In our pursuit of high-power terahertz (THz) wave generation, we propose innovative edge-terminated single-drift region (SDR) multi-quantum well (MQW) impact avalanche transit time (IMPATT) structures based on the Al_xGa_1−xN/GaN/Al_xGa_1−xN material system, with a fixed aluminum mole fraction of x = 0.3. Two distinct MQW diode configurations, namely p⁺-n junction-based and Schottky barrier diode structures, were investigated for their THz potential. To enhance reverse breakdown characteristics, we propose employing mesa etching and nitrogen ion implantation for edge termination, mitigating issues related to premature and soft breakdown. The THz performance is comprehensively evaluated through steady-state and high-frequency characterizations using a self-consistent quantum drift-diffusion (SCQDD) model. Our proposed Al_0.3Ga_0.7N/GaN/Al_0.3Ga_0.7N MQW diodes, as well as GaN-based single-drift region (SDR) and 3C-SiC/Si/3C-SiC MQW-based double-drift region (DDR) IMPATT diodes, are simulated. The Schottky barrier in the proposed diodes significantly reduces device series resistance, enhancing peak continuous wave power output to approximately 300 mW and DC to THz conversion efficiency to nearly 13% at 1.0 THz. Noise performance analysis reveals that MQW structures within the avalanche zone mitigate noise and improve overall performance. Benchmarking against state-of-the-art THz sources establishes the superiority of our proposed THz sources, highlighting their potential for advancing THz technology and its applications. Full article

Brugada syndrome is a rare arrhythmogenic syndrome associated mainly with pathogenic variants in the SCN5A gene. Right ventricle outflow tract fibrosis has been reported in some cases of patients diagnosed with Brugada syndrome. Pulmonary atresia with an intact ventricular septum is characterized by the lack of a functional pulmonary valve, due to the underdevelopment of the right ventricle outflow tract. We report, for the first time, a 4-year-old boy with pulmonary atresia with an intact ventricular septum who harbored a pathogenic de novo variant in SCN5A, and the ajmaline test unmasked a type-1 Brugada pattern. We suggest that deleterious variants in the SCN5A gene could be implicated in pulmonary atresia with an intact ventricular septum embryogenesis, leading to overlapping phenotypes. Full article

Nanoplastics, created by the fragmentation of larger plastic debris, are a serious pollutant posing substantial environmental and health risks. Here, we developed a polystyrene nanoparticle (PS-NP) exposure model during mice pregnancy to explore their effects on embryonic development. We found that exposure to 30 nm PS-NPs during pregnancy resulted in reduced mice placental weight and abnormal embryonic development. Subsequently, our transcriptomic dissection unveiled differential expression in 102 genes under PS-NP exposure and the p38 MAPK pathway emerged as being significantly altered in KEGG pathway mapping. Our findings also included a reduction in the thickness of the trophoblastic layer in the placenta, diminished cell invasion capabilities, and an over-abundance of immature red cells in the blood vessels of the mice. In addition, we validated our findings through the human trophoblastic cell line, HTR-8/SVneo (HTR). PS-NPs induced a drop in the vitality and migration capacities of HTR cells and suppressed the p38 MAPK signaling pathway. This research highlights the embryotoxic effects of nanoplastics on mice, while the verification results from the HTR cells suggest that there could also be certain impacts on the human trophoblast layer, indicating a need for further exploration in this area. Full article

Optical power splitters (OPSs) are utilized extensively in integrated photonic circuits, drawing significant interest in research on power splitters with adjustable splitting ratios. This paper introduces a compact, low-loss 1 × 2 asymmetric multimode interferometric (MMI) optical power splitter on a silicon-on-insulator (SOI) platform. The device is simulated using the finite difference method (FDM) and eigenmode expansion solver (EME). It is possible to attain various output power splitting ratios by making the geometry of the MMI central section asymmetric relative to the propagation axis. Six distinct optical power splitters are designed with unconventional splitting ratios in this paper, which substantiates that the device can achieve any power splitter ratios (PSRs) in the range of 95:5 to 50:50. The dimensions of the multimode section were established at 2.9 × (9.5–10.9) μm. Simulation results show a range of unique advantages of the device, including a low extra loss of less than 0.4 dB, good fabrication tolerance, and power splitting ratio fluctuation below 3% across the 1500 nm to 1600 nm wavelength span. Full article

