Search Results (85)

Suzetrigine represents a groundbreaking advancement in acute pain management as the first FDA-approved selective Na_v1.8 inhibitor. This comprehensive review synthesizes data from clinical trials, pharmacological studies, and prescribing information to evaluate its mechanism, efficacy, safety, and clinical implications. With demonstrated superiority over placebo in pivotal trials (SPID48: 29.3–48.4; p < 0.0001) and a favorable safety profile devoid of opioid-like addiction risks, suzetrigine offers a much-needed alternative in the opioid crisis era. However, its modest effect size compared to full-dose opioids, CYP3A-mediated drug interactions, and limited long-term data warrant judicious use. This article provides a balanced perspective on suzetrigine’s role in modern pain management protocols. Full article

In remote sensing, object classification often suffers from severe degradation caused by atmospheric turbulence and low-signal conditions. Traditional image reconstruction approaches are computationally expensive and fragile under such conditions. In this work, we propose a novel image-free classification framework using single-pixel imaging (SPI), which directly classifies targets from 1D measurements without reconstructing the image. A learnable sampling matrix is introduced for structured light modulation, and a hybrid CNN-Transformer network (Hybrid-CTNet) is employed for robust feature extraction. To enhance resilience against turbulence and enable efficient deployment, we design a $(N+1)\times L$ hybrid strategy that integrates convolutional and Transformer blocks in every stage. Extensive simulations and optical experiments validate the effectiveness of our approach under various turbulence intensities and sampling rates as low as 1%. Compared with existing image-based and image-free methods, our model achieves superior performance in classification accuracy, computational efficiency, and robustness, which is important for potential low-resource real-time remote sensing applications. Full article

Background/Objectives: Heparosan is a component of the capsular polysaccharide in Escherichia coli K5 and Pasteurella multocida Type D. It shares a similar glycan structure with heparin and can be enzymatically modified to produce bioactive heparin. Methods: In this study, the probiotic strain E. coli Nissle 1917 (EcN), which naturally produces heparosan, was genetically engineered to utilize sucrose as a carbon source for growth while achieving high-yield heparosan biosynthesis. Results: By expressing the sucrose hydrolase genes sacA (from Bacillus subtilis) or spI (from Bifidobacterium adolescentis), EcN was enabled to utilize sucrose, achieving heparosan titers of 131 mg/L and 179 mg/L, respectively. Further metabolic engineering was performed to block the glycolytic and pentose phosphate pathways, thereby redirecting sucrose-derived glucose-6-phosphate and fructose-6-phosphate toward heparosan biosynthesis, while glycerol was supplemented as an auxiliary carbon source to support cell growth. Finally, the key biosynthesis genes galU, kfiD, and glmM were overexpressed, resulting in an engineered strain with a heparosan titer of 622 mg/L. Conclusions: This study represents the first successful engineering of EcN to utilize sucrose as the carbon source for growth, while achieving enhanced heparosan production through synergistic carbon source utilization. These findings establish a foundational strategy for employing this strain in the sucrose-based biosynthesis of other glycosaminoglycans. Full article

Accurately estimating 3D human pose and body shape from a single monocular image remains challenging, especially under poor lighting or occlusions. Traditional RGB-based methods struggle in such conditions, whereas single-pixel imaging (SPI) in the Near-Infrared (NIR) spectrum offers a robust alternative. NIR penetrates clothing and adapts to illumination changes, enhancing body shape and pose estimation. This work explores an SPI camera (850–1550 nm) with Time-of-Flight (TOF) technology for human detection in low-light conditions. SPI-derived point clouds are processed using a Vision Transformer (ViT) to align poses with a predefined SMPL-X model. A self-supervised PointNet++ network estimates global rotation, translation, body shape, and pose, enabling precise 3D human mesh reconstruction. Laboratory experiments simulating night-time conditions validate NIR-SPI’s potential for real-world applications, including human detection in rescue missions. Full article

In this study, we aimed to develop soy protein-derived edible porous hydrogel scaffolds for cultured meat based on mechanical anisotropy to mimic the physical and biochemical properties of muscle tissues. Based on the traditional Japanese Ito-Kanten (thread agar) freeze–thaw process, we used liquid nitrogen directional freezing combined with ion crosslinking to fabricate an aligned scaffold composed of soy protein isolate (SPI), carrageenan (CA), and sodium alginate (SA). SPI, CA, and SA were dissolved in water, heated, mixed, and subjected to directional freezing in liquid nitrogen. The frozen gel was immersed in Ca²⁺ and K⁺ solutions for low-temperature crosslinking, followed by a second freezing step and lyophilization to create the SPI/CA/SA cryogel scaffold with anisotropic pore structure. Furthermore, C2C12 myoblasts were seeded onto the scaffold. After 14 d of dynamic culture, the cells exhibited significant differentiation along the aligned structure of the scaffold. Overall, our developed anisotropic scaffold provided a biocompatible environment to promote directed cell differentiation, showing potential for cultured meat production and serving as a sustainable protein source. Full article

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the progressive destruction of insulin-producing β-cells in the pancreas. Currently, no therapy exists to halt or cure T1D. Vaccination with diabetic autoantigens may offer protection against T1D development. Genetically modified, attenuated Salmonella utilizing the Salmonella-Pathogenicity Island 2 (SPI2)-encoded Type Three Secretion System (T3SS) can elicit robust immune responses, making it an attractive vaccine platform. Using SPI2-T3SS to deliver an autoantigen alongside immunomodulators and anti-CD3 antibodies induces antigen-specific regulatory T-cells. Our preclinical studies demonstrated the efficacy of a Salmonella-based vaccine in both preventing and reversing autoimmune diabetes in non-obese diabetic (NOD) mice while also exploring its genetic modifications, underlying mechanisms, and delivery strategies. This review evaluates the advantages of an oral T1D vaccine employing live, attenuated Salmonella for autoantigen delivery. We also discuss future directions for advancing this strategy in the treatment of other autoimmune diseases. Full article

With increasing global meat consumption, meat–plant hybrid products have gained interest as a sustainable alternative. Soy proteins have been used in small quantities (2–3%) as meat extenders, yet limited data exist on their use at higher levels. Here, five commercial soy proteins (four isolates: SPI-A to -D; one concentrate: SPC) were used for meat replacement in lean meat batters with 0/40/80% added water. Cooking loss, texture, light micrographs, and T₂ relaxation were analyzed. At 33% and 66% meat replacement, soy protein treatments maintained comparable or reduced cooking loss; SPI-D and SPC were the least and most effective, respectively. Complete replacement eliminated cooking loss in 0% and 40% water systems but failed to form self-supporting gels in the 80% system. At 33% replacement, SPI-A to -C generally increased hardness, whereas increasing the replacement level further to 66% decreased it. In the 0% and 80% systems, SPI-A treatments exhibited hardness comparable to controls, SPI-D treatments drastically reduced hardness, and SPC treatments maintained greater hardness than the controls even at 66% replacement. Micrographs offered potential explanations for these macroscopic measurements. NMR T₂ data indicated that soy proteins restricted water mobility both pre- and post-cooking. Specifically, in the 40% and 80% systems, the T₂₂ peaks (expelled liquid) of the hybrid samples containing 33% SPI-A were ~350 ms and 760 ms, compared to ~570 ms and 1170 ms for the meat controls, respectively. In conclusion, most soy proteins (except SPI-D) enhanced water binding, with SPI-A showing optimal texture and SPC showing promise as a more economical alternative. Full article

Currently, small object detection in complex remote sensing environments faces significant challenges. The detectors designed for this scenario have limitations, such as insufficient extraction of spatial local information, inflexible feature fusion, and limited global feature acquisition capability. In addition, there is a need to balance performance and complexity when improving the model. To address these issues, this paper proposes an efficient and lightweight SCM-YOLO detector improved from YOLOv5 with spatial local information enhancement, multi-scale feature adaptive fusion, and global sensing capabilities. The SCM-YOLO detector consists of three innovative and lightweight modules: the Space Interleaving in Depth (SPID) module, the Cross Block and Channel Reweight Concat (CBCC) module, and the Mixed Local Channel Attention Global Integration (MAGI) module. These three modules effectively improve the performance of the detector from three aspects: feature extraction, feature fusion, and feature perception. The ability of SCM-YOLO to detect small objects in complex remote sensing environments has been significantly improved while maintaining its lightweight characteristics. The effectiveness and lightweight characteristics of SCM-YOLO are verified through comparison experiments with AI-TOD and SIMD public remote sensing small object detection datasets. In addition, we validate the effectiveness of the three modules, SPID, CBCC, and MAGI, through ablation experiments. The comparison experiments on the AI-TOD dataset show that the mAP50 and mAP50-95 metrics of SCM-YOLO reach 64.053% and 27.283%, respectively, which are significantly better than other models with the same parameter size. Full article

Background: Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line strategies. Moreover, immunotherapeutic success in CLL has been stifled by its pro-tumor microenvironment milieu and low mutational burden, cultivating poor antigenicity and limited ability to generate anti-tumor immunity through adaptive immune cell engagement. Previously, we have demonstrated how a three-carbon-linker spirocyclic dimer (SpiD3) promotes futile activation of the unfolded protein response (UPR) in CLL cells through immense misfolded-protein mimicry, culminating in insurmountable ER stress and programmed CLL cell death. Method: Herein, we used flow cytometry and cell-based assays to capture the kinetics and magnitude of SpiD3-induced damage-associated molecular patterns (DAMPs) in CLL cell lines and primary samples. Result: SpiD3 treatment, in vitro and in vivo, demonstrated the capacity to propagate immunogenic cell death through emissions of classically immunogenic DAMPs (CALR, ATP, HMGB1) and establish a chemotactic gradient for bone marrow-derived dendritic cells. Conclusions: Thus, this study supports future investigation into the relationship between novel therapeutics, manners of cancer cell death, and their contributions to adaptive immune cell engagement as a means for improving anti-cancer therapy in CLL. Full article

Acoustic analysis of voice enables objective assessment of voice to diagnose changes in voice characteristics, and track the progress of therapy. In contrast to subjective assessment, objective measurements provide mathematical results referring to specific parameters and can be analyzed statistically. Changes in the voice of patients with partial deafness (PD) were not widely described in the literature, and recent studies referred to the voice parameters measured in this group of patients only using the multi-dimensional voice program (MDVP) by Kay Pentax. This paper describes the results of acoustic analysis of voice in patients with PD using VOXplot, and compares the results with those achieved with MDVP. Background/Objectives: The purpose of this study was a VOXplot objective analysis of voice in individuals with PD and to assess consistency with results obtained using MDVP and with perceptual assessment. Methods: Voice samples from 22 post-lingual PD individuals were recorded. They included continuous speech (cs) and sustained vowels (sv). The control group consisted of 22 healthy individuals with no history of voice or hearing dysfunction. The samples were analyzed with MDVP followed by VOXplot version 2.0.0 Beta. Statistical analysis was performed using a t-test paired with two samples for means. All individuals were also subjected to a perceptual voice assessment using the GRBAS by Hirano. Results: Differences were observed in 13 VOXplot parameters measured in voice samples of adults with PD compared with those in the control group. Both multiparametric indices, AVQI and ABI, showed a statistical increase. When it comes to MDVP parameters correlating with breathiness, all of them (shim dB, APQ, NHR, SPI, and NSH) increased in patients with partial deafness, reflecting a breathy voice. Only one increase in the SPI was not statistically significant. Seven MDVP parameters correlating with hoarseness were elevated, and five (Jitt%, vF0, Shim dB, APQ, and NHR) showed a statistically significant increase. Correlations were found of VOXplot and MDVP parameters with perceptual voice assessment. Conclusions: Both programs for objective assessment showed voice abnormalities in patients with PD compared with the control groups. There was a poor to moderate level of consistency in the results achieved using both systems. Correlations were also found with GRBAS assessment results. Full article

Diagnostics often require specialized equipment and trained personnel in laboratory settings, creating a growing need for point-of-care tests (POCTs). Among the genetic testing methods available, Loop-mediated Isothermal Amplification (LAMP) offers a viable solution for developing genetic POCT due to its compatibility with simplified devices. This study aimed to create a genetic test that integrates all steps from sample processing to analyzing results while minimizing the complexity, handling, equipment, and time required. Several challenges were addressed to achieve this goal: (1) the development of a buffer for bacterial DNA extraction that is compatible with both LAMP and immunochromatographic tests; (2) the adaption of the LAMP protocol for use with the SPID device; and (3) the optimization of the detection protocol for specific test conditions, with a lateral flow immunoassay format selected for its POCT compatibility. Following these developments, the test was validated using Escherichia coli (E. coli) and non-E. coli strains. A portable heating station was also developed to enable amplification without costly equipment. The resulting genetic POCT achieved 100% sensitivity and 85% specificity, with results available in 60 to 75 min. This study demonstrated that our POCT efficiently performs DNA extraction, amplification, and detection for bacterial identification. The test’s simplicity and cost-effectiveness will support its implementation in various settings. Full article

Stored products, such as grains and processed foods, are susceptible to infestation by various insects. The early detection of insects in the supply chain is crucial, as introducing invasive pests to new environments may cause disproportionate harm. The STAR Center at Stevens Institute of Technology developed the Acoustic Stored Product Insect Detection System (A-SPIDS) to detect pests in stored products. The system, which comprises a sound-insulated container for product samples with a built-in internal array of piezoelectric sensors and additional electret microphones to record outside noise, was used to conduct numerous measurements of the vibroacoustic signatures of various insects, including the Callosobruchus maculatus, Tribolium confusum, and Tenebrio molitor, in different materials. A normalization method was implemented using the ambient noise of the sensors as a reference, to accommodate for the proprietary, non-calibrated sensors and allowing to set relative detection thresholds for unknown sensitivities. The normalized envelope of the filtered signals was used to characterize and compare the insect signals by estimating the Normalized Signal Pulse Amplitude (NSPA) and the Normalized Spectral Energy Level (NSEL). These parameters characterize the insect detection Signal Noise Ratio (SNR) for pulse-based detection (NSPA) and averaged energy-based detection (NSEL). These metrics provided an initial step towards the design of a reliable detection algorithm. In the conducted tests NSPA was significantly larger than NSEL. The NSPA reached 70 $\mathrm{d}$$\mathrm{B}$ for T. molitor in corn flakes. The insect signals were lower in flour where the averaged NSPA and NSEL values were around 40 dB and 11 $\mathrm{d}$$\mathrm{B}$ to 16 $\mathrm{d}$$\mathrm{B}$, respectively. Full article

Osteosarcoma is a primary malignant tumor found in the bones of children and adolescents. Unfortunately, many patients do not respond well to treatment and succumb to the illness. Therefore, it is necessary to discover novel bioactive compounds to overcome therapeutic limitations. Liriope platyphylla Wang et Tang is a well-known herb used in oriental medicine. Studies have shown that metabolic diseases can be clinically treated using the roots of L. platyphylla. Recent studies have demonstrated the anticarcinoma potential of root extracts; however, the exact mechanism remains unclear. The aim of this study was to examine the anti-osteosarcoma activity of a single compound extracted from the dried roots of L. platyphylla. We purified Spicatoside A (SpiA) from the dried roots of L. platyphylla. SpiA significantly inhibited the proliferation of human osteosarcoma MG63 cells in a dose- and time-dependent manner. SpiA also regulated the expression of various downstream proteins that mediate apoptosis (PARP, Bcl-2, and Bax), cell growth (cyclin D1, Cdk4, and Cdk6), angiogenesis (VEGF), and metastasis (MMP13). The Proteome Profiler Human Phospho-Kinase Array Kit showed that the AKT signaling protein was a target of SpiA in osteosarcoma cells. We also found that SpiA suppressed the constitutive activation of the PI3K-AKT-mTOR-p70S6K1 signaling pathway. We further validated the effects of SpiA on the AKT signaling pathway. SpiA induced autophagosome formation and suppressed necroptosis (a form of programmed cell death). SpiA increased the generation of reactive oxygen species (ROS) and led to the loss of mitochondrial membrane potential. N-acetylcysteine (NAC)-induced inhibition of ROS generation reduced SpiA-induced AKT inhibition, apoptotic cell death, and anti-metastatic effects by suppressing cell migration and invasion. Overall, these results highlight the anti-osteosarcoma effect of SpiA by inhibiting the AKT signaling pathway through ROS generation, suggesting that SpiA may be a promising compound for the treatment of human osteosarcoma. Full article

As a protein extracted from soybeans, soy protein isolate (SPI) may undergo the Maillard reaction (MR) with co-existing saccharides during the processing of soy-containing foods, potentially altering its structural and functional properties. This work aimed to investigate the effect of mono- and polysaccharides on the structure and functional properties of SPI during MR. The study found that compared to oat β-glucan, the reaction rate between SPI and D-galactose was faster, leading to a higher degree of glycosylation in the SPI–galactose conjugate. D-galactose and oat β-glucan showed different influences on the secondary structure of SPI and the microenvironment of its hydrophobic amino acids. These structural variations subsequently impact a variety of the properties of the SPI conjugates. The SPI–galactose conjugate exhibited superior solubility, surface hydrophobicity, and viscosity. Meanwhile, the SPI–galactose conjugate possessed better emulsifying stability, capability to produce foam, and stability of foam than the SPI–β-glucan conjugate. Interestingly, the SPI–β-glucan conjugate, despite its lower viscosity, showed stronger hypoglycemic activity, potentially due to the inherent activity of oat β-glucan. The SPI–galactose conjugate exhibited superior antioxidant properties due to its higher content of hydroxyl groups on its molecules. These results showed that the type of saccharides had significant influences on the SPI during MR. Full article

The concealed Molai Zn-Pb±(Ag,Ge) stratiform deposit in southeastern Peloponnese is hosted in Triassic intermediate tuffs, ignimbrites and subaerial andesitic flows. The host rocks display trace element signatures of a Supra-Subduction Zone (SSZ) setting. Three ore-forming stages are recognized, with stages I and II related to formation of the epigenetic, stratiform, massive-to-semi-massive ore and a late stage III associated with vein-type mineralization. The O and D isotope geochemistry of gangue chlorite and epidote reveal mixing with fresh meteoric water during the weaning stages of the hydrothermal activity of the late stage II due to uplifting of the hydrothermal system. Sphalerite is the major ore phase, with three different varieties formed during stages I (Sp-I) and II (Sp-II and Sp-III). All sphalerite varieties coexist, depicting gradual change in the chemistry of the ore-forming fluids. Molai ores are characterized by elevated Ag and Ge contents. Tetrahedrite is the major Ag carrier, while among the three sphalerite varieties, early Sp-I comprises the highest Ge contents. The Molai Zn-Pb±(Ag,Ge) deposit is characterized by intermediate features between bimodal felsic massive sulfides and subaerial epithermal systems based on the shallow formation depth, the presence of hydraulic breccias associated with phase separation, the ore formation along high-angle faults, the relatively low ore-forming temperatures below 250 °C obtained from geothermometry, and the absence of the typical structure of bimodal felsic type ores. Full article