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Intelligent manufacturing technologies, including databases, mathematical modeling, and information systems have played a significant role in process control, production management, and supply chain management in traditional Chinese medicine(TCM) industry. However, their ability to process and utilize unstructured data, such as research and development reports, batch production records, quality inspection records, and supplier documents, is relatively weak. For text, images, language, and other unstructured data, generative artificial intelligence(AI) technology has shown strong potential for development in extracting information, extracting knowledge, semantic retrieval, and content generation. Generative AI is expected to provide a feasible set of tools for the utilization of unstructured data resources in the TCM industry. Based on years of research and industrial application experience in TCM intelligent manufacturing technology, this study reviewed the current situation of intelligent manufacturing in TCM and the utilization of unstructured data, analyzed the application value of generative AI in the TCM manufacturing process and supply chain, summarized four typical application scenarios, including intelligent pharmaceutical knowledge base/knowledge graph, intelligent on-the-job trai-ning, intelligent production quality control, and intelligent supply chain. Furthermore, this study also explained the data collection and processing, business process design, application potential, and value of each scenario based on industry demands. Finally, based on the integration of generative AI and TCM industrial models, the study proposed a preliminary concept of a smart industrial brain for TCM, aiming to provide a reference for the application of AI technology in the field of TCM manufacturing.
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Inteligência Artificial , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Controle de Qualidade , HumanosRESUMO
Dysbiosis of the gut microbiota has been implicated in hypertension, and drug-host-microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)-shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB-modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well-controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB-modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post-FMT, especially with a decreased abundance of Lactobacillus, Aggregatibacter, and Desulfovibrio. Moreover, ARB-treated microbes contributed to increased intestinal Ciart, Per1, Per2, Per3, and Cipc gene levels and decreased Nfil3 and Arntl expression were detected in response to ARB-treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB-FMT rats, including 6beta-Hydroxytestosterone and Thromboxane B2. In conclusion, ARB-modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross-talk between antihypertensive medicines and the gut microbiome.
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Tropical and subtropical evergreen broadleaved forests (TEFs) contribute more than one-third of terrestrial gross primary productivity (GPP). However, the continental-scale leaf phenology-photosynthesis nexus over TEFs is still poorly understood to date. This knowledge gap hinders most light use efficiency (LUE) models from accurately simulating the GPP seasonality in TEFs. Leaf age is the crucial plant trait to link the dynamics of leaf phenology with GPP seasonality. Thus, here we incorporated the seasonal leaf area index of different leaf age cohorts into a widely used LUE model (i.e., EC-LUE) and proposed a novel leaf age-dependent LUE model (denoted as LA-LUE model). At the site level, the LA-LUE model (average R2 = .59, average root-mean-square error [RMSE] = 1.23 gC m-2 day-1) performs better than the EC-LUE model in simulating the GPP seasonality across the nine TEFs sites (average R2 = .18; average RMSE = 1.87 gC m-2 day-1). At the continental scale, the monthly GPP estimates from the LA-LUE model are consistent with FLUXCOM GPP data (R2 = .80; average RMSE = 1.74 gC m-2 day-1), and satellite-based GPP data retrieved from the global Orbiting Carbon Observatory-2 (OCO-2) based solar-induced chlorophyll fluorescence (SIF) product (GOSIF) (R2 = .64; average RMSE = 1.90 gC m-2 day-1) and the reconstructed TROPOspheric Monitoring Instrument SIF dataset using machine learning algorithms (RTSIF) (R2 = .78; average RMSE = 1.88 gC m-2 day-1). Typically, the estimated monthly GPP not only successfully represents the unimodal GPP seasonality near the Tropics of Cancer and Capricorn, but also captures well the bimodal GPP seasonality near the Equator. Overall, this study for the first time integrates the leaf age information into the satellite-based LUE model and provides a feasible implementation for mapping the continental-scale GPP seasonality over the entire TEFs.