Glucose-derived carbon hybrids were synthesized by hydrothermal treatment in the presence of oxidized carbon nanotubes. Additionally, iron and nitrogen functionalities were incorporated into the carbon structure using different methodologies. The introduction of iron and nitrogen in a single step under a H₂ atmosphere favored the formation of quaternary nitrogen and oxidized nitrogen, whereas the incorporation of nitrogen under an N₂ atmosphere after doping the hybrids with iron mainly produced pyridinic nitrogen. The samples were characterized by scanning electron microscopy, X-ray spectroscopy, adsorption isotherms, inductively coupled plasma optical emission spectrometry, and Raman spectroscopy. The presence of iron and nitrogen in the carbons increases the onset potential toward oxygen reduction in KOH 0.1 mol L⁻¹ by 130 mV (0.83 V), in comparison to carbonized glucose, whereas the reaction mechanism shifts closer to a direct pathway and the formation of HO₂⁻ decreases to 25% (3.5 electrons). The reaction rate also increased in comparison to the carbonized glucose, as observed by the decrease in the Tafel slope value from 117 to 61 mV dec⁻¹. Furthermore, the incorporation of iron and nitrogen in a single step enhanced the short-term performance of the prepared electrocatalysts, which may also be due to the higher relative amount of quaternary nitrogen. Full article

Perioperative anxiety is common among patients undergoing surgery, potentially leading to negative outcomes. Immersive virtual reality (VR) has shown promise in reducing anxiety in various clinical settings. This study aimed to evaluate the effectiveness of VR in reducing perioperative anxiety in patients undergoing gynecological oncology surgery and was conducted as a single-center, double-arm, single-blinded randomized controlled trial at the Gold Coast University Hospital, Queensland, Australia. Participants were randomized into the VR intervention + care as usual (CAU) group (n = 39) and the CAU group (n = 41). Anxiety scores were assessed using a six-tier visual facial anxiety scale at baseline, after the intervention/CAU on the same day, and, several days up to weeks later, immediately before surgery. There was no significant difference in baseline anxiety scores, type of operation, or suspected cancer between the two groups. The VR intervention significantly reduced anxiety scores from baseline to preoperative assessment (p < 0.001). The median anxiety score in the VR intervention group decreased from 3 (interquartile range 2 to 5) at baseline to 2 (2 to 3) prior to surgery, while the control group’s scores were 4 (2 to 5) and 4 (3 to 5), respectively. Multivariate analysis showed that group assignment was the sole outcome predictor, not age, type of procedure, or the time elapsed until surgery. Thus, VR exposure was effective in reducing perioperative anxiety in patients undergoing gynecological oncology surgery. The use of VR as a preparation tool may improve patient experience and contribute to better surgical outcomes, warranting further research into exploring the potential benefits of VR in other surgical specialties and its long-term impact on patient recovery. Full article

Titanites can be excellent markers of element transfer in medium-temperature retrograde metamorphism. Euhedral titanites from several alpine fissures from Mont Blanc, particularly those of Périades and Courtes, crystallised at the end of the main quartz stage and are synchronous with the formation of green biotites and albite before chlorite formation. Micro-XRF, SEM, electron probe, and LA-ICP-MS analyses show that these titanites have a wide range of Al₂O₃ content from 1 to 8%, are dominated by -OH versus F, and have a wide range of Nb (up to 4500 ppm), Y (up to 3000 ppm), Zr (up to 1800 ppm), and Sn (up to 1400 ppm) concentrations. The allanite from the granite, partly destabilised into epidote, is the most likely source of Nb, Y, Zr, Sn, and REE. Titanites are enriched in HREE and show variations in LREE depending on the studied sites. Like quartz, they formed at around 400 ± 20 °C, which is compatible with the formation of green biotites after the destabilisation of granite Fe-Mg silicates. This early stage of fluid circulation, synchronous with the Mont Blanc massif uplift, is therefore marked by the titanite formation at the transition between the biotite and chlorite stability fields. Full article

