Search Results (73)

Canine coronavirus (CCoV), an alphacoronavirus belonging to the Coronaviridae family, is primarily associated with enteric infections in dogs. The ongoing evolution of coronaviruses through genetic recombination and mutation leads to the emergence of novel strains with increased pathogenicity, thereby raising the risk of cross-species transmission and spillover events. In this context, viral entry inhibitors represent a promising strategy, as they can serve as pivotal tools to prevent initial infection and subsequent viral replication. The S2 subunit of the spike (S) glycoprotein contains two heptad repeat regions (HRN and HRC), which play essential roles in the conformational changes required for viral fusion. In this study, we describe the design, synthesis, and functional evaluation of a peptide derived from the HRC domain of the CCoV S glycoprotein. First, we assessed the cytotoxicity of the CCoV-HRC peptide in two cell lines, HE293T and A72, and determined CC₅₀ values > 100 μM. At non-toxic concentrations, the peptide effectively blocked membrane fusion mediated by the CCoV S glycoprotein and significantly reduced viral infection, as demonstrated both in cell–cell fusion assays and in live virus experiments. These findings were supported by in silico docking and molecular dynamics simulations, which provided structural insight into the interaction between CCoV-HRC and the S fusion core. Then, molecular analyses were conducted to evaluate the expression of the gene encoding the viral S protein, confirming the antiviral potential of CCoV-HRC peptide. Overall, these findings provide a solid foundation for the development of peptide-based therapeutics to treat or prevent CCoV infections. Full article

Nanomaterial-based hole transport layers (HTLs) play a vital role in regulating interfacial charge extraction and recombination in perovskite solar cells (PSCs). To improve PSC efficiency, hydrothermally synthesized CeO₂@MoS₂ nanocomposites (CM NCs) were incorporated as an interfacial buffer layer into a NiO_X/MeO-2PACz HTL. The introduction of CM NCs induces strong interfacial interactions, where Mo sites in MoS₂ interact with NiO_X, modulating the Ni²⁺/Ni³⁺ ratio and reducing the interfacial trap density. Moreover, CeO₂ promotes the formation of oxygen vacancies, collectively improving the conductivity and hole transport capability of the NiO_X HTL. The MoS₂-grafted CeO₂ interlayer effectively tailors the interfacial energetics and creates an effective channel for hole transfer, thereby reducing open-circuit voltage (V_OC) loss and enhancing device performance. This interface modification efficiently enhances hole extraction, and non-radiative recombination is effectively suppressed at the NiO_X/MeO-2PACz/perovskite interface. Thereby, incorporating 2 vol% CM NCs into PSCs achieved a power conversion efficiency (PCE) of 17.93%, compared to 17.50% for a 1 vol% CM NCs-based device and 17.01% for the unmodified control device. The enhanced performance at the optimized CM NCs concentration is attributed to effective defect passivation, reduced V_OC loss, and improved interfacial band alignment, which together facilitate hole extraction and suppress non-radiative recombination. However, excessive CM NCs incorporation (4 vol%) leads to increased interfacial resistance, partial hole blocking effects associated with the n-type nature of CeO₂, and aggravated recombination, resulting in degraded device performance. These results demonstrate that precise control over CM NCs interlayer thickness and concentration is critical for maximizing device performance, providing a robust strategy for designing high-efficiency and stable NiO_X-based PSCs and advancing nanocomposite-enabled interfacial engineering for photovoltaic applications. Full article

Reusable enzyme carriers are valuable for proteomic workflows, yet many supports are expensive or lack robustness. This study describes the covalent immobilization of recombinant trypsin on micrometer-sized corundum particles and assesses their performance in protein digestion and antibody analysis. The corundum surface was cleaned with potassium hydroxide, silanized with 3-aminopropyltriethoxysilane and activated with glutaraldehyde. Recombinant trypsin was then attached, and the resulting imines were reduced with sodium cyanoborohydride. Aromatic amino acid analysis (AAAA) estimated an enzyme loading of approximately 1 µg/mg. Non-specific adsorption of human plasma proteins was suppressed by blocking residual aldehydes with a Tris-glycine-lysine buffer. Compared with free trypsin, immobilization shifted the temperature optimum from 50 to 60 °C and greatly improved stability in 1 M guanidinium hydrochloride. Activity remained above 80% across several reuse cycles, and storage at 4 °C preserved functionality for weeks. When applied to digesting the NISTmAb, immobilized trypsin provided peptide yields and sequence coverage comparable to soluble enzyme and outperformed it at elevated temperatures. MALDI-TOF MS analysis of Herceptin digests yielded fingerprint spectra that correctly identified the antibody and achieved >60% sequence coverage. The combination of low cost, robustness and analytical performance makes corundum-immobilized trypsin an attractive option for research and routine proteomic workflows. Full article

Increasingly frequent intense rainfall is increasing landslide occurrence and risk. In southern China in particular, steep slopes and thin residual soils produce frequent landslide events with pronounced spatial heterogeneity. Therefore, displacement prediction methods that function across sites and deformation regimes in similar settings are essential for early warning. Most existing approaches adopt a multistage pipeline that decomposes, predicts, and recombines, often leading to complex architectures with weak cross-domain transfer and limited adaptability. To address these limitations, we present CRAFormer, a causal role-aware Transformer guided by a dynamic-lag Bayesian network-style causal graph learned from historical observations. In our system, the discovered directed acyclic graph (DAG) partitions drivers into five causal roles and induces role-specific, non-anticipative masks for lightweight branch encoders, while a context-aware Top-2 gate sparsely fuses the branch outputs, yielding sample-wise attributions. To safely exploit exogenous rainfall forecasts, next-day rainfall is entered exclusively through an ICS tail with a leakage-free block mask, a non-negative readout, and a rainfall monotonicity regularizer. In this study, we curate two long-term GNSS datasets from Guangxi (LaMenTun and BaYiTun) that capture slow creep and step-like motions during extreme rainfall. Under identical inputs and a unified protocol, CRAFormer reduces the MAE and RMSE by 59–79% across stations relative to the strongest baseline, and it lowers magnitude errors near turning points and step events, demonstrating robust performance for two contrasting landslides within a shared regional setting. Ablations confirm the contributions of the DBN-style causal masks, the leakage-free ICS tail, and the monotonicity prior. These results highlight a practical path from causal discovery to forecast-compatible neural predictors for rainfall-induced landslides. Full article

We introduce a fully solution-processed interlayer strategy for n–p CdS/PbS thin film solar cells that combines a sol–gel ZnO compact coating with an electrospun ZnO nanofiber network. The synthesis and characterization of ZnO, CdS, and PbS thin films, complemented by electrospun ZnO nanofibers, are aimed at low-cost photovoltaic applications. Sol–gel ZnO films exhibited a hexagonal wurtzite structure with a bandgap (Eg) of approximately 3.28 eV, functioning effectively as electron transport and hole-blocking layers. CdS films prepared by chemical bath deposition (CBD) showed mixed cubic and hexagonal phases with an Eg of about 2.44 eV. PbS films deposited at low temperature displayed a cubic galena structure with a bandgap of approximately 0.40 eV. Scanning Electron Microscopy revealed uniform ZnO and CdS surface coatings and a conformal 1D ZnO network with nanofibers measuring about 50 nm in diameter (ranging from 49.9 to 53.4 nm), which enhances interfacial contact coverage. PbS films exhibited dense grains ranging from 50 to 150 nm, and EDS confirmed the expected stoichiometries. Electrical characterization indicated low carrier densities and high resistivities consistent with low-temperature processing, while mobilities remained within reported ranges. The incorporation of ZnO layers and nanofibers significantly improved device performance, particularly at the CdS/PbS heterojunction. The device achieved a V_oc of 0.26 V, an J_sc of 3.242 mA/cm², and an efficiency of 0.187%. These improvements are attributed to enhanced electron transport selectivity and reduced interfacial recombination provided by the percolated 1D ZnO network, along with effective hole blocking by the compact film and increased surface area. Fill-factor limitations are linked to series resistance losses, suggesting potential improvements through fiber densification, sintering, and control of the compact layer thickness. This work is a proof-of-concept of a fully solution-processed and low-temperature CdS/PbS architecture. Efficiencies remain modest due to low carrier concentrations typical of low-temperature CBD films and the deliberate omission of high-temperature annealing/ligand exchange. Overall, this non-vacuum, low-temperature coating method establishes electrospun ZnO as a tunable functional interlayer for CdS/PbS devices and offers a practical pathway to elevate power output in scalable productions. These findings highlight the potential of nanostructured intermediate layers to optimize charge separation and transport in low-cost PbS/CdS/ZnO solar cell architectures. Full article

In recent years, most proposed digital image encryption algorithms have primarily focused on encrypting raw pixel data, often neglecting the integration with image compression techniques. Image compression algorithms, such as JPEG, are widely utilized in internet applications, highlighting the need for encryption methods that are compatible with compression processes. This study introduces an innovative color image encryption algorithm integrated with JPEG compression, designed to enhance the security of images susceptible to attacks or tampering during prolonged transmission. The research addresses critical challenges in achieving an optimal balance between encryption security and compression efficiency. The proposed encryption algorithm is structured around three key compression phases: Discrete Cosine Transform (DCT), quantization, and entropy coding. At each stage, the algorithm incorporates advanced techniques such as block segmentation, block replacement, DC coefficient confusion, non-zero AC coefficient transformation, and RSV (Run/Size and Value) pair recombination. Extensive simulations and security analyses demonstrate that the proposed algorithm exhibits strong robustness against noise interference and data loss, effectively meeting stringent security performance requirements. Full article

Non-traumatic intracerebral hemorrhage (ICH) is one of the most devastating and disabling forms of stroke; however, there are no effective pharmacological therapies available following the insult. Angiogenesis appears as a key step to overcoming the damage and promoting functional recovery. In this context, endothelial progenitor cells (EPCs) mobilization improves oxidative stress and promotes neovascularization, which has been linked to beneficial outcomes following both ischemic and hemorrhagic stroke. The TNF-like weak inducer of apoptosis (TWEAK), binding to its receptor Fn14, has been suggested as an inducer of EPCs differentiation, viability and migration to the injury site in a model of myocardial infarction. Here, we have performed a proof-of-concept preclinical study in a rat model of ICH where we report that a 50 μg/kg dose of rat recombinant TWEAK (rTWEAK) promotes blood progenitor cells mobilization, mainly EPCs. As soon as 72 h post-injury, brain neovascularization, and, importantly, long-term hematoma reduction and improved functional recovery is reported. In contrast, a higher dose of 150 μg/kg blocked those beneficial outcomes. Therefore, a low dose of rTWEAK treatment promotes neovascularization and reduces brain damage in a rat model of ICH. Further clinical studies will be needed to demonstrate if rTWEAK could represent a new strategy to promote recovery following ICH. Full article

Cancers that arise from germline mutations of breast cancer associated gene 1 (BRCA1), which is a crucial player in homologous recombination (HR) DNA repair, are vulnerable to DNA-damaging agents such as platinum and PARP inhibitors (PARPis). Increasing evidence suggests that BRCA1 is an essential driver of all phases of the cell cycle, thereby maintaining orderly steps during cell cycle progression. Specifically, loss of BRCA1 activity causes the S-phase, G₂/M, spindle checkpoints, and centrosome duplication to be dysregulated, thereby blocking cell proliferation and inducing apoptosis. In vertebrates, loss of HR genes such as BRCA1 and/or BRCA2 is lethal, since HR is a prerequisite for genome integrity. Thus, cancer cells utilize alternative DNA repair pathways such as non-homologous end joining (NHEJ) to cope with the loss of BRCA1 function. In this review, we attempt to update and discuss how these novel components are crucial for regulating DNA damage repair (DDR) in BRCA1-deficient cancers. Full article

Semantic segmentation-based Complex Waterway Scene Understanding has shown great promise in the environmental perception of Unmanned Surface Vehicles. Existing methods struggle with estimating the edges of obstacles under conditions of blurred water surfaces. To address this, we propose the Lightweight Dual-branch Mamba Network (LDMNet), which includes a CNN-based Deep Dual-branch Network for extracting image features and a Mamba-based fusion module for aggregating and integrating global information. Specifically, we improve the Deep Dual-branch Network structure by incorporating multiple Atrous branches for local fusion; we design a Convolution-based Recombine Attention Module, which serves as the gate activation condition for Mamba-2 to enhance feature interaction and global information fusion from both spatial and channel dimensions. Moreover, to tackle the directional sensitivity of image serialization and the impact of the State Space Model’s forgetting strategy on non-causal data modeling, we introduce a Hilbert curve scanning mechanism to achieve multi-scale feature serialization. By stacking feature sequences, we alleviate the local bias of Mamba-2 towards image sequence data. LDMNet integrates the Deep Dual-branch Network, Recombine Attention, and Mamba-2 blocks, effectively capturing the long-range dependencies and multi-scale global context information of Complex Waterway Scene images. The experimental results on four benchmarks show that the proposed LDMNet significantly improves obstacle edge segmentation performance and outperforms existing methods across various performance metrics. Full article

DNA double strand breaks (DSBs) are critical for the efficacy of radiotherapy as they lead to cell death if not repaired. DSBs caused by ionizing radiation (IR) initiate histone modifications and accumulate DNA repair proteins, including 53BP1, which forms distinct foci at damage sites and serves as a marker for DSBs. DSB repair primarily occurs through Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). NHEJ directly ligates DNA ends, employing proteins such as DNA-PK_cs, while HR, involving proteins such as Rad54, uses a sister chromatid template for accurate repair and functions in the S and G2 phases of the cell cycle. Both pathways are crucial, as illustrated by the IR sensitivity in cells lacking DNA-PK_cs or Rad54. We generated mouse embryonic stem (mES) cells which are knockout (KO) for DNA-PK_cs and Rad54 to explore the combined role of HR and NHEJ in DSB repair. We found that cells lacking both DNA-PK_cs and Rad54 are hypersensitive to X-ray radiation, coinciding with impaired 53BP1 focus resolution and a more persistent G2 phase cell cycle block. Additionally, mES cells deficient in DNA-PK_cs or both DNA-PK_cs and Rad54 exhibit an increased nuclear size approximately 18–24 h post-irradiation. To further explore the role of Rad54 in the absence of DNA-PK_cs, we generated DNA-PK_cs KO mES cells expressing GFP-tagged wild-type (WT) or ATPase-defective Rad54 to track the Rad54 foci over time post-irradiation. Cells lacking DNA-PK_cs and expressing ATPase-defective Rad54 exhibited a similar phenotypic response to IR as those lacking both DNA-PK_cs and Rad54. Despite a strong G2 phase arrest, live-cell imaging showed these cells eventually progress through mitosis, forming micronuclei. Additionally, mES cells lacking DNA-PK_cs showed increased Rad54 foci over time post-irradiation, indicating an enhanced reliance on HR for DSB repair without DNA-PK_cs. Our findings underscore the essential roles of HR and NHEJ in maintaining genomic stability post-IR in mES cells. The interplay between these pathways is crucial for effective DSB repair and cell cycle progression, highlighting potential targets for enhancing radiotherapy outcomes. Full article

Anemia plays an important role in chronic kidney disease (CKD) progression because it worsens the quality of life and increases the risk of cardiovascular complications in CKD patients. In such cases, anemia is mainly caused by endogenous erythropoietin (EPO) and iron deficiencies. Therefore, KDIGO and ERBP guidelines for anemia treatment in CKD patients focus on recombinant EPO and iron supplementation. A recent new treatment option for anemia in CKD patients involves blocking the hypoxia-inducible factor (HIF) system with prolyl hydroxylase inhibitors (PHIs), what causes increasing endogenous EPO production and optimizing the use of iron. Clinical studies have shown that the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) covered in this manuscript—roxadustat, vadadustat, daprodustat, and molidustat—effectively increase hemoglobin (Hb) levels in both non-dialyzed and dialyzed CKD patients. Moreover, these medicines reduce blood lipid levels and do not accelerate CKD progression. However, blockage of the HIF system by HIF-PHIs may be associated with adverse effects such as cardiovascular complications, tumorogenesis, hyperkalemia. and retinopathy. More extensive and long-term clinical trials of HIF-PHIs-based anemia treatment in CKD patients are needed, and their results will indicate whether HIF-PHIs represent an effective and safe alternative to EPO and iron supplementation for anemia treatment in CKD patients. Full article

We investigated the basic characteristics of a new murine cytomegalovirus (MCMV) vector platform. Using BAC technology, we engineered replication-competent recombinant MCMVs with deletions of up to 26% of the wild-type genome. To this end, we targeted five gene blocks (m01-m17, m106-m109, m129-m141, m144-m158, and m159-m170). BACs featuring deletions from 18% to 26% of the wild-type genome exhibited delayed virus reconstitution, while smaller deletions (up to 16%) demonstrated reconstitution kinetics similar to those of the wild type. Utilizing an innovative methodology, we introduced large genomic DNA segments, up to 35 kbp, along with reporter genes into a newly designed vector with a potential cloning capacity of 46 kbp (Q4). Surprisingly, the insertion of diverse foreign DNAs alleviated the delayed plaque formation phenotype of Q4, and these large inserts remained stable through serial in vitro passages. With reporter-gene-expressing recombinant MCMVs, we successfully transduced not only mouse cell lines but also non-rodent mammalian cells, including those of human, monkey, bovine, and bat origin. Remarkably, even non-mammalian cell lines derived from chickens exhibited successful transduction. Full article

Vaccination with transiently activated replication-competent controlled herpesviruses (RCCVs) expressing influenza A virus hemagglutinins broadly protects mice against lethal influenza virus challenges. The non-replicating RCCVs can be activated to transiently replicate with high efficiency. Activation involves a brief heat treatment to the epidermal administration site in the presence of a drug. The drug co-control is intended as a block to inadvertent reactivation in the nervous system and, secondarily, viremia under adverse conditions. While the broad protective effects observed raise an expectation that RCCVs may be developed as universal flu vaccines, the need for administering a co-activating drug may dampen enthusiasm for such a development. To replace the drug co-control, we isolated keratin gene promoters that were active in skin cells but inactive in nerve cells and other cells in vitro. In a mouse model of lethal central nervous system (CNS) infection, the administration of a recombinant that had the promoter of the infected cell protein 8 (ICP8) gene of a wild-type herpes simplex virus 1 (HSV-1) strain replaced by a keratin promoter did not result in any clinical signs, even at doses of 500 times wild-type virus LD₅₀. Replication of the recombinant was undetectable in brain homogenates. Second-generation RCCVs expressing a subtype H1 hemagglutinin (HA) were generated in which the infected cell protein 4 (ICP4) genes were controlled by a heat switch and the ICP8 gene by the keratin promoter. In mice, these RCCVs replicated efficiently and in a heat-controlled fashion in the epidermal administration site. Immunization with the activated RCCVs induced robust neutralizing antibody responses against influenza viruses and protected against heterologous and cross-group influenza virus challenges. Full article

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein. Full article

Forward bias hole injection from 10-nm-thick p-type nickel oxide layers into 10-μm-thick n-type gallium oxide in a vertical NiO/Ga₂O₃ p–n heterojunction leads to enhancement of photoresponse of more than a factor of 2 when measured from this junction. While it takes only 600 s to obtain such a pronounced increase in photoresponse, it persists for hours, indicating the feasibility of photovoltaic device performance control. The effect is ascribed to a charge injection-induced increase in minority carrier (hole) diffusion length (resulting in improved collection of photogenerated non-equilibrium carriers) in n-type β-Ga₂O₃ epitaxial layers due to trapping of injected charge (holes) on deep meta-stable levels in the material and the subsequent blocking of non-equilibrium carrier recombination through these levels. Suppressed recombination leads to increased non-equilibrium carrier lifetime, in turn determining a longer diffusion length and being the root-cause of the effect of charge injection. Full article