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Florestas , Folhas de Planta , Tecnologia de Sensoriamento Remoto , Estações do Ano , Folhas de Planta/crescimento & desenvolvimento , Fotossíntese , Modelos Teóricos , Luz , Árvores/crescimento & desenvolvimento , Modelos Biológicos , Clima TropicalRESUMO
Objective: This study aims to investigate the agreement between the Huaxi Emotional Index (HEI) and the Nurses' Global Assessment of Suicide Risk (NGASR) in assessing high suicide risk and to explore the predictive value of HEI in identifying high suicide risk among patients with depression. Methods: Convenience sampling was used and 386 inpatients with depression were included in this cross-sectional study. All patients were admitted to the Mental Health Center, West China Hospital between June and December 2023. The inclusion criteria were as follows, a diagnosis of depression according to the International Classification of Diseases, Tenth Revision (ICD-10), age over 18, and completion of both NGASR and HEI assessments. According to the exclusion criteria, depression patients who had other comorbid mental disorders or those who had severe cognitive impairments and were unable to communicate effectively were excluded. The study was approved by the Biomedical Ethics Review Committee of West China Hospital (Approval No. 647, 2021). Demographic data such as age, sex, ethnicity, marital status, and educational attainment were collected using a self-designed questionnaire. Both the HEI and NGASR were applied to evaluate the patients. We conducted statistical analyses with SPSS 27, employing Spearman's rank correlation for correlation analysis, Kappa tests for consistency between the two instruments, and receiver operating characteristic (ROC) curves for evaluating the predictive performance of HEI scores for high suicide risk, with the optimal HEI cutoff value determined on the basis of the Youden Index. Results: The study included 386 depression inpatients with an average age of 32 years and an average length-of-stay of 14 days. Of these participants, 252 were female (65.3%) and 134 were male (34.7%). Regarding ethnicity, most of the participants were Han Chinese (89.4%), Tibetans accounted for 7.3%, and other minorities, 3.3%. Regarding marital status, 51.3% of the participants were married, 41.2% single, 6.5% divorced, and 1.0% widowed. Regarding educational attainment, 26.2% had an undergraduate or graduate education, 20.7% had junior college education, 24.8% had high school or secondary technical school education, and 28.2% had middle school education or less. The NGASR identified 57.3% of the participants as being at high suicide risk, while the HEI identified 53.6% as having severe emotional distress. There was a moderate agreement between the HEI and the NGASR scores, with a Kappa value of 0.518 ( P<0.001), indicating statistically significant differences. At an HEI score of 17, the Youden Index peaked at 0.52, predicting high suicide risk with a specificity of 76.36%, a sensitivity of 76.02%, and an area under the ROC curve of 0.829 (95% CI: 0.787-0.871), demonstrating statistically significant differences. Conclusion: HEI and NGASR demonstrate moderate agreement in assessing high suicide risk among depression patients. The HEI questionnaire effectively predicts high suicide risk in patients with depression, with 17 being the optimal cutoff value for assessing high suicide risk.
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Depressão , Pacientes Internados , Suicídio , Humanos , Feminino , Masculino , Depressão/diagnóstico , Depressão/etiologia , Estudos Transversais , Inquéritos e Questionários , Suicídio/psicologia , Suicídio/estatística & dados numéricos , China/epidemiologia , Medição de Risco/métodos , Emoções , Adulto , Fatores de Risco , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are usually considered safe to use in patients with Parkinson's disease (PD), there are mixed data about their effectiveness, and only a few investigations have led to a total improvement of depressive symptoms in patients with PD. OBJECTIVES: We aimed to conduct a comprehensive systematic review and meta-analysis of all studies that investigated the effectiveness of SSRIs in treating depression in the context of PD. METHODS: From its commencement to June 2024, the databases of MEDLINE via PubMed, Scopus, Embase, and Google Scholar were electronically searched for the relevant papers. All full-text journal articles assessing the effectiveness of SSRIs in treating depression in patients with PD were included. The tool developed by the Cochrane Collaboration was utilized to evaluate the bias risk. Data were analyzed utilizing a pair-wise comparison meta-analysis using the standardized mean difference. RESULTS: A total of 19 articles and 22 separate interventions were included. We found that SSRI treatment attenuated depression in patients with PD (1.242 standardized mean difference, 95% confidence interval 0.956, 1.529, p < 0.001). The general heterogeneity of the studies was medium (Ï°2 = 72.818, T2 = 0.317, df = 21, I2 = 71.15%, p < 0.001). The funnel plot was reasonably symmetrical. However, three studies were trimmed to the left of the mean. Begg's test (p = 0.080), Egger's test (p = 0.121), and funnel plot showed no significant risk of publication bias. The meta-regression showed that the treatment effect increased as a function of paroxetine treatment duration (slope p = 0.001) but decreased as a function of sertraline treatment duration (slope p = 0.019). CONCLUSIONS: There are few controlled antidepressant trials on the PD population, even though patients with PD frequently experience depression and use antidepressants. Clinical studies that are larger and better structured are needed in the future to determine if antidepressants are useful for treating patients with PD with depression.
