Search Results (2,778)

In the aerospace industry, thin-web gears are preferred for achieving high power-density transmission. However, thin-webbed structures always lead to out-of-plane resonance during the transmission process, which commonly happens in helical gears, manifesting as severe vibration at a specific rotational speed. To address this, a shaft–web–ring dynamic model is proposed. The shaft, gear web, and gear ring are modelled based on the Timoshenko straight beam, Mindlin plate, and Timoshenko bent beam theory. Simultaneously, the potential energy caused by the time-varying meshing stiffness is coupled to the gear ring. The kinetic and potential energies of each discretized finite element of the components are derived based on elastic deformation theory, and the governing equations of each element are obtained using Hamilton’s principle. The model is verified through a modal experiment. The comparison with traditional rotor-gear models has demonstrated the significance of gear body flexibility in helical gears with thin webs. The effects of the web thickness and helix angle on dynamic response are studied, revealing that gear web elasticity and an appropriately high helix angle can effectively reduce vibrations at the support bearing, prevent excessive vibrations, and contribute to vibration and noise reduction in the transmission system. Full article

This study presents the design, simulation, and experimental validation of a novel sector-shaped thread rolling machine aimed at improving forming efficiency, structural compactness, and process controllability compared with conventional linear thread rolling systems. A systematic engineering framework integrating mechanism design, curved-die implementation, motion control, finite-element simulation, and experimental verification is established. DEFORM-3D simulations are performed to investigate the effects of friction coefficient and die spacing on material flow and thread profile formation, and the results are used to guide machine construction and parameter optimization. Experimental results demonstrate that the proposed mechanism can simultaneously form four screws within a single rotation cycle, significantly enhancing production efficiency. Under optimized parameters, the relative errors of pitch diameter and helix angle are maintained within 5%, showing good agreement with simulation predictions. The findings confirm the feasibility, controllability, and stable forming capability of the proposed system, providing a practical and efficient solution for next-generation compact and high-productivity thread rolling equipment. Full article

Pancreatic lipase (PL) inhibition is a promising dietary strategy for obesity management. In this study, the inhibitory mechanisms and structural basis of polyphenols extracted from different sugarcane fractions were investigated using in vitro enzyme assays, spectroscopy, and molecular docking analyses. PL inhibitory activity was evaluated using p-nitrophenyl laurate (pNPL) as the substrate, with all assays performed in triplicate and results statistically analyzed. Among the extracts, sugarcane peel polyphenols (SP) exhibited the strongest inhibition, with a half-maximal inhibitory concentration (IC₅₀) of 31.56 mg/mL, significantly lower than that of sugarcane juice polyphenols (SJ, 55.86 mg/mL) and sugarcane bagasse polyphenols (SB, 65.31 mg/mL). Enzyme kinetic analyses revealed a reversible mixed-type inhibition mechanism. In contrast to crude extracts, individual phenolic monomers showed substantially lower IC₅₀ values (0.13–1.33 mg/mL), highlighting the intrinsic dilution. Compositional analysis identified ferulic acid, gallic acid, chlorogenic acid, and schaftoside as key contributors to PL inhibition. Fourier transform infrared (FTIR) and fluorescence spectroscopy demonstrated that polyphenols altered PL secondary structure by modulating α-helix and β-sheet contents and perturbed the microenvironment of tryptophan (Trp) and tyrosine (Tyr) residues. Molecular docking further indicated that these compounds bind within or near the substrate-binding channel via hydrogen bonding and hydrophobic interactions, engaging critical residues including Ser152, His263, and Phe77, and potentially influencing conformational elements involved in active-site accessibility. Collectively, these results suggest that sugarcane, particularly its peel, represents a valuable natural source of PL inhibitors. Despite the relatively high IC₅₀ values of crude extracts, their inhibitory activity arises from multicomponent contributions and supports their potential application as dietary modulators of fat digestion rather than as pharmaceutical lipase inhibitors. Full article

