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1.
Sci Rep ; 14(1): 15346, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961201

RESUMEN

Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.

2.
Cell Rep ; 43(7): 114429, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38968074

RESUMEN

Social deficits are frequently observed in patients suffering from neurodevelopmental disorders, but the molecular mechanisms regulating sociability are still poorly understood. We recently reported that the loss of the microRNA (miRNA) cluster miR-379-410 leads to hypersocial behavior and anxiety in mice. Here, we show that ablating miR-379-410 in excitatory neurons of the postnatal mouse hippocampus recapitulates hypersociability, but not anxiety. At the cellular level, miR-379-410 loss in excitatory neurons leads to larger dendritic spines, increased excitatory synaptic transmission, and upregulation of an actomyosin gene network. Re-expression of three cluster miRNAs, as well as pharmacological inhibition of the actomyosin activator ROCK, is sufficient to reinstate normal sociability in miR-379-410 knockout mice. Several actomyosin genes and miR-379-410 family members are reciprocally dysregulated in isogenic human induced pluripotent stem cell (iPSC)-derived neurons harboring a deletion present in patients with Williams-Beuren syndrome, characterized by hypersocial behavior. Together, our results show an miRNA-actomyosin pathway involved in social behavior regulation.

3.
J Environ Sci (China) ; 146: 67-80, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38969463

RESUMEN

Groundwater is the main source of drinking water for the rural population in the chronic kidney disease of unknown etiology (CKDu) zone of the North Central Province (NCP) in Sri Lanka. In this study, a total of 334 groundwater samples (311 dug wells, 21 tube wells and 2 springs) during the wet season from two aquifers in the NCP were collected, and investigated their chemical characteristics and evaluate their water quality, including groundwater chemistry, main ion sources, the corrosion and scaling potential of groundwater. The results showed that the two hydrochemical types of groundwater in the NCP were mainly of the Ca-HCO3, Na·Ca-HCO3 types, with the main HCO3-, Na+ and Ca2+ ions in both types of groundwater originating from silicate and evaporite salt dissolution and influenced by alternating cation adsorption, while the presence of NO3- was mainly anthropogenic. Evaluation of water stability using namely Langelier saturation index (LSI), Ryznar stability index (RSI), Puckorius scaling index (PSI) and Larson-Skold index (LS), indicated that most groundwater presents corrosion potential and has corrosion behavior tendency of metals to some degrees. The water quality of Polonnaruwa was better than that of Anuradhapura in the NCP, and when the groundwater was worse than the "good" grade, which must be properly treated before it is used as drinking water.


Asunto(s)
Monitoreo del Ambiente , Agua Subterránea , Contaminantes Químicos del Agua , Sri Lanka , Agua Subterránea/química , Contaminantes Químicos del Agua/análisis , Calidad del Agua , Insuficiencia Renal Crónica , Agua Potable/química , Agua Potable/análisis , Abastecimiento de Agua
4.
Sci Rep ; 14(1): 15222, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956233

RESUMEN

The critical value of rock failure is determined by irreversible deformation (inelastic deformation, damage, and other internal dissipation) processes and external conditions before rock failure. Nevertheless, a thorough explanation of the mechanism causing cracks in rock material has not yet been provided. The strain energy theory is applied in this work to assess the initiation of rock cracks and investigate the relationship between energy digestion and rock strength. Firstly, the uniaxial compression test was conducted on sandstone samples under quasi-static loading conditions and the results of energy evolution, non-linear cumulative digestion, and stored ultimate energy were obtained. Then, a novel algorithm for assessing the initiation of rock cracks has been put forth. The concept of energy digestion index (EDI), which is the ratio of digested energy over the external loading energy, has been developed to characterize the energy absorption capacity of rock material. The result shows a relationship between the maximum growth rate of energy digestion and the increasing rate of variable elasticity modulus and crack initiation. The mechanical characteristics and peak strength of the rock material are negatively correlated with the EDI. By monitoring the digested energy status, an evaluation of the residual strength is introduced based on the relationships, which will initiate further research into in-situ monitoring and failure prediction.