This study explores the spatiotemporal variability and determinants of rainfall patterns during the March to May (MAM) season in Rwanda, incorporating an analysis of teleconnections with oceanic–atmospheric indices over the period 1983–2021. Utilizing the Climate Hazards Group Infrared Precipitation with Stations (CHIRPS) dataset, the study employs a set of statistical tools including standardized anomalies, empirical orthogonal functions (EOF), Pearson correlation, the Mann–Kendall (MK) trend test, and Sen’s slope estimator to dissect the intricacies of rainfall variability, trends, and their association with large-scale climatic drivers. The findings reveal a distinct southwest to northwest rainfall gradient across Rwanda, with the MK test signaling a decline in annual precipitation, particularly in the southwest. The analysis for the MAM season reveals a general downtrend in rainfall, attributed in part to teleconnections with the Indian Ocean Sea surface temperatures (SSTs). Notably, the leading EOF mode for MAM rainfall demonstrates a unimodal pattern, explaining a significant 51.19% of total variance, and underscoring the pivotal role of atmospheric dynamics and moisture conveyance in shaping seasonal rainfall. The spatial correlation analysis suggests a modest linkage between MAM rainfall and the Indian Ocean Dipole, indicating that negative (positive) phases are likely to result in anomalously wet (dry) conditions in Rwanda. This comprehensive assessment highlights the intricate interplay between local rainfall patterns and global climatic phenomena, offering valuable insights into the meteorological underpinnings of rainfall variability during Rwanda’s critical MAM season. Full article

A healthy gut microbiome is crucial for the immune system and overall development of infants. Bifidobacterium has been known to be a predominant species in the infant gut; however, an emerging concern is the apparent loss of this genus, in particular, Bifidobacterium longum subsp. infantis (B. infantis) in the gut microbiome of infants in industrialized nations, underscoring the importance of restoring this beneficial bacterium. With the growing understanding of the gut microbiome, probiotics, especially infant-type human-residential bifidobacteria (HRB) strains like B. infantis, are gaining prominence for their unique ability to utilize HMOs and positively influence infant health. This article delves into the physiology of a probiotic strain, B. infantis M-63, its symbiotic relationship with HMOs, and its potential in improving gastrointestinal and allergic conditions in infants and children. Moreover, this article critically assesses the role of HMOs and the emerging trend of supplementing infant formulas with the prebiotic HMOs, which serve as fuel for beneficial gut bacteria, thereby emulating the protective effects of breastfeeding. The review highlights the potential of combining B. infantis M-63 with HMOs as a feasible strategy to improve health outcomes in infants and children, acknowledging the complexities and requirements for further research in this area. Full article

Supplementation with fish oil rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) effectively reduces acute and chronic alcohol-induced hepatic steatosis. We aimed to find molecular mechanisms underlying the effects of n-3 PUFAs in alcohol-induced hepatic steatosis. Because free fatty acid receptor 4 (FFA4, also known as GPR120) has been found as a receptor for n-3 PUFAs in an ethanol-induced liver steatosis model, we investigated whether n-3 PUFAs protect against liver steatosis via FFA4 using AH7614, an FFA4 antagonist, and Ffa4 knockout (KO) mice. N-3 PUFAs and compound A (CpdA), a selective FFA4 agonist, reduced the ethanol-induced increase in lipid accumulation in hepatocytes, triglyceride content, and serum ALT levels, which were not observed in Ffa4 KO mice. N-3 PUFAs and CpdA also reduced the ethanol-induced increase in lipogenic sterol regulatory element-binding protein-1c expression in an FFA4-dependent manner. In Kupffer cells, treatment with n-3 PUFA and CpdA reversed the ethanol-induced increase in tumor necrosis factor-α, cyclooxygenase-2, and NLR family pyrin domain-containing 3 expression levels in an FFA4-dependent manner. In summary, n-3 PUFAs protect against ethanol-induced hepatic steatosis via the anti-inflammatory actions of FFA4 on Kupffer cells. Our findings suggest FFA4 as a therapeutic target for alcoholic hepatic steatosis. Full article