Loop-mediated isothermal amplification (LAMP) is a widely used nucleic acid detection method, but its application is often limited by the suboptimal performance of wild-type Bacillus stearothermophilus (Bst) DNA polymerase. This study employed a combined deep learning and semi-rational design strategy to engineer Bst DNA polymerase. High-throughput screening identified the A0A150MFP3 sequence and the L105M mutation, which increased enzymatic activity by 32.92%. Fusion with the CL7 protein generated a CL7-Bst mutant with enhanced thermal stability and tolerance to common inhibitors, including 7% (v/v) ethanol, 0.18‰ (w/v) SDS, 80 mmol/L NaCl, and 0.8 mmol/L EDTA. Systematic optimization of the LAMP reaction system determined the optimal pH (9.0), enzyme concentration (0.20 U/μL), and temperature (64 °C). When applied to Escherichia coli O157:H7 detection, the CL7-Bst mutant achieved Tt values of 15.13 and 12.78 for crude and purified DNA, respectively, with a limit of detection of 1 × 10³ CFU/mL. In summary, integrating deep learning with semi-rational design and fusion protein engineering yielded a high-performance DNA polymerase that facilitates rapid, sensitive, and field-deployable LAMP-based pathogen detection. Full article

Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutation subtype in non-small cell lung cancer (NSCLC), accounting for approximately 4–12% of all EGFR-mutated cases. Unlike classical EGFR mutations, ex20ins mutations confer inherent resistance to first-, second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) due to unique structural alterations that lock the αC-helix in an active orientation, creating steric hindrance within the drug-binding pocket. Until recently, platinum-based chemotherapy remained the standard first-line treatment, with objective response rates (ORR) of 19–47% and a median progression-free survival (PFS) of 6–7 months. Over the past five years, the therapeutic landscape has shifted, driven by the development of selective inhibitors and bispecific antibodies. Amivantamab, a bispecific EGFR–mesenchymal–epithelial transition factor (MET) antibody combined with chemotherapy, demonstrated superior efficacy in the PAPILLON trial, with an ORR of 73% and a median PFS of 11.4 months in the first-line setting. Sunvozertinib, an oral, selective EGFR inhibitor, received U.S. Food and Drug Administration (FDA) accelerated approval in 2025, with an ORR of 46% and a median duration of response (DOR) of 11.1 months in platinum-pretreated patients. Emerging therapies, including zipalertinib and furmonertinib, have shown promising results in early-phase trials, with zipalertinib demonstrating activity in patients pretreated with amivantamab (ORR 31.5%) and furmonertinib achieving remarkable responses in treatment-naive patients (ORR 78.6% at 240 mg). This comprehensive review analyzes the molecular biology, structural mechanisms, current therapeutic options, and novel investigational agents for EGFR ex20ins-mutated NSCLC. Full article

Kappa-carrageenan (κ-CRG) forms thermo-reversible physical hydrogels via a coil–helix transition and helix bundling, but its sulfate-driven electrostatic repulsion limits mechanical robustness and control over aqueous disintegration. Here, we show that plant-derived polyphenols reprogram κ-CRG gel through sulfate-directed binding in a structure-dependent manner. Tannic acid (TA) selectively engages κ-CRG sulfate groups, yielding transparent gels and a >5-fold increase in storage modulus, whereas the same TA triggers turbidity and precipitation in sulfate-free agarose, supporting sulfate-mediated specificity. Using monomeric pyrogallol as a galloyl analogue, we demonstrate that monovalent interactions partially reinforce κ-CRG but lack cooperative stabilization. Intervention timing further separates mechanism. Pyrogallol produces pathway-dependent mechanics and gelation temperature, while TA is stage-insensitive, consistent with multivalent network annealing. In simulated gastric/intestinal fluids, pyrogallol/κ-CRG gels retain morphology longer, whereas TA/κ-CRG ones disintegrate rapidly yet exhibit strong adhesion to rough substrates and human skin. These findings provide a fully food-grade route to tune κ-CRG mechanics, thermal behavior, adhesion and programmed disintegration. Full article

