RESUMEN

Humic acid (HA), a principal constituent of natural organic matter (NOM), manifests ubiquitously across diverse ecosystems and can significantly influence the environmental behaviors of Cd(II) in aquatic systems. Previous studies on NOM-Cd(II) interactions have primarily focused on the immobilization of Cd(II) solids, but little is known about the colloidal stability of organically complexed Cd(II) particles in the environment. In this study, we investigated the formation of HA-Cd(II) colloids and quantified their aggregation, stability, and transport behaviors in a saturated porous media representative of typical subsurface conditions. Results from batch experiments indicated that the relative quantity of HA-Cd(II) colloids increased with increasing C/Cd molar ratio and that the carboxyl functional groups of HA dominated the stability of HA-Cd(II) colloids. The results of correlation analysis between particle size, critical aggregation concentration (CCC), and zeta potential indicated that both Derjaguin-Landau-Verwey-Overbeek (DLVO) and non-DLVO interactions contributed to the enhanced colloidal stability of HA-Cd(II) colloids. Column results further confirmed that the stable HA-Cd(II) colloid can transport fast in a saturated media composed of clean sand. Together, this study provides new knowledge of the colloidal behaviors of NOM-Cd(II) nanoparticles, which is important for better understanding the ultimate cycling of Cd(II) in aquatic systems.

Asunto(s)

Cadmio , Coloides , Sustancias Húmicas , Contaminantes Químicos del Agua , Sustancias Húmicas/análisis , Cadmio/química , Coloides/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Nanopartículas del Metal/química , Modelos Químicos , Nanopartículas/química

RESUMEN

BACKGROUND: The reconstruction of complex wounds of the hand still has challenges in achieving aesthetic, functional and sensory recovery. We presented our experience of using the polyfoliate and chimeric radial collateral artery perforator flaps (RCAPF) to repair complex hand defects, aiming to explore the feasibility of special-form RCAPFs in hand coverage and enhance the comprehension of their respective indications. METHODS: From June 2014 to March 2021, 26 cases (19 males and 7 females, mean 44.4 years) underwent defect and sensation reconstruction of their hands with special-form RCAPFs, which manifested as multiple adjacent or irregular single wounds and composite tissue defects complicated with a degree of nerve injury. The clinical effects of the free RCAPFs were evaluated by integrating the postoperative and long-term follow-up outcomes of all cases. RESULTS: Altogether 8 polyfoliate flaps, 17 chimeric flaps and 1 polyfoliate-chimeric flap were harvested. Of them, 23 flaps survived uneventfully in one stage. Venous congestion occurred in 3 cases, two of which survived through vascular exploration and another one was finally repaired by the contralateral RCAPF. The follow-up results showed that the appearance of both the recipient and donor sites mostly recovered satisfactory. All the bone flaps properly healed. The BMRC sensory evaluation results of all skin flaps were S4 in 8 flaps, S3 in 18 flaps, and S2 in 9 flaps. CONCLUSIONS: The free RCAPFs can be designed in various forms with a reliable blood supply, contributing to reconstructing simple and multiple wounds of the hand with or without bone defects and dead space.

Asunto(s)

Traumatismos de la Mano , Colgajo Perforante , Procedimientos de Cirugía Plástica , Arteria Radial , Humanos , Femenino , Masculino , Colgajo Perforante/irrigación sanguínea , Adulto , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Arteria Radial/trasplante , Traumatismos de la Mano/cirugía , Mano/cirugía , Mano/irrigación sanguínea , Adulto Joven , Estudios de Seguimiento , Resultado del Tratamiento , Estudios de Factibilidad

