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Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D3 and lumisterol (L3) exert photoprotective and antiproliferative effects on the skin, while UV radiation is a major environmental risk factor for melanoma. Thus, many natural metabolites and synthetic analogs of steroidal and secosteroidal molecules have been tested on various cancer cells and in animal models. In this study, we tested the anti-melanoma properties of several natural derivatives of vitamin D3 and L3 in comparison to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). A significant decrease in melanoma cell proliferation and cell mobility was observed for selected derivatives, with (25R)-27-hydroxyL3 showing the highest potency (lowest IC50) in A375 cells but lower potency in SK-MEL-28 cells, whereas the parent L3 failed to inhibit proliferation. The efficacy (% inhibition) by 1,24,25(OH)3D3 and 1,25(OH)2D3 were similar in both cell types. 1,25(OH)2D3 showed higher potency than 1,24,25(OH)3D3 in SK-MEL-28 cells, but lower potency in A375 cells for the inhibition of proliferation. As for 1,25(OH)2D3, but not the other derivatives tested, treatment of melanoma cells with 1,24,25(OH)3D3 markedly increased the expression of CYP24A1, enhanced translocation of the vitamin D receptor (VDR) from the cytoplasm to the nucleus and also decreased the expression of the proliferation marker Ki67. The effects of the other compounds tested were weaker and occurred only under certain conditions. Our data indicate that 1,24,25(OH)3D3, which has undergone the first step in 1,25(OH)2D3 inactivation by being hydroxylated at C24, still shows anti-melanoma properties, displaying higher potency than 1,25(OH)2D3 in SK-MEL-28 cells. Furthermore, hydroxylation increases the potency of some of the lumisterol hydroxy-derivatives, as in contrast to L3, (25R)-27(OH)L3 effectively inhibits proliferation and migration of the human malignant melanoma cell line A375. [ABSTRACT FROM AUTHOR]

Introduction: Despite the long-term use of intramuscular and intraosseous lidocaine trigger point injections (LTPI) in the treatment of patients with low back pain, there have been no studies examining their efficiency in treatment of residual pain after degenerative lumbar spinal stenosis (DLSS) decompression surgery. The purpose of our research is to examine the LTPI efficiency in the treatment of residual lumbar pain after DLSS decompression surgery and to compare the analgesic and recovery effects of intramuscular and intraosseous LTPI administered in the L4–S1 region and in the posterior superior iliac spine (PSIS) after treatment and during four months of follow-up. Materials and Methods: We observed 99 patients (F:50, M:49) aged 42 to 59 years with residual neurological disorders after DLSS decompression surgery. In all patients, the pain syndrome exceeded 6 points on the VAS and averaged 7.2 ± 0.11 points. The control group (n = 21) underwent only pharmacotherapy. In addition to pharmacotherapy, the LTPI group underwent intramuscular LTPI in L4–S1 (n = 20), intramuscular LTPI in the PSIS (n = 19), intraosseous LTPI in L5, S1 (n = 20), and intraosseous LTPI in the PSIS (n = 19). A neurological examination was carried out before treatment, 7 days after completion of treatment, and at the end of the second and fourth months of the follow-up period. Results: In the control group, intramuscular LTPI in L4–S1 subgroup, intramuscular LTPI in PSIS subgroup, intraosseous LTPI in L5, S1 subgroup, and intraosseous LTPI in PSIS subgroup, the severity of pain decreased after treatment by 27.1% (p ≤ 0.05), 41.7% (p ≤ 0.01), 50.7% (p ≤ 0.01), 69% (p ≤ 0.01), and 84.7% (p ≤ 0.01), respectively, and at the end of the second month of follow-up, by 14.3% (p > 1), 29.2% (p ≤ 0.05), 38% (p ≤ 0.01), 53.5% (p ≤ 0.01), and 72.2% (p ≤ 0.01), respectively. Reduction of neurogenic claudication, regression of sensory deficit, increase of daily step activity, and improvement of quality of life after treatment were noted in intramuscular LTPI subgroups by 19.6% (p ≤ 0.05), 36.4 (p ≤ 0.05), 40.3% (p ≤ 0.01), and 21.0% (p ≤ 0.05), respectively, and in interosseous LTPI subgroups by 48.6% (p ≤ 0.01), 67.4% (p ≤ 0.01), 68.3% (p ≤ 0.01), and 46% (p ≤ 0.01), respectively. Conclusions: LTPI is highly effective in the treatment of patients with residual pain after DLSS decompression surgery. High analgesic effect, significant regression of sensory deficits and gait disorders, and remarkable improvement of daily step activity and quality of life are noted not only after the end of LTPI treatment but also continue for at least 2 months after treatment. Intraosseous LTPI is more effective than intramuscular LTPI by 92%, and LTPI in PSIS is more effective than LTPI in L4–S1 by 28.6%. [ABSTRACT FROM AUTHOR]

