lakes during the non-glacial period. â¡ Hg, Cd, and As were moderately polluted, and Ni was mildly polluted in the surface sediments of the lake. The overall performance was at a high risk level, and the pollution level during the non-ice-sealing period was higher than that during the ice-sealing period. The main environmental risk factors were Hg and Cd, which showed high risk and moderate risk, respectively. ⢠The sources of heavy metals in lake surface sediments were mainly industrial sources from mining and transportation, agricultural sources, and natural sources. As, Ni, Pb, and Hg were mainly affected by industrial sources, with contribution rates of 62.67%, 75.31%, 77.47%, and 80.11%, respectively. The main sources of Cu and Zn were natural sources, and Cd was greatly affected by agricultural sources. The contribution rate was 81.57%. The source of Cr was mainly affected by natural factors, and the influence of human activities and unknown sources require further attention.