Dengue has become a public health concern in Indonesia since it was first found in 1968. This study aims to determine dengue hotspot areas and analyze the spatiotemporal distribution of dengue and its association with dominant climate parameters nationally. Monthly data for dengue and climate observations (i.e., rainfall, relative humidity, average, maximum, and minimum temperature) at the regency/city level were utilized. Dengue hotspot areas were determined through K-means clustering, while Singular Value Decomposition (SVD) determined dominant climate parameters and their spatiotemporal distribution. Results revealed four clusters: Cluster 1 comprised cities with medium to high Incidence Rates (IR) and high Case Densities (CD) in a narrow area. Cluster 2 has a high IR and low CD, and clusters 3 and 4 featured medium and low IR and CD, respectively. SVD analysis indicated that relative humidity and rainfall were the most influential parameters on IR across all clusters. Temporal fluctuations in the first mode of IR and climate parameters were clearly delineated. The spatial distribution of heterogeneous correlation between the first mode of rainfall and relative humidity to IR exhibited higher values, which were predominantly observed in Java, Bali, Nusa Tenggara, the eastern part of Sumatra, the southern part of Kalimantan, and several locations in Sulawesi. Full article

A stratigraphic complex composed of mass transport deposits (MTDs), where the gas occurrence allows for the formation of a gas chimney and pipe structure, is identified based on seismic interpretation in the QiongDongNan area of the northern South China Sea. During the Fifth Gas Hydrate Drilling Expedition of the Guangzhou Marine Geological Survey, this type of complex morphology that has close interaction with local gas hydrate (GH) distribution was eventually confirmed. A flow-reaction model is built to explore the spatial–temporal matching evolution process of massive GH reservoirs since 30 kyr before the present (BP). Five time snapshots, including 30, 20, 10, and 5 kyr BP, as well as the present, have been selected to exhibit key strata-evolving information. The results of in situ tensile estimation imply fracturing emergence occurs mostly at 5 kyr BP. Six other environmental scenarios and three cases of paleo-hydrate existence have been compared. The results almost coincide with field GH distribution below the bottom MTD from drilling reports, and state layer fracturing behaviors always feed and probably propagate in shallow sediments. It can be concluded that this complex system with 10% pre-existing hydrates results in the exact distribution and occurrence in local fine-grained silty clay layers adjacent to upper MTDs. Full article

A rugged handheld sensor for rapid in-field classification of cannabis samples based on their THC content using ultra-compact near-infrared spectrometer technology is presented. The device is designed for use by the Austrian authorities to discriminate between legal and illegal cannabis samples directly at the place of intervention. Hence, the sensor allows direct measurement through commonly encountered transparent plastic packaging made from polypropylene or polyethylene without any sample preparation. The measurement time is below 20 s. Measured spectral data are evaluated using partial least squares discriminant analysis directly on the device’s hardware, eliminating the need for internet connectivity for cloud computing. The classification result is visually indicated directly on the sensor via a colored LED. Validation of the sensor is performed on an independent data set acquired by non-expert users after a short introduction. Despite the challenging setting, the achieved classification accuracy is higher than 80%. Therefore, the handheld sensor has the potential to reduce the number of unnecessarily confiscated legal cannabis samples, which would lead to significant monetary savings for the authorities. Full article