To better regulate the speed of diesel engines and optimize the speed overshoot and fast response, a speed control method combining the improved salp swarm algorithm (ISSA) with the proportional integral and differential (PID) controller was proposed. A real-time simulation model for a high-pressure common rail diesel engine was established. Addressing the challenges of the salp swarm algorithm (SSA), such as uneven population distribution and its tendency to become trapped in local optima, logistic-tent chaotic mapping, adaptive parameters was introduced, as well as adaptive dynamic inertia weights, elite strategy, and a dynamic inverse strategy. These enhancements bolstered the algorithm's precision and efficiency in both global and local searches. Using the enhanced SSA, the parameters of the PID controller for the diesel engine model was optimized. The results indicated that the ISSA offers superior parameter identification precision, strengthening speed control stability. During sudden changes in speed and load, the overshoot decreased by an average of more than 30.3% and more than 8.6%, respectively. Moreover, the settling time decreased by an average of more than 0.76 s and 1.52 s, respectively, significantly enhancing the quality of diesel engine speed control. [ABSTRACT FROM AUTHOR]

The maintenance of electrical grids is crucial for improving their reliability, performance, and cost-effectiveness. It involves employing various strategies to ensure smooth operation and address potential issues. With the advancement of digital technologies, utilizing time-series prediction has emerged as a valuable approach to enhance maintenance practices in electrical systems. The utilization of various recorded data from electrical grid components plays a crucial role in digitally enabled maintenance. However, the comprehensive exploration of time-series data prediction for maintenance is still lacking. This review paper extensively explores different time series that can be utilized to support maintenance efforts in electrical grids with regard to different maintenance strategies and grid components. The digitization of the electrical grids has enabled the collection of diverse time-series data from various network components. In this context, the paper provides an overview of how these time-series and historical-fault data can be utilized for maintenance purposes in electrical grids. Various maintenance levels and time series used for maintenance purposes in different components of the electrical grid are presented. [ABSTRACT FROM AUTHOR]

Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes. [ABSTRACT FROM AUTHOR]

Respiratory viral infections are a leading global cause of disease with multiple viruses detected in 20–30% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral–viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV), followed by influenza A virus (IAV) after 3 days. The results suggest that IAV reduced the rate of RSV production, while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios that had not been examined experimentally, including a different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight-loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis shows that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to the slower clearance of IAV-infected cells by the other viruses. The improved outcome when IAV followed RV, on the other hand, could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral–viral coinfections in this way provides new insights about how viral–viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation. [ABSTRACT FROM AUTHOR]

Room-temperature vulcanized rubber is an excellent polymer material with excellent electrical insulation and mechanical properties, which can be used for field insulation of high-voltage bare wire. In this paper, a room-temperature cured coating material was prepared from α,ω-dihydroxy polydimethylsiloxane (PDMS), polyurethane-modified silicone material (PU-Si), and Methyltris(methylethylketoxime) silane (MOS). The study showed that the coating made by adding PDMS (70 g), PU-Si (30 g), CaCO3 (90 g), MOS (7 g), KH792 (5 g), and Mg(OH)2 (30 g) had a surface drying time of 19.1 min, tensile strength of 3.2 Mpa, volume resistivity greater than 4 × 1014 Ω·cm, breakdown voltage greater than 20 kV/mm, and flame retardant performance of the FV-1 level. The comprehensive performance of the insulation material meets the national standard of "Aerial insulated cables for rated voltage of 10 kV" (GB/T14049-2008), while the insulation material has been successfully applied to the overhead line renovation project of the State Grid Hubei Electric Power Company (Wuhan, China). [ABSTRACT FROM AUTHOR]

Unsuccessful wound closure in chronic wounds can be linked to altered keratinocyte activation and their inability to re-epithelize. Suggested mechanisms driving this impairment involve unbalanced cytokine signaling. However, the molecular events leading to these aberrant responses are poorly understood. Among cytokines affecting keratinocyte responses, Transforming Growth Factor-β (TFG-β) is thought to have a great impact. In this study, we have used a previously characterized skin epidermal in vitro model, HaCaT cells continuously exposed to TGF-β1, to study the wound recovery capabilities of chronified/senescent keratinocytes. In this setting, chronified keratinocytes show decreased migration and reduced activation in response to injury. Amniotic membrane (AM) has been used successfully to manage unresponsive complicated wounds. In our in vitro setting, AM treatment of chronified keratinocytes re-enabled migration in the early stages of wound healing, also promoting proliferation at later stages. Interestingly, when checking the gene expression of markers known to be altered in TGF-β chronified cells and involved in cell cycle regulation, early migratory responses, senescence, and chronic inflammation, we discovered that AM treatment seemed to reset back to keratinocyte status. The analysis of the evolution of both the levels of keratinocyte activation marker cytokeratin 17 and the spatial-temporal expression pattern of the proliferation marker Ki-67 in human in vivo biopsy samples suggests that responses to AM recorded in TGF-β chronified HaCaT cells would be homologous to those of resident keratinocytes in chronic wounds. All these results provide further evidence that sustained TGF-β might play a key role in wound chronification and postulate the validity of our TGF-β chronified HaCaT in vitro model for the study of chronic wound physiology. [ABSTRACT FROM AUTHOR]

