Search Results (69,029)

mTOR plays a crucial role in cell growth by controlling ribosome biogenesis, metabolism, autophagy, mRNA translation, and cytoskeleton organization. It is a serine/threonine kinase that is part of two distinct extensively described protein complexes, mTORC1 and mTORC2. We have identified a rapamycin-resistant mTOR complex, called mTORC3, which is different from the canonical mTORC1 and mTORC2 complexes in that it does not contain the Raptor, Rictor, or mLST8 mTORC1/2 components. mTORC3 phosphorylates mTORC1 and mTORC2 targets and contains the ETS transcription factor ETV7, which binds to mTOR and is essential for mTORC3 assembly in the cytoplasm. Tumor cells that assemble mTORC3 have a proliferative advantage and become resistant to rapamycin, indicating that inhibiting mTORC3 may have a therapeutic impact on cancer. Here, we investigate which domains or amino acid residues of ETV7 and mTOR are involved in their mutual binding. We found that the mTOR FRB and LBE sequences in the kinase domain interact with the pointed (PNT) and ETS domains of ETV7, respectively. We also found that forced expression of the mTOR FRB domain in the mTORC3-expressing, rapamycin-resistant cell line Karpas-299 out-competes mTOR for ETV7 binding and renders these cells rapamycin-sensitive in vivo. Our data provide useful information for the development of molecules that prevent the assembly of mTORC3, which may have therapeutic value in the treatment of mTORC3-positive cancer. Full article

This study explored the green synthesis of silver nanoparticles (AgNPs) using the extracellular filtrate of Fusarium oxysporum as a reducing agent and evaluated their antitumor potential through in vitro and in silico approaches. The biosynthesis of AgNPs was monitored by visual observation of the color change and confirmed by UV–Vis spectroscopy, revealing a characteristic peak at 418 nm. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses showed spherical nanoparticles ranging from 6.53 to 21.84 nm in size, with stable colloidal behavior and a negative zeta potential of −15.5 mV. Selected area electron diffraction (SAED) confirmed the crystalline nature of the AgNPs, whereas energy-dispersive X-ray (EDX) indicated the presence of elemental silver at 34.35%. A face-centered central composite design (FCCD) was employed to optimize the biosynthesis process, yielding a maximum AgNPs yield of 96.77 µg/mL under the optimized conditions. The antitumor efficacy of AgNPs against MCF-7 and HepG2 cancer cell lines was assessed, with IC₅₀ values of 35.4 µg/mL and 7.6 µg/mL, respectively. Molecular docking revealed interactions between Ag metal and key amino acids of BCL-2 (B-cell lymphoma-2) and FGF19 (fibroblast growth factor 19), consistent with in vitro data. These findings highlight the potential of biologically derived AgNPs as promising therapeutic agents for cancer treatment and demonstrate the utility of these methods for understanding the reaction mechanisms and optimizing nanomaterial synthesis. Full article

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite new treatments, the HCC rate remains important, making it necessary to develop novel therapeutic strategies. Photodynamic therapy (PDT) using a Rose-Bengal (RB) photosensitizer (RB-PDT) could be a promising approach for liver tumor treatment. However, the lack of standardization in preclinical research and the diversity of illumination parameters used make comparison difficult across studies. This work presents and characterizes a novel illumination device based on one green light-emitting diode (CELL-LED-550/3) dedicated to an in vitro RB-PDT. The device was demonstrated to deliver a low average irradiance of 0.62 mW/cm² over the 96 wells of a multi-well plate. Thermal characterization showed that illumination does not cause cell heating and can be performed inside an incubator, allowing a more rigorous assessment of cell viability after PDT. An in vitro cytotoxic study of the RB-PDT on an HCC cell line (HepG2) demonstrated that RB-PDT induces a significant decrease in cell viability: almost all the cells died after a light dose irradiation of 0.3 J/cm² using 75 µM of RB (<10% of viability). In conclusion, the RB-PDT could be a therapeutic option to treat unresectable liver lesions and subclinical disease remaining in the post-resection tumor surgical margin. Full article

The crested porcupine (Hystrix cristata) is present in central Italy with an estimated population of 1800 individuals. Despite the local abundance, little data are available on the diseases affecting free-ranging individuals. We describe a case of an epidermoid cyst (EC) in a male adult porcupine found in the municipality of Sovicille, province of Siena (Tuscany). At necropsy, a firm rounded nodule was noted on the left ventricle wall. Histological examination revealed a cystic formation lined by stratified squamous epithelium. The cyst was filled with lamellar keratin, while hair shafts were not present. The adjacent epicardium was infiltrated by lymphoplasmacytic cells in reaction to the rupture of the cyst with the spilling of keratinaceous debris. The lesion was diagnosed as a ruptured epicardial epidermoid cyst. EC are most commonly found in the skin, both in human and animal patients, though infrequently, they can occur in any internal organ. Cardiac EC has not been reported in domestic animals, and this is the first report of EC in a wild animal species. Clinical veterinarians should consider the possibility of similar cardiac lesions in captive subjects since the long lifespan of these rodents could allow the growth of the cyst with the compression of the adjacent tissues. Full article

The size of peanut pods and seeds, which directly affects yield and quality, also has significant implications for mechanized production and market efficiency. Identifying relevant loci and mining candidate genes is crucial for cultivating high-yield peanut varieties. In this study, we employed advanced generation recombinant inbred lines developed by crossbreeding Huayu 44 and DF12 as the experimental material. Quantitative trait locus (QTL) mapping for traits related to pod and seed size was conducted across six environments. A total of 44 QTLs were detected, distributed on chromosomes A02, A05, B04, B08, and B10. An enrichment region for multiple QTLs was also identified on chromosome A05 (19.28~52.32 cm). In this region, 10 KASP markers were developed, narrowing the enrichment area to two candidate gene hotspot regions of 600.9 kb and 721.2 kb. By combining gene prediction and functional annotation within the intervals, 10 candidate genes, including those encoding cytochrome P450 protein, polyamine synthase, mannose-1-phosphate guanylyltransferase, pentatricopeptide repeat protein, and E2F transcription factor, were identified as regulators of pod and seed size. This study provides technical support for the genetic improvement and key gene identification of peanut pod and seed size. Full article

Utilizing calcium-based adsorbents for CO₂ adsorption through cyclic calcination/carbonization is one of the most cost-effective methods for carbon emission reduction. In order to improve the cycle stability of the adsorbents and the capture efficiency of CO₂, this study used industrial solid waste coal fly ash for the hydration treatment of calcium-based adsorbent to explore the variations in the cyclic adsorption performance of the adsorbent under different doping ratios and hydration conditions. By means of various characterization techniques, the microscopic mechanism for improving the performance of the modified adsorbent was analyzed from the perspectives of chemical composition, physical structure, and surface functional groups of the adsorbents. The results demonstrated that the modification of coal fly ash could significantly enhance the carbonation performance and cycle stability of the adsorbent in multiple CO₂ capture processes. The modified material doped with 5% coal fly ash had the highest total CO₂ adsorption capacity, which increased by 13.7% compared to before modification. Additionally, the modified material doped with 10% coal fly ash exhibited the strongest cyclic adsorption capacity, which was 14.0% higher than that before modification, and the adsorption attenuation rate decreased by 32.2%. The characterization results showed that the reaction between calcium oxide and coal fly ash formed CaSiO₃ and Ca₁₂Al₁₄O₃₃ during the modification process, which was the primary reason for the improvement in the CO₂ capture performance of the modified materials. This study provided a new perspective on the resource utilization of solid waste fly ash and efficient CO₂ capture. Full article

Chinese cabbage is an important vegetable from both a nutritional and an economic standpoint, with the leafy head serving as the primary harvested organ. However, the nutrient accumulation as well as influencing factors within the leafy head have not yet been elucidated. Thus, the distribution of metabolites (soluble sugars, minerals, carotenoids, vitamin C, flavonoid compounds, glucosinolates, and total phenolic compounds) were investigated in different leaf layers of Chinese cabbage with varying head types. The results showed that the inner leaves consistently displayed markedly higher levels of fructose and glucose when contrasted with the outer leaves. Similarly, there was an accumulation of glucosinolates in the inner leaves. By contrast, however, the antioxidants content exhibited a consistent decline from the outer leaves towards the central core, in line with the diminishing antioxidant capacity. This descending trend was also apparent in the mineral content, encompassing calcium, sodium, magnesium and sulfur. These results will provide dietary instruction, especially for consumers who have particular dietary needs. Full article

The development of a rapid, sensitive, specific method for detecting foodborne pathogens is paramount for supplying safe food to enhance public health safety. Despite the significant improvement in pathogen detection methods, key issues are still associated with rapid methods, such as distinguishing living cells from dead, the pathogenic potential or health risk of the analyte at the time of consumption, the detection limit, and the sample-to-result. Mammalian cell-based assays analyze pathogens’ interaction with host cells and are responsive only to live pathogens or active toxins. In this study, a human embryonic kidney (HEK293) cell line expressing Toll-Like Receptor 5 (TLR-5) and chromogenic reporter system (HEK dual hTLR5) was used for the detection of viable Salmonella in a 96-well tissue culture plate. This cell line responds to low concentrations of TLR5 agonist flagellin. Stimulation of TLR5 ligand activates nuclear factor-kB (NF-κB)—linked alkaline phosphatase (AP-1) signaling cascade inducing the production of secreted embryonic alkaline phosphatase (SEAP). With the addition of a ρ-nitrophenyl phosphate as a substrate, a colored end product representing a positive signal is quantified. The assay’s specificity was validated with the top 20 Salmonella enterica serovars and 19 non-Salmonella spp. The performance of the assay was also validated with spiked food samples. The total detection time (sample-to-result), including shortened pre-enrichment (4 h) and selective enrichment (4 h) steps with artificially inoculated outbreak-implicated food samples (chicken, peanut kernel, peanut butter, black pepper, mayonnaise, and peach), was 15 h when inoculated at 1–100 CFU/25 g sample. These results show the potential of HEK-Dual^TM hTLR5 cell-based functional biosensors for the rapid screening of Salmonella. Full article

Due to the radial network structures, small cross-sectional lines, and light loads characteristic of existing AC distribution networks in mountainous areas, the development of active distribution networks (ADNs) in these regions has revealed significant issues with integrating distributed generation (DGs) and consuming renewable energy. Focusing on this issue, this paper proposes a wide-range thyristor-controlled series compensation (TCSC)-based ADN and presents a deep reinforcement learning (DRL)-based optimal operation strategy. This strategy takes into account the complementarity of hydropower, photovoltaic (PV) systems, and energy storage systems (ESSs) to enhance the capacity for consuming renewable energy. In the proposed ADN, a wide-range TCSC connects the sub-networks where PV and hydropower systems are located, with ESSs configured for each renewable energy generation. The designed wide-range TCSC allows for power reversal and improves power delivery efficiency, providing conditions for the optimization operation. The optimal operation issue is formulated as a Markov decision process (MDP) with continuous action space and solved using the twin delayed deep deterministic policy gradient (TD3) algorithm. The optimal objective is to maximize the consumption of renewable energy sources (RESs) and minimize line losses by coordinating the charging/discharging of ESSs with the operation mode of the TCSC. The simulation results demonstrate the effectiveness of the proposed method. Full article

Background: Numerous anatomical features of the first carpometacarpal (CMC I) joint have been investigated as potential predispositions for CMC I osteoarthritis (OA). Even though load transmission through the CMC I joint—and, therefore, the development of osteoarthritis—is believed to be influenced by the geometry of the first metacarpal (MC I) bone, there is no common definition of the MC I axes. Methods: CT scans of twenty healthy volunteers and pre- and postoperative CT scans of six patients with CMC I OA undergoing Wilson osteotomy were analyzed. We proposed a calculation method based on anatomical landmarks for the proximal joint surface axis (PA) angle and the definition of an anatomical (AA) and a mechanical (MA) longitudinal axis. We hypothesized that for an MC I extension osteotomy to be effective, the AA and MA need to be aligned surgically. Results: To align AA and MA, an average correction angle of 22.60° (SD 2.53°) at 1 cm and 26.73° (SD 2.55°) at 1.5 cm distal to the CMC I joint line is required. Conclusions: The hereby proposed method for patient-specific calculation of the correction can be used to improve the surgical technique. Full article

It is well known that experiences of extreme adversity strongly impact caregiving and family dynamics. In this study, we explore how caregiving is shaped by experiences of war and displacement among a community experiencing protracted, ongoing conflict and displacement, namely, Congolese Banyamulenge refugee families in Rwanda. The findings are based on six months of ethnographic team research with Banyamulenge refugee families living in semi-urban southern Rwanda. Among the caregivers, including people who arrived several years ago and others who have lived in Rwanda for over two decades, we found a strong longing for home and past cattle-herding life. We also found that caregivers emphasized the transmission of “survival tactics” as well as Banyamulenge identity and culture. We argue that these caregiving objectives and practices speak to the community’s experiences of material and existential losses in the past, as well as those anticipated in the unknown future. Second, parental caregiving efforts appear to lead to increased intergenerational dissonance, with children wishing to integrate into their host community. While this finding appears in line with much of the migration literature about intergenerational family relationships and conflict, we find that children’s orientation is not only informed by the host environment but also stems from a desire to relieve their parents’ suffering from loss and help them invest in more optimistic futures. Finally, while our findings suggest profound changes in social and cultural reproduction in the long term, we argue for caution, as ongoing changes in war dynamics in DR Congo may inform shifts in ideas on belonging among the children. The findings provide new insights for understanding how caregiving may be affected by war and displacement while effecting change in war-affected, displaced communities. Full article

Durum wheat (DW) is one of the major crops grown in the Mediterranean area, a climate-vulnerable region where the increase in day/night (d/n) temperature is severely threatening DW yield stability. In order to improve DW heat tolerance, the introgression of chromosomal segments derived from the wild gene pool is a promising strategy. Here, four DW-Thinopyrum spp. near-isogenic recombinant lines (NIRLs) were assessed for their physiological response and productive performance after intense heat stress (IH, 37/27 °C d/n) had been applied for 3 days at anthesis. The NIRLs included two primary types (R5, R112), carriers (+) of a differently sized Th. ponticum 7el1L segment on the DW 7AL arm, and two corresponding secondary types (R69-9/R5, R69-9/R112), possessing a Th. elongatum 7EL segment distally inserted into the 7el1L ones. Their response to the IH stress was compared to that of corresponding non-carrier sib lines (−) and the heat-tolerant cv. Margherita. Overall, the R112+, R69-9/R5+ and R69-9/R112+ NIRLs exhibited a tolerant behaviour towards the applied stress, standing out for the maintenance of leaf relative water content but also for the accumulation of proline and soluble sugars in the flag leaf and the preservation of photosynthetic efficiency. As a result, all the above three NIRLs (R112+ > R69-9/R5+ > R69-9/R112+) displayed good yield stability under the IH, also in comparison with cv. Margherita. R112+ particularly relied on the strength of spike fertility/grain number traits, while R69-9/R5+ benefited from efficient compensation by the grain weight increase. This work largely confirmed and further substantiated the value of exploiting the wild germplasm of Thinopyrum species as a useful source for the improvement of DW tolerance to even extreme abiotic stress conditions, such as the severe heat treatment throughout day- and night-time applied here. Full article

Fifth-generation mobile networks (5G) are designed to support enhanced Mobile Broadband, Ultra-Reliable Low-Latency Communications, and massive Machine-Type Communications. To meet these diverse needs, 5G uses technologies like network softwarization, network slicing, and artificial intelligence. Multi-connectivity is crucial for boosting mobile device performance by using different Wireless Access Technologies (WATs) simultaneously, enhancing throughput, reducing latency, and improving reliability. This paper presents a multi-connectivity testbed from the 5G-CLARITY project for performance evaluation. MultiPath TCP (MPTCP) was employed to enable mobile devices to send data through various WATs simultaneously. A new MPTCP scheduler was developed, allowing operators to better control traffic distribution across different technologies and maximize aggregated throughput. Our proposal mitigates the impact of limitations on one path affecting others, avoiding the Head-of-Line blocking problem. Performance was tested with real equipment using 5GNR, Wi-Fi, and LiFi —complementary WATs in the 5G-CLARITY project—in both static and dynamic scenarios. The results demonstrate that the proposed scheduler can manage the traffic distribution across different WATs and achieve the combined capacities of these technologies, approximately 1.4 Gbps in our tests, outperforming the other MPTCP schedulers. Recovery times after interruptions, such as coverage loss in one technology, were also measured, with values ranging from 400 to 500 ms. Full article

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitation of MO-OH-Nap tropolone (MO-OH-Nap) in mouse plasma. MO-OH-Nap is an α-substituted tropolone with anti-proliferative properties in various cancer cell lines. Detection and separation of analytes was achieved on an ACE Excel C18 (1.7 µm, 100 × 2.1 mm, MAC-MOD Analytical, Chadds Ford, PA, USA) column with mobile phase consisting of 0.05% trifluoroacetic acid in water (mobile phase A) and 0.05% trifluoroacetic acid in acetonitrile (mobile phase B), with an isocratic elution of 15:85% (A:B) at a total flow rate of 0.25 mL/min. The LC-MS/MS system was operated at unit resolution in multiple reaction monitoring (MRM) mode, using precursor ion > product ion combination of 249.10 > 202.15 m/z for MO-OH-Nap and 305.10 > 215.05 m/z for the internal standard (IS), BA-SM-OM. The MS/MS response was linear over a concentration range of 1 to 500 ng/mL with a correlation coefficient (r²) of ≥0.987. The within- and between-batch precision (%RSD) and accuracy (%Bias) were within acceptable limits. The validated method was successfully applied to determine MO-OH-Nap metabolic stability, plasma protein binding, and bio-distribution studies of MO-OH-Nap in CD-1 mice. Full article

The accessibility of the “last kilometre” of a tourist city has a profound impact on the travelling experience of tourists. In-depth understanding of the characteristics and spatial effects of the “last-kilometre” traffic accessibility in tourist cities is conducive to further enhancing the accessibility of traffic travel and forming a new industry development pattern of deep integration of traffic and tourism. The results show that: (1) Private transport accessibility is significantly better than public transport accessibility, and the strong economic strength of large cities such as Peking, Shanghai, and Nanjing support a wider coverage of public transport compared with cities such as Qinhuangdao, Dalian, Ningbo, etc. Even for the middle-income and high-income groups of the large cities, the advantage of the broader travelling cost of public transport is still significant. (2) The average values of the fluctuation coefficients of travel time of public transport in tourist cities are all smaller than those of private transport, and public transport is less sensitive to traffic congestion, making it a more reliable choice for tourist travel. The higher number of public transport grids with more anomalous fluctuations and much larger fluctuations than private transport grids suggests that there is an urgent need to strengthen the standardisation of public transport services in the corresponding areas. (3) Urban tourism development has been moving from single-line to network development, and the impact of urban transport on urban–regional tourism development has been manifested in the place fission effect, corridor diffusion effect, and regional equilibrium effect. In general, our findings have been useful in understanding the accessibility characteristics of the “last kilometre” in tourist cities, optimizing the efficiency of inter-regional and intra-city transport connections, constructing a fast and convenient travel transport system, improving the accessibility of transport trips, and forming a new development pattern for the deep integration of transport and tourism. Full article