Anti-toppling helical piles exhibit superior load-bearing performance due to enhanced interaction between the helices and the underlying soil; however, rigorous theoretical frameworks for their compressive analysis remain scarce. To address this limitation, this study proposes a computationally efficient analytical model utilizing the Modified Cam-Clay (MCC) constitutive framework to calibrate plane strain elements for pile–soil interaction simulations. Wedge-shaped and bulb-shaped fictitious soil pile models are introduced to accurately capture vertical capacity mobilization beneath the helix and pile tip, respectively. After successfully validating the framework against 3D finite element simulations and field test data, extensive parametric analyses were conducted. The key findings reveal that (1) unlike conventional piles, skin friction for anti-toppling helical piles increases monotonically with depth; (2) an optimal helix-to-pile diameter ratio of approximately 1.5 maximizes coordinated bearing capacity; (3) increasing pile length below a fixed helix depth provides negligible additional capacity; and (4) the critical state parameter M strictly controls the ultimate bearing threshold. Full article

Living Labs offer immersive learning in Higher Education Institutions (HEIs), yet their core nature and value for competency development remain underexplored, particularly from the perspective of lab leaders. To address the knowledge gap, this study examines the perspectives of lab leaders on the potential of living labs as dynamic learning settings. Specifically, it explores two dimensions: (1) how living labs structure learning processes, and (2) the influence of collaboration with societal partners on learning outcomes, framed by the Quadruple Helix Model (academia, industry, government, and community). The study adopts a qualitative research design via semi-structured interviews with seven laboratory leaders across five well-established living labs in Finnish Universities of Applied Sciences. Interview transcripts were analyzed using Julius.ai and in vivo coding to identify and categorize themes. The respondents highlighted that in their experience, combining physical and digital settings often facilitates experiential, reflective, and innovative learning while equipping students with practical skills and competencies that improve their employability. Furthermore, the respondents reported that engagement with stakeholders fosters co-creation and well-rounded innovation. These collaborations also help ensure that the living labs can effectively sustain their operation, offering students the opportunities to engage in globally relevant issues such as digital transformation. Nonetheless, obstacles include resource limitations, maintaining enduring teamwork, and adjusting to rapid technological changes. The paper concludes that living labs serve as supplementary instruments and their adoption can help match academic learning curricula and practices with industry needs, while also enhancing student learning in preparation for the world of work. Full article

Surimi-based products are widely popular in the market owing to their unique texture and nutritional properties; however, traditional processing methods often result in reduced lipid content, despite lipids playing a crucial role in health. This study evaluated the effects of adding glycosylated fish gelatin emulsifying gel (prepared by glycosylating fish gelatin (FG) with D(+)-glucose (Glu) or β-cyclodextrin (β-CD) for 2 h) at 5%, 10%, and 15% (w/w) to hairtail surimi on its gel properties. The results indicated that both emulsified gels significantly enhanced gel strength, texture, and visual whiteness of hairtail surimi gel, with FG-βCD showing more pronounced improvements. FG-βCD also substantially reduced exudation and improved moisture distribution, resulting in a 69.81% decrease in juice loss. Furthermore, the addition of gelatin emulsifying gels shifted protein secondary structures toward more ordered forms, increasing α-helix and β-sheet content while reducing disordered components. Chemical interaction analysis revealed that hydrophobic interactions and nonspecific binding contributed to the reinforcement of gel formation. In conclusion, these findings highlighted that glycosylated emulsifying gels, as functional exogenous additives for surimi, offer a viable strategy for developing lipid-enriched, high-quality surimi products that meet emerging nutritional demands. Full article

The actinobacterial strain DEC002 was isolated recently from volcanic soils of Deception Island. Its taxonomic identity was resolved through a polyphasic strategy integrating morphology, physiological profiling, multilocus phylogeny, and genome-wide comparisons to resolve its identity. Concatenated core gene trees together with average nucleotide identity and digital DNA–DNA hybridization values place DEC002 within Actinacidiphila fildesensis with robust support. This is the first molecular confirmation of the species beyond King George Island and secures a second verified locality within the South Shetland Archipelago. Growth at low temperature with tolerance to moderate salinity indicates a psychrotolerant lifestyle. Cell-free supernatants inhibited representatives of foodborne Gram-negative and Gram-positive bacteria, including representatives of Enterobacteriaceae, Vibrio, Staphylococcus and Streptococcus. Genome analysis revealed enrichment in multiple biosynthetic gene clusters for nonribosomal peptides, polyketides, terpenes, and ribosomally synthesized and post-translationally modified peptides (RiPPs), supporting the biosynthetic potential of the strain. Functional annotations emphasize replication and repair modules, mobile element-associated proteins, helix–turn–helix regulators, and versatile transport systems, features coherent with cold stress and oligotrophic soils. Antibiotic susceptibility assays indicate a broad resistance phenotype under the experimental conditions tested, together with extracellular antimicrobial activity. These data refine the biogeography of A. fildesensis and indicate DEC002 as a credible Antarctic source of specialized metabolites with antimicrobial promise. Full article