Water can be an irritant to a power transformer, as it is recognized as a major hazard to the operation of transformers. The water content of a transformer insulation system comprises the water in the transformer insulation oil and in the cellulose paper. The increase in the water content in the insulation system leads to reduced breakdown voltage, accelerated aging of the oil–paper insulation system, and the possibility of producing bubbles at high temperatures. Therefore, various techniques have been applied to measure the water content in both oil and paper insulation. This article comprehensively reviews and analyzes the methods (technically or nontechnically) that have been used to monitor the water content in transformer insulation systems. Apart from discussing the advantages and major drawbacks of these methods, the accuracy, measurement time, and cost of each technique are also elucidated in this review. This review can be extremely useful to the utility in monitoring and maintaining the good condition of transformers. Based on the reviewed methods and their challenges, a few future research directions and prospects for determining the water content in transformer insulation systems are outlined, such as utilizing artificial intelligence and enhancing current techniques. [ABSTRACT FROM AUTHOR]

Rising greenhouse gas emissions stemming from fossil fuel-driven vehicles are causing damage to the environment. To counteract this, one solution is the adoption of electric vehicles (EV) for transportation requirements. In this regard, one category of EVs that requires special attention is light electric vehicle (LEV), mainly because of their wide potential in public transportation—especially in developing countries. To realise widespread adoption of LEVs for this purpose, it is imperative to make their charging systems more robust. Consequently, the subject of LEV charging has gained considerable traction, and numerous research works have been reported on this subject in recent years. Hence, this paper aims to chronicle recent research developments on LEV charging techniques, by placing special attention on DC-DC converter topologies used in both on-board and off-board chargers. This review explores recent LEV charger DC-DC converters in literature by segregating them into isolated and non-isolated topologies. Lastly, this work explores challenges and emerging trends in LEV charging, which can potentially be explored by researchers in the future. [ABSTRACT FROM AUTHOR]

In nature, viral coinfection is as widespread as viral infection alone. Viral coinfections often cause altered viral pathogenicity, disrupted host defense, and mixed-up clinical symptoms, all of which result in more difficult diagnosis and treatment of a disease. There are three major virus–virus interactions in coinfection cases: viral interference, viral synergy, and viral noninterference. We analyzed virus–virus interactions in both aspects of viruses and hosts and elucidated their possible mechanisms. Finally, we summarized the protocol of viral coinfection studies and key points in the process of virus separation and purification. [ABSTRACT FROM AUTHOR]

Caligus rogercresseyi is the main ectoparasite that affects the salmon industry in Chile. The mechanisms used by the parasite to support its life strategy are of great interest for developing control strategies. Due to the critical role of insect peritrophins in host–parasite interactions and response to pest control drugs, this study aimed to identify and characterize the peritrophin-like genes present in C. rogercresseyi. Moreover, the expression of peritrophin-like genes was evaluated on parasites exposed to delousing drugs such as pyrethroids and azamethiphos. Peritrophin genes were identified by homology analysis among the sea louse transcriptome database and arthropods peritrophin-protein database obtained from GenBank and UniProt. Moreover, the gene loci in the parasite genome were located. Furthermore, peritrophin gene expression levels were evaluated by RNA-Seq analysis in sea louse developmental stages and sea lice exposed to delousing drugs deltamethrin, cypermethrin, and azamethiphos. Seven putative peritrophin-like genes were identified in C. rogercresseyi with high homology with other crustacean peritrophins. Differences in the presence of signal peptides, the number of chitin-binding domains, and the position of conserved cysteines were found. In addition, seven peritrophin-like gene sequences were identified in the C. rogercresseyi genome. Gene expression analysis revealed a stage-dependent expression profile. Notably, differential regulation of peritrophin genes in resistant and susceptible populations to delousing drugs was found. These data are the first report and characterization of peritrophin genes in the sea louse C. rogercresseyi, representing valuable knowledge to understand sea louse biology. Moreover, this study provides evidence for a deeper understanding of the molecular basis of C. rogercresseyi response to delousing drugs. [ABSTRACT FROM AUTHOR]

