Explore the vast range of titles available.

The 3C-like protease (3CLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV) cleaves 11 sites in the polyproteins, including its own N- and C-terminal autoprocessing sites, by recognizing P4–P1 and P1′. In this study, we determined the crystal structure of 3CLpro with the C-terminal prosequence and the catalytic-site C145A mutation, in which the enzyme binds the C-terminal prosequence of another molecule. Surprisingly, Phe at the P3′ position [Phe(P3′)] is snugly accommodated in the S3′ pocket. Mutations of Phe(P3′) impaired the C-terminal autoprocessing, but did not affect N-terminal autoprocessing. This difference was ascribed to the P2 residue, Phe(P2) and Leu(P2), in the C- and N-terminal sites, as follows. The S3′ subsite is formed by Phe(P2)-induced conformational changes of 3CLpro and the direct involvement of Phe(P2) itself. In contrast, the N-terminal prosequence with Leu(P2) does not cause such conformational changes for the S3′ subsite formation. In fact, the mutation of Phe(P2) to Leu in the C-terminal autoprocessing site abolishes the dependence on Phe(P3′). These mechanisms explain why Phe is required at the P3’ position when the P2 position is occupied by Phe rather than Leu, which reveals a type of subsite cooperativity. Moreover, the peptide consisting of P4–P1 with Leu(P2) inhibits protease activity, whereas that with Phe (P2) exhibits a much smaller inhibitory effect, because Phe(P3′) is missing. Thus, this subsite cooperativity likely exists to avoid the autoinhibition of the enzyme by its mature C-terminal sequence, and to retain the efficient C-terminal autoprocessing by the use of Phe(P2).

Twisted bilayer systems with discrete magic angles, such as twisted bilayer graphene featuring moiré superlattices, provide a versatile platform for exploring novel physical properties. Here, we discover a class of superflat bands in general twisted bilayer systems beyond the low-energy physics of magic-angle twisted counterparts. By considering continuous lattice dislocation, we obtain intrinsic localized states, which are spectrally isolated at lowest and highest energies and spatially centered around the AA stacked region, governed by the macroscopic effective energy potential well. Such localized states exhibit negligible inter-cell coupling and support the formation of superflat bands in a wide and continuous parameter space, which can be mimicked using a twisted bilayer nanophotonic system. Our finding suggests that general twisted bilayer systems can realize continuously tunable superflat bands and the corresponding localized states for various photonic, phononic, and mechanical waves.

A novel 3D detector with a semi-spherical electrode detector structure is proposed in this study. The semi-spherical electrode is formed by concentric deep circular-type trenches of varying depths. These concentric trenches can be simultaneously deep-etched using DRIE (Deep Reactive-Ion Etching) depths obtained from our calculations for a certain time at a given aspect ratio. The focus of this work is the conceptualization, design considerations, 3D modeling, and electrical simulation of the proposed 3D detector. The detector’s electrical properties, including electric potential distribution, electric field distribution, electron concentration distribution, full depletion voltage, leakage current, and capacitance, were simulated using a technology computer-aided design (TCAD) tool. Simulation and analysis of the detector’s performance post-irradiation were also conducted. The small capacitance of our semi-spherical electrode detector renders it highly suitable for applications in photon sciences (e.g., X-ray).

The adhesion between asphalt and aggregate significantly influences the durability and lifespan of road structures. This study employs molecular dynamics simulations to investigate the interface behavior between asphalt and aggregates with varying defect sizes under chloride salt solution immersion and ion infiltration (physical erosion without chemical reactions). The interfacial adhesion energy (Eint), relative ion concentration (RC), mean square displacement (MSD), and hydrogen bond count were analyzed to assess the adhesion performance of asphalt at the defective aggregate interface. The effects of chloride concentration and temperature on adhesion were also examined. Results indicate that aggregate surface defects enhance local asphalt adhesion within the defect region, although larger defects reduce the global interfacial adhesion energy normalized by total area: the adhesion energy decreases from −417 kcal/mol (defect-free) to −315 kcal/mol (20 Å) and −277 kcal/mol (30 Å), with a reduction of 24–34%. Additionally, defects accelerate ion diffusion significantly, with diffusion coefficients of water and ions increasing by up to 69%, promoting chloride ion accumulation, which exacerbates erosion physical interface deterioration. Both elevated temperature and chloride concentration further accelerate this degradation physical interface weakening, with high temperatures causing severe interface damage: adhesion energy decreases by about 28% as temperature rises from 290 K to 340 K, and by 15% as NaCl concentration increases from 0% to 20%. These findings offer a theoretical foundation for understanding the adhesion mechanisms of the asphalt–aggregate interface under chloride erosion chloride ion infiltration and physical erosion and provide insights into enhancing chloride resistance to chloride ion infiltration of road materials.

An adaptive neural network dynamic surface control method for strict feedback non‐linear systems with model uncertainty is proposed in this paper. The uncertain parts are approached by RBF neural network; meanwhile, the virtual controller is designed to make system stable according to dynamic surface control. The method of Lyapunov is used to prove the stability and convergence of the system. The simulation results prove the feasibility of this controller and prove that the controller has an advantage to approach the uncertain non‐linear system and make system have well convergence and traceability. A simplified adaptive neural network dynamic surface control method for strict feedback non‐linear systems with model uncertainty is proposed in this paper.

In this paper, an innovative design of a silicon spiral drift detector (SDD) has been proposed. In this design, gaps under the SiO2 layer between the cathode rings are kept constant, with a minimum value to reduce the surface leakage current. The cathode pitch profile Pr as a function of radius r is allowed to change in an arbitrary way to achieve the optimum field distribution. The concept, design considerations, modeling and electrical simulations have been carried out for this novel structure with a hexagonal spiral silicon drift detector. Using one-dimensional analyses, we obtain the exact solution of the spiral design r=rθ  with a near-arbitrary pitch profile Pr=P1rr11η, with η as an arbitrary real number. We also obtained the electric potential and field profiles on both surfaces of the detector. Using a Technology Computer-Aided Design (TCAD) tool, we made 3D simulations of the detector’s electrical properties. The hexagonal spiral silicon drift detector has excellent electrical properties: a uniform electric field, smooth distribution of electric potential and electron concentration, and a clear electron drift channel. The distributions of the electric field, electric potential, and electron concentration are symmetrical and smooth, which is beneficial for applications in photon sciences (X-ray) and safeguards and homeland security (particle radiation). The theoretical work and simulation results serve as solid foundations for the detector design and the expansion of semiconductor technology.

BackgroundDespite the proven efficacy of KRAS G12C inhibitors (KRAS G12Ci) in solid tumors, evidence from direct comparisons with standard of care is scarce, and no analysis has investigated the potential immunological basis for differential responses.MethodsPubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) involving solid tumors patients who had received KRAS G12Ci were retrieved from inception to March 28, 2026. Individual participant data on progression-free survival (PFS) and overall survival (OS) were extracted from the published Kaplan-Meier survival curves. When available, subgroup data by programmed death ligand 1 (PD-L1) expression were extracted to explore immune-related correlates of treatment response.ResultsA total of 4 articles with 3 RCTs and 949 participants were selected. In 1-stage reconstructed individual patient data meta-analyses, PFS was better in the KRAS G12Ci group (HR, 0.62; 95% CI, 0.53-0.74; P < 0.001). However, no statistical difference in OS was observed (HR, 0.93; 95% CI, 0.74-1.16; P = 0.495). The results were confirmed by 2-stage meta-analyses which additionally exhibited an objective response rate (ORR) of 3.60 (95% CI; 2.01-6.46; P < 0.001; I2 = 39.7%). Regarding PD-L1 expression, PFS benefits were observed in patients with expression levels <1% (HR, 0.56; 95% CI: 0.38-0.83; P = 0.004) and 1%-49% (HR, 0.58; 95% CI: 0.43-0.78; P < 0.001). KRAS G12Ci demonstrated a better safety profile, apart from diarrhea and rash.ConclusionsA similar OS, but better PFS and ORR with a superior safety profile were observed in patients receiving KRAS G12Ci, suggesting that KRAS G12Ci may be more suitable for later-line therapy. Older patients, those without liver metastases, or those with PD-L1<50% may be the target population. These subgroup observations are hypothesis-generating and require prospective validation.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251146769.

Landslides are widespread geohazards in mountainous regions and pose serious threats to human safety, infrastructure, and ecosystems. Accurate detection from high-resolution optical remote sensing imagery remains challenging because landslide targets often exhibit irregular morphology, large scale variation, weak boundaries, and strong background interference. To address these issues, this study proposes L-SAINet, a shape-adaptive and inner-scale interaction network for landslide detection in complex remote sensing scenarios. Built on a lightweight one-stage detection framework, the proposed method introduces an L-SAI module that integrates adaptive deformable convolution, channel–spatial attention, and inner-scale feature interaction. The shape-adaptive branch improves geometric alignment for irregular and elongated landslide bodies, while the attention branch enhances semantic discrimination under heterogeneous background conditions. The two branches are further fused at the same feature scale to construct a more unified landslide representation. Experiments on the Bijie Landslide Remote Sensing Dataset show that L-SAINet consistently outperforms the baseline detector and single-branch variants in Precision, Recall, mAP@0.5, and mAP@0.5:0.95. Additional analyses based on precision–recall curves, confusion matrices, convergence behavior, model complexity, and representative complex-scene examples further confirm its effectiveness and robustness. The results demonstrate that jointly modeling geometric adaptability and semantic refinement is an effective strategy for landslide detection in complex mountain environments.

Ferroptosis has important value in cancer treatment. It is significant to explore the new ferroptosis-related lncRNAs prediction model in Hepatocellular carcinoma (HCC) and the potential molecular mechanism of ferroptosis-related lncRNAs. We constructed a prognostic multi-lncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HCC. qRT-PCR was applied to determine the expression of lncRNA in HCC cells. The biological roles of NRAV in vitro and in vivo were determined by performing a series of functional experiments. Furthermore, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of NRAV with miR-375-3P . We identified 6 differently expressed lncRNAs associated with the prognosis of HCC. Kaplan–Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HCC. Moreover, the AUC of the lncRNAs signature showed utility in predicting HCC prognosis. Further functional experiments show that the high expression of NRAV can strengthen the viciousness of HCC. Interestingly, we found that NRAV can enhance iron export and ferroptosis resistance. Further study showed that NRAV competitively binds to miR-375-3P and attenuates the inhibitory effect of miR-375-3P on SLC7A11 , affecting the prognosis of patients with HCC. In conclusion, We developed a novel ferroptosis-related lncRNAs prognostic model with important predictive value for the prognosis of HCC. NRAV is important in ferroptosis induction through the miR-375-3P / SLC7A11 axis.

This study aims to optimize the ceramic-to-backing thickness ratio ( R th ) of B 4 C/UHMWPE composite armor to enhance the anti-penetration performance while maintaining lightweight requirements. Its primary innovation lies in systematically quantifying, through combined finite element method (FEM) and ballistic testing, the coupling mechanism of thickness ratio ( R th : 0.4-2.0), areal density ( AD : 25.0–30.0 kg/m²), and impact velocity ( V 0 : 400.0–550.0 m/s) governing the anti-penetration performance of composite armor. The results reveal that the ballistic limit velocity ( V bl ) initially increases and then decreases as R th increases from 0.4 to 2.0, peaking at R th = 1.4–1.6 across all AD cases. Notably, this optimal R th range remains consistent across AD variations, with both projectile mass loss ratio ( R II m,l ) and kinetic energy loss ratio ( R II ke,l ) during the first two penetration stages peaking within this range, demonstrating robust design applicability. Furthermore, a key finding and significant contribution is the dynamic shift in the optimal R th for minimizing projectile residual velocity ( V re ) when V 0 exceeds V bl : Under fixed AD , higher V 0 reduces the optimal R th due to shortened projectile-armor interaction time, necessitating thicker UHMWPE laminate to prevent premature ceramic fracture failure and enhance the backing-plate energy dissipation. Conversely, under constant V₀ , higher AD elevates the optimal R th , where AD and V₀ show opposite effects on the variation of optimal R th , and the optimal R th converges to 1.4–1.6 as the highest V bl corresponding to given AD approaches V 0 . Critically, this study establishes a quantitative framework for V 0 - AD - R th coupling effects, providing actionable guidelines for designing lightweight composite armor against diverse ballistic threats.