Kynurenic acid (KYNA), a metabolite of the L-kynurenine pathway of L-tryptophan degradation, is an endogenous blocker of glutamate ionotropic excitatory amino acid (EAA) receptors and nicotinic acetylcholine receptors (nAChRs). KYNA plays a significant role in various neuropsychiatric disorders and the aging process. Some researchers have suggested that KYNA may contribute to memory impairment. In this study, we examined the impact of L-kynurenine (a KYNA substrate) and the anti-dementia drugs D-cycloserine and Cerebrolysin on kynurenine aminotransferase (KAT) activity, an enzyme forming KYNA, in liver homogenates of Helix pomatia snails. Furthermore, a memory model was established using these snails, wherein tentacle shortening served as an indicator of learning activity. In vitro experiments on Helix pomatia demonstrated the significant impact of L-kynurenine and anti-dementia drugs on KYNA synthesis. KYNA levels increased significantly in the presence of L-kynurenine in liver homogenate. However, KYNA formation decreased when anti-dementia drugs, including Cerebrolysin or D-cycloserine, were administered to the snails’ liver homogenate. L-kynurenine has been shown to impair the learning process in vivo in snails, but an anti-dementia drug has been demonstrated to reverse this effect. Significant inhibition of tentacle lowering was observed in response to L-kynurenine treatment, which corresponded with elevated KYNA levels in the central nervous system. Administering D-cycloserine or Cerebrolysin alongside L-kynurenine reversed its effects. The Helix pomatia memory model is a valuable tool for studying learning and memory formation in various conditions and in the presence of different pharmacological agents. A drug or natural extract that blocks KYNA synthesis has the ability to increase tentacle lowering and could be considered an anti-dementia agent. Furthermore, this metabolite may also protect against aging and delay damage to the central nervous system related to memory. Full article

Na⁺,K⁺-ATPase possesses a highly conserved glycine (G358 in the α3 isoform) that—together with a nearby isoleucine (I363 in α3)—is targeted by mutations causing some of the most severe neurological phenotypes of the clinical spectrum of α3-Na⁺,K⁺-ATPase mutations. The disease mutations α3-G358V and α3-I363N affect Na⁺ and K⁺ transport to an extent incompatible with cell growth. However, alanine replacement of the corresponding glycine G363 in the α1 isoform is compatible with cell growth, allowing the effects on Na⁺,K⁺-ATPase function to be addressed using enzymatic assays on plasma membranes isolated from transfected cells. Occlusion of Na⁺ appears to be defective in mutant G363A, resulting in a reduced rate of phosphorylation from ATP. Furthermore, the mutation displaces the major conformational equilibrium of Na⁺,K⁺-ATPase such that the K⁺-occluded state is destabilized and occluded K⁺ is released faster, thereby leading to accumulation of a non-productive state without bound Na⁺ or K⁺. The critical function of the glycine can be ascribed to a strategic location at the bending point between an α helix and a β strand, where it connects the catalytic ATP hydrolysis site in the cytoplasmic P domain with the ion-binding region in the membrane and coordinates important intramolecular domain movements during the Na⁺,K⁺-ATPase transport cycle. Full article

