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Objective To explore the effects and molecular mechanisms of naringenin (Nar) on the proliferation, migration and collagen synthesis of keloid fibroblasts (KFs). Methods KFs were divided into control group and Nar group treated with Nar at concentrations of 10, 25, 50, 100 and 150 μmol/L, and the effects of Nar on the proliferation of KFs were analyzed using CCK-8 assay. Western blot was performed to detect the effects of Nar on the expression levels of Col-1, FN, α-SMA, and MMP9, and the expression levels of Smad2/3 and p-Smad2/3 in KFs pretreated with TGF-β1. Results Compared with the control group, the proliferation ability of KFs was significantly inhibited by Nar at a concentration of ≥50 μmol/L (P

In coal seam groups where the spacing between the upper and lower seams is small, the lower seam working face is significantly influenced by residual coal pillars from the upper seam and the void spaces created during mining. This presents considerable challenges for underground mining safety. Through field investigations, the layout of the coal seam quarry above the working face of the 3−1 coal seam in Yanghuopan Mine was examined, along with the distribution of the residual coal pillars. This allowed for the identification of the interlayer rock strata characteristics. Subsequently, we analyzed the mechanism of directional hydraulic fracturing and decompression to determine the key parameters of the 3−1 coal seam. Using the Rock Fracture Process Analysis 3D (RFPA 3D) numerical simulation, we evaluated the effects of various factors on the initiation and propagation of hydraulic fracturing-induced cracks, formulated the evolution law of these fractures, and incorporated the damage variables into the analysis. Additionally, we assessed the influence of different parameters on crack initiation and extension during hydraulic fracturing, using RFPA 3D simulations to derive the evolution law governing directional hydraulic fractures. This allowed us to define the hydraulic fracturing parameters for the 3−1 interbedded rock layers by integrating the process parameter calculations with the damage variables. Based on these findings, an on-site implementation plan was developed and executed, followed by a comprehensive evaluation of the construction results. The study concludes that directional hydraulic fracturing and decompression effectively contribute to the prevention and control of roof-related disasters in the mining of lower coal seams where seam spacing is minimal. This research offers valuable theoretical insights and practical reference for disaster prevention and control in similar geological conditions.

Water inrush from separation layers is a special type of water inrush disaster that occurs during coal mining. It is characterized by the absence of precursors before the inrush, a sudden and massive influx of water, strong destructive power, and significant difficulty in prevention and control. This disaster causes substantial economic losses and casualties in mines. To study the dynamic evolution characteristics of the overlying rock strata in Guojiahe coal mine, field investigations, theoretical analysis, physical simulations, and numerical simulations were conducted. The development state of the overlying rock strata and the height of the water-conducting fractures in the 1304 working face during continuous mining were analyzed, and the spatial position of the strata where water hazards could form was determined. Through theoretical calculations, the height of the water-conducting fracture zone was found to be approximately 205 m, forming a water-storable separation space about 248 m above the coal seam roof. A physical similarity model was constructed to study the development state of overlying rock strata separation in the 1304 working face. Experimental results indicate that, as the working face advances, the rock strata gradually develop lateral separation spaces from bottom to top, and vertical fractures increase progressively in a similar manner. The spaces and fractures formed in the early stages of the working face advance gradually close and form a compaction zone. However, new fractures develop near the working face side. As mining continues, the asynchronous movement of the overlying rock promotes the development of vertical fractures, providing water-conducting channels for water inrush from the separation. Based on numerical simulation analysis of the development state of overlying rock strata separation and the height of the water-conducting fracture zone, it can be concluded that the water-storable separation space develops between the 8th layer of the formation of sandy mudstone and the 9th layer of the Yijun Formation conglomerate, which is 248 m from the coal seam roof. When excavated to 280 m, the separation space reaches its maximum, with a width of about 19 m and a height of about 1.2 m, and the water storage capacity increases to its maximum. The height of the water-conducting fracture zone eventually increases to 202 m.