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Depressão , Doença de Parkinson , Inibidores Seletivos de Recaptação de Serotonina , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Depressão/tratamento farmacológico , Depressão/etiologiaRESUMO
The Golgi apparatus is an essential organelle constructed by the stacking of flattened vesicles, that is widely distributed in eukaryotic cells and is dynamically regulated during cell cycles. It is a central station which is responsible for collecting, processing, sorting, transporting, and secreting some important proteins/enzymes from the endoplasmic reticulum to intra- and extra-cellular destinations. Golgi-specific fluorescent probes provide powerful non-invasive tools for the real-time and in situ visualization of the temporal and spatial fluctuations of bioactive species. Over recent years, more and more Golgi-targeting probes have been developed, which are essential for the evaluation of diseases including cancer. However, when compared with systems that target other important organelles (e.g. lysosomes and mitochondria), Golgi-targeting strategies are still in their infancy, therefore it is important to develop more Golgi-targeting probes. This review systematically summarizes the currently reported Golgi-specific fluorescent probes, and highlights the design strategies, mechanisms, and biological uses of these probes, we have structured the review based on the different targeting groups. In addition, we highlight the future challenges and opportunities in the development of Golgi-specific imaging agents and therapeutic systems.
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Corantes Fluorescentes , Complexo de Golgi , Complexo de Golgi/metabolismo , Corantes Fluorescentes/química , Humanos , AnimaisRESUMO
This review aims to explore the current application of Cranial Ultrasound Screening (CUS) in the diagnosis and treatment of brain diseases in extremely preterm infants. It also discusses the potential role of emerging ultrasound-derived technologies such as Super Microvascular Structure Imaging (SMI), Shear Wave Elastography (SWE), Ultrafast Doppler Ultrasound (UfD), and 3D ventricular volume assessment and automated segmentation techniques in clinical practice. A systematic search of medical databases was conducted using the keywords "(preterm OR extremely preterm OR extremely low birth weight) AND (ultrasound OR ultrasound imaging) AND (neurodevelopment OR brain development OR brain diseases OR brain injury OR neuro*)" to identify relevant literature. The titles, abstracts, and full texts of the identified articles were carefully reviewed to determine their relevance to the research topic. CUS offers unique advantages in early screening and monitoring of brain diseases in extremely preterm infants, as it can be performed at the bedside without the need for anesthesia or special monitoring. This technique facilitates early detection and intervention of conditions such as intraventricular hemorrhage, white matter injury, hydrocephalus, and hypoxic-ischemic injury in critically ill preterm infants. Continuous refinement of the screening and follow-up processes provides reliable clinical decision-making support for healthcare professionals and parents. Emerging ultrasound technologies, such as SWE, SMI, and UfD, are being explored to provide more accurate and in-depth understanding of brain diseases in extremely preterm infants. SWE has demonstrated its effectiveness in assessing the elasticity of neonatal brain tissue, aiding in the localization and quantification of potential brain injuries. SMI can successfully identify microvascular structures in the brain, offering a new perspective on neurologic diseases. UfD provides a high-sensitivity and quantitative imaging method for the prevention and treatment of neonatal brain diseases by detecting subtle changes in red blood cell movement and accurately assessing the status and progression of brain diseases. CUS and its emerging technologies have significant applications in the diagnosis and treatment of brain diseases in extremely preterm infants. Future research aims to address current technical challenges, optimize and enhance the clinical decision-making capabilities related to brain development, and improve the prevention and treatment outcomes of brain diseases in extremely preterm infants.
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P91 steel and P91 steel joints experience performance degradation after serving for 30,000 h in working conditions. To clarify the damage and failure behavior and remaining life of the joints during subsequent service, further creep testing was conducted on the welded joints of P91 steel that had been in service for 30,000 h at three temperatures: 550 °C, 575 °C, and 600 °C. The fracture surface and the cross-section damage behavior were characterized by SEM and EBSD methods. The results show that there are two types of fracture modes in the joints at different temperatures: ductile cracking occurring at the BM, and type IV cracking occurring in the FGHAZ. The threshold stress for fracture mode transition decreases with an increase in working temperature. Type IV cracking near the HAZ is the main reason for the premature failure of joints during service. And based on the fracture mode, the dual-constant L-M method was proposed to predict the strength of in-service joint materials. The testing data are discussed and classified based on the fracture mode in this method, which has high accuracy and can prevent the premature failure of joints.
