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Balancing the water consumption of agricultural and ecological is the key point of sustainable social and economic development in an inland river basin. The growth of desert riparian forests in inland river basins mainly depends on a certain phreatic water table depth (PWTD). The main object of this study was to allocate and schedule water resources to regulate the PWTD and satisfy agricultural water demand. Therefore, a multi-objective double layer optimal allocation and scheduling framework based on the computationally efficient integrated surface water-groundwater model (ISGWM), which can simulate the surface water processes, groundwater recharge and discharge processes, and PWTD changes, was constructed and applied to the mainstream of Tarim River Basin (TRB). The top layer model of the framework is an optimal ecological water allocation model, and its optimal allocation results are used as the initial solution of the bottom layer model. The results show that under 5 different inflow frequencies, the agricultural water shortage rate is 0, 17.38 %, 17.41 %, 14.06 %, and 19.94 %, respectively. The PWTD regulation has a great performance. After the optimal scheduling, the proportions of good growth of the control area behind the gate under different inflow frequencies were 98.18 %, 98.18 %, 98.18 %, 90.91 %, and 94.55 %. Agricultural water shortage is mainly due to the non-uniformity distribution of intra-annual inflow and the lack of controlling hydraulic engineering. The regulation of PWTD can guarantee the growth of desert riparian forests on both sides of the mainstream of TRB. Besides, we explored the feasibility of exploiting groundwater to supplement agricultural water consumption. The groundwater exploitation should be controlled within the scope of not causing excessive increase of PWTD (difference between PWTD and target depth <1 m), due to the groundwater exploitation to supplement agricultural water will lead to the increase of PWTD. Overall, this framework, which regulates the PWTD with the change of ecological water supply based on the ISGWM, provides a new idea for the allocation and scheduling of agricultural and ecological water resources in arid inland river basins. It also provides a new method for the coupled cooperative operation of surface water and groundwater.
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Agua Subterránea , Modelos Teóricos , Ríos , Abastecimiento de Agua , AgriculturaRESUMEN
Brain metastases (BMs) and high-grade gliomas (HGGs) are the most common and aggressive types of malignant brain tumors in adults, with often poor prognosis and short survival. As their clinical symptoms and image appearances on conventional magnetic resonance imaging (MRI) can be astonishingly similar, their accurate differentiation based solely on clinical and radiological information can be very challenging, particularly for "cancer of unknown primary", where no systemic malignancy is known or found. Non-invasive multiparametric MRI and radiomics offer the potential to identify these distinct biological properties, aiding in the characterization and differentiation of HGGs and BMs. However, there is a scarcity of publicly available multi-origin brain tumor imaging data for tumor characterization. In this paper, we introduce a multi-center, multi-origin brain tumor MRI (MOTUM) imaging dataset obtained from 67 patients: 29 with high-grade gliomas, 20 with lung metastases, 10 with breast metastases, 2 with gastric metastasis, 4 with ovarian metastasis, and 2 with melanoma metastasis. This dataset includes anonymized DICOM files alongside processed FLAIR, T1-weighted, contrast-enhanced T1-weighted, T2-weighted sequences images, segmentation masks of two tumor regions, and clinical data. Our data-sharing initiative is to support the benchmarking of automated tumor segmentation, multi-modal machine learning, and disease differentiation of multi-origin brain tumors in a multi-center setting.
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Neoplasias Encefálicas , Glioma , Imagen por Resonancia Magnética , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Glioma/patología , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/patología , Melanoma/diagnóstico por imagen , Melanoma/patologíaRESUMEN
Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction-associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH-associated hepatocellular carcinoma (MASH-HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA-16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH-HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH-fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.
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Carcinoma Hepatocelular , Disbiosis , Microbioma Gastrointestinal , Neoplasias Hepáticas , Ratones Endogámicos C57BL , Animales , Ratones , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/microbiología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/microbiología , Neoplasias Hepáticas/etiología , Disbiosis/microbiología , Masculino , Hígado Graso/metabolismo , Hígado Graso/patología , Hígado Graso/microbiología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Metabolismo de los Lípidos , Hígado/metabolismo , Hígado/patologíaRESUMEN
BACKGROUND: Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability (MSI) (MSI-H) metastatic colorectal cancer. However, the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI (MSI-L), and microsatellite stable (MSS) metastatic colorectal cancer remains unclear. AIM: To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer, and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months. METHODS: We conducted a retrospective cohort study using the National Cancer Database (NCDB) to evaluate the overall survival (OS) of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy. The study population was stratified by MSI status (MSI-H, MSI-L, and MSS). Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS, adjusting for potential confounders. RESULTS: A total of 21951 patients with metastatic colorectal cancer were included in the analysis, of which 2358 were MSI-H, and 19593 were MSI-L/MSS. In the MSI-H cohort, immunotherapy treatment (n = 142) was associated with a significantly improved median OS compared to chemotherapy (n = 860). After adjusting for potential confounders, immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort [adjusted hazard ratio (aHR): 0.57, 95% confidence interval (95%CI): 0.43-0.77, P < 0.001]. In the MSS cohort, no significant difference in median OS was observed between immunotherapy treatment and chemotherapy (aHR: 0.94, 95%CI: 0.69-1.29, P = 0.715). CONCLUSION: In this population-based study using the NCDB, immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer, but not in those with MSI-L/MSS metastatic colorectal cancer. Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.
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The sensitive and stable detection of trace heavy metals in liquid is crucial given its profound impact on various aspects of human life. Currently, nanoparticle-enhanced laser-induced breakdown spectroscopy (NELIBS) with dried droplet method (DDM) is widely applied for heavy metals detection. Nevertheless, the coffee ring effect (CRE) in DDM affects the stability, accuracy, and sensitivity of NELIBS. Here, we developed a slippery surface-aggregated substrate (SS substrate) to suppress the CRE and enrich analytes, and form a plasmonic platform for NELIBS detection. The SS substrate was prepared by infiltrating perfluorinated lubricant into the pores of PTFE membrane. The droplet, with targeted elements and gold nanoparticles, was dried on the SS substate to form the plasmonic platform for NELIBS analysis. Then, trace heavy metal elements copper (Cu) and manganese (Mn) were analyzed by NELIBS. The results of Cu (RSD = 5.60%, LoD = 3.72 µg/L) and Mn (RSD = 7.42%, LoD = 6.37 µg/L), illustrated the CRE suppression and analytes enrichment by the SS substrate. The results verified the realization of stable, accurate and sensitive NELIBS detection. And the LoDs succeeded to reach the standard limit of China (GB/T 14848-2017). Furthermore, the results for groundwater detection (relative error: 5.92% (Cu) and 4.74% (Mn)), comparing NELIBS and inductively coupled plasma mass spectrometry (ICP-MS), validated the feasibility of the SS substrate in practical applications. In summary, the SS substrate exhibits immense potential for practical application such as water quality detection and supervision.
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The origin of fast radio bursts (FRBs), the brightest cosmic explosion in radio bands, remains unknown. We introduce here a novel method for a comprehensive analysis of active FRBs' behaviors in the time-energy domain. Using "Pincus Index" and "Maximum Lyapunov Exponent", we were able to quantify the randomness and chaoticity, respectively, of the bursting events and put FRBs in the context of common transient physical phenomena, such as pulsar, earthquakes, and solar flares. In the bivariate time-energy domain, repeated FRB bursts' behaviors deviate significantly (more random, less chaotic) from pulsars, earthquakes, and solar flares. The waiting times between FRB bursts and the corresponding energy changes exhibit no correlation and remain unpredictable, suggesting that the emission of FRBs does not exhibit the time and energy clustering observed in seismic events. The pronounced stochasticity may arise from a singular source with high entropy or the combination of diverse emission mechanisms/sites. Consequently, our methodology serves as a pragmatic tool for illustrating the congruities and distinctions among diverse physical processes.
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Sheep milk is rich in fat, protein, vitamins and minerals and is also one of the most important sources of natural bioactives. Several biopeptides in sheep milk have been reported to possess antibacterial, antiviral and anti-inflammatory properties, and they may prevent type 2 diabetes (T2D), disease and cancer. However, the precise mechanism(s) underlying the protective role of sheep milk against T2D development remains unclear. Therefore, in the current study, we investigated the effect of sheep milk on insulin resistance and glucose intolerance in high-fat diet (HFD)-fed mice, by conducting intraperitoneal glucose tolerance tests, metabolic cage studies, genomic sequencing, polymerase chain reaction, and biochemical assays. Hyperinsulinemic-euglycemic clamp-based experiments revealed that mice consuming sheep milk exhibited lower hepatic glucose production than mice in the control group. These findings further elucidate the mechanism by which dietary supplementation with sheep milk alleviates HFD-induced systemic glucose intolerance.
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Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Resistencia a la Insulina , Ovinos , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Intolerancia a la Glucosa/metabolismo , Intolerancia a la Glucosa/prevención & control , Diabetes Mellitus Tipo 2/prevención & control , Leche/metabolismoRESUMEN
This study aimed to explore the role of melatonin in oxidative stress-induced injury on retinal ganglion cells and the underlying mechanisms. The immortalized RGC-5 cells were treated with H2O2 to induce oxidative injury. Cell viability was measured by Cell Counting Kit-8, and apoptosis was determined by flow cytometry and western blot assays. Reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels were examined to evaluate oxidative stress levels. In addition, Thioredoxin-1 (Trx1) was silenced in RGC-5 cells using small interfering RNA followed by signaling pathway examination to explore the underlying mechanisms of melatonin in alleviating oxidative injury. Melatonin pre-treatment significantly alleviated H2O2-induced apoptosis in RGC-5 cells. Melatonin also markedly reversed the upregulation of cleaved-caspase 3, cleaved-caspase 9, and Bax expression and downregulation of Bcl-2 expression induced by H2O2. Further analyses presented that melatonin significantly attenuated the increase of ROS, LDH, and MDA levels in RGC-5 cells after H2O2 treatment. Melatonin also abolished the downregulated expression of Superoxide dismutase type 1, Trx1, and Thioredoxin reductase 1, and the reduced activity of thioredoxin reductase in RGC-5 cells after H2O2 treatment. Notably, Trx1 knockdown significantly mitigated the protective effect of melatonin in alleviating H2O2-induced apoptosis and oxidative stress, while administration of compound C, a common inhibitor of c-Jun N-terminal kinase (JNK) signaling, partially reversed the effect of Trx1 silencing, thereby ameliorating the apoptosis and oxidative injury induced by H2O2 in RGC-5 cells. Melatonin could significantly alleviate oxidative stress-induced injury of retinal ganglion cells via modulating Trx1-mediated JNK signaling pathway.
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Burkholderia gladioli pv. cocovenenans is a serious safety issue in black fungus due to the deadly toxin, bongkrekic acid. This has triggered the demand for an efficient toxigenic phenotype recognition method. The objective of this study is to develop an efficient method for the recognition of toxin-producing B. gladioli strains. The potential of multilocus sequence typing and a back propagation neural network for the recognition of toxigenic B. cocovenenans was explored for the first time. The virulent strains were isolated from a black fungus cultivation environment in Qinba Mountain area, Shaanxi, China. A comprehensive evaluation of toxigenic capability of 26 isolates were conducted using Ultra Performance Liquid Chromatography for determination of bongkrekic acid and toxoflavin production in different culturing conditions and foods. The isolates produced bongkrekic acid in the range of 0.05-6.24 mg/L in black fungus and a highly toxin-producing strain generated 201.86 mg/L bongkrekic acid and 45.26 mg/L toxoflavin in co-cultivation with Rhizopus oryzae on PDA medium. Multilocus sequence typing phylogeny (MLST) analysis showed that housekeeping gene sequences have a certain relationship with a strain toxigenic phenotype. We developed a well-trained, back-propagation neutral network for prediction of toxigenic phenotype in B. gladioli based on MLST sequences with an accuracy of 100% in the training set and an accuracy of 86.7% in external test set strains. The BP neutral network offers a highly efficient approach to predict toxigenic phenotype of strains and contributes to hazard detection and safety surveillance.
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BACKGROUND: The triglyceride-glucose index (TyG), an established indicator of insulin resistance, is closely correlated with the prognosis of several metabolic disorders. This study aims to investigate the association between the TyG index and the incidence of critical delirium in patients aged 65 years and older. METHODS: We focused on evaluating patients aged 65 years and older diagnosed with critical delirium. Data were obtained from the Medical Information Database for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Multivariate logistic regression and restricted cubic spline (RCS) regression were used to determine the relationship between the TyG index and the risk of delirium. RESULTS: Participants aged 65 years and older were identified from the MIMIC-IV (n = 4,649) and eICU-CRD (n = 1,844) databases. Based on optimal thresholds derived from RCS regression, participants were divided into two cohorts: Q1 (< 8.912), Q2 (≥ 8.912). The logistic regression analysis showed a direct correlation between the TyG index and an increased risk of critical delirium among ICU patients aged 65 and older. These findings were validated in the eICU-CRD dataset, and sensitivity analysis further strengthened our conclusions. In addition, the subgroup analysis revealed certain differences. CONCLUSION: This study highlights a clear, independent relationship between the TyG index and the risk of critical delirium in individuals aged 65 years and older, suggesting the importance of the TyG index as a reliable cardio-cerebrovascular metabolic marker for risk assessment and intervention.
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Cuidados Críticos , Delirio , Humanos , Bases de Datos Factuales , Glucosa , Triglicéridos , Delirio/diagnóstico , Delirio/epidemiología , Glucemia , Biomarcadores , Factores de RiesgoRESUMEN
Malignant glioma is a highly vascularized tumor. Therefore, inhibition of angiogenesis is an effective treatment strategy for it. Alphastatin is a 24amino acid peptide that has been demonstrated to inhibit glioma angiogenesis and tumor growth. Adiposederived stem cells (ADSCs) are considered an ideal targeted drug delivery system for glioma therapy due to their targeted tropism for cancer and the intrinsic attribute of autologous transplantation. The aim of the present study was to construct an ADSCmediated alphastatin targeted delivery system and investigate its effects on angiogenesis in glioma. The sequence encoding the human neurotrophin4 signal peptide and alphastatin fusion gene fragment was transferred into ADSCs using a lentiviral vector to construct the ADSCmediated alphastatin targeted delivery system (AlADSCs). Flow cytometry was used to detect the stem cell surface markers of AlADSCs. Western blot analysis and ELISA were used to detect the expression and secretion of alphastatin peptide in AlADSCs. Cell migration assay was used to detect the tendency of AlADSCs to target CD133+ glioma stem cells (GSCs). The effects of AlADSCs on angiogenesis in vitro were detected by tube formation assay. A Cell Counting Kit8 assay was used to detect the effects of AlADSCs on endothelial cell (EC) proliferation. Wound healing assay was used to examine the effects of AlADSCs on EC migration. Intracranial xenograft models were constructed and in vivo fluorescence imaging was used to examine the effects of AlADSCs on glioma growth. Fluorescence microscopy was used to detect the distribution of AlADSCs in glioma tissue and CD133 immunofluorescence staining was used to detect the effects of AlADSCs on GSCs in glioma tissue. The results revealed that ADSCs exhibited more marked tropism to GSCs than to other types of cells (P<0.01). AlADSCs maintained the surface markers of ADSCs and there was no significant difference between the ADSCs and AlADSCs regarding tropism to GSCs (P=0.639 for GSCsSHG44 cells; and P=0.386 for GSCsU87 cells). AlADSCs were able to successfully secrete and express alphastatin peptide and inhibited ECmediated angiogenesis (P<0.01) and EC migration (P<0.01) and proliferation (P<0.01) in vitro. In vivo, AlADSCs were detected in glioma tissue and were able to inhibit tumor growth. In addition, the AlADSCs reduced the number of GSCs and microvascular density (P<0.01) in the tumors. Overall, the results of the present study indicated that the AlADSCs were able to target glioma tissue and inhibit glioma angiogenesis and tumor growth. This antiangiogenic targeted therapy system may provide a new strategy for the treatment of glioma.
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Neoplasias Encefálicas , Glioma , Humanos , Glioma/tratamiento farmacológico , Glioma/metabolismo , Fibrinógeno/metabolismo , Péptidos/metabolismo , Proliferación Celular , Células Madre/metabolismo , Línea Celular Tumoral , Células Madre Neoplásicas/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismoRESUMEN
Endophytic microbes are a ubiquitous group of plant-associated communities that colonize the intercellular or intracellular host tissues while providing numerous beneficial effects to the plants. All the plant species are thought to be associated with endophytes, majorly constituted with bacteria and fungi. During the last two decades, there has been a considerable movement toward the study of endophytes associated with coffee plants. In this review, the main consideration is given to address the coffee-associated endophytic bacteria and fungi, particularly their action on plant growth promotion and the biocontrol of pests. In addition, we sought to identify and analyze the gaps in the available research. Additionally, the potential of endophytes to improve the quality of coffee seeds is briefly discussed. Even though there are limited studies on the subject, the potentiality of coffee endophytes in plant growth promotion through enhancing nitrogen fixation, availability of minerals, nutrient absorption, secretion of phytohormones, and other bioactive metabolites has been well recognized. Further, the antagonistic effect against various coffee pathogenic bacteria, fungi, nematodes, and also insect pests leads to the protection of the crop. Furthermore, it is recognized that endophytes enhance the sensory characteristics of coffee as a new field of study.
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OBJECTIVES: Postponed open necrosectomy or minimally invasive intervention has become the treatment option for necrotizing pancreatitis. Nevertheless, several studies point to the safety and efficacy of early intervention for necrotizing pancreatitis. Therefore, we conducted a systematic review and meta-analysis to compare clinical outcomes of acute necrotizing pancreatitis between early and late intervention. METHODS: Literature search was performed in multiple databases for articles that compared the safety and clinical outcomes of early (<4 weeks from the onset of pancreatitis) versus late intervention (≥4 weeks from the onset of pancreatitis) for necrotizing pancreatitis published up to August 31, 2022. The meta-analysis was performed to determine pooled odds ratio (OR) of mortality rate and procedure-related complications. RESULTS: Fourteen studies were included in the final analysis. For open necrosectomy intervention, the overall pooled OR of mortality rate with the late intervention compared with early intervention was 7.09 (95% confidence interval [CI] 2.33-21.60; I2 = 54%; P = 0.0006). For minimally invasive intervention, the overall pooled OR of mortality rate with the late intervention compared with early intervention was 1.56 (95% CI 1.11-2.20; I2 = 0%; P = 0.01). The overall pooled OR of pancreatic fistula with the late minimally invasive intervention compared with early intervention was 2.49 (95% CI 1.75-3.52; I2 = 0%; P < 0.00001). CONCLUSION: These results showed the benefit of late interventions in patients with necrotizing pancreatitis in both minimally invasive procedures and open necrosectomy. Late intervention is preferred in the management of necrotizing pancreatitis.
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Pancreatitis Aguda Necrotizante , Humanos , Pancreatitis Aguda Necrotizante/cirugía , Drenaje/métodos , Resultado del Tratamiento , Fístula PancreáticaRESUMEN
Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Papilar , Humanos , Femenino , Carcinoma Ductal de Mama/metabolismo , Supervivencia sin Enfermedad , Carcinoma Papilar/patología , Neoplasias de la Mama/metabolismo , Metaboloma , Metiltransferasas/metabolismo , Pronóstico , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Represoras/metabolismoRESUMEN
Posttranslational modification (PTM) of proteins is essential for increasing protein diversity and maintaining cellular homeostasis, but uncontrolled modification may lead to tumorigenesis. Arginine methylation is a tumorigenesisrelated PTM that affects protein function through proteinprotein and proteinnucleic acid interactions. Protein arginine methyltransferases (PRMTs) have vital roles in signalling pathways of tumourintrinsic and tumourextrinsic microenvironments. The present review summarizes the modifications and functions of PRMTs in histone methylation and nonhistone methylation, their roles in RNA splicing and DNA damage repair and the currently known functions in tumour metabolism and immunotherapy. In conclusion, this article reviews the latest research progress on the role of PRMTs in tumour signal transduction, providing a theoretical basis for clinical diagnosis and treatment. Targeting PRMTs is expected to provide new directions for tumour therapy.
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Neoplasias , Humanos , Neoplasias/genética , Epigénesis Genética , Procesamiento Proteico-Postraduccional , Transducción de Señal , Carcinogénesis/genética , Arginina/genética , Arginina/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Microambiente Tumoral/genéticaRESUMEN
Introduction: Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease related to metabolic syndrome. However, ecological shifts in the saliva microbiome in patients with MAFLD remain unknown. This study aimed to investigate the changes to the salivary microbial community in patients with MAFLD and explore the potential function of microbiota. Methods: Salivary microbiomes from ten MAFLD patients and ten healthy participants were analyzed by 16S rRNA amplicon sequencing and bioinformatics analysis. Body composition, plasma enzymes, hormones, and blood lipid profiles were assessed with physical examinations and laboratory tests. Results: The salivary microbiome of MAFLD patients was characterized by increased α-diversity and distinct ß-diversity clustering compared with control subjects. Linear discriminant analysis effect size analysis showed a total of 44 taxa significantly differed between the two groups. Genera Neisseria, Filifactor, and Capnocytophaga were identified as differentially enriched genera for comparison of the two groups. Co-occurrence networks suggested that the salivary microbiota from MAFLD patients exhibited more intricate and robust interrelationships. The diagnostic model based on the salivary microbiome achieved a good diagnostic power with an area under the curve of 0.82(95% CI: 0.61-1). Redundancy analysis and spearman correlation analysis revealed that clinical variables related to insulin resistance and obesity were strongly associated with the microbial community. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to metabolism were more prevalent in the two groups. Conclusions: Patients with MAFLD manifested ecological shifts in the salivary microbiome, and the saliva microbiome-based diagnostic model provides a promising approach for auxiliary MAFLD diagnosis.
