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R-2-hydroxyglutarate (R-2HG), produced at high levels by mutant isocitrate dehydrogenase 1/2 (IDH1/2) enzymes, was reported as an oncometabolite. We show here that R-2HG also exerts a broad anti-leukemic activity in vitro and in vivo by inhibiting leukemia cell proliferation/viability and by promoting cell-cycle arrest and apoptosis. Mechanistically, R-2HG inhibits fat mass and obesity-associated protein (FTO) activity, thereby increasing global N6-methyladenosine (m6A) RNA modification in R-2HG-sensitive leukemia cells, which in turn decreases the stability of MYC/CEBPA transcripts, leading to the suppression of relevant pathways. Ectopically expressed mutant IDH1 and S-2HG recapitulate the effects of R-2HG. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. Collectively, while R-2HG accumulated in IDH1/2 mutant cancers contributes to cancer initiation, our work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CEBPA signaling.
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Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Glutaratos/farmacología , Leucemia/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Adenosina/análogos & derivados , Adenosina/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Animales , Antineoplásicos/uso terapéutico , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Línea Celular Tumoral , Glutaratos/uso terapéutico , Células HEK293 , Humanos , Células Jurkat , Ratones , Proteínas Proto-Oncogénicas c-myc/metabolismo , Procesamiento Postranscripcional del ARNRESUMEN
Cyanobacteriota, the sole prokaryotes capable of oxygenic photosynthesis (OxyP), occupy a unique and pivotal role in Earth's history. While the notion that OxyP may have originated from Cyanobacteriota is widely accepted, its early evolution remains elusive. Here, by using both metagenomics and metatranscriptomics, we explore 36 metagenome-assembled genomes from hot spring ecosystems, belonging to two deep-branching cyanobacterial orders: Thermostichales and Gloeomargaritales. Functional investigation reveals that Thermostichales encode the crucial thylakoid membrane biogenesis protein, vesicle-inducing protein in plastids 1 (Vipp1). Based on the phylogenetic results, we infer that the evolution of the thylakoid membrane predates the divergence of Thermostichales from other cyanobacterial groups and that Thermostichales may be the most ancient lineage known to date to have inherited this feature from their common ancestor. Apart from OxyP, both lineages are potentially capable of sulfide-driven AnoxyP by linking sulfide oxidation to the photosynthetic electron transport chain. Unexpectedly, this AnoxyP capacity appears to be an acquired feature, as the key gene sqr was horizontally transferred from later-evolved cyanobacterial lineages. The presence of two D1 protein variants in Thermostichales suggests the functional flexibility of photosystems, ensuring their survival in fluctuating redox environments. Furthermore, all MAGs feature streamlined phycobilisomes with a preference for capturing longer-wavelength light, implying a unique evolutionary trajectory. Collectively, these results reveal the photosynthetic flexibility in these early-diverging cyanobacterial lineages, shedding new light on the early evolution of Cyanobacteriota and their photosynthetic processes.
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Cianobacterias , Fotosíntesis , Fotosíntesis/genética , Cianobacterias/genética , Cianobacterias/metabolismo , Evolución Biológica , Filogenia , Oxígeno/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Evolución MolecularRESUMEN
Mitochondrial DNA (mtDNA) encodes several key components of respiratory chain complexes that produce cellular energy through oxidative phosphorylation. mtDNA is vulnerable to damage under various physiological stresses, especially oxidative stress. mtDNA damage leads to mitochondrial dysfunction, and dysfunctional mitochondria can be removed by mitophagy, an essential process in cellular homeostasis. However, how damaged mtDNA is selectively cleared from the cell, and how damaged mtDNA triggers mitophagy, remain mostly unknown. Here, we identified a novel mitophagy receptor, ATAD3B, which is specifically expressed in primates. ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy. Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA. Our findings uncover a new pathway to selectively remove damaged mtDNA and reveal that increasing ATAD3B activity is a potential therapeutic approach for mitochondrial diseases.