Current evidence suggests that achieving the desired level of osseointegration necessitates a hierarchical approach to implant design. This is particularly relevant for osseointegration around implant systems such as those presenting vertical decompression chambers and acid-etched surfaces which could further be augmented by non-thermal plasma (NTP) treatment. Three implant systems were compared in this study: (i) ND (GM Helix Acqua Implant; Neodent^®, Curitiba, PR, Brazil—hybrid, acid-etched thread design treated with isotonic sodium chloride solution), (ii) Sin (Epikut Plus; S.I.N. Implant System, São Paulo, Brazil—V-shaped, acid-etched thread design treated with nano-hydroxyapatite), and (iii) Mp (Maestro; Implacil De Bortoli, São Paulo, Brazil—buttress, acid-etched thread design with decompressing vertical chambers). The ND and Sin implants were used directly as supplied by the manufacturer. For the Mp implants, the manufacturer-supplied surface was subjected to supplemental acid etching with 37% hydrochloric acid followed by Argon-based NTP treatment administered with a pulsed plasma generator prior to implantation into the iliac crest of n = 12 adult female sheep. Histomorphometric analysis was conducted at 3- and 12-week post-implantation (n = 6 sheep per time point) to assess bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). After 3 weeks in vivo, the healing chambers of all implant groups consisted predominantly of newly forming woven bone. By 12 weeks, bone maturation was observed, with the presence of remodeling sites and some areas of well-organized lamellar structures occupying the healing chambers. At both 3 and 12 weeks, the Mp implants demonstrated significantly higher BAFO values relative to ND (p = 0.015 and p = 0.008, respectively). The combination of vertical healing chambers, acid etching, and NTP treatment promoted early vascular infiltration and sustained bone deposition. Full article

At present, the characteristics of key enzyme genes in the upstream pathway for triterpenoid saponin biosynthesis in P. grandiflorum, as well as their expression patterns over the growth duration, have not been systematically analyzed. This study, at the whole-genome level, conducts the first bioinformatics and expression analyses of the SS and SE gene families in P. grandiflorum. Four PgSS and seven PgSE genes were identified and distributed across six chromosomes. Members within the same subfamily exhibited highly conserved sequences and structures, while distinct structural divergence was observed between different subfamilies. Phylogenetic analysis showed that PgSS and PgSE genes were closely related to those of dicotyledons such as Panax ginseng and Polygala tenuifolia, suggesting high evolutionary conservation. Promoter analysis revealed abundant light- and hormone-responsive elements and MYB/MYC binding sites, indicating regulation by multiple signals. Protein secondary structures were dominated by the Alpha helix and were structurally stable. Quantitative real-time polymerase chain reaction (qPCR) demonstrated that expression levels of PgSS and PgSE in one-year-old Platycodonis Radix were significantly higher than in perennial Platycodonis Radix, especially for the PgSE family. This study characterized the basic biological features and growth-stage-dependent expression patterns of the SS and SE gene families in P. grandiflorum. The results identify key candidate genes and molecular targets for regulating triterpenoid saponin biosynthesis, and provide data supporting quality improvement and active metabolite research in this medicinal plant. Full article

Background: Malaria parasites import essential nutrients from plasma into their host erythrocytes through the plasmodial surface anion channel (PSAC), a conserved ion and nutrient channel on the infected cell surface. A parasite-encoded ternary complex consisting of CLAG3, RhopH2, and RhopH3 determines PSAC activity, but the precise contributions of each member to formation of the nutrient uptake pore remains uncertain. Methods: Here, we devised a two-step CRIPSR transfection strategy to examine an amphipathic CLAG3 helix, termed α-helix 44 (α-H44), as a candidate pore-lining domain. Results: A CLAG3 truncation protein without α-H44 phenocopies a CLAG3 knockout line, suggesting a critical role of α-H44 in formation of the nutrient channel; CLAG3 restoration using a recodonized α-H44 restores PSAC activity fully. A saturation mutagenesis library that splits the helix into four sequential segments was devised and implemented. Two engineered mutants exhibit distinct PSAC phenotypes; their cultures failed to expand in a modified medium that approximates in vivo nutrient availability. Conclusions: These studies support a α-H44 role in channel permeation and block by a strain-specific inhibitor. Our strategy will enable saturation mutagenesis to determine how PSAC achieves its unique ion and nutrient selectivity and should help guide drug discovery against this antimalarial target. Full article