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Microbiota , Enfermedad del Hígado Graso no Alcohólico , Humanos , Metagenoma , Enfermedad del Hígado Graso no Alcohólico/microbiología , Filogenia , ARN Ribosómico 16S/genética , Saliva/microbiologíaRESUMEN
INTRODUCTION: ALDH2, IGSF9, and PRDM16 play crucial roles in regulating diverse cellular pathophysiologic functions. The current study was to evaluate the effect of the 3 proteins on clinicopathologic features and prognosis of patients with breast cancer. MATERIALS AND METHODS: The formalin-fixed and paraffin-embedded tissue specimens were collected from breast cancer patients by immunohistochemistry (IHC) were analyzed. RESULTS: Of the 216 patients enrolled, ALDH2 high expression was significantly correlated with the age (p = .040), larger tumor size (p = .001), LVI (p < .001), LNM (p < .001), advanced TNM staging (p < .001), PR (p = .027), HER2 status (p = .002), and molecular subtype (p = .003). IGSF9 low expression was significantly correlated with the LV1 (p = .024), LNM (p = .024), advanced TNM staging (p = .001). The low expression of PRDM16 was significantly correlated with age (p = .023), and LNM (p = .014). The A+I-P- expression (13.4%) were markedly correlated with lymphatic vessel invasion (LVI) (p < .001), lymph node metastasis (LNM) (p < .001), advanced TNM staging (p < .001). Furthermore, patients with A+I-P- expression had significantly advanced-stage breast cancer [stage III (72.4%) vs. (23.0%)]. Univariate and multivariate analysis identified variables (ie, larger tumor size, lymph node involvement, and A+I-P- expression) as independent prognostic factors for survival. CONCLUSION: Our results reveal ALDH2 high expression, IGSF9 and PRDM16 low expression, A+I-P- expression was associated with advanced clinicopathological characteristics, and shorter OS and DFS in breast cancer patients. The 3 proteins may be potential prognosis markers and therapeutic targets for breast cancer patients.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Pronóstico , Estadificación de Neoplasias , Receptor ErbB-2/metabolismo , Biomarcadores de Tumor , Metástasis Linfática , Factores de Transcripción , Aldehído Deshidrogenasa Mitocondrial , Inmunoglobulinas , Proteínas del Tejido Nervioso , Proteínas de Unión al ADNRESUMEN
The attribution of single particle sources of atmospheric aerosols is an essential problem in the study of air pollution. However, it is still difficult to qualitatively analyze the source of a single aerosol particle using noncontact in situ techniques. Hence, we proposed using optical trapping to combine gated Raman spectroscopy with laser-induced breakdown spectroscopy (LIBS) in a single levitated micron aerosol. The findings of the spectroscopic imaging indicated that the particle plasma formed by a single particle ablation with a pulsed laser within 7 ns deviates from the trapped particle location. The LIBS acquisition field of view was expanded using the 19-bundle fiber, which also reduces the fluctuation of a single particle signal. In addition, gated Raman was utilized to suppress the fluorescence and increase the Raman signal-to-noise ratio. Based on this, Raman can measure hard-to-ionize substances with LIBS, such as sulfates. The LIBS radical can overcome the restriction that Raman cannot detect ionic chemicals like fluoride and chloride in halogens. To test the capability of directly identifying distinctive feature compounds utilizing spectra, we detected anions using Raman spectroscopy and cations using LIBS. Four typical mineral aerosols are subjected to precise qualitative evaluations (marble, gypsum, baking soda, and activated carbon adsorbed potassium bicarbonate). To further validate the application potential for substances with indistinctive feature discrimination, we employed machine learning algorithms to conduct a qualitative analysis of the coal aerosol from ten different origin regions. Three data fusion methodologies (early fusion, intermediate fusion, and late fusion) for Raman and LIBS are implemented, respectively. The accuracy of the late fusion model prediction using StackingClassifier is higher than that of the LIBS data (66.7%) and Raman data (86.1%) models, with an average accuracy of 90.6%. This research has the potential to provide online single aerosol analysis as well as technical assistance for aerosol monitoring and early warning.
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Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n = 25) and IDC (n = 26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.