5.
Sci Total Environ ; : 174651, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38992376

RESUMEN

The understanding of global carbon has rarely extended to small-scale tropical river basins. To address these uncertainties, this study aims to investigate the importance of rock weathering and organic matter turnover in the carbon cycle in a terrain dominated by crystalline silicate rocks. The geochemical composition of the dissolved and particulate carbon phases (DIC, DOC and POC) and their stable carbon isotopes were studied in the Deduru Oya River in Sri Lanka. Dissolved inorganic carbon (DIC) was the most dominant carbon phase and its contribution to the total carbon pool varied between 67 and 89 %. Furthermore, the δ13CDIC values in the river varied between -1.1 and -16.5 ‰. The lithological characteristics and molar ratios between Ca2+, Mg2+ and HCO3- indicated rock weathering mainly by CO2 and carbonic acid. The δ13CDIC values for groundwater input were -15.9 ‰, while for carbonate weathering, mainly due to fertiliser input, they reached a value of -12.7 ‰. This input was fed into an isotope mass balance to determine the relative contributions. However, the isotope mass balance was only plausible after correcting for the effects on the δ13CDIC caused by degassing and photosynthesis. Our study demonstrated that carbonate weathering and organic matter turnover are essential components of the river carbon cycle even in a silicate dominated catchment. They can represent up to 60 % of the DIC pool. Combined with the higher organic matter turnover and high pCO2 in the river water, it can be suggested that the Deduru Oya River acts as a net source of CO2 in the atmosphere. Our study shows that CO2 degassing and in-stream photosynthesis in tropical river systems need to be considered along with chemical weathering to account for carbon transport and turnover in tropical rivers.

6.
Heliyon ; 10(12): e33043, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38984312

RESUMEN

The intrusive bodies in the study area are categorized into two intrusive units, γπK2 and ηoπK2, based on rock structure characteristics and intrusive contact relationships. The primary lithologies are granite porphyry and quartz monzonite porphyry. Through LA-ICP-MS zircon U-Pb dating, the weighted mean ages of zircon ^206Pb/^238U for these two units were determined to be 84.09 ± 0.86 Ma and 86.10 ± 0.76 Ma, respectively. According to geochemical characteristics and Sr-Yb granite classification, the quartz monzonite porphyry is classified as Zhejiang-Fujian type granite, and the granite porphyry as Nanling type granite. The study explores the geodynamic significance of granites in the area based on Sr-Yb granite classification, identifying the lower crust metamorphic facies as amphibolite facies. The source rocks are primarily basic granulites and felsic granulites, reflecting a thermally active lower crust with poorly developed fluids. Additionally, Sr-Yb granite classification aids in determining the crustal thickness of the lower crust, which is crucial for understanding continental geological evolution. This paper discusses the optimal locations and conditions for mineralizing fluid precipitation, noting that tungsten-tin mineralization is associated with Nanling type granites and that the mineralization process generally occurs later than the diagenetic process under conditions of low pressure and low oxygen fugacity. Tungsten-tin prospecting should focus on areas where the surrounding rock temperature ranges from 300 to 500 °C, with particular attention to the contact zones of sedimentary rocks or near structural fault zones.

7.
J Environ Manage ; 366: 121702, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38986376

RESUMEN

Phosphorus (P) fertilisers are under scrutiny due to resource constraints and environmental impacts. Simple rock phosphate (RP) modifications with acids and co-applied with microbial inoculum could offer sustainable alternative P fertiliser products. We evaluated the effects of acid-treated rock phosphate (RP) in combination with fungal inoculum on plant establishment, environmental impacts (nutrient leaching) and soil quality in a 5-month pot trial. The treatments were evaluated in a clayey Vertisol and a silty Acrisol using cotton (Gossypium hirsutum) as a model plant. The RP treatments - apart from the unmodified and HCl products - were effective in promoting plant establishment with two of the microbial formulations superior to conventional P fertilisers by an average factor of 2 in both soil types (p < 0.05). All RP products restricted P leaching compared with conventional P fertilisers (p < 0.05), by an average factor of 5 for diammonium phosphate (DAP) in both soil types and 3 for the triple superphosphate TSP (only in Acrisol). Nitrate leaching from all treatments was high although much lower from the RP treatments compared with the conventional fertilisers towards the end of the establishment trial, by an average factor of 1.5 (p < 0.05). Ranking analysis revealed that some RP treatments showed evidence for improved ongoing soil quality, including decreased P leaching and soil acidification risks. Microbial analysis showed complex interactions between treatment and soil type. Nonetheless, inoculum persistence at the end of the plant establishment phase was observed for all pots analysed. Our results demonstrate that relatively simple modifications to RP could pave the way for developing sustainable P fertilisers.