Global Navigation Satellite System (GNSS) radio occultation (RO) technology has been widely used in Earth atmospheric detection and has a significant impact on numerical weather prediction (NWP), climate detection, and other fields. Cosmic-2 LEO-1 (C2E1) is a well-known RO data provider; however, its observations are confined to 45°S and 45°N. Recently, the Binhu meteorological observation test satellite (BH) has provided global coverage of RO data, including refractivity, specific humidity, and temperature data. In this study, RO data from BH and C2E1 are analyzed and compared from 8 February 2022 to 17 February 2022. Employing the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis (ERA-5) data as a reference, both BH and C2E1 RO data agree with the ERA data, with the refractivity, temperature, and specific humidity profiles reflecting the real conditions of the natural atmosphere. In addition, BH data are comparable to C2E1 data at low and middle latitudes (0–45°), and BH data at middle and high latitudes (45–90°) are of better quality than those at low and middle latitudes (0–45°). For example, without considering the errors introduced by the interpolation of the ERA-5 data for comparative analysis, the BH refractivity profiles show a mean absolute bias of 0.73 N at low and middle latitudes and only 0.23 N at middle and high latitudes, and that for BH specific humidity profiles at middle and high latitudes is 0.015 g/kg, which is only half of that at low and middle latitudes. The BH temperature and specific humidity data show promising data accuracy. Therefore, BH RO data may provide important supplementary data at higher latitudes and may improve future NWPs through assimilation. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this retrospective observational study was to evaluate perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) in hospitals with a high-volume of robotic-assisted surgeries. This study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions from December 2011 to June 2020. Compared with other studies, our results revealed the equivalent or superior perioperative and short-term oncological outcomes. Hence, RRS is an effective, safe, and feasible technique for patients with rectal cancers in high-volume hospitals. The perioperative and short-term oncological outcomes of robotic-assisted rectal surgery (RRS) are unclear. This retrospective observational study enrolled patients with rectal adenocarcinoma undergoing RRS from three high-volume institutions in Taiwan. Of the 605 enrolled patients, 301 (49.75%), 176 (29.09%), and 116 (19.17%) had lower, middle, and upper rectal cancers, respectively. Low anterior resection (377, 62.31%) was the most frequent surgical procedure. Intraoperative blood transfusion was performed in 10 patients (2%). The surgery was converted to an open one for one patient (0.2%), and ten (1.7%) patients underwent reoperation. The overall complication rate was 14.5%, including 3% from anastomosis leakage. No deaths occurred during surgery and within 30 days postoperatively. The positive rates of distal resection margin and circumferential resection margin were observed in 21 (3.5%) and 30 (5.0%) patients, respectively. The 5-year overall and disease-free survival rates for patients with stage I–III rectal cancer were 91.1% and 86.3%, respectively. This is the first multi-institutional study in Taiwan with 605 patients from three high-volume hospitals. The overall surgical and oncological outcomes were equivalent or superior to those estimated in other studies. Hence, RRS is an effective and safe technique for rectal resection in high-volume hospitals. [ABSTRACT FROM AUTHOR]

There is a good body of literature about digital-game-based language learning (DGBL), but research has mainly focused on students as game players rather than as future educators. This paper reports on a research conducted among 154 teacher candidates at a higher-education institution in Spain regarding the adoption of digital games in education. It analyzes the participants' knowledge of and attitudes toward digital games in foreign language learning. Quantitative and qualitative data were gathered through a pre/post-test, digital game presentations, and student blog posts. The research comprised five stages associated with critical thinking skills (definition, selection, demonstration, discussion, and reflection), including a game learning module. In the first two stages, preservice teachers completed the module activities and selected different games aimed at teaching English to children in preschool and elementary education. In the last two, they illustrated, discussed, and evaluated the digital games in class following a rubric and reflected on their perception in blog posts. In this four-week research based on a mixed method and convenience sampling, quantitative and qualitative data were gathered through a pre- and post-test survey about student perceptions toward the use of video game in the classroom, class discussion, and blog posts. Statistical data analysis unveiled gender-based differences related to gameplay frequency and genre preferences. The Wilcoxon signed-rank test was used as a nonparametric statistical hypothesis test to compare the two sets of scores resulting from the same participants, and it showed a significant difference (p ≤ 0.05) after the treatment in two of the five dimensions in the survey about teacher candidates' attitudes toward game usage in education, namely, usefulness (U) and preference for video games (PVG). Research findings revealed preservice teachers' positive attitudes but lack of practical knowledge about the use of digital games in foreign-language learning. [ABSTRACT FROM AUTHOR]

California's highly variable climate and growing water demands combine to pose both water-supply and flood-hazard challenges to resource managers. Recently important efforts to more fully integrate the management of floods and water resources have begun, with the aim of benefitting both sectors. California is shown here to experience unusually large variations in annual precipitation and streamflow totals relative to the rest of the US, variations which mostly reflect the unusually small average number of wet days per year needed to accumulate most of its annual precipitation totals (ranging from 5 to 15 days in California). Thus whether just a few large storms arrive or fail to arrive in California can be the difference between a banner year and a drought. Furthermore California receives some of the largest 3-day storm totals in the country, rivaling in this regard the hurricane belt of the southeastern US. California's largest storms are generally fueled by landfalling atmospheric rivers (ARs). The fractions of precipitation and streamflow totals at stations across the US that are associated with ARs are documented here and, in California, contribute 20-50% of the state's precipitation and streamflow. Prospects for long-lead forecasts of these fractions are presented. From a meteorological perspective, California's water resources and floods are shown to derive from the same storms to an extent that makes integrated flood and water resources management all the more important. [ABSTRACT FROM AUTHOR]

Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation. [ABSTRACT FROM AUTHOR]

SALL4, a member of the SALL family, is an embryonic stem cell regulator involved in self-renewal and pluripotency. Recently, SALL4 overexpression was found in malignant cancers, including lung cancer, hepatocellular carcinoma, breast cancer, gastric cancer, colorectal cancer, osteosarcoma, acute myeloid leukemia, ovarian cancer, and glioma. This review updates recent advances of our knowledge of the biology of SALL4 with a focus on its mechanisms and regulatory functions in tumors and human hematopoiesis. SALL4 overexpression promotes proliferation, development, invasion, and migration in cancers through activation of the Wnt/β-catenin, PI3K/AKT, and Notch signaling pathways; expression of mitochondrial oxidative phosphorylation genes; and inhibition of the expression of the Bcl-2 family, caspase-related proteins, and death receptors. Additionally, SALL4 regulates tumor progression correlated with the immune microenvironment involved in the TNF family and gene expression through epigenetic mechanisms, consequently affecting hematopoiesis. Therefore, SALL4 plays a critical oncogenic role in gene transcription and tumor growth. However, there are still some scientific hypotheses to be tested regarding whether SALL4 is a therapeutic target, such as different tumor microenvironments and drug resistance. Thus, an in-depth understanding and study of the functions and mechanisms of SALL4 in cancer may help develop novel strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is increasingly viewed as a cell cycle disease in that the dysregulation of the cell cycle machinery is a common feature in cancer. The Hippo signaling pathway consists of a core kinase cascade as well as extended regulators, which together control organ size and tissue homeostasis. The aberrant expression of cell cycle regulators and/or Hippo pathway components contributes to cancer development, and for this reason, we specifically focus on delineating the roles of the Hippo pathway in the cell cycle. Improving our understanding of the Hippo pathway from a cell cycle perspective could be used as a powerful weapon in the cancer battlefield. Cell cycle progression is an elaborate process that requires stringent control for normal cellular function. Defects in cell cycle control, however, contribute to genomic instability and have become a characteristic phenomenon in cancers. Over the years, advancement in the understanding of disrupted cell cycle regulation in tumors has led to the development of powerful anti-cancer drugs. Therefore, an in-depth exploration of cell cycle dysregulation in cancers could provide therapeutic avenues for cancer treatment. The Hippo pathway is an evolutionarily conserved regulator network that controls organ size, and its dysregulation is implicated in various types of cancers. Although the role of the Hippo pathway in oncogenesis has been widely investigated, its role in cell cycle regulation has not been comprehensively scrutinized. Here, we specifically focus on delineating the involvement of the Hippo pathway in cell cycle regulation. To that end, we first compare the structural as well as functional conservation of the core Hippo pathway in yeasts, flies, and mammals. Then, we detail the multi-faceted aspects in which the core components of the mammalian Hippo pathway and their regulators affect the cell cycle, particularly with regard to the regulation of E2F activity, the G1 tetraploidy checkpoint, DNA synthesis, DNA damage checkpoint, centrosome dynamics, and mitosis. Finally, we briefly discuss how a collective understanding of cell cycle regulation and the Hippo pathway could be weaponized in combating cancer. [ABSTRACT FROM AUTHOR]

The mechanical discontinuities in the upper crust (i.e., faults and related fractures) lead to the uprising of geothermal fluids to the Earth's surface. If fluids are enriched in Ca2+ and HCO3-, masses of CaCO3 (i.e., travertine deposits) can form mainly due to the CO2 leakage from the thermal waters. Among other things, fissure-ridge-type deposits are peculiar travertine bodies made of bedded carbonate that gently to steeply dip away from the apical part where a central fissure is located, corresponding to the fracture trace intersecting the substratum; these morpho-tectonic features are the most useful deposits for tectonic and paleoseismological investigation, as their development is contemporaneous with the activity of faults leading to the enhancement of permeability that serves to guarantee the circulation of fluids and their emergence. Therefore, the fissure ridge architecture sheds light on the interplay among fault activity, travertine deposition, and ridge evolution, providing key geo-chronologic constraints due to the fact that travertine can be dated by different radiometric methods. In recent years, studies dealing with travertine fissure ridges have been considerably improved to provide a large amount of information. In this paper, we report the state of the art of knowledge on this topic refining the literature data as well as adding original data, mainly focusing on the fissure ridge morphology, internal architecture, depositional facies, growth mechanisms, tectonic setting in which the fissure ridges develop, and advantages of using the fissure ridges for neotectonic and seismotectonic studies. [ABSTRACT FROM AUTHOR]

Four streams in the Guadiana watershed were followed up to assess hydrogeomorphological and physicochemical characteristics, and to analyze its correlation with land use/land cover (LULC), analyzing their possible influence in reservoir water quality and possible influence in the reservoir water quality. The highest amounts of organic descriptors and nutrients were quantified in streams with the major percentage of olive groves and vineyards and urban land cover classes. Streams more influenced by agro-silvo-pastoral class presented better water quality, as this type of LULC acts as a buffer of the contamination runoff. The results highlighted that the hydrogeomorphology of the streams may influence the transfer of pollutants loads to reservoirs. Hence, in intermittent streams characterized by coarse particles in the sediment, high amounts of pollutants are accumulated when the flow ceases, and are further transported to the reservoirs when the flow retakes. On the contrary, streams with sediments characterized by a great percentage of fine particles and organic matter do not induce so much stress in reservoirs, since these allow the adsorption of nutrients and trace elements, without their transfer to reservoirs. [ABSTRACT FROM AUTHOR]