Fossil identification is an essential and fundamental task for conducting palaeontological research. Because the manual identification of fossils requires extensive experience and is time-consuming, automatic identification methods are proposed. However, these studies are limited to a few or dozens of species, which is hardly adequate for the needs of research. This study enabled the automatic identification of hundreds of species based on a newly established fossil dataset. An available “bivalve and brachiopod fossil image dataset” (BBFID, containing >16,000 “image-label” data pairs, taxonomic determination completed) was created. The bivalves and brachiopods contained in BBFID are closely related in morphology, ecology and evolution that have long attracted the interest of researchers. We achieved >80% identification accuracy at 22 genera and ∼64% accuracy at 343 species using EfficientNetV2s architecture. The intermediate output of the model was extracted and downscaled to obtain the morphological feature space of fossils using t-distributed stochastic neighbor embedding (t-SNE). We found a distinctive boundary between the morphological feature points of bivalves and brachiopods in fossil morphological feature distribution maps. This study provides a possible method for studying the morphological evolution of fossil clades using computer vision in the future.

Introduction: Despite many recent emerging therapeutic modalities that have prolonged the survival of melanoma patients, the prognosis of melanoma remains discouraging, and further understanding of the mechanisms underlying melanoma progression is needed. Melanoma patients often have multiple genetic mutations, with BRAF mutations being the most common. In this study, public databases were exploited to explore a potential therapeutic target for BRAF-mutated melanoma.Methods: In this study, we analyzed differentially expressed genes (DEGs) in normal tissues and melanomas, Braf wild-type and Braf mutant melanomas using information from TCGA databases and the GEO database. Subsequently, we analyzed the differential expression of CYTL1 in various tumor tissues and its effect on melanoma prognosis, and resolved the mutation status of CYTL1 and its related signalling pathways. By knocking down CYTL1 in melanoma cells, the effects of CYTL1 on melanoma cell proliferation, migration and invasion were further examined by CCK8 assay, Transwell assay and cell migration assay.Results: 24 overlapping genes were identified by analyzing DEGs common to melanoma and normal tissue, BRAF-mutated and BRAF wild-type melanoma. Among them, CYTL1 was highly expressed in melanoma, especially in BRAF-mutated melanoma, and the high expression of CYTL1 was associated with epithelial-mesenchymal transition (EMT), cell cycle, and cellular response to UV. In melanoma patients, especially BRAF-mutated melanoma patients, clinical studies showed a positive correlation between increased CYTL1 expression and shorter overall survival (OS) and disease-free survival (DFS). In vitro experiments further confirmed that the knockdown of CYTL1 significantly inhibited the migration and invasive ability of melanoma cells.Conclusion: CYTL1 is a valuable prognostic biomarker and a potentially effective therapeutic target in melanoma, especially BRAF-mutated melanoma.

Glucosamine hydrochloride (GAH) is a natural component of glycoproteins present in almost all human tissues and participates in the construction of human tissues and cell membranes. GAH has a wide range of biological activities, particularly in anti-inflammatory and osteogenic damage repair. At present, little is known about how GAH functions in angiogenesis. To determine the role of GAH on vascular development and impairment repair, we used the inhibitors VRI, DMH1, and dorsomorphin (DM) to construct vascular-impaired models in Tg(kdrl: mCherry) transgenic zebrafish. We then treated with GAH and measured its repair effects on vascular impairment through fluorescence intensity, mRNA, and protein expression levels of vascular-specific markers. Our results indicate that GAH promotes vascular development and repairs impairment by regulating the vascular endothelial growth factor (VEGF) signaling pathway through modulation of bone morphogenetic protein (BMP) signaling. This study provides an experimental basis for the development of GAH as a drug to repair vascular diseases.