RESUMEN

So-called strength-ductility trade-off is usually an inevitable scenario in precipitation-strengthened alloys. To address this challenge, high-density coherent nanoprecipitates (CNPs) as a microstructure effectively promote ductility though multiple interactions between CNPs and dislocations (i.e., coherency, order, or Orowan mechanism). Although some strain hardening theories have been reported for individual strengthening, how to increase, artificially and quantitatively, the ductility arising from cooperative strengthening due to the multiple interactions has not been realized. Accordingly, a dislocation-based theoretical framework for strain hardening is constructed in terms of irreversible thermodynamics, where nucleation, gliding, and annihilation arising from dislocations have been integrated, so that the cooperative strengthening can be treated through thermodynamic driving force ∆G and the kinetic energy barrier. Further combined with synchrotron high-energy X-ray diffraction, the current model is verified. Following the modeling, the yield stress σy is proved to be correlated with the modified strengthening mechanism, whereas the necking strain εn is shown to depend on the evolving dislocation density and, essentially, the enhanced activation volume. A criterion of high ∆G-high generalized stability is proposed to guarantee the volume fraction of CNPs improving σy and the radius of CNPs accelerating εn. This strategy of breaking the strength-ductility trade-off phenomena by controlling the cooperative strengthening can be generalized to designing metallic structured materials.

RESUMEN

Breast cancer stands as the cancer with the highest incidence and mortality rates among women globally, in which triple-negative breast cancer has been ranked as the most difficult one. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM), has been exhibited notable inhibitory effect on both hormone-dependent breast cancer cells and triple-negative breast cancer cells, but showing very low in vivo effeacy. In order to obtain more effective antitumor derivatives than BZA, we have employed a structurally diverse design and synthesis of 57 novel 2-phenylindole amides for detecting their cytotoxities against triple-negative mammary cancer cell line, CMT-7364. Among them, 21 compounds demonstrated significant inhibitory activity against CMT-7364 cells (IC50 < 20 µM). Notably, compound 49 stood out, displaying both similar tumor cell inhibition (20 % reduce in IC50 value) and higher selectivity (4.6 times higher in SI value), compared to Bazedoxifene. Additionally, compound 49 exhibited desirable antitumor effects in a CMT-7364 cell-derived mouse in vivo model, achieving the best inhibition rate of 43.1 % and establishing strong molecular bonding with GP130. Our findings are also supported by comprehensive SAR and 3D-QSAR analyses. Furthermore, the best potent compound 49 was determined to block the cell cycle of canine breast cancer cells in the G0G1 phase in a time-dependent manner, by inducing apoptosis and autophagy. In conclusion, this work presents a valuable lead compound as a potential GP130 inhibitor against triple-negative breast cancer cell lines, laying the foundation for further antitumor drug development.

RESUMEN

The environmental impact of dissolved trace element (DTE) pollution is becoming increasingly well understood. The southeastern edge of the Qinghai-Tibet Plateau is a region with high environmental vulnerability, making it highly susceptible to various anthropogenic disturbances. The Lancang River (LCR), as the most representative river in this area, serving as the largest international river in Southeast Asia, the LCR is crucial for the downstream regions, supporting fisheries, agriculture, and even economic development, earning it the title of the "water tower" for these areas. This study mainly focuses on the upstream unbuilt dam area. In this study, we gathered 25 surface water samples from the upstream of the LCR and examined the geographical distribution, primary sources, and associated human health risks of seven dissolved trace elements (Mn, Cr, Fe, Co, Cu, Ni, Zn). Cr, Fe, Co, Ni, and Cu in the main stream are primarily associated with natural sources, including rock weathering, soil erosion, and similar processes. Mn, however, predominantly originates from human activities such as industrial construction and road transportation. Zn mainly originates from the specialized fertilizers used for highland barley in plateau regions. Almost all DTE concentrations exhibited a downward trend from upstream to downstream. However, due to inputs from various sources along the way, there will be some abnormal points. The concentrations of DTE in the study area were within the acceptable limits set by drinking water standards in China, the USA, and the WHO. Overall, the water quality in this region is considered good. The results from a Monte Carlo simulation assessing health risks indicate that the non-carcinogenic health risk caused by DTE in the upper reaches of Lancang River was very weak. The primary pathway through which DTE can harm human health is ingestion, with children being particularly vulnerable. These findings offer a critical scientific basis for understanding the migration of DTE in aquatic environments and for the ecological stewardship of the Lancang River.

Asunto(s)

Monitoreo del Ambiente , Ríos , Oligoelementos , Contaminantes Químicos del Agua , Ríos/química , Contaminantes Químicos del Agua/análisis , Oligoelementos/análisis , Medición de Riesgo , Humanos , China , Tibet

RESUMEN

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates formed by the structured accumulation of immune cells such as B cells and T cells in non-lymphoid tissues induced by infection, inflammation, and tumors. They play a crucial role in the immune response, particularly in association with tumor development, where they primarily exert anti-tumor immune functions during tumorigenesis. Current research suggests that TLSs inhibit tumor growth by facilitating immune cell infiltration and are correlated with favorable prognosis in various solid tumors, serving as an indicator of immunotherapy effectiveness to some extent. Therefore, TLSs hold great promise as a valuable biomarker. Most importantly, immunotherapies aimed to prompting TLSs formation are anticipated to be potent adjuncts to current cancer treatment. This review focuses on the formation process of TLSs and their potential applications in cancer therapy.

RESUMEN

Long-chain acyl-CoA synthetases (LACSs), belonging to the acyl-activating enzyme superfamily, play crucial roles in lipid biosynthesis and fatty acid catabolism. Here, we identified 11 LACS genes in the tomato reference genome, and these genes were clustered into six subfamilies. Gene structure and conserved motif analyses indicated that LACSs from the same subfamily shared conserved gene and protein structures. Expression analysis revealed that SlLACS1 was highly expressed in the outer epidermis of tomato fruits and leaves. Subcellular localization assay results showed that SlLACS1 was located in the endoplasmic reticulum. Compared with wild-type plants, the wax content on leaves and fruits decreased by 22.5-34.2 % in SlLACS1 knockout lines, confirming that SlLACS1 was involved in wax biosynthesis in both leaves and fruits. Water loss, chlorophyll extraction, water-deficit, and toluidine blue assays suggested that cuticle permeability was elevated in SlLACS1 knockout lines, resulting in reduction in both drought stress resistance and fruit shelf-life. Overall, our analysis of the LACSs in tomato, coupled with investigations of SlLACS1 function, yielded a deeper understanding of the evolutionary patterns of LACS members and revealed the involvement of SlLACS1 in wax accumulation contribute to drought resistance and extended fruit shelf-life in tomato.

Asunto(s)

Coenzima A Ligasas , Regulación de la Expresión Génica de las Plantas , Solanum lycopersicum , Ceras , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Frutas/genética , Frutas/metabolismo , Familia de Multigenes , Filogenia , Epidermis de la Planta/metabolismo , Epidermis de la Planta/genética , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Solanum lycopersicum/enzimología , Ceras/metabolismo

RESUMEN

Zearalenone (ZEN) is a fungal toxin produced by Fusarium exospore, which poses a significant threat to both animal and human health due to its reproductive toxicity. Removing ZEN through ZEN lactonase is currently the most effective method reported, however, all published ZEN lactonases suffer from the poor thermal stability, losing almost all activity after 10 min of treatment at 55℃. In this study, we heterologously expressed ZHD11A from Phialophora macrospora and engineered it via semi-rational design. A mutant I160Y-G242S that can retain about 40 % residual activity at 55℃ for 10 min was obtained, which is the most heat-tolerant ZEN hydrolase reported to date. Moreover, the specific activity of the I160Y-G242S was also elevated 2-fold compared to ZHD11A from 220 U/mg to 450 U/mg, which is one of the most active ZEN lactonses reported. Dynamics analysis revealed that the decreased flexibility of the main-chain carbons contributes to increased thermal stability and the improved substrate binding affinity and catalytic turnover contribute to enhanced activity of variant I160Y-G242S. In all, the mutant I160Y-G242S is an excellent candidate for the industrial application of ZEN degradation.

Asunto(s)

Estabilidad de Enzimas , Zearalenona , Zearalenona/metabolismo , Zearalenona/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Cinética , Ingeniería de Proteínas , Hidrolasas/metabolismo , Hidrolasas/genética , Hidrolasas/química , Lactonas/metabolismo , Lactonas/química , Calor , Especificidad por Sustrato

RESUMEN

Studying the apportionment of source-specific health risks and control factors for heavy metal pollution in karst regions is crucial for prevention and management. A typical karst basin was chosen in this study to investigate the pollution characteristics of heavy metals, source-specific health risks, and control factors. The results indicate that during the rainy season, As, Cd, and Pb, as well as As during the dry season, were the primary elements responsible for water pollution in the watershed. Comparative analyses showed that the absolute principal component-multiple linear regression (APCS-MLR) model better identifies and quantifies the sources of heavy metals in karst basin waters. The analysis of health risks revealed that during the dry season, heavy metals in the basin posed a moderate cancer risk to adults (10-4 < total cancer risk (TCR) < 10-3), whereas during the rainy season, these heavy metals posed a non-cancer risk (total hazard index (THI) > 1) and a moderate to high cancer risk (10-4 < TCR < 10-2). The APCS-MLR model combined with the health risk analysis showed that Industrial waste discharge sources are the main contributors to the health of basin residents (29.39%-52.57%), making dry season As a non-cancer risk for basin residents, as well as rainy season As and Cd a non-cancer risk and a high cancer risk for basin residents. Therefore, reasonable planning for upstream industrial production should be developed, and priority should be given to monitoring and treating As and Cd pollution in water. Analyses also showed that input pathways, dilution effects, and hydrochemical characteristics may influence the spatial and temporal variability of heavy metals in the basin. The results provide essential information and significant reference for prioritising and managing the health risks associated with heavy metal pollution in water bodies in karst areas.

Asunto(s)

Metales Pesados , Contaminantes Químicos del Agua , Metales Pesados/análisis , China , Contaminantes Químicos del Agua/análisis , Humanos , Medición de Riesgo , Monitoreo del Ambiente , Estaciones del Año

RESUMEN

Activated persulfate and hydrothermal treatment (HTT) are often employed to treat waste activated sludge, which can improve the efficiency of subsequent sludge treatment and change the distribution of pollutants in the sludge. However, the impact of sludge solid content and temperature on the occurrence and aging of microplastics (MPs) during HTT remains poorly understood. This study investigated the effects of persulfate-HTT (SPS-HTT) co-treatment on the migration, occurrence, and aging of MPs in sludge with different solid contents (2% and 5% solid content). The results indicated that SPS-HTT co-treatment triggers both the disruption of sludge flocs and the melting deformation of MPs at high temperatures, leading to variations in the increasing trend of MP concentration in the solid-liquid phase at different solid contents. 5% solid content sludge showed a weak release of MPs from the solid phase. The proportion of fiber MPs first increased and then decreased with increasing temperature, while no significant changes were observed in the color and type of MPs. Higher temperature and solid content induced the melting deformation of MPs, exacerbated the aging of polypropylene MPs, and resulted in rough surfaces, higher carbonyl index, and variations in crystallinity. Moreover, the correlation between the carbonyl index and aging indicators increased with increasing solid content. The MP-derived dissolved organic matter under HTT primarily comprised soluble microbial by-products and humic acid-like substances. These findings underscore the significance of sludge solid content in affecting the migration and aging of MPs during HTT, and offer novel insights into the application of HTT to MP management in sludge treatment.

Asunto(s)

Microplásticos , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisis , Temperatura , Sulfatos/química

RESUMEN

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

RESUMEN

Fleshy fruits become more susceptible to pathogen infection when they ripen; for example, changes in cell wall properties related to softening make it easier for pathogens to infect fruits. The need for high-quality fruit has driven extensive research on improving pathogen resistance in important fruit crops such as tomato (Solanum lycopersicum). In this review, we summarize current progress in understanding how changes in fruit properties during ripening affect infection by pathogens. These changes affect physical barriers that limit pathogen entry, such as the fruit epidermis and its cuticle, along with other defenses that limit pathogen growth, such as preformed and induced defense compounds. The plant immune system also protects ripening fruit by recognizing pathogens and initiating defense responses involving reactive oxygen species production, mitogen-activated protein kinase signaling cascades, and jasmonic acid, salicylic acid, ethylene, and abscisic acid signaling. These phytohormones regulate an intricate web of transcription factors (TFs) that activate resistance mechanisms, including the expression of pathogenesis-related genes. In tomato, ripening regulators, such as RIPENING INHIBITOR and NON_RIPENING, not only regulate ripening but also influence fruit defenses against pathogens. Moreover, members of the ETHYLENE RESPONSE FACTOR (ERF) family play pivotal and distinct roles in ripening and defense, with different members being regulated by different phytohormones. We also discuss the interaction of ripening-related and defense-related TFs with the Mediator transcription complex. As the ripening processes in climacteric and non-climacteric fruits share many similarities, these processes have broad applications across fruiting crops. Further research on the individual contributions of ERFs and other TFs will inform efforts to diminish disease susceptibility in ripe fruit, satisfy the growing demand for high-quality fruit and decrease food waste and related economic losses.

RESUMEN

The thin soil layer with uneven distribution in karst areas facilitates the migration of phosphorus (P) to groundwater, threatening the safety of water sources seriously. To offer a scientific guidance for water pollution control and land use planning in karst areas, this study examined the relationships between land use and P in groundwater and surface water, and quantified the phosphate sources in Gaoping river basin, a small typical watershed in karst areas. Spatial distribution analysis revealed that the highest mean P concentrations in groundwater and surface water were in farmland and construction-farmland zones, respectively. Land use impact analysis showed that the concentration of P in groundwater was influenced positively by farmland but negatively by forest land. In contrast, the concentration of P in surface water was influenced positively by both farmland and construction land. The mixed end-element and Bayesian-based Stable Isotope Analysis in R (SIAR) model results showed that agricultural fertilizers were the main phosphate source for groundwater in farmland and forest-farmland zones, while urban sewage was the main source in the construction-farmland zone. For surface water, the main phosphate source was agricultural fertilizers in both farmland and construction-farmland zones. This study indicates that controlling P pollution in local water bodies should pay close attention to the management of land use related to human activities, including regulating sewage discharge from construction land and agricultural fertilizer usage.

Asunto(s)

Agricultura , Monitoreo del Ambiente , Agua Subterránea , Fosfatos , Fósforo , Agua Subterránea/análisis , Agua Subterránea/química , Fósforo/análisis , Fosfatos/análisis , Contaminantes Químicos del Agua/análisis , Fertilizantes/análisis , Ríos/química

RESUMEN

The functional investigation of proteins holds immense significance in unraveling physiological and pathological mechanisms of organisms as well as advancing the development of novel pharmaceuticals in biomedicine. However, the study of cellular protein function using conventional genetic manipulation methods may yield unpredictable outcomes and erroneous conclusions. Therefore, precise modulation of protein activity within cells holds immense significance in the realm of biomedical research. Chromophore-assisted light inactivation (CALI) is a technique that labels photosensitizers onto target proteins and induces the production of reactive oxygen species through light control to achieve precise inactivation of target proteins. Based on the type and characteristics of photosensitizers, different excitation light sources and labeling methods are selected. For instance, KillerRed forms a fusion protein with the target protein through genetic engineering for labeling and inactivates the target protein via light activation. CALI is presently predominantly employed in diverse biomedical domains encompassing investigations into protein functionality and interaction, intercellular signal transduction research, as well as cancer exploration and therapy. With the continuous advancement of CALI technology, it is anticipated to emerge as a formidable instrument in the realm of life sciences, yielding more captivating outcomes for fundamental life sciences and precise disease diagnosis and treatment.