Pediatric neuroblastomas (NBs) are heterogeneous, aggressive, therapy-resistant embryonal tumors that originate from cells of neural crest origin committed to the sympathoadrenal progenitor cell lineage. Stress- and drug-resistance mechanisms drive post-therapeutic relapse and metastatic progression, the characterization and inhibition of which are major goals in improving therapeutic responses. Stress- and drug-resistance mechanisms in NBs include alternative TrkAIII splicing of the neurotrophin receptor tropomyosin-related kinase A (NTRK1/TrkA), which correlates with post-therapeutic relapse and advanced-stage metastatic disease. The TrkAIII receptor variant exerts oncogenic activity in NB models by mechanisms that include stress-induced mitochondrial importation and activation. In this study, we characterize novel targetable and non-targetable participants in this pro-survival mechanism in TrkAIII-expressing SH-SY5Y NB cells, using dithiothreitol (DTT) as an activator and a variety of inhibitors by regular and immunoprecipitation Western blotting of purified mitochondria and IncuCyte cytotoxicity assays. We report that stress-induced TrkAIII misfolding initiates this mechanism, resulting in Grp78, Ca²⁺-calmodulin, adenosine ribosylating factor (Arf) and Hsp90-regulated mitochondrial importation. TrkAIII imported into inner mitochondrial membranes is cleaved by Omi/high temperature requirement protein A2 (HtrA2) then activated by a mechanism dependent upon calmodulin kinase II (CaMKII), alpha serine/threonine kinase (Akt), mitochondrial Ca²⁺ uniporter and reactive oxygen species (ROS), involving inhibitory mitochondrial protein tyrosine phosphatase (PTPase) oxidation, resulting in phosphoinositide 3 kinase (PI3K) activation of mitochondrial Akt, which enhances stress resistance. This novel pro-survival function for misfolded TrkAIII mitigates the cytotoxicity of mitochondrial Ca²⁺ homeostasis disrupted during integrated stress responses, and is prevented by clinically approved Trk and Akt inhibitors and also by inhibitors of 78kDa glucose regulated protein (Grp78), heat shock protein 90 (Hsp90), Ca²⁺-calmodulin and PI3K. This identifies Grp78, Ca²⁺-calmodulin, Hsp90, PI3K and Akt as novel targetable participants in this mechanism, in addition to TrkAIII, the inhibition of which has the potential to enhance the stress-induced elimination of TrkAIII-expressing NB cells, with the potential to improve therapeutic outcomes in NBs that exhibit TrkAIII expression and activation. Full article

Although migraine belongs to the main causes of disability worldwide, the mechanisms of its pathogenesis are poorly known. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective auxiliary markers to support clinical diagnosis. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. We chose the interictal phase as the episodic migraine patients were recruited from the outpatient clinic and had monthly migraine days as low as 1–2 in many cases. Migraine patients displayed lower urinary levels of 5-HIAA (p < 0.01) and KYNA (p < 0.05), but KYN and QA were enhanced, as compared with the controls (p < 0.05 and 0.001, respectively). Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios (p < 0.001 for all). Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score and monthly migraine and monthly headache days. There was a negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be further explored to assess its suitability as an easy-to-determine marker of migraine. Full article

Fish fry counting has been vital in fish farming, but current computer-based methods are not feasible enough to accurately and efficiently calculate large number of fry in a single count due to severe occlusion, dense distribution and the small size of fish fry. To address this problem, we propose the deconvolution enhancement keypoint network (DEKNet), a method for fish fry counting that features a single-keypoint approach. This novel approach models the fish fry as a point located in the central part of the fish head, laying the foundation for our innovative counting strategy. To be specific, first, a fish fry feature extractor (FFE) characterized by parallel dual branches is designed for high-resolution representation. Next, two identical deconvolution modules (TDMs) are added to the generation head for a high-quality and high-resolution keypoint heatmap with the same resolution size as the input image, thus facilitating the precise counting of fish fry. Then, the local peak value of the heatmap is obtained as the keypoint of the fish fry, so the number of these keypoints with coordinate information equals the number of fry, and the coordinates of the keypoint can be used to locate the fry. Finally, FishFry-2023, a large-scale fish fry dataset, is constructed to evaluate the effectiveness of the method proposed by us. Experimental results show that an accuracy rate of 98.59% was accomplished in fish fry counting. Furthermore, DEKNet achieved a high degree of accuracy on the Penaeus dataset (98.51%) and an MAE of 13.32 on a public dataset known as Adipocyte Cells. The research outcomes reveal that DEKNet has superior comprehensive performance in counting accuracy, the number of parameters and computational effort. Full article

Under the Paris Agreement, countries must articulate their most ambitious mitigation targets in their Nationally Determined Contributions (NDCs) every five years and regularly submit interconnected information on greenhouse gas (GHG) aspects, including national GHG inventories, NDC progress tracking, mitigation policies and measures (PAMs), and GHG projections in various mitigation scenarios. Research highlights significant gaps in the definition of mitigation targets and the reporting on GHG-related elements, such as inconsistencies between national GHG inventories, projections, and mitigation targets, a disconnect between PAMs and mitigation scenarios, as well as varied methodological approaches across sectors. To address these challenges, the Mitigation-Inventory Tool for Integrated Climate Action (MITICA) provides a methodological framework that links national GHG inventories, PAMs and GHG projections, applying a hybrid decomposition approach that integrates machine learning regression techniques with classical forecasting methods for developing GHG emission projections. MITICA enables mitigation scenario generation until 2050, incorporating over 60 PAMs across Intergovernmental Panel on Climate Change (IPCC) sectors. It is the first modelling approach that ensures consistency between reporting elements, aligning NDC progress tracking and target setting with IPCC best practices while linking climate change with sustainable economic development. MITICA’s results include projections that align with observed trends, validated through cross-validation against test data, and employ robust methods for evaluating PAMs, thereby establishing its reliability. Full article

Low-alloy wear-resistant steel often requires the addition of trace alloy elements to enhance its performance while also considering the cost-effectiveness of production. In order to comparatively analyze the strengthening mechanisms of Mo and Cr elements and further explore economically feasible production processes, we designed two types of low-alloy wear-resistant steels, based on C-Mn series wear-resistant steels, with individually added Mo and Cr elements, comparing and investigating the roles of the alloying elements Mo and Cr in low-alloy wear-resistant steels. Utilizing JMatPro software to calculate Continuous Cooling Transformation (CCT) curves, conducting thermal simulation quenching experiments using a Gleeble-3800 thermal simulator, and employing equipment such as a metallographic microscope, transmission electron microscope, and tensile testing machine, this study comparatively investigated the influence of Mo and Cr on the microstructural transformation and mechanical properties of low-alloy wear-resistant steels under different cooling rates. The results indicate that the addition of the Mo element in low-alloy wear-resistant steel can effectively suppress the transformation of ferrite and pearlite, reduce the martensitic transformation temperature, and lower the critical cooling rate for complete martensitic transformation, thereby promoting martensitic transformation. Adding Cr elements can reduce the austenite transformation zone, decrease the rate of austenite formation, and promote the occurrence of low-temperature phase transformation. Additionally, Mo has a better effect on improving the toughness of low-temperature impact, and Cr has a more significant improvement in strength and hardness. The critical cooling rates of C-Mn-Mo steel and C-Mn-Cr steel for complete martensitic transition are 13 °C/s and 24 °C/s, respectively. With the increase in the cooling rate, the martensitic tissues of the two experimental steels gradually refined, and the characteristics of the slats gradually appeared. In comparison, the C-Mn-Mo steel displays a higher dislocation density, accompanied by dislocation entanglement phenomena, and contains a small amount of residual austenite, while granular ε-carbides are clearly precipitated in the C-Mn-Cr steel. The C-Mn-Mo steel achieves its best performance at a cooling rate of 25 °C/s, whereas the C-Mn-Cr steel only needs to increase the cooling rate to 35 °C/s to attain a similar comprehensive performance to the C-Mn-Mo steel. Full article

In the modern era of Aquaculture, biofloc technology (BFT) systems have attained crucial attention. This technology is used to reduce water renewal with the removal of nitrogen and to provide additional feed. In BFT, microorganisms play a crucial role due to their complex metabolic properties. Pathogens can be controlled through multiple mechanisms using probiotics, which can promote host development and enhance the quality of the culture environment. During culturing in a biofloc technology system, the supplementation of microalgae and its accompanying bacteria plays a beneficial role in reducing nitrogenous compounds. This enhances water quality and creates favorable environmental conditions for specific bacterial groups, while simultaneously reducing the dependency on carbon sources with higher content. The fluctuations in the bacterial communities of the intestine are closely associated with the severity of diseases related to shrimp and are used to evaluate the health status of shrimp. Overall, we will review the microbes associated with shrimp culture in BFT and their effects on shrimp growth. We will also examine the microbial impacts on the growth performance of L. vannamei in BFT, as well as the close relationship between probiotics and the intestinal microbes of L. vannamei. Full article

In permafrost regions with warm frozen soil, the pile foundation is commonly used, but most currently available models for the WFS foundation pile–soil system are either highly empirical or overcomplicated, without a simplified theoretical manner in engineering. This study derives a novel and simplified calculated model of the WFS pile–soil system. The model is formulated in terms of the shear deformation theory and load transfer method based on the rigorous deformation mechanism of the WFS foundation soil around the pile. Considering the different depth soil features and the equilibrium state of the pile–soil system, dividing warm frozen soil foundation into three regions (TPPR, ER, and BPPR) to calculate the D_p and D_s can simply obtain the total displacement of pile under different loads. The results demonstrate that the present theoretical model can well predict the WFS foundation load–displacement response of the pile. The present model provides a simple, practical, and effective approach for the estimation of the load–displacement behavior of piles installed in the WFS foundation. Full article

Given the difficulty of explaining the unwrapping process through traditional teaching methodologies, this article presents the design, development, and validation of an immersive Virtual Reality (VR) serious game, named Unwrap 3D Virtual: Ready (UVR), aimed at facilitating the learning of unwrapping 3D models. The game incorporates animations to aid users in understanding the unwrapping process, following Mayer’s Cognitive Theory of Multimedia Learning and Gamification principles. Structured into four levels of increasing complexity, users progress through different aspects of 3D model unwrapping, with the final level allowing for result review. A sample of 53 students with experience in 3D modeling was categorized based on device (PC or VR) and previous experience (XP) in VR, resulting in Low-XP, Mid-XP, and High-XP groups. Hierarchical clustering identified three clusters, reflecting varied user behaviors. Results from surveys assessing game experience, presence, and satisfaction show higher immersion reported by VR users despite greater satisfaction being observed in the PC group due to a bug in the VR version. Novice users exhibited higher satisfaction, which was attributed to the novelty effect, while experienced users demonstrated greater control and proficiency. Full article

G protein-coupled receptors (GPCRs) are relevant targets for health and disease as they regulate various aspects of metabolism, proliferation, differentiation, and immune pathways. They are implicated in several disease areas, including cancer, diabetes, cardiovascular diseases, and mental disorders. It is worth noting that about a third of all marketed drugs target GPCRs, making them prime pharmacological targets for drug discovery. Numerous functional assays have been developed to assess GPCR activity and GPCR signaling in living cells. Here, we review the current literature of genetically encoded cell-based assays to measure GPCR activation and downstream signaling at different hierarchical levels of signaling, from the receptor to transcription, via transducers, effectors, and second messengers. Singleplex assay formats provide one data point per experimental condition. Typical examples are bioluminescence resonance energy transfer (BRET) assays and protease cleavage assays (e.g., Tango or split TEV). By contrast, multiplex assay formats allow for the parallel measurement of multiple receptors and pathways and typically use molecular barcodes as transcriptional reporters in barcoded assays. This enables the efficient identification of desired on-target and on-pathway effects as well as detrimental off-target and off-pathway effects. Multiplex assays are anticipated to accelerate drug discovery for GPCRs as they provide a comprehensive and broad identification of compound effects. Full article