Already installed cables are aging and the cable network is growing rapidly. Improved condition monitoring methods are required for greater visibility of insulation defects in the cable networks. One of the critical challenges for continuous monitoring is the large amount of partial discharge (PD) data that poses constraints on the diagnostic capabilities. This paper presents the performance comparison of two data acquisition techniques based on phase resolved partial discharge (PRPD) and pulse acquisition (PA). The major contribution of this work is to provide an in-depth understanding of these techniques considering the perspective of randomness of the PD mechanism and improvements in the reliability of diagnostics. Experimental study is performed on the medium voltage (MV) cables in the laboratory environment. It has been observed that PRPD based acquisition not only requires a significantly larger amount of data but is also susceptible to losing the important information especially when multiple PD sources are being investigated. On the other hand, the PA technique presents improved performance for PD diagnosis. Furthermore, the use of the PA technique enables the efficient practical implementation of the continuous PD monitoring by reducing the amount of data that is acquired by extracting useful signals and discarding the silent data intervals. [ABSTRACT FROM AUTHOR]

Damage to the annulus fibrosus (AF), the outer region of the intervertebral disc (IVD), results in an undesirable condition that may accelerate IVD degeneration causing low back pain. Despite intense research interest, attempts to regenerate the IVD have failed so far and no effective strategy has translated into a successful clinical outcome. Of particular significance, the failure of strategies to repair the AF has been a major drawback in the regeneration of IVD and nucleus replacement. It is unlikely to secure regenerative mediators (cells, genes, and biomolecules) and artificial nucleus materials after injection with an unsealed AF, as IVD is exposed to significant load and large deformation during daily activities. The AF defects strongly change the mechanical properties of the IVD and activate catabolic routes that are responsible for accelerating IVD degeneration. Therefore, there is a strong need to develop effective therapeutic strategies to prevent or reconstruct AF damage to support operational IVD regenerative strategies and nucleus replacement. By the way of this review, repair and regenerative strategies for AF reconstruction, their current status, challenges ahead, and future outlooks were discussed. [ABSTRACT FROM AUTHOR]

Tunneling nanotubes (TNTs) are thin membrane elongations among the cells that mediate the trafficking of subcellular organelles, biomolecules, and cues. Mesenchymal stem cells (MSCs) receive substantial attention in tissue engineering and regenerative medicine. Many MSCs-based clinical trials are ongoing for dreadful diseases including cancer and neurodegenerative diseases. Mitochondrial trafficking through TNTs is one of the mechanisms used by MSCs to repair tissue damage and to promote tissue regeneration. Preclinical studies linked with ischemia, oxidative stress, mitochondrial damage, inflammation, and respiratory illness have demonstrated the therapeutic efficacy of MSCs via TNTs-mediated transfer of mitochondria and other molecules into the injured cells. On the other hand, MSCs-based cancer studies showed that TNTs may modulate chemoresistance in tumor cells as a result of mitochondrial trafficking. In the present review, we discuss the role of TNTs from preclinical studies associated with MSCs treatment. We discuss the impact of TNTs formation between MSCs and cancer cells and emphasize to study the importance of TNTs-mediated MSCs protection in disease models. [ABSTRACT FROM AUTHOR]

Mobile devices have penetrated all spheres of human activities, including education. Previous research has shown that smartphones are becoming widely used in learning as they can improve knowledge retention and increase student engagement. The purpose of this study was to discuss students' perception of the use of a mobile application aimed at learning new English vocabulary and phrases and describe its strengths and weaknesses as perceived by the students. In total, 28 university students answered a pen and paper questionnaire survey after experiencing the app during one semester. Overall, the students' agreement to the positive aspects displayed in the questionnaire prevailed over their disagreement or neutral opinions. The mobile app helped students prepare for the final achievement test, learning was accessible from anywhere and at any time, students appreciated the corrective feedback and would opt for the implementation of the mobile app in other courses taught at the faculty. On the other hand, as the findings indicate, the students reported that the app was not very supportive regarding communication performance; they did not find the teachers' notifications encouraging and they did not use the pronunciation support much, which was caused by various factors, such as offering students words and phrases without context or not testing all the items in the final credit test. The findings of this study contribute to the existing knowledge of students' perceptions of the use of mobile apps for learning purposes. [ABSTRACT FROM AUTHOR]

In this study, we reviewed articles on technology-enhanced language learning and teaching. We aimed to summarize the content of reviewed articles in the following categories: (1) the number of articles published by journals and by year; (2) languages and skills; (3) technology used; (4) promising technologies. We reviewed 398 research articles. The highest number of articles was published in 2017 (n = 80), whereas the lowest number was published in 2014 (n = 53). The Computer Assisted Language Learning journal published the highest number of articles (n = 100), whereas the lowest number of published articles appeared in IEEE Transactions on Learning Technologies (n = 3). The most common target language was English (n = 267). Writing, speaking, and vocabulary gained the most attention in published articles. Twenty-three different technologies were identified and they were used 406 times. Based on our results, we made several implications and suggestions for future studies. This review study can serve as a guide for teaching and research communities who plan on designing language learning and teaching activities supported by technologies. [ABSTRACT FROM AUTHOR]

Background: The Golgi apparatus undergoes disorganization in response to stress, but it is able to restore compact and perinuclear structure under recovery. This self-organization mechanism is significant for cellular homeostasis, but remains mostly elusive, as does the role of giantin, the largest Golgi matrix dimeric protein. Methods: In HeLa and different prostate cancer cells, we used the model of cellular stress induced by Brefeldin A (BFA). The conformational structure of giantin was assessed by proximity ligation assay and atomic force microscopy. The post-BFA distribution of Golgi resident enzymes was examined by 3D SIM high-resolution microscopy. Results: We detected that giantin is rather flexible than an extended coiled-coil dimer and BFA-induced Golgi disassembly was associated with giantin monomerization. A fusion of the nascent Golgi membranes after BFA washout is forced by giantin re-dimerization via disulfide bond in its luminal domain and assisted by Rab6a GTPase. GM130-GRASP65-dependent enzymes are able to reach the nascent Golgi membranes, while giantin-sensitive enzymes appeared at the Golgi after its complete recovery via direct interaction of their cytoplasmic tail with N-terminus of giantin. Conclusion: Post-stress recovery of Golgi is conducted by giantin dimer and Golgi proteins refill membranes according to their docking affiliation rather than their intra-Golgi location. [ABSTRACT FROM AUTHOR]

The ubiquitously expressed family of inward rectifier potassium (KIR) channels, encoded by KCNJ genes, is primarily involved in cell excitability and potassium homeostasis. Channel mutations associate with a variety of severe human diseases and syndromes, affecting many organ systems including the central and peripheral neural system, heart, kidney, pancreas, and skeletal muscle. A number of mutations associate with altered ion channel expression at the plasma membrane, which might result from defective channel trafficking. Trafficking involves cellular processes that transport ion channels to and from their place of function. By alignment of all KIR channels, and depicting the trafficking associated mutations, three mutational hotspots were identified. One localized in the transmembrane-domain 1 and immediately adjacent sequences, one was found in the G-loop and Golgi-export domain, and the third one was detected at the immunoglobulin-like domain. Surprisingly, only few mutations were observed in experimentally determined Endoplasmic Reticulum (ER)exit-, export-, or ER-retention motifs. Structural mapping of the trafficking defect causing mutations provided a 3D framework, which indicates that trafficking deficient mutations form clusters. These "mutation clusters" affect trafficking by different mechanisms, including protein stability. [ABSTRACT FROM AUTHOR]

Power transformers are the most important assets of electric power substations. The reliability in the operation of electric power transmission and distribution is due to the correct operation and maintenance of power transformers. The parameters that are most used to assess the health status of power transformers are dissolved gas analysis (DGA), oil quality analysis (OQA) and content of furfuraldehydes (FFA) in oil. The parameter that currently allows for simple online monitoring in an energized transformer is the DGA. Although most of the DGA continues to be done in the laboratory, the trend is online DGA monitoring, since it allows for detection or diagnosis of the faults throughout the life of the power transformers. This study presents a review of the main DGA monitors, single- or multi-gas, their most important specifications, accuracy, repeatability and measurement range, the types of installation, valve or closed loop, and number of analogue inputs and outputs. This review shows the differences between the main existing DGA monitors and aims to help in the selection of the most suitable DGA monitoring approach according to the needs of each case. [ABSTRACT FROM AUTHOR]

Rainfall patterns in the San Francisco Bay Area (SFBA) are highly influenced by local topography. It has been a forecasting challenge for the main US forecast models. This study investigates the ability of the Weather Research and Forecasting (WRF) model to improve upon forecasts, with particular emphasis on the rain shadow common to the southern end of the SFBA. Three rain events were evaluated: a mid-season atmospheric river (AR) event with copious rains; a typical non-AR frontal passage rain event; and an area-wide rain event in which zero rain was recorded in the southern SFBA. The results show that, with suitable choices of parameterizations, the WRF model with a resolution around 1 km can forecast the observed rainfall patterns with good accuracy, and would be suitable for operational use, especially to water and emergency managers. Additionally, the three synoptic situations were investigated for further insight into the common ingredients for either flooding rains or strong rain shadow events. [ABSTRACT FROM AUTHOR]

The epithelial cells in an adult woman's breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment. However, current evidence suggests that alterations to the communication between MaSCs, epithelial progenitors and their microenvironment plays an important role in breast carcinogenesis. In this article, we review the current knowledge regarding the role of the breast tissue microenvironment in regulating the special functions of normal and cancer stem cells. Understanding the crosstalk between MaSCs and their microenvironment will provide new insights into how an altered breast tissue microenvironment could contribute to breast cancer development, progression and therapy response and the implications of this for the development of novel therapeutic strategies to target cancer stem cells. [ABSTRACT FROM AUTHOR]