8.
Biochim Biophys Acta Gen Subj ; : 130669, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38996990

RESUMEN

BACKGROUND: Dysregulation of Rho-associated coiled coil-containing protein kinases (ROCKs) is involved in the metastasis and progression of various malignant tumors. However, how one of the isomers, ROCK1, regulates glycolysis in tumor cells is incompletely understood. Here, we attempted to elucidate how ROCK1 influences pancreatic cancer (PC) progression by regulating glycolytic activity. METHODS: The biological function of ROCK1 was analyzed in vitro by establishing a silenced cell model. Coimmunoprecipitation confirmed the direct binding between ROCK1 and c-MYC, and a luciferase reporter assay revealed the binding of c-MYC to the promoter of the PFKFB3 gene. These results were verified in animal experiments. RESULTS: ROCK1 was highly expressed in PC tissues and enriched in the cytoplasm, and its high expression was associated with a poor prognosis. Silencing ROCK1 inhibited the proliferation and migration of PC cells and promoted their apoptosis. Mechanistically, ROCK1 directly interacted with c-MYC, promoted its phosphorylation (Ser 62) and suppressed its degradation, thereby increasing the transcription of the key glycolysis regulatory factor PFKFB3, enhancing glycolytic activity and promoting PC growth. Silencing ROCK1 increased gemcitabine (GEM) sensitivity in vivo and in vitro. CONCLUSIONS: ROCK1 promotes glycolytic activity in PC cells and promotes PC tumor growth through the c-MYC/PFKFB3 signaling pathway. ROCK1 knockdown can inhibit PC tumor growth in vivo and increase the GEM sensitivity of PC tumors, providing a crucial clinical therapeutic strategy for PC.

9.
Sci Rep ; 14(1): 15773, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982212

RESUMEN

We carried out uniaxial compression tests on brittle red sandstone with different heights. The test results show that the uniaxial compressive strength of rock sample increases first and then tends to be stable with the increase of the size, which is approximately stable between 75 and 81 MPa. Both elastic energy and dissipated energy increase with the increase of rock sample size. In order to further analyze the mechanism behind these phenomena, we combined advanced numerical simulation and theoretical analysis to explain these phenomena, and systematically analyzed the end face effect as one of the key factors affecting the uniaxial compression characteristics of brittle red sandstone for the first time. Small sized rock samples are very sensitive to end effect. The middle of the large sized rock samples is in a uniform compression state, and the effect of end effect is weakend. When there are rigid pads at both ends of the rock sample, there is an obvious elastic vertebral body during the loading process of the rock sample. The bearing capacity of rock samples with rigid pads is greater than that of rock samples without rigid pads, and the energy released during instantaneous failure of rock samples without rigid pads is greater than that of rock samples with rigid pads. The findings of this paper make a valuable contribution to establishing optimal study sample sizes and advancing the utilization of laboratory test mechanics parameters in engineering applications.

10.
Sci Rep ; 14(1): 15795, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982275

RESUMEN

To address the design challenge of the rock-socketed piles posed by the void located below the pile tip, the physical laboratory model tests were designed and performed to simulate rock socketed piles using similar materials. The study investigates the behavior of the single pile under axial loading with the void located at varying distances from the pile tip. Through multi-level load tests, the variations of unit pile side friction, pile tip resistance, pile axial force and pile settlement are obtained for different positions of the void from the pile tip, as well as after grouting. Its comparison to the rock-socketed pile without void is performed as a reference to quantify the reduction in its bearing capacity. The results are presented in the form of graphs for different void positions and its grouting shows the influence on pile bearing capacity and emphasizes the importance of its detailed cautious investigation and introduction in the analysis. The 2D finite element modeling of the model pile-the void based on ABAQUS is performed to further investigate the influence of the void below pile tip on the bearing capacity of model pile, applying the Mohr Coulomb model as the constitutive model of rock mass behavior. The critical distance of the void below the pile tip is determined.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38979935

RESUMEN

A key characteristic of cancer cells is their ability to induce changes in their microenvironment that render it permissive to tumor growth, invasion and metastasis. Indeed, these changes are required for tumor progression. Consequently, the tumor microenvironment is emerging as a key source of new targets against cancer, with novel therapies aimed at reversing tumor-promoting changes, reinstating a tumor-hostile microenvironment and suppressing disease progression. RHO-ROCK signaling, and consequent tension within the cellular actomyosin cytoskeleton, regulates a paracrine signaling cascade that establishes a tumor-promoting microenvironment. Here, we show that consistent with our observations in breast cancer, enhanced ROCK activity and consequent production of CRELD2 is associated with the recruitment and tumor-promoting polarization of cancer-associated fibroblasts in cutaneous squamous cell carcinoma. Our observations provide support for the notion that the role of RHO-ROCK signaling in establishing a tumor-promoting microenvironment may be conserved across patients and potentially also different cancer types.