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ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Mitofagia , Estrés Oxidativo , ATPasas Asociadas con Actividades Celulares Diversas/química , ATPasas Asociadas con Actividades Celulares Diversas/genética , Animales , Células Cultivadas , Daño del ADN , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Células HEK293 , Células HeLa , Humanos , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Mitocondriales/química , Proteínas Mitocondriales/genética , Unión ProteicaRESUMEN
Aryl amines are one of the most common moieties in biologically active molecules, and approximately 37% of drug candidates contain aromatic amines. Recent advancements in medicinal chemistry, coined "escaping from flatland", have led to a greater focus on accessing highly functionalized C (sp3)-rich amines to improve the physicochemical and pharmacokinetic properties of compounds. This article presents a modular and operationally straightforward three-component alkyl Petasis boron-Mannich (APBM) reaction that utilizes ubiquitous starting materials, including amines, aldehydes, and alkyl boronates. By adaptation of this transformation to high-throughput experimentation (HTE), it offers rapid access to an array of diverse C(sp3)-rich complex amines, amenable for rapid identification of drug candidates.
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A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.
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Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Etopósido , Filgrastim , Movilización de Célula Madre Hematopoyética , Linfoma , Mieloma Múltiple , Polietilenglicoles , Humanos , Filgrastim/administración & dosificación , Filgrastim/uso terapéutico , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Femenino , Masculino , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Adulto , Linfoma/tratamiento farmacológico , Linfoma/terapia , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Estudios Prospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Movilización de Célula Madre Hematopoyética/métodos , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. METHODS: To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. RESULTS: Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p < 0.0001) and the CRC subcutaneous murine model (35.0 ± 2.6, p < 0.0001). CCR8 was found to be preferentially expressed on these tumor-infiltrating Tregs (CRC patients: 63.6 ± 16.0, p < 0.0001; CRC murine model: 65.3 ± 9.5, p < 0.0001), which correlated with poor survival. We found that majority of the CCR8+ Tregs expressed activation markers and exhibited strong suppressive functions. Treatment with anti-CCR8 antibody hampered the growth of subcutaneous CRC tumor through effectively restoring the anti-tumor immunity of CD4+ conventional T cells (CD4+ Tconvs) and CD8+ T cells, which was confirmed in the ex vivo examinations. CONCLUSIONS: Collectively, these findings illustrate the importance of CCR8+ Tregs for an immunosuppressive microenvironment in CRC tumors by functional inhibition of CD4+ Tconvs and CD8+ T cells, and suggest for the applicable value of CCR8-targeted therapy for CRC.
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Linfocitos T CD8-positivos , Neoplasias Colorrectales , Linfocitos Infiltrantes de Tumor , Receptores CCR8 , Linfocitos T Reguladores , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Inmunidad , Linfocitos Infiltrantes de Tumor/inmunología , Ratones Endogámicos BALB C , Linfocitos T Reguladores/inmunología , AncianoRESUMEN
Addressing recurrent cervical cancer poses a substantial challenge. Osimertinib, an FDA-approved EGFR inhibitor, has emerged as a promising option. Our study examined its potential to enhance paclitaxel's efficacy against cervical cancer. Osimertinib effectively hindered cancer cell growth and induced apoptosis across multiple cell lines. Combined with paclitaxel, it exhibited synergy in suppressing cervical cancer cells. Importantly, osimertinib's inhibitory effect was EGFR-independent; it targeted Mnk phosphorylation, reducing eIF4E activity. In mice, the combined osimertinib-paclitaxel treatment surpassed individual drugs in inhibiting cancer growth. These preclinical findings suggest osimertinib's repurposing as a means to improve paclitaxel's effectiveness in cervical cancer treatment.