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Plant growth-promoting endophytes (PGPE) can effectively regulate plant growth and metabolism. The regulation is modulated by metabolic signals, and the resulting metabolites can have considerable effects on the plant yield and quality. Here, tissue culture Houttuynia cordata Thunb., was inoculated with Rhizobium sp. (BH46) to determine the effect of BH46 on H. cordata growth and metabolism, and elucidate associated regulatory mechanisms. The results revealed that BH46 metabolized indole-3-acetic acid and induced 1-aminocyclopropane-1-carboxylate deaminase to decrease ethylene metabolism. Host peroxidase synthesis MPK3/MPK6 genes were significantly downregulated, whereas eight genes associated with auxins, cytokinins, abscisic acid, jasmonic acid, and antioxidant enzymes were significantly upregulated. Eight genes associated with flavonoid biosynthesis were significantly upregulated, with the CPY75B1 gene regulating the production of rutin and quercitrin and the HCT gene directly regulating the production of chlorogenic acid. Therefore, BH46 influences metabolic signals in H. cordata to modulate its growth and metabolism, in turn, enhancing yield and quality of H. cordata.
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Endófitos , Houttuynia , Proteínas de Plantas , Houttuynia/microbiologia , Houttuynia/metabolismo , Houttuynia/genética , Endófitos/metabolismo , Endófitos/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Ácidos Indolacéticos/metabolismo , Rhizobium/genética , Rhizobium/metabolismo , Flavonoides/metabolismo , Ácido Abscísico/metabolismo , Etilenos/metabolismo , Carbono-Carbono Liases/metabolismo , Carbono-Carbono Liases/genéticaRESUMO
BACKGROUND: Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases. AIM: To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE-/-) mouse model and an in vitro cellular model. METHODS: ApoE-/- mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways. RESULTS: DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway. CONCLUSION: This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/- mice on a HFD, and could be of greater value in stem cell-based treatments for AS.
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Information metasurface has shown great potential in wireless communications owing to its ability to flexibly control electromagnetic waves. However, it is still a big challenge to achieve high-security and large-channel capacity wireless communications by a simple system. Here, we propose a space-polarization-division multiplexing secure wireless communication system with information camouflage capability based on the information metasurface, which can realize multichannel encrypted wireless communications with different polarization coding strategies independently and simultaneously. A polarization mask key is introduced to encrypt the target message, and the cipher message is further concealed behind a cover image with steganography and sent to the user by using the polarization modulation strategy. Different polarization mask keys can be adopted in each individual communication by changing the polarization coding strategy to enhance the system security. The proposed scheme integrates computational algorithm encryption and physical layer security together and thus has the advantages of high security, large channel capacity, and strong camouflage ability.
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Background: Esophageal malignancies have a high morbidity rate worldwide, and minimally invasive surgery has emerged as the primary approach for treating esophageal cancer. In recent years, there has been increasing discussion about the potential of employing inflatable mediastinoscopic and laparoscopic approaches as an option for esophagectomy. Building on the primary modification of the inflatable mediastinoscopic technique, we introduced a secondary modification to further minimize surgical trauma. Methods: We conducted a retrospective analysis of patients who underwent inflatable mediastinoscopy combined with laparoscopic esophagectomy at the Second Affiliated Hospital of Naval Medical University from March 2020 to March 2023. The patients were allocated to the following two groups: the traditional (primary modification) group, and the secondary modification group. Operation times, intraoperative bleeding, and postoperative complications were compared between the groups. Results: The procedure was successfully performed in all patients, and conversion to open surgery was not required in any case. There were no statistically significant differences in the surgical operation time, intraoperative bleeding, number of dissected lymph nodes, and rate of postoperative anastomotic leakage between the two groups. However, a statistically significant difference was observed in the length of the mobilized esophagus between the two groups. The mobilization of esophagus to the level of diaphragmatic hiatus via the cervical incision was successfully achieved in more patients in the secondary modification group than the primary modification group. Conclusions: Inflatable mediastinoscopy combined with single-incision plus one-port laparoscopic esophagectomy is a safe and effective surgical procedure. The use of a 5-mm flexible endoscope, ultra-long five-leaf forceps, and LigaSure Maryland forceps facilitates esophageal mobilization and lymph node dissection through a single cervical incision.
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An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.