12.
Sci Rep ; 14(1): 15614, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971871

RESUMEN

The extraction of underground coal resources induces the fracture and movement of overlying strata, leading to geological hazards such as surface deformation, cracks, and even subsidence. Utilizing the analogous hyperbola model of overlying strata movement, we conducted a mechanical analysis to examine the asymmetric fracture mechanism resulting from coal seam mining in thick loose strata. An asymmetric analogous hyperbola model was established by introducing distinct virtual half-axis lengths (b). The thickness impact of thick loose layers (H) and bedrock layer (h) on the asymmetric movement of overlying rock during mining was also discussed. Similarity model tests were conducted to research the migration characteristics and surface subsidence patterns of overburdened rock and thick loose layers at different mining stages and validate the hypothesis of asymmetric overburdened rock migration. Additionally, the discrete element numerical model for thick and loose layers mining was established by using UDEC and discussed the asymmetric analogous hyperbola behaviour of overburden movement and surface subsidence. The comparison results show that the established asymmetric hyperbolic model can effectively predict the movement law of overlying strata and surface subsidence characteristics. Therefore, the proposed model can provide valuable theoretical support for predicting the movement patterns of overburden under thick loose layers and mitigating surface subsidence disasters.

13.
Ecotoxicol Environ Saf ; 281: 116681, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38964063

RESUMEN

Fluoride exposure has been implicated as a potential risk factor for hypertension, but the underlying mechanisms remain unclear. This study investigated the role of the RhoA/ROCK signaling pathway in fluoride-induced hypertension. Male Wistar rats were divided into different groups and exposed to varying concentrations of sodium fluoride (NaF) or sodium chloride (NaCl) via drinking water. The rats' blood pressure was measured, and their aortic tissue was utilized for high-throughput sequencing analysis. Additionally, rat and A7r5 cell models were established using NaF and/or Fasudil. The study evaluated the effects of fluoride exposure on blood pressure, pathological changes in the aorta, as well as the protein/mRNA expression levels of phenotypic transformation indicators (a-SMA, calp, OPN) in vascular smooth muscle cells (VSMCs), along with the RhoA/ROCK signaling pathway (RhoA, ROCK1, ROCK2, MLC/p-MLC). The results demonstrated that fluoride exposure in rats led to increased blood pressure. High-throughput sequencing analysis revealed differential gene expression associated with vascular smooth muscle contraction, with the RhoA/ROCK signaling pathway emerging as a key regulator. Pathological changes in the rat aorta, such as elastic membrane rupture and collagen fiber deposition, were observed following NaF exposure. However, fasudil, a ROCK inhibitor, mitigated these pathological changes. Both in vitro and in vivo models confirmed the activation of the RhoA/ROCK signaling pathway and the phenotypic transformation of VSMCs from a contractile to a synthetic state upon fluoride exposure. Fasudil effectively inhibited the activities of ROCK1 and ROCK2 and attenuated the phenotypic transformation of VSMCs. In conclusion, fluoride has the potential to induce hypertension through the activation of the RhoA/ROCK signaling pathway and phenotypic changes in vascular smooth muscle cells. These results provide new insights into the mechanism of fluoride-induced hypertension.


Asunto(s)
Hipertensión , Músculo Liso Vascular , Ratas Wistar , Transducción de Señal , Quinasas Asociadas a rho , Animales , Quinasas Asociadas a rho/metabolismo , Masculino , Hipertensión/inducido químicamente , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Ratas , Transducción de Señal/efectos de los fármacos , Proteína de Unión al GTP rhoA/metabolismo , Fluoruro de Sodio/toxicidad , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/patología , Fenotipo , Presión Sanguínea/efectos de los fármacos , Fluoruros/toxicidad , Proteínas de Unión al GTP rho
14.
Sensors (Basel) ; 24(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39000906

RESUMEN

Rock image classification represents a challenging fine-grained image classification task characterized by subtle differences among closely related rock categories. Current contrastive learning methods prevalently utilized in fine-grained image classification restrict the model's capacity to discern critical features contrastively from image pairs, and are typically too large for deployment on mobile devices used for in situ rock identification. In this work, we introduce an innovative and compact model generation framework anchored by the design of a Feature Positioning Comparison Network (FPCN). The FPCN facilitates interaction between feature vectors from localized regions within image pairs, capturing both shared and distinctive features. Further, it accommodates the variable scales of objects depicted in images, which correspond to differing quantities of inherent object information, directing the network's attention to additional contextual details based on object size variability. Leveraging knowledge distillation, the architecture is streamlined, with a focus on nuanced information at activation boundaries to master the precise fine-grained decision boundaries, thereby enhancing the small model's accuracy. Empirical evidence demonstrates that our proposed method based on FPCN improves the classification accuracy mobile lightweight models by nearly 2% while maintaining the same time and space consumption.

15.
Transl Stroke Res ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980519

RESUMEN

Cerebral cavernous malformation (CCM) is a hemorrhagic cerebrovascular disease where lesions develop in the setting of endothelial mutations of CCM genes, with many cases also harboring somatic PIK3CA gain of function (GOF) mutations. Rapamycin, an mTORC1 inhibitor, inhibited progression of murine CCM lesions driven by Ccm gene loss and Pik3ca GOF, but it remains unknown if rapamycin is beneficial in the absence of induction of Pik3ca GOF. We investigated the effect of rapamycin at three clinically relevant doses on lesion development in the Ccm3-/-PDGFb-icreERPositive murine model of familial CCM disease, without induction of Pik3ca GOF. Lesion burden, attrition, and acute and chronic hemorrhaging were compared between placebo and rapamycin-treated mice. Plasma miRNome was compared to identify potential biomarkers of rapamycin response. Outlier, exceptionally large CCM lesions (> 2 SD above the mean lesion burden) were exclusively observed in the placebo group. Rapamycin, across all dosages, may have prevented the emergence of large outlier lesions. Yet rapamycin also appeared to exacerbate mean lesion burden of surviving mice when outliers were excluded, increased attrition, and did not alter hemorrhage. miR-30c-2-3p, decreased in rapamycin-treated mouse plasma, has gene targets in PI3K/AKT and mTOR signaling. Progression of outlier lesions in a familial CCM model may have been halted by rapamycin treatment, at the potential expense of increased mean lesion burden and increased attrition. If confirmed, this can have implications for potential rapamycin treatment of familial CCM disease, where lesion development may not be driven by PIK3CA GOF. Further studies are necessary to determine specific pathways that mediate potential beneficial and detrimental effects of rapamycin treatment, and whether somatic PIK3CA mutations drive particularly aggressive lesions.

16.
Int J Chron Obstruct Pulmon Dis ; 19: 1591-1601, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005647

RESUMEN

Background: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear. Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1ß, TNF-α, and RhoA/ROCK were determined by Western blotting. Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably. Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.


Asunto(s)
Diafragma , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Atrofia Muscular , Enfermedad Pulmonar Obstructiva Crónica , Transducción de Señal , Quinasas Asociadas a rho , Proteína de Unión al GTP rhoA , Animales , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Quinasas Asociadas a rho/metabolismo , Masculino , Atrofia Muscular/prevención & control , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Atrofia Muscular/etiología , Proteína de Unión al GTP rhoA/metabolismo , Diafragma/metabolismo , Diafragma/fisiopatología , Diafragma/patología , Línea Celular , Proteínas de Unión al GTP rho/metabolismo , Terapia por Ejercicio/métodos , Ratones , Pulmón/patología , Pulmón/metabolismo , Pulmón/fisiopatología , Mediadores de Inflamación/metabolismo , Condicionamiento Físico Animal
17.
Am J Cancer Res ; 14(6): 2852-2867, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005692

RESUMEN

Cholangiocarcinoma (CCA) is a common malignancy of the digestive system, and its treatment is greatly challenged by rising chemoresistance. Long non-coding RNAs (lncRNAs) have been shown to play critical roles in the development of drug resistance in tumors. However, the role of the lncRNA CCAT1 in erlotinib resistance in CCA remains unclear. In this investigation, we identified CCAT1 as a pivotal factor contributing to erlotinib resistance in CCA. Furthermore, we uncovered that lncRNA CCAT1 modulated epithelial-mesenchymal transition (EMT) through Rho-associated coiled-coil-forming protein kinase 2 (ROCK2), thereby conferring erlotinib resistance upon CCA cells. Mechanistically, we demonstrated that miR-181a-5p interacted with CCAT1 to modulate the expression of ROCK2. Collectively, these findings shed light on the significant role of CCAT1 in the development of erlotinib resistance in CCA. The functional suppression of CCAT1 holds promise in enhancing the sensitivity to erlotinib by reversing EMT through the miR-181a-5p/ROCK2 signaling pathway. These findings provide valuable insights into the mechanisms underlying erlotinib resistance in CCA and the potential strategies for its treatment.

