Search Results (3,257)

Given the critical role of true triaxial strength assessment in underground rock and soil engineering design and construction, this study explores sandstone true triaxial strength using data-driven machine learning approaches. Fourteen distinct sandstone true triaxial test datasets were collected from the existing literature and randomly divided into training (70%) and testing (30%) sets. A Multilayer Perceptron (MLP) model was developed with uniaxial compressive strength (UCS, ${\sigma }_c$), intermediate principal stress (${\sigma }_2$), and minimum principal stress (${\sigma }_3$) as inputs and maximum principal stress (${\sigma }_1$) at failure as the output. The model was optimized using the Harris hawks optimization (HHO) algorithm to fine-tune hyperparameters. By adjusting the model structure and activation function characteristics, the final model was made continuously differentiable, enhancing its potential for numerical analysis applications. Four HHO-MLP models with different activation functions were trained and validated on the training set. Based on the comparison of prediction accuracy and meridian plane analysis, an HHO-MLP model with high predictive accuracy and meridional behavior consistent with theoretical trends was selected. Compared to five traditional strength criteria (Drucker–Prager, Hoek–Brown, Mogi–Coulomb, modified Lade, and modified Weibols–Cook), the optimized HHO-MLP model demonstrated superior predictive performance on both training and testing datasets. It successfully captured the complete strength variation in principal stress space, showing smooth and continuous failure envelopes on the meridian and deviatoric planes. These results underscore the model’s ability to generalize across different stress conditions, highlighting its potential as a powerful tool for predicting the true triaxial strength of sandstone in geotechnical engineering applications. Full article

Antibody–drug conjugates (ADCs) consist of an antibody backbone that recognizes and binds to a target antigen expressed on tumor cells and a small molecule chemotherapy payload that is conjugated to the antibody via a linker. ADCs are one of the most promising therapeutic modalities for the treatment of various cancers. However, many patients have developed resistance to this form of therapy. Extensive efforts have been dedicated to identifying an effective combination of ADCs with other types of anticancer therapies to potentially overcome this resistance. A recent clinical study demonstrated that a combination of the ADC enfortumab vedotin (EV) with the immune checkpoint inhibitor (ICI) pembrolizumab can achieve remarkable clinical efficacy as the first-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC)—leading to the first approval of a combination therapy of an ADC with an ICI for the treatment of cancer patients. In this review, we highlight knowledge and understanding gained from the successful development of EV and the combination therapy of EV with ICI for the treatment of la/mUC. Using urothelial carcinoma as an example, we will focus on dissecting the underlying mechanisms necessary for the development of this type of combination therapy for a variety of cancers. Full article

LMNA-related dilated cardiomyopathy (DCM) is an autosomal-dominant genetic condition with cardiomyocyte and conduction system dysfunction often resulting in heart failure or sudden death. The condition is caused by mutation in the Lamin A/C (LMNA) gene encoding Type-A nuclear lamin proteins involved in nuclear integrity, epigenetic regulation of gene expression, and differentiation. The molecular mechanisms of the disease are not completely understood, and there are no definitive treatments to reverse progression or prevent mortality. We investigated possible mechanisms of LMNA-related DCM using induced pluripotent stem cells derived from a family with a heterozygous LMNA c.357-2A>G splice-site mutation. We differentiated one LMNA-mutant iPSC line derived from an affected female (Patient) and two non-mutant iPSC lines derived from her unaffected sister (Control) and conducted single-cell RNA sequencing for 12 samples (four from Patients and eight from Controls) across seven time points: Day 0, 2, 4, 9, 16, 19, and 30. Our bioinformatics workflow identified 125,554 cells in raw data and 110,521 (88%) high-quality cells in sequentially processed data. Unsupervised clustering, cell annotation, and trajectory inference found complex heterogeneity: ten main cell types; many possible subtypes; and lineage bifurcation for cardiac progenitors to cardiomyocytes (CMs) and epicardium-derived cells (EPDCs). Data integration and comparative analyses of Patient and Control cells found cell type and lineage-specific differentially expressed genes (DEGs) with enrichment, supporting pathway dysregulation. Top DEGs and enriched pathways included 10 ZNF genes and RNA polymerase II transcription in pluripotent cells (PP); BMP4 and TGF Beta/BMP signaling, sarcomere gene subsets and cardiogenesis, CDH2 and EMT in CMs; LMNA and epigenetic regulation, as well as DDIT4 and mTORC1 signaling in EPDCs. Top DEGs also included XIST and other X-linked genes, six imprinted genes (SNRPN, PWAR6, NDN, PEG10, MEG3, MEG8), and enriched gene sets related to metabolism, proliferation, and homeostasis. We confirmed Lamin A/C haploinsufficiency by allelic expression and Western blot. Our complex Patient-derived iPSC model for Lamin A/C haploinsufficiency in PP, CM, and EPDC provided support for dysregulation of genes and pathways, many previously associated with Lamin A/C defects, such as epigenetic gene expression, signaling, and differentiation. Our findings support disruption of epigenomic developmental programs, as proposed in other LMNA disease models. We recognized other factors influencing epigenetics and differentiation; thus, our approach needs improvement to further investigate this mechanism in an iPSC-derived model. Full article

With the rapid consumer adoption of mobile devices such as tablets and smart phones, tele-traffic has experienced a tremendous growth, making low-power technologies highly desirable for future communication networks. In this paper, we consider an ambient backscatter (AB)-based user cooperation (UC) scheme for mmWave wireless-powered communication networks (WPCNs) with lens antenna arrays. Firstly, we formulate an optimization problem to maximize the minimum rate of two users by jointly designing power and time allocation. Then, we introduce auxiliary variables and transform the original problem into a convex form. Finally, we propose an efficient algorithm to solve the transformed problem. Simulation results demonstrate that the proposed AB-based UC scheme outperforms the competing schemes, thus improving the fairness performance of throughput in WPCNs. Full article

Magnetic resonance imaging (MRI) has emerged as a promising and appealing alternative to endoscopy in the objective assessment of patients with inflammatory bowel disease (IBD). Diffusion-weighted imaging (DWI) is a specialized imaging technique that enables the mapping of water molecule diffusion within biological tissues, eliminating the need for intravenous gadolinium contrast injection. It is expanding the capability of traditional MRI sequences in Ulcerative Colitis (UC). Recently, there has been growing interest in the application of intravoxel incoherent motion (IVIM) imaging in the field of IBD. This technique combines diffusion and perfusion information, making it a valuable tool for assessing IBD treatment response. Previous studies have extensively studied the use of DWI techniques for evaluating the severity of activity in IBD. However, the majority of these studies have primarily focused on Crohn’s disease (CD), with only a limited number of reports specifically examining UC. Therefore, this review briefly introduces the basics of DWI and IVIM imaging and conducts a review of relevant studies that have investigated its application in UC to show whether these techniques are useful techniques for evaluating patients with UC in terms of detection, characterization, and quantification of disease activity. Through the extensive literature survey, most of these studies indicate that DWI proves valuable in the differential diagnosis of UC and could be used as an effective modality for staging UC. Full article

The bHLH (basic helix–loop–helix) transcription factor AtCFLAP2 regulates epidermal wax accumulation, but the underlying molecular mechanism remains unknown. We obtained BnUC1^mut (BnaA05g18250D homologous to AtCFLAP2) from a Brassica napus mutant with up-curling leaves (Bnuc1) and epidermal wax deficiency via map-based cloning. BnUC1^mut contains a point mutation (N200S) in the conserved dimerization domain. Overexpressing BnUC1^mut in ZS11 (Zhongshuang11) significantly decreased the leaf epidermal wax content, resulting in up-curled and glossy leaves. In contrast, knocking out BnUC1^mut in ZS11-NIL (Zhongshuang11-near-isogenic line) restored the normal leaf phenotype (i.e., flat) and significantly increased the leaf epidermal wax content. The point mutation weakens the ability of BnUC1^mut to bind to the promoters of VLCFA (very-long-chain fatty acids) synthesis-related genes, including KCS (β-ketoacyl coenzyme synthase) and LACS (long-chain acyl CoA synthetase), as well as lipid transport-related genes, including LTP (non-specific lipid transfer protein). The resulting sharp decrease in the transcription of genes affecting VLCFA biosynthesis and lipid transport disrupts the normal accumulation of leaf epidermal wax. Thus, BnUC1 influences epidermal wax formation by regulating the expression of LTP and genes associated with VLCFA biosynthesis. Our findings provide a foundation for future investigations on the mechanism mediating plant epidermal wax accumulation. Full article

Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine. Data on the comparative effectiveness of biological therapies such as vedolizumab (VDZ) and ustekinumab (UST) remain limited. This retrospective study compared the effectiveness and safety of VDZ and UST in UC patients. Between November 2018 and November 2023, 106 patients were included: 64 received VDZ and 42 received UST. Bio-failure was significantly higher (p = 0.005) in the UST group versus the VDZ group. The remission rates at 6, 22, and 54 weeks in VDZ group were 51.6%, 61.3%, and 66.7%. The remission rates at 8, 24, and 56 weeks in the UST group were 66.7%, 65.0%, and 66.7%, respectively. Both treatments were comparable in inducing and maintaining clinical remission over 54–56 weeks, with no significant differences observed in the Lichtiger clinical activity index. Subgroup analyses highlighted the potential short-term effectiveness of UST among cases of bio-failure and a white blood cell level ≥ 9000/µL. Safety profiles were generally favorable, with no significant adverse events. Usutekinumab demonstrated effectiveness as a salvage therapy in patients who failed VDZ. Despite the increased disease severity in the UST group compared to the VDZ group, both groups demonstrated similar remission rates, suggesting UST shows significant efficacy even in moderate to severe UC. Full article

Expansive soil is prone to rapid strength degradation caused by repeated volume swelling and shrinkage under alternating dry–wet conditions. Basalt fiber (BF) and cement are utilized to stabilize expansive soil, aiming to curb its swelling and shrinkage, enhance its strength, and ensure its durability in dry–wet cycles. This study examines the impact of varying content (0–1%) of BF on the physical and mechanical characteristics of expansive soil stabilized with a 6% cement content. We investigated these effects through a series of experiments including compaction, swelling and shrinkage, unconfined compressive strength (UCS), undrained and consolidation shear, dry–wet cycles, and scanning electron microscope (SEM) analyses. The experiments yielded the following conclusions: Combining cement and BF to stabilize expansive soil leverages cement’s chemical curing ability and BF’s reinforcing effect. Incorporating 0.4% BFs significantly improves the swelling and shrinkage characteristics of cement-stabilized expansive soils, reducing expansion by 36.17% and contraction by 28.4%. Furthermore, it enhances both the initial strength and durability of these soils under dry–wet cycles. Without dry–wet cycles, the addition of 0.4% BFs increased UCS by 24.8% and shear strength by 24.6% to 40%. After 16 dry–wet cycles, the UCS improved by 38.87% compared to cement-stabilized expansive soil alone. Both the content of BF and the number of dry–wet cycles significantly influenced the UCS of cement-stabilized expansive soils. Multivariate nonlinear equations were used to model the UCS, offering a predictive framework for assessing the strength of these soils under varying BF contents and dry–wet cycles. The cement hydrate adheres to the fiber surface, increasing adhesion and friction between the fibers and soil particles. Additionally, the fibers form a network structure within the soil. These factors collectively enhance the strength, deformation resistance, and durability of cement-stabilized expansive soils. These findings offer valuable insights into combining traditional cementitious materials with basalt fiber to manage expansive soil hazards, reduce resource consumption, and mitigate environmental impacts, thereby contributing to sustainable development. Full article

Previous studies have indicated a critical role of intestinal bacteria in the pathogenesis of ulcerative colitis (UC). B. salyersiae is a commensal species from the human gut microbiota. However, what effect it has on UC development has not been investigated. In the present study, we explored this issue and demonstrated for the first time that oral administration of B. salyersiae CSP6, a bacterium previously isolated from the fecal sample of a healthy individual, protected against dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. In particular, B. salyersiae CSP6 improved mucosal damage and attenuated gut dysbiosis in the colon of DSS-fed mice. Specifically, B. salyersiae CSP6 decreased the population of pathogenic Escherichia-Shigella spp. and increased the abundance of probiotic Dubosiella spp. and Bifidobacterium pseudolongum. Additionally, by reshaping the colonic microbiota, B. salyersiae CSP6 remarkably increased the fecal concentrations of equol, 8-deoxylactucin, and tiglic acid, three beneficial metabolites that have been well documented to exert strong anti-inflammatory effects. Altogether, our study provides novel evidence that B. salyersiae is a candidate probiotic species with potential anti-colitis properties in the human colon, which has applications for the development of next-generation probiotics. Full article

Lead (Pb) contamination in loess poses a significant environmental challenge that impedes sustainable development. Microbially induced carbonate precipitation (MICP) is an innovative biomimetic mineralization technology that shows considerable promise in remediating soil contaminated with heavy metals. However, the toxicity of lead ions to Bacillus pasteurii reduces the efficiency of mineralization, subsequently diminishing the effectiveness of remediation. Although biochar can immobilize heavy metal ions, its adsorption instability presents a potential risk. In this study, we first compared the pH, electrical conductivity (EC), unconfined compressive strength (UCS), permeability coefficient, and toxicity leaching performance of lead-contaminated loess specimens remediated using biochar (BC), red mud (RM), red-mud-modified biochar (MBC), and MICP technology. Additionally, we evaluated the mechanism of MICP combined with varying amounts of MBC in remediating lead-contaminated loess combing Zeta potential, X-ray diffraction (XRD) analyses, and scanning electron microscopy (SEM) tests. The results showed that MICP technology outperforms traditional methods such as RM, BC, and MBC in the remediation of lead-contaminated loess. When MICP is combined with MBC, an increase in MBC content results in a higher pH (8.71) and a lower EC (232 us/cm). Toxic leaching tests reveal that increasing MBC content reduces the lead leaching concentration in loess, with optimal remediation being achieved at 5% MBC. Microscopic analysis indicates that the remediation mechanisms of MICP combined with MBC involve complexation, electrostatic adsorption, ion exchange, and precipitation reactions. The synergistic application of MICP and MBC effectively adsorbs and immobilizes lead ions in loess, enhancing its properties and demonstrating potential for pollution remediation and engineering applications. Full article

Canine urothelial carcinoma (UC) and prostatic carcinoma (PC) often present diagnostic challenges due to their anatomical locations. The BRAF V595E mutation, analogous to the human BRAF V600E mutation, has been identified in UC and PC. Digital PCR of urine is a non-invasive diagnostic method of mutation detection, but the availability of the necessary equipment is limited. This study aimed to develop a conventional PCR to detect the BRAF V595E mutation in urine and prostatic wash specimens from dogs with UC or PC. Specific primers for detecting wild-type and mutant BRAF V595E genes were validated in 34 formalin-fixed paraffin-embedded (FFPE) tissues, 116 urine samples, and 9 prostatic wash specimens. The results showed that the BRAF V595E mutation detection rate for UC and PC in the tissues was 51.6%. The detection rate in liquid specimens from dogs with lower urinary tract or prostate masses was 53.2%. Of the 41 cases with follow-up, 16 were further diagnosed with UC or PC, with 75% of liquid specimens from these dogs showing the BRAF V595E mutation. This conventional PCR method provides a reliable and non-invasive screening tool for UC and PC in dogs, especially in settings without advanced equipment. Full article

Cadmium (Cd) is a toxic metal which is harmful to humans and the environment. Cd levels and adverse effects may be associated with genetic polymorphisms in genes involved in its toxicokinetics. This study investigated Cd levels in 198 residents of a condominium in Rio de Janeiro, Brazil, built on industrial steel slag waste and the influence of glutathione S-transferase pi isoform 1 (GSTP1) rs1695 A>G polymorphism. Polymorphism was genotyped using a validated TaqMan assay; Cd levels were measured in blood (BCd) and urine (UCd) by graphite furnace atomic absorption spectrometry. Associations were evaluated by multiple logistic regression, odds ratios (ORs), and 95% confidence intervals (CIs). The mean Cd levels were 0.70 ± 0.20 µg L⁻¹ (BCd), 0.58 ± 0.57 µg L⁻¹ (UCd), and 0.61 ± 0.65 µg g⁻¹ in urine corrected by creatinine (UcCd), and the Cd results were above tolerable levels (BCd > 0.5 µg L⁻¹) in 87.4% of subjects. Higher blood Cd levels (>0.69 µg L⁻¹) were associated with respiratory disease (OR = 2.4; 95%CI = 1.2–5.0), as almost 30% of people with respiratory diseases had higher Cd levels. The GSTP1 rs1695AA genotype frequency was 38.1%, and there were no significant differences between the SNP and Cd levels. High Cd levels and a high prevalence of diseases highlight the importance of implementing public policies and the continuous monitoring of this at-risk population. Full article

Researching the mechanical characteristics of concrete subjected to the freeze–thaw cycle is crucial for building engineering in cold climates. As a result, uniaxial compression tests were performed on concrete samples exposed to various freeze–thaw (F–T) cycles, and the measurements of the pore size distribution, porosity, and P-wave velocity of the saturated concrete samples were obtained, both before and after being exposed to the F–T cycles. Concrete’s F–T damage mechanism and damage evolution model were thoroughly examined. Using rock structure and moisture analysis test equipment to observe the T₂ spectrum, the results showed that the F–T cycles can cause the internal structure of the samples to deteriorate. Porosity and F–T cycles have a positive correlation, although P-wave velocity has a negative correlation with the F–T cycles. As the F–T cycles increased, the specimens’ peak strength and elastic modulus steadily declined, while the peak strain clearly exhibited an increasing trend. A microscopic F–T damage model that takes into account the pore size distribution was developed, based on the relative changes in the pore structure distribution (PSD), before and after the F–T cycles. The concrete sample damage evolution law under various F–T cycles was examined using the following metrics: total energy, pore size distribution, static and dynamic elastic moduli, porosity, and P-wave velocity. Uniaxial compressive strength (UCS) and peak strain tests were used to evaluate the accuracy of the pore size distribution damage model, as well as that of five other widely used damage models. Full article

This paper investigates the effectiveness of applying continuous high-compression pressure on the initial setting of fresh concrete to produce hardened concrete materials with excellent mechanical properties. A novel experimental apparatus was self-designed and used for the pre-setting pressure application. The utilization of the completely decomposed granite (CDG) soil as an alternative aggregate in concrete production was also explored. A total of twenty-eight specimens were fabricated using two types of fine aggregates, six mix ratios, two initial pressure values, and two distinct durations of the initial pressure application. The density and uniaxial compressive strength (UCS) of the specimens were examined to evaluate their mechanical qualities, while micro-CT tests with image analysis were used to quantify their porosity. The results indicated that the 10 MPa initial pre-setting pressurization can effectively eliminate the excess air and voids within the fresh concrete, therefore enhancing the mechanical properties of the hardened concrete specimens of various types. Compared with non-pressurized specimens, the porosity values of pressurized specimens were reduced by 73.11% to 86.53%, the density values were increased by 1.43% to 8.31%, and the UCS values were increased by 8.42% to 187.43%. These findings provide a reference for using a continuous high pre-setting compression pressure and using CDG soil as an aggregate in the fabrication of concrete materials with improved mechanical performance. Full article

Inflammatory bowel disease (IBD), which encompasses both ulcerative colitis (UC) and Crohn’s disease (CD), is a major health burden worldwide. There are increasing concerns surrounding the impacts of this disease due to significant rises in the prevalence rates of IBD across the world. In consideration of the complexities of managing IBD along with this marked rise in prevalence and incidence, developing new forms of treatment for this condition has become a major priority. In recent years, a potential new form of treatment for IBD has emerged in the form of biologic therapies. While there is a high level of optimism due to the development of these therapies, there is also a clear need to evaluate their effectiveness, and their overall safety profiles. For this review, we have evaluated three specific biologics used for the treatment IBD. More precisely, the focus of this review is to analyze and critically appraise the literature for vedolizumab, ustekinumab, and golimumab, and determine their roles in the management of UC and CD, respectively. After doing so, we have also briefly synthesized important new findings regarding the role of dietary and nutritional approaches. In doing so, we have aimed to contextualize the findings regarding biologics, and, in order to evaluate potential new treatment approaches for the future to augment biologic therapies, we have discussed the potential for combined approaches that incorporate the usage of both biologics and nutritional interventions for patients. Full article