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Acrilamidas , Compuestos de Anilina , Paclitaxel , Neoplasias del Cuello Uterino , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Humanos , Acrilamidas/farmacología , Acrilamidas/uso terapéutico , Femenino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Animales , Ratones , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Línea Celular Tumoral , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Indoles , PirimidinasRESUMEN
A Gram-stain-negative, non-endospore-forming, motile, short rod-shaped strain, designated SYSU G07232T, was isolated from a hot spring microbial mat, sampled from Rehai National Park, Tengchong, Yunnan Province, south-western China. Strain SYSU G07232T grew at 25-50â°C (optimum, 37â°C), at pH 5.5-9.0 (optimum, pH 6.0) and tolerated NaCl concentrations up to 1.0â% (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SYSU G07232T showed closest genetic affinity with Chelatococcus daeguensis K106T. The genomic features and taxonomic status of this strain were determined through whole-genome sequencing and a polyphasic approach. The predominant quinone of this strain was Q-10. Major cellular fatty acids comprised C19â:â0 cyclo ω8c and summed feature 8. The whole-genome length of strain SYSU G07232T was 4.02 Mbp, and the DNA G+C content was 69.26âmol%. The average nucleotide identity (ANIm ≤84.85â% and ANIb ≤76.08ââ%) and digital DNA-DNA hybridization (≤ 21.9â%) values between strain SYSU G07232T and the reference species were lower than the threshold values recommended for distinguishing novel prokaryotic species. Thus, based on the provided phenotypic, phylogenetic, and genetic data, it is proposed that strain SYSU G07232T (=KCTC 8141T=GDMCC 1.4178T) be designated as representing a novel species within the genus Chelatococcus, named Chelatococcus albus sp. nov.
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Beijerinckiaceae , Manantiales de Aguas Termales , Filogenia , ARN Ribosómico 16S/genética , Composición de Base , China , Ácidos Grasos/química , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , BacteriasRESUMEN
Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 µg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 µg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.
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Estrógenos , Animales , Masculino , Femenino , Microcistinas/toxicidad , Ranidae/genética , Ranidae/metabolismo , Toxinas Marinas , Contaminantes Químicos del Agua/toxicidadRESUMEN
Microorganisms are integral to freshwater ecological functions and, reciprocally, their activity and diversity are shaped by the ecosystem state. Yet, the diversity of bacterial community and its driving factors at a large scale remain elusive. To bridge this knowledge gap, we delved into an analysis of 16S RNA gene sequences extracted from 929 water samples across China. Our analyses revealed that inland water bacterial communities showed a weak latitudinal diversity gradient. We found 530 bacterial genera with high relative abundance of hgcI clade. Among them, 29 core bacterial genera were identified, that is strongly linked to mean annual temperature and nutrient loadings. We also detected a non-linear response of bacterial network complexity to the increasing of human pressure. Mantel analysis suggested that MAT, HPI and P loading were the major factors driving bacterial communities in inland waters. The map of taxa abundance showed that the abundant CL500-29 marine group in eastern and southern China indicated high eutrophication risk. Our findings enhance our understanding of the diversity and large-scale biogeographic pattern of bacterial communities of inland waters and have important implications for microbial ecology.
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Bacterias , ARN Ribosómico 16S , China , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , ARN Ribosómico 16S/análisis , ARN Ribosómico 16S/genética , Biodiversidad , Microbiología del Agua , Agua Dulce/microbiologíaRESUMEN
Traditional long-wave infrared polarimetry usually relies on complex optical setups, making it challenging to meet the increasing demand for system miniaturization. To address this problem, we design an all-silicon broadband achromatic polarization-multiplexing metalens (BAPM) operating at the wavelength range of 9-12 µm. A machine-learning-based design method is developed to replace the tedious and computationally intensive simulation of a large number of meta-atoms. The results indicate that the coefficients of variation in focal length of the BAPM are 3.95% and 3.71%, and the average focusing efficiencies are 41.3% and 40.5% under broadband light incidence with x- and y-polarizations, respectively.
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OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical reirradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.
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Neoplasias Nasofaríngeas , Traumatismos por Radiación , Radiodermatitis , Radioterapia de Intensidad Modulada , Reirradiación , Humanos , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias Nasofaríngeas/patología , Úlcera/etiología , Dosificación Radioterapéutica , Traumatismos por Radiación/etiología , Estudios Retrospectivos , Nasofaringe/patología , Radiodermatitis/etiologíaRESUMEN
Previous research showed that suicide risk was associated with the anger trait and the facial expression of anger when advising on life dilemmas. We investigated if suicide risk was associated with the facial expression of anger during rest, a state when individuals often reflect upon their lives. Participants took a 1-min rest before being assessed for suicide risk. We measured 147 participants' frontal-view facial expressions during their rest 1475-3694 times using automated facial expression analysis technology. Participants' suicide risk was significantly positively correlated with their anger and disgust during the rest, which may be related to psychological pain and death-related thoughts among individuals with suicide risk. Therefore, rest for clinical patients should not be seen simply as a "rest" for the mind. Rather, for counselors, rest may open a window to look into patients' inner thoughts that may be important to their lives.
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Asco , Suicidio , Humanos , Emociones , Ira , Expresión FacialRESUMEN
The application of nitrification inhibitors (nitrapyrin) and urease inhibitors (N-(N-butyl) thiophosphoric triamide) under conventional water resources has been considered as an effective means to improve nitrogen utilization efficiency and mitigate soil greenhouse gas emissions. However, it is not known whether the inhibitors still have an inhibitory effect under unconventional water resources (reclaimed water and livestock wastewater) irrigation and whether their use in combination with biochar improves the mitigation effect. Therefore, unconventional water resources were used for irrigation, with groundwater (GW) control. Nitrapyrin and N-(N-butyl) thiophosphoric triamide were used alone or in combination with biochar in a pot experiment, and CO2, N2O, and CH4 emissions were measured. The results showed that irrigation of unconventional water resources exacerbated global warming potential (GWP). All exogenous substance treatments increased CO2 and CH4 emissions and suppressed N2O emissions, independent of the type of water, compared to no substances (NS). The inhibitors were ineffective in reducing the GWP whether or not in combination with biochar, and the combined application of inhibitors with biochar further increased the GWP. This study suggests that using inhibitors and biochar in combination to regulate the greenhouse effect under unconventional water resources irrigation should be done with caution.
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Agricultura , Carbón Orgánico , Ganado , Compuestos Organofosforados , Animales , Agricultura/métodos , Aguas Residuales , Calentamiento Global , Dióxido de Carbono/análisis , Óxido Nitroso/análisis , Suelo , Fertilizantes , MetanoRESUMEN
The toll-like receptor 4 (TLR4) signaling pathway constitutes an intricate network of protein interactions primarily involved in inflammation and cancer. This pathway triggers intracellular signaling cascades, modulating transcription factors that regulate gene expression related to immunity and malignancy. Previous studies showed that colon cancer patients with low TLR4 expression exhibit extended survival times and the TLR4 signaling pathway holds a significant role in CRC pathogenesis. In recent years, traditional Chinese medicines (TCMs) have garnered substantial attention as an alternative therapeutic modality for CRC, primarily due to their multifaceted composition and ability to target multiple pathways. Emerging evidence indicates that specific TCM products, such as andrographolide, rosmarinic acid, baicalin, etc., have the potential to impede CRC development through the TLR4 signaling pathway. Here, we review the role and biochemical processes of the TLR4 signaling pathway in CRC, and natural products from TCMs affecting the TLR4 pathway. This review sheds light on potential treatment strategies utilizing natural TLR4 inhibitors for CRC, which contributes to the advancement of research and accelerates their clinical integration into CRC treatment.
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Productos Biológicos , Neoplasias Colorrectales , Medicamentos Herbarios Chinos , Transducción de Señal , Receptor Toll-Like 4 , Humanos , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Transducción de Señal/efectos de los fármacos , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacología , Productos Biológicos/química , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicina Tradicional China , Animales , Medicina de Hierbas/métodosRESUMEN
The connectivity of urban river networks plays an important role in cities in many aspects, such as urban water safety, water quality (WQ), and aquatic ecological balance. This study focuses on the river network and the Majiawan Wetland in the Chaoyang District of Beijing by establishing a two-dimensional hydrological WQ model employing various water allocation schemes between the river network and the wetland. Water circulation and WQ are the main indexes, and the effects of different scenarios on improving water circulation and WQ are simulated and compared. This study demonstrates that the addition of water replenishment at the intersection of river network and internal slow-water zones of the wetland (Scheme 2) has greater effectiveness in improving both hydrology and WQ compared to two other schemes. The water area of the Majiawan Wetland has expanded, and water velocity has increased. Using chemical oxygen demand, total nitrogen, and total phosphorus as the index values for determining the water class, the WQ of about 20% of the wetland area was reached Water Class II (domestic drinking water), with Water Class III (general industrial water) accounting for the other 80%. This study provides valuable evaluation and reference for similar areas of urban river network connectivity.
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Ríos , Calidad del Agua , Humedales , Ríos/química , Ciudades , Modelos Teóricos , China , Simulación por ComputadorRESUMEN
Based on the insulin receptor substrate(IRS)/phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) pathway, the intervention effect of Yupingfeng Powder on type 2 diabetes mellitus(T2DM) rats was studied, and the potential mechanism of improving T2DM hepatic insulin resistance was explored. A T2DM rat model was established by feeding with high-fat and high-sugar feed combined with intraperitoneal injection of streptozotocin. Successfully modeled rats were selected and divided into a model group, a positive control group(MET), and a Yupingfeng Powder group. At the same time, a blank group was set up, and corresponding drugs were given by gavage. The model group and blank group were given an equal amount of physiological saline by gavage. During the experiment, body mass and fasting blood glucose were regularly measured, and glucose tolerance and insulin tolerance were measured at the end of the experiment. After the experiment, the levels of blood glucose, insulin, blood lipids, and related liver function indicators were measured; changes in liver pathological damage were observed, levels of liver monoamine oxidase were detected, and qRT-PCR was used to detect mRNA expression levels of IRS/PI3K/Akt pathway related genes. Compared with the model group, the Yupingfeng Powder group had an increase in body weight, a decrease in fasting blood glucose, fasting insulin, and steady-state model evaluation index, a decrease in the area under the curve of glucose tolerance and insulin tolerance tests, a decrease in serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol content, and an increase in high-density lipoprotein cholesterol content. Compared with the model group, the Yupingfeng Powder group showed a decrease in liver monoamine oxidase levels, a decrease in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels, and an increase in total protein and albumin levels. Hematoxylin-eosin(HE) staining showed a reduction in pathological liver cell damage. Compared with the model group, the Yupingfeng Powder group showed a significant increase in the mRNA expression levels of IRS1, PI3K, and Akt in the liver of rats, as well as a significant decrease in the mRNA expression levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α). This indicates that Yupingfeng Powder can regulate the IRS/PI3K/Akt signaling pathway and glucose and lipid metabolism disorders, increase insulin sensitivity, improve hepatic insulin resistance, and thus play a therapeutic role in T2DM.
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Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Proteínas Sustrato del Receptor de Insulina , Resistencia a la Insulina , Hígado , Fosfatidilinositol 3-Quinasas , Polvos , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Ratas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Hígado/metabolismo , Hígado/efectos de los fármacos , Masculino , Proteínas Sustrato del Receptor de Insulina/metabolismo , Proteínas Sustrato del Receptor de Insulina/genética , Transducción de Señal/efectos de los fármacos , Ratas Sprague-Dawley , Glucemia/metabolismo , Insulina/metabolismo , HumanosRESUMEN
BACKGROUND: Calcific insertional Achilles tendinopathy(CIAT) with Haglund deformity is a type of recalcitrant tendinopathy. The necessity of concomitant removal of Haglund deformity during CIAT treatment is controversial. The present study aimed to evaluate the functional outcomes between Haglund resection and Haglund non-resection in the treatment of CIAT with Haglund deformity. METHODS: A retrospective study included 29 patients who were underwent Achilles tendon debridement, bursal excision, and subsequent tendon reattachment.for CIAT with Haglund deformity. All patients were divided into 2 groups according to Haglund resection (resection group, n = 16) and Haglund non-resection (non-resection group, n = 13) using the parallel line method on lateral calcaneal X ray after surgery. Patients were evaluated in terms of the American Orthopedic Foot and Ankle Society (AOFAS), Visual Analog Scale (VAS) and Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and the mean time of activities of daily living (ADL). Anatomy changes included the Fowler-Philip angle, calcaneal pitch angle and Achilles tendon force arm were measured with radiography preoperatively and postoperatively. RESULTS: Both groups exhibited a significant increase in AOFAS, VAS and VISA-A scores after surgery. There were no significant differences between the resection group and the non-resection group for the AOFAS (92.38 ± 5.7 vs. 93.15 ± 12.17; P = 0.82), VAS (0.5 ± 0.52 vs. 0.61 ± 0.87; P = 0.66) and VISA-A questionnaire (82.56 ± 13.46 vs. 74.92 ± 16.4; P = 0.18) at the latest follow-up. The mean time of ADL in the non-resection group was significantly faster compared to that of the resection group (8.15 ± 2.51 weeks vs. 11.31 ± 4.06 weeks, P = 0.02). The Fowler-Philip angle of the resection group decreased from 55.55° ± 12.34° preoperatively to 44.52° ± 10.24° at the latest follow-up (P = 0.001). The Fowler-Philip angle of the non-resection group decreased from 54.38° ± 8.41° preoperatively to 46.52° ± 8.02° at the latest follow-up (P = 0.016). The calcaneal pitch angle of the resection group increased from 22.76° ± 5.37° preoperatively to 25.98° ± 6. 4° at the latest follow-up (P = 0.018). The Achilles tendon force arm of the resection group decreased from 178.50 mm ± 5.37 mm preoperatively to 173.90 mm ± 8.07 mm at the latest follow-up (P = 0.018). CONCLUSION: Resection or non-resection of the posterosuperior calcaneal tuberosity for CIAT with Haglund deformity would both provide satisfactory functional outcomes. Haglund non-resection may expedite patients' return to their daily activities, suggesting a Haglund deformity resection may be unnecessary in the surgical treatment for CIAT with Haglund deformity.
Asunto(s)
Tendón Calcáneo , Calcinosis , Tendinopatía , Humanos , Tendón Calcáneo/cirugía , Tendón Calcáneo/diagnóstico por imagen , Estudios Retrospectivos , Tendinopatía/cirugía , Tendinopatía/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Adulto , Calcinosis/cirugía , Calcinosis/diagnóstico por imagen , Calcáneo/cirugía , Calcáneo/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Three dimensional (3D) framework structure is one of the most effective ways to achieve uniform zinc deposition and thus inhibit the Zn dendrites growth in working Zn metallic anode. A major challenge facing for the most commonly used 3D zincophilic hosts is that the zincophilic layer tends to peel off during repeatedly cycling, making it less stable. Herein, for the first time, a hetero-superlattice Zn/ZnLi (HS-Zn/ZnLi) anode containing periodic arrangements of metallic Zn phase and zincophilic ZnLi phase at the nanoscale, is well designed and fabricated via electrochemical lithiation method. Based on binding energy and stripping energy calculation, and the operando optical observation of plating/stripping behaviors, the zincophilic ZnLi sites with a strong Zn adsorption ability in the interior of the 3D ZnLi framework structure can effectively guide uniform Zn nucleation and dendrite-free zinc deposition, which significantly improves the cycling stability of the HS-Zn/ZnLi alloy (over 2800 h without a short-circuit at 2 mA cm-2). More importantly, this strategy can be extended to HS-Zn/ZnNa and HS-Zn/ZnK anodes that are similar to the HS-Zn/ZnLi microstructure, also displaying significantly enhanced cycling performances in AZIBs. This study can provide a novel strategy to develop the dendrite-free metal anodes with stable cycling performance.
RESUMEN
Quasi-solid zinc-ion batteries using hydrogel electrolytes show great potential in energy storage devices owing to their intrinsic safety, fewer side reactions and wide electrochemical windows. However, the dendrite issues on the zinc anodes cannot be fundamentally eliminated and the intrinsic anode-electrolyte interfacial interspace is rarely investigated. Here, we design a dynamically healable gelatin-based hydrogel electrolyte with a highly reversible sol-gel transition, which can construct a conformal electrode-electrolyte interface and further evolve into a stable solid-solid interface by in situ solidification. The unique helical gelatin chain structure provides a uniform channel for zinc ion transport by the bridging effect of sulfate groups. As a consequence, the dynamically healable interface enables dendrite-free zinc anodes and repeatedly repairs the anode-electrolyte interfacial interspaces by the reversible sol-gel transition of gelatin electrolyte to retain long-lasting protection for sustainable zinc-ion batteries.