18.
Sci Rep ; 14(1): 15880, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38982101

RESUMEN

The geological phenomenon of igneous rock invading coal seam is widely distributed, which induces mining risk and affects efficient mining. The pre-splitting blasting method of igneous rock is feasible but difficult to implement accurately, resulting in unnecessary safety and environmental pollution risks. In this paper, the blasting model with penetrating structural plane and the multi-hole blasting model with different hole spacing were established based on the Riedel-Hiermaier-Thoma (RHT) damage constitutive to explore the stress wave propagation law under detonation. The damage cloud diagram and damage degree algorithm were used to quantitatively describe the spatio-temporal evolution of blasting damage. The results show that the explosion stress wave presents a significant reflection stretching effect under the action of the structural plane, which can effectively aggravate the presplitting blasting degree of the rock mass inside the structural plane. The damage range of rock mass is synchronously evolved with the change of blasting hole spacing. The blasting in the igneous rock intrusion area of the 21,914 working face is taken as an application example, and the damage degree of rock mass is reasonably evaluated by the box-counting dimension and K-means clustering method, which proves the effectiveness of the blasting scheme and provides reference value for the implementation of related blasting projects.

19.
Sci Total Environ ; 946: 174375, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960175

RESUMEN

Groundwater contamination by nitrate and sulfate in mining areas is a significant challenge. Consequently, the inputs sources of these contaminants and their evolution have received considerable attention, with the knowledge gained critical for improved management of water quality. This study integrated data on multiple stable isotopes and water chemistry data and a Bayesian isotope mixing model to investigate the relative contributions of inputs sources of sulfate and nitrate sources to bodies of water in a karst mining area in southwest China. The outcomes indicated that hydrochemical component in the water bodies of the study area is mainly derived from the dissolution of silicate rocks, carbonate rocks and sulfate minerals as well as the oxidation of sulfides. The human and agricultural wastewater, soil nitrogen, and fertilizers were the predominant inputs sources of nitrate to the mine water environment; the predominant inputs sources of sulfide were mineral oxidation, evaporite dissolution, atmospheric deposition, and sewage. Groundwater is mainly recharged from atmospheric precipitation, and surface water is closely hydraulically connected to groundwater. Nitrogen and oxygen isotope composition and water chemistry indicative of nitrification dominate the nitrogen cycle in the study area. The oxidation of pyrite and bacterial sulfate reduction (SRB) had no significant impact on the stable isotopes of groundwater. The results of this study demonstrate the inputs of different sources to nitrate and sulfate in karst mines and associated transformation processes. The results of this study can assist in the conservation of groundwater quality in mining areas and can act as a reference for future related studies.

20.
Materials (Basel) ; 17(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38998194

RESUMEN

Epoxy resin, known for its excellent corrosion resistance, water resistance, and high-temperature resistance, is extensively utilized in construction and water-related projects. Within water conservancy projects, natural factors such as water impact and weathering often result in cracks within rock formations. Consequently, the application of epoxy resin materials for repair and reinforcement has emerged as a common solution. This research investigates the impact of five epoxy grouting materials, YDS (100:6.4), RH-1 (6.1:1), PSI (9:1), TK (100:8), and HK-G (5:1), on the repair and reinforcement of faulted rock at the Yebatan Hydropower Station. Penetration experiments were conducted on rock samples, and the strength of the epoxy grout samples was tested under ambient conditions of 20 °C, 15 °C, and 0 °C. The experimental results indicate that all five epoxy grout materials successfully penetrated the faulted rock samples. Among them, the PSI (9:1) epoxy grouting material exhibited the most exceptional reinforcing effect across different temperatures, with grouting samples demonstrating strengths in the range of 20 to 25 MPa. This paper confirms that epoxy resin effectively repairs and reinforces rock structures, thereby enhancing the safety and durability of water conservancy projects.

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