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Plastic contamination can cause damage to the water quality of fish farm ponds, and also affect the quality of the final product. Pseudomonas mendocina was found to biodegrade plastics. Our study aimed to investigate the physicochemical properties and drug resistance of P. mendocina isolated from local freshwater aquaculture farms. Firstly, the strain was isolated from aquaculture water and then identified by matrix-assisted flight mass spectrometry and 16S rDNA sequencing. Then, biochemical and antibiotic resistance analyses were performed, and a microbial high-throughput growth detector was used to assess the growth of the strain. Finally, PCR and proteomics analyses were conducted to determine drug-resistance-related genes/proteins. According to the results of the spectrum diagram and sequencing, the isolated bacteria were identified as P. mendocina, and were positive for reactions of ADH, MTE, LAC, MNE, FRU, CIT, MLT, ONPG, and ACE. P. mendocina was sensitive to most of the antibiotics, and its resistance to CHL, MIN, and TIC/CLA was intermediate. Additionally, gyrB was the resistance gene, and mdtA2, mdtA3, mdaB, and emrK1 were closely related to the drug resistance of P. mendocina. Our results show the biochemical properties of P. mendocina in isolated aquaculture water, and provide a new perspective for P. mendocina involved in the biological removal of plastics or microplastics in freshwater aquaculture farms.
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Aquicultura , Água Doce , Pseudomonas mendocina , Água Doce/microbiologia , Pseudomonas mendocina/genética , Pseudomonas mendocina/isolamento & purificação , RNA Ribossômico 16S/genética , Antibacterianos/farmacologia , Filogenia , Fazendas , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/genética , AnimaisRESUMO
BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.
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Fish germ cell transplantation holds great potential for conserving endangered species, improving cultured fish breeds, and exploring reproductive techniques. However, low transplantation efficiency is a common issue in heterotransplantation. This study transplanted fat greenling (Hexagrammos otakii) spermatogonia into the testes of spotted sea bass (Lateolabrax maculatus) to investigate factors that might affect the colonization and fixation of heterologous transplanted germ cells. Results indicated that transplanted fat greenling spermatogonia cells were successfully detected in the early transplantation phase in spotted sea bass. Their numbers gradually decreased over time, and after 10 days post-transplantation, more than 90% of the transplanted cells underwent apoptosis. Transcriptome sequencing analysis of the testes of spotted sea bass and fat greenling spermatogonia on days 1 and 10 post-transplantation revealed that this apoptosis process involved many immune-related genes and their associated signaling pathways. Acute immune rejection marker genes prf1 and gzmb were detected in the spotted sea bass testes, while immune tolerance genes lck and zap-70 were expressed in the fat greenling spermatogonia. Additionally, differential expression of prf1 and gzmb genes was screened from spotted sea bass, with experimental evidence indicating that PRF1 and GZMB protein from spotted sea bass primarily induce apoptosis in transplanted fat greenling spermatogonia via the mitochondrial apoptosis pathway, at the protein level. This suggests that the difficulties in heterotransplantation are primarily related to acute immune rejection, with PRF1 and GZMB playing significant roles.
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Bass , Xenoenxertos , Espermatogônias , Animais , Masculino , Apoptose , Bass/genética , Bass/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Perforina/metabolismo , Perforina/genética , Espermatogônias/metabolismo , Testículo/metabolismo , Xenoenxertos/imunologia , Conservação dos Recursos NaturaisRESUMO
Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal dysplasia that primarily affects females. The only known causative gene is IKBKG, and the most common genetic cause is the recurrent IKBKGâ³4-10 deletion resulting from recombination between two MER67B repeats. Detection of variants in IKBKG is challenging due to the presence of a highly homologous non-pathogenic pseudogene IKBKGP1. In this study, we successfully identified four pathogenic variants in four IP patients using a strategy based on single-tube long fragment read (stLFR) sequencing with a specialized analysis pipeline. Three frameshift variants (c.519-3_519dupCAGG, c.1167dupC, and c.700dupT) were identified and subsequently validated by Sanger sequencing. Notably, c.519-3_519dupCAGG was found in both IKBKG and IKBKGP1, whereas the other two variants were only detected in the functional gene. The IKBKGâ³4-10 deletion was identified and confirmed in one patient. These results demonstrate that the proposed strategy can identify potential pathogenic variants and distinguish whether they are derived from IKBKG or its pseudogene. Thus, this strategy can be an efficient genetic testing method for IKBKG. By providing a comprehensive understanding of the whole genome, it may also enable the exploration of other genes potentially associated with IP. Furthermore, the strategy may also provide insights into other diseases with detection challenges due to pseudogenes.
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An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4 array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of â¼2.446 kg m-2 h-1 and an impressive solar energy conversion efficiency of â¼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.