RESUMEN

Cancer is a significant global public health issue with increasing morbidity and mortality rates. To address this challenge, novel drug carriers such as nano-materials, liposomes, hydrogels, fibers, and microspheres have been extensively researched and utilized in oncology. Among them, polymer microspheres are gaining popularity due to their ease of preparation, excellent performance, biocompatibility, and drug-release capabilities. This paper categorizes commonly used materials for polymer microsphere preparation, summarizes various preparation methods (emulsification, phase separation, spray drying, electrospray, microfluidics, and membrane emulsification), and reviews the applications of polymer microspheres in cancer diagnosis, therapy, and postoperative care. The current status and future development directions of polymer microspheres in cancer treatment are analyzed, highlighting their importance and potential for improving patient outcomes.

Asunto(s)

Microesferas , Neoplasias , Polímeros , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Polímeros/química , Portadores de Fármacos/química , Animales , Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos

RESUMEN

Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.

Asunto(s)

Proteínas Bacterianas , Burkholderia pseudomallei , Macrófagos , Mitocondrias , Mitofagia , Burkholderia pseudomallei/metabolismo , Burkholderia pseudomallei/patogenicidad , Burkholderia pseudomallei/fisiología , Burkholderia pseudomallei/genética , Animales , Ratones , Mitocondrias/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Humanos , Macrófagos/microbiología , Macrófagos/metabolismo , Ubiquitinación , Melioidosis/microbiología , Melioidosis/metabolismo , Interacciones Huésped-Patógeno , Especies Reactivas de Oxígeno/metabolismo , Sistemas de Secreción Tipo III/metabolismo , Sistemas de Secreción Tipo III/genética , Ratones Endogámicos C57BL , Membranas Mitocondriales/metabolismo , Células HEK293 , Células RAW 264.7

RESUMEN

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment.

Asunto(s)

Neoplasias de la Mama , Proliferación Celular , Histonas , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glucólisis/genética , Histonas/metabolismo , L-Lactato Deshidrogenasa/metabolismo , L-Lactato Deshidrogenasa/genética , Lactato Deshidrogenasa 5/metabolismo , Lactato Deshidrogenasa 5/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Metástasis de la Neoplasia , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Canales de Potasio de Dominio Poro en Tándem/genética , Pronóstico , Regulación hacia Arriba/genética

RESUMEN

The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC50 of 14.3 µM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1ß and IL-8 at 10 µM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.

Asunto(s)

Antivirales , Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos , Iridoides , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Humanos , Iridoides/farmacología , Iridoides/química , Antivirales/farmacología , Antivirales/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Células A549 , Células HEK293 , COVID-19 , Proteasas 3C de Coronavirus/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Coronavirus Humano OC43/efectos de los fármacos

RESUMEN

Plant invasions severely threaten natural ecosystems, and invasive plants often outcompete native plants across various ecosystems. Arbuscular mycorrhizal (AM) fungi, serving as beneficial microorganisms for host plants, can greatly influence the competitive outcomes of invasive plants against native plants. However, it remains unclear how AM fungi alter the competitive balance between native and invasive species. A competitive experiment was conducted using an invasive Eupatorium adenophorum paired with a native congener Eupatorium lindleyanum. Specifically, both species were inoculated with (M+) or without (M-) the fungus Glomus etunicatum under intraspecific (Intra-) and interspecific (Inter-) competition. Plant traits were measured and analyzed regarding the growth and nutrition of both species. The results exhibited that the AM fungus significantly increased the height, diameter, biomass, C, N, and P acquisition of both the invasive E. adenophorum and the native E. lindleyanum. The root mycorrhizal colonization and the mycorrhizal dependency of native E. lindleyanum were greater than those of invasive E. adenophorum. Under M+, the Inter-competition inhibited the growth and nutrition of invasive E. adenophorum compared to the Intra- competition. Further, native E. lindleyanum exhibited higher competitiveness than invasive E. adenophorum in growth and nutrition. Meanwhile, the AM fungus significantly improved the competitiveness of native E. lindleyanum over invasive E. adenophorum. In conclusion, AM fungus improved the competitive advantage of native E. lindleyanum over invasive E. adenophorum in growth and nutrition, potentially contributing to native species competitively resisting the invasion of exotic species. These findings emphasize the importance of AM fungi in helping native plants resist the invasion of exotic plants and further contribute to understanding plant invasion prevention mechanisms.