Low back pain (LBP), commonly induced by intervertebral disc degeneration, is a lumbar disease with worldwide prevalence. However, the mechanism of degeneration remains unclear. The intervertebral disc is a nonvascular organ consisting of three components: Nucleus pulposus, annulus fibrosus, and endplate cartilages. The disc is structured to support our body motion and endure persistent external mechanical pressure. Thus, there is a close connection between force and intervertebral discs in LBP. It is well established that with aging, disordered mechanical stress profoundly influences the fate of nucleus pulposus and the alignment of collagen fibers in the annulus fibrosus. These support a new understanding that disordered mechanical stress plays an important role in the degeneration of the intervertebral discs. Tissue-engineered regenerative and reparative therapies are being developed for relieving disc degeneration and symptoms of lower back pain. In this paper, we will review the current literature available on the role of disordered mechanical stress in intervertebral disc degeneration, and evaluate the existing tissue engineering treatment strategies of the current therapies. [ABSTRACT FROM AUTHOR]

The development and growth of vertebrate axial muscle have been studied for decades at both the descriptive and molecular level. The zebrafish has provided an attractive model system for investigating both muscle patterning and growth due to its simple axial musculature with spatially separated fibre types, which contrasts to complex muscle groups often deployed in amniotes. In recent years, new findings have reshaped previous concepts that define how final teleost muscle form is established and maintained. Here, we summarise recent findings in zebrafish embryonic myogenesis with a focus on fibre type specification, followed by an examination of the molecular mechanisms that control muscle growth with emphasis on the role of the dermomyotome-like external cell layer. We also consider these data sets in a comparative context to gain insight into the evolution of axial myogenic patterning systems within the vertebrate lineage. [ABSTRACT FROM AUTHOR]

In power converters, the fast switching of the power conversion components results in rapid changes in voltage and current, which results in oscillations and high-level electromagnetic interference (EMI), so the power components become a source of internal electromagnetic interference. Taking SiC Metal-Oxide-Semiconductor Field-Effect Transistor (MOSFET) as an example, an intelligent control method to suppressing interference sources is proposed in this paper. The combination of open-loop and closed-loop methods can simultaneously reduce the electromagnetic interference generated by voltage and current. Firstly, this paper analyzes how to select a reference signal. The relationship between the time domain and the frequency domain of the noise signal is analyzed. The convolution of the trapezoidal signal and the Gaussian signal is selected as the reference signal, which is named S-shaped signal in this paper. The S-shaped signal has continuous infinitely conductive characteristics, so its spectrum has a large attenuation in the high frequency region. Secondly, a new topology is proposed. Based on the closed-loop gate control, a current control signal is added, which can simultaneously shape the output voltage and control the output current slope. Both the simulation results and the experimental results show that the output voltage can follow the reference signal, S-shaped signal, and the slope and overshoot of output current can be changed. Compared with classical gate driver method, the spectrum of output voltage and output current obtained by the method proposed in this paper has a large attenuation, in other words, the electromagnetic interference is significantly reduced. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that gamma-tocotrienol (γ-T3), a vitamin E isomer, has potent anti-cancer properties against a wide-range of cancers. γ-T3 not only inhibited the growth and survival of cancer cells in vitro, but also suppressed angiogenesis and tumour metastasis under in vivo conditions. Recently, γ-T3 was found to target cancer stem cells (CSCs), leading to suppression of tumour formation and chemosensitisation. Despite its promising anti-cancer potential, the exact mechanisms responsible for the effects of γ-T3 are still largely unknown. Here, we report the identification of Ang-1 (Angiopoietin-1)/Tie-2 as a novel γ-T3 downstream target. In prostate cancer cells, γ-T3 treatment leads to the suppression of Ang-1 at both the mRNA transcript and protein levels. Supplementing the cells with Ang-1 was found to protect them against the anti-CSC effect of γ-T3. Intriguingly, inactivation of Tie-2, a member receptor that mediates the effect of Ang-1, was found to significantly enhance the cytotoxic effect of γ-T3 through activation of AMP-activated protein kinase (AMPK) and subsequent interruption of autophagy. Our results highlighted the therapeutic potential of using γ-T3 in combination with a Tie-2 inhibitor to treat advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Ion channels are transmembrane proteins that conduct specific ions across biological membranes. Ion channels are present at the onset of many cellular processes, and their malfunction triggers severe pathologies. Potassium channels (KChs) share a highly conserved signature that is necessary to conduct K+ through the pore region. To be functional, KChs require an exquisite regulation of their subcellular location and abundance. A wide repertoire of signatures facilitates the proper targeting of the channel, fine-tuning the balance that determines traffic and location. These signature motifs can be part of the secondary or tertiary structure of the protein and are spread throughout the entire sequence. Furthermore, the association of the pore-forming subunits with different ancillary proteins forms functional complexes. These partners can modulate traffic and activity by adding their own signatures as well as by exposing or masking the existing ones. Post-translational modifications (PTMs) add a further dimension to traffic regulation. Therefore, the fate of a KCh is not fully dependent on a gene sequence but on the balance of many other factors regulating traffic. In this review, we assemble recent evidence contributing to our understanding of the spatial expression of KChs in mammalian cells. We compile specific signatures, PTMs, and associations that govern the destination of a functional channel. [ABSTRACT FROM AUTHOR]