MPD is one of the effective means to solve the drilling problems in deep-water and deep-stratum complex formations such as narrow pressure window. To reduce the cost, it is mostly implemented only in complex and narrow pressure window strata. However, at present, there is no scientific method to determine the MPD matching stratum interval under the “conventional + MPD” composite drilling mode. Aiming at this problem, by introducing the methods of risk quantitative evaluation and taking the principle of “avoiding risk and reducing MPD cost”, combined with the accurate ECD calculation method considering multiphase flow, this paper puts forward the accurate determination method of matching the stratum interval of MPD, which can reduce the section of MPD construction as much as possible and optimize the casing level on the premise of ensuring safety. Based on the artificial bee colony algorithm, the intelligent determination method of casing level and setting depth under the condition of pressure control is established, which can quickly and accurately obtain the maximum casing setting depth and its corresponding optimal pressure control parameters in the open-hole section. The case analysis shows that, compared with the conventional drilling mode, the “upper conventional + lower MPD” drilling method can save one layer of casing while ensuring safety. The proposed method can provide theoretical and scientific basis for the accurate calculation of MPD matching stratum interval under the “conventional + MPD” compound drilling mode and the scientific and efficient design of casing levels and setting depth under the condition of pressure control.

Abstract The current outbreak of coronavirus disease 2019 (COVID-19) has become a global crisis due to its quick and wide spread over the world. A good understanding of the dynamic of the disease would greatly enhance the control and prevention of COVID19. However, to the best of our knowledge, the unique features of the outbreak have limited the applications of all existing dynamic models. In this paper, a novel stochastic model was proposed aiming to account for the unique transmission dynamics of COVID-19 and capture the effects of intervention measures implemented in Mainland China. We found that: (1) instead of aberration, there was a remarkable amount of asymptomatic virus carriers, (2) a virus carrier with symptoms was approximately twice more likely to pass the disease to others than that of an asymptomatic virus carrier, (3) the transmission rate reduced significantly since the implementation of control measures in Mainland China, and (4) it was expected that the epidemic outbreak would be contained by early March in the selected provinces and cities in China.

The evolutionary relationships within Archaea remain unresolved. Here, the authors used genomic approaches to study the Undinarchaeota, a previously uncharacterized clade of DPANN, shed light on their position in an updated archaeal phylogeny and illuminate the history of archaeal genome evolution.

Abstract Respiratory tract microbiome is closely related to respiratory tract infections, while characterization of oropharyngeal microbiome in recovered coronavirus disease 2019 (COVID‐19) patients is not studied. Herein, oropharyngeal swabs are collected from confirmed cases (CCs) with COVID‐19 (73 subjects), suspected cases (SCs) (36), confirmed cases who recovered (21), suspected cases who recovered (36), and healthy controls (Hs) (140) and then completed MiSeq sequencing. Oropharyngeal microbial α‐diversity is markedly reduced in CCs versus Hs. Opportunistic pathogens are increased, while butyrate‐producing genera are decreased in CCs versus Hs. The classifier based on eight optimal microbial markers is constructed through a random forest model and reached great diagnostic efficacy in both discovery and validation cohorts. Notably, the classifier successfully diagnosed SCs with positive IgG antibody as CCs and is demonstrated from the perspective of the microbiome. Importantly, several genera with significant differences gradually increase and decrease along with recovery from COVID‐19. Forty‐four oropharyngeal operational taxonomy units (OTUs) are closely correlated with 11 clinical indicators of SARS‐CoV‐2 infection and Hs based on Spearman correlation analysis. Together, this research is the first to characterize oropharyngeal microbiota in recovered COVID‐19 cases and suspected cases, to successfully construct and validate the diagnostic model for COVID‐19 and to depict the correlations between microbial OTUs and clinical indicators.

The eastern Hengduan Mountains are located in the transition zone between the Qinghai-Tibet Plateau and the Sichuan Basin and are important for global biodiversity and water conservation in China. However, their landscape pattern vulnerability index (LVI) and its influencing factors have not been systematically studied. Therefore, the spatial distribution patterns, LVI, and the landscape artificial disturbance intensity (LHAI) of Ganzi Prefecture were analyzed using ArcGIS software based on landscape data and Digital Elevation Model (DEM) digital elevation data. Then, the LVI response to LHAI and elevation was discussed. The results showed that Ganzi Prefecture was dominated by low- and middle-LVI areas, together accounting for 56.45% of the total area. LVI values were highest in the northern regions, followed by the southern and eastern regions. Batang and Derong counties had the highest LVI values. Most areas in Ganzi Prefecture had very low- or low-LHAI values, accounting for 81.48% of the total area, whereas high-LHAI areas accounted for 2.32% of the total area. Both the LVI and LHAI of Ganzi Prefecture had clustered distributions. Spearman analysis indicated that when elevation exceeded 4500 m, it was the most important factor affecting LVI and LHAI. In the range of 4500–5400 m, the relationship between elevation and LVI shifted from a weak positive correlation to a negative correlation, whereas LHAI was positively correlated with elevation. In addition, LVI also responded significantly to LHAI. However, the relationship kept changing as elevation increased. Hence, the ecological vulnerability of high elevation areas above 4500 m deserves greater attention. In addition, pasture areas in the upstream reaches of the Yalong River in the northern region, the coastal area in the downstream reaches of the Jinsha River in the southern region, and the eastern mining area, should be prioritized for protection and restoration. This research provides a basis for appropriate environmental planning mechanisms and policy protections at the landscape level.

Recently, the requirements regarding the environment of nursing homes are high, because the elderly are a vulnerable group with limited adaptive capacity to respond to transient environmental change. This paper presents a field investigation on the influence of transient thermal comfort changes between the indoor and outdoor spaces (i.e., air temperature (Ta), solar radiation (SR), relative humidity (RH), wind speed (WS), and the thermal comfort indices of Universal Thermal Index (UTCI)) on the willingness of the elderly to use outdoor spaces of the Wanxia nursing home of Chengdu City. Results indicated that, in summer, the mean UTCI values of indoor and corridor spaces corresponded to the level of moderate heat stress, while those of road and garden corresponded to the strong heat stress level. Road and garden spaces even showed moderate heat stress in spring. Approximately 28.93% (139) of the elderly living here used outdoor spaces every day. The morning period (from 9:00 a.m. to 10:00 a.m.) was the elderly’s favorited period for using outdoor spaces in seasons. The microclimatic transient differences between indoor and outdoor spaces ranged from 0.47 °C to 2.93 °C (|ΔTa|), from 86.09 W/m2 to 206.76 W/m2 (|ΔSR|), from 5.29% to 14.76% (ΔRH), from 0.01 m/s to 0.07 m/s (|ΔWS|), and from 0.25 °C to 2.25 °C (ΔUTCI). These big microclimate differences could cause enormous health risks for the elderly in the process of indoor and outdoor space conversion. The minimal transient change occurred between corridors and indoors. Pearson correlation analysis indicated ΔTa and ΔRH between indoor and outdoor spaces were the primary meteorological factors that influenced the elderly’s willing to use outdoor spaces. The elderly preferred to live in a constant Ta and RH environment. Only when the ΔTa and ΔRH are small enough to resemble a steady-state (ΔUTCI ≤ 0.5 °C), ΔWS and ΔSI could affect the elderly’s choice of using outdoor space. Optimal design strategies were put forward for reducing the transient differences between indoor and outdoor microclimates to inspire the elderly to use outdoor spaces safely, including improving outdoor canopy coverage and indoor mechanical ventilation.

With the decrease in high-grade chalcopyrite resources, the copper extraction from low-grade chalcopyrite has attracted more and more attention. However, the kinetic rates of chalcopyrite leaching with traditional oxidants are usually very slow due to the formation of the passivation layer. In this study, a novel reagent of chlorinated oxidant, trichloroisocyanuric acid (TCCA), was used to leach chalcopyrite for the first time. The experimental results showed that when the initial oxidant concentration for TCCA was 0.054 mol·L−1, the leaching temperature was kept at 55 °C, and the pH of the pulp was controlled at 1, the oxidation efficiency of Cu can reach above 90% in less than 30 min. Various analyses of chalcopyrite mineral ore and its oxidized residues, such as chemical composition analysis, X-ray diffraction analysis, scanning electron microscopy analysis and X-ray photoelectron spectroscopy, were conducted, respectively. No obvious passivation layer was found on the chalcopyrite surface, though the sulfur product can also be generated during the leaching. Reaction kinetic analysis results showed that the different influence of surface reaction and diffusion process on the dissolution of chalcopyrite is little due to the fast leaching speed. After calculation, the activation energy of the whole leaching reaction is 9.06 kJ·mol−1, much lower than that in other reports. The mechanism was also proposed that TCCA was hydrolyzed in the solution to form hypochlorous acid, which is the strong oxidant, and cyanuric acid, which prevents the formation of a passivation layer. The processing in this study is expected to be applied as a novel method for atmospheric leaching of chalcopyrite.

Heat stress can particularly affect the kidney because of its high rate of adenosine triphosphate consumption. Competition between apoptosis and autophagy-mediated survival always exists in damaged tissue. And Hsp90 can enhance cellular protection to resist heat stress. However, the relationship between Hsp90 and the above competition and its underlying mechanism in the kidney are unclear. The present study found that heat stress induced obvious histopathological and oxidative injury, which was connected with cellular apoptosis and autophagy in the kidney and was associated with the levels of Hsp90 expression or function. The data showed that during heat stress, Hsp90 activated the PKM2-Akt signaling pathway to exert antiapoptotic effects and induce Hsp70 expression regulated by HSF-1, stimulated autophagy-mediated survival through the HIF-1α-BNIP3/BNIP3L pathway, and finally protected the kidney from heat-stress injury. Moreover, the nuclear translocation of PKM2, (p-) Akt, HSF-1, and HIF-1α was enhanced by heat stress, but only intranuclear p-Akt and HSF-1 were specifically influenced by Hsp90, contributing to regulate the cellular ability of resisting heat-stress damage. Our study provided new insights regarding the molecular mechanism of Hsp90 in the kidney in response to heat-stress injury, possibly contributing to finding new targets for the pharmacological regulation of human or animal acute kidney injury from heat stress in future research.

Heat stress (HS) often causes sudden death of humans and animals due to heart failure, mainly resulting from the contraction of cardiac microvasculature followed by myocardial ischemia. Cardiac microvascular endothelial cells (CMVECs) play an important role in maintaining vasodilatation. Aspirin (ASA) is well known for its protective abilities of febrile animals. However, there is little knowledge about molecular resistance mechanisms of CMVECs and which role ASA may play in this context. Therefore, we used a heat stress model of rat cardiac microvascular endothelial cell cultures in vitro and investigated the cell injuries and molecular resistance mechanism of CMVECs caused by heat stress, and the effect of aspirin (ASA) on it. HS induced severe pathological damage of CMVECs and cellular oxidative stress and dysfunction of NO release. Hsp90 was proven to be indispensable for resisting HS-injury of CMVECs through PI3K-Akt and PKM2 signaling pathways. Meanwhile, PKM2 functioned in reducing Akt phosphorylation. ASA treatment of CMVECs induced a significant expression of Hsp90, which promoted both Akt and PKM2 signals, which are beneficial for relieving HS damage and maintaining the function of CMVECs. Akt activation also promoted HSF-1 that regulates the expression of Hsp70, which is known to assist Hsp90′s molecular chaperone function and when released to the extracellular liquid to protect myocardial cells from HS damage. To the best of our knowledge, this is the first study to show that HS damages CMVECs and the protection mechanism of Hsp90 on it, and that ASA provides a new potential strategy for regulating cardiac microcirculation preventing HS-induced heart failure.

Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17β-HSD I, and 17β-HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats.