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Porcine circovirus type 2 (PCV2), porcine circovirus type 3 (PCV3), and pseudorabies virus (PRV) are major pathogens posing significant threats to the swine industry. Viral evolution and mutations have limited the efficacy of current commercial vaccines, necessitating the development of more effective prophylactic strategies. In this study, a novel recombinant virus strain, designated as rPRV-ΔTK-PCV3(Cap)/ΔgIgE-PCV2(Cap), was generated using PRV SX-10 variant as the backbone. CRISPR/Cas9-mediated deletion of TK and gE/gI genes was performed, followed by insertion of PCV3 and PCV2 capsid protein genes into the respective loci. The engineered recombinant strain demonstrated stable proliferation in BHK-21 cells, efficiently expressed heterologous PCV3 and PCV2 capsid proteins, while maintaining biological properties comparable to its parental strain. The rPRV-ΔTK-PCV3(Cap)/ΔgIgE-PCV2(Cap) demonstrated favorable safety and immunogenicity profiles in mice and piglets, eliciting robust immune responses characterized by high titers of specific antibodies against PRV, PCV3, and PCV2, along with significantly elevated levels of cytokines (IFN-γ, IL-2, and IL-4). Histopathological analysis and viral load quantification demonstrated that rPRV-ΔTK-PCV3(Cap)/ΔgIgE-PCV2(Cap) immunization significantly attenuated tissue lesions and decreased viral copies of PRV and PCV in mice and piglets. Collectively, these findings suggest that rPRV-ΔTK-PCV3(Cap)/ΔgIgE-PCV2(Cap) serves as a promising candidate vaccine against PRV and PCV infections. •Generated novel recombinant virus rPRV-ΔTK-PCV3(Cap)/ΔgIgE-PCV2(Cap) via CRISPR/Cas9.•Demonstrated stable virus proliferation and efficient PCV3/PCV2 capsid protein expression.•Induced robust immune responses against PRV, PCV3, and PCV2.•Provided valuable insights for the development of trivalent vaccine candidates.

African Swine Fever (ASF) is a highly lethal viral disease in swine. The emergence and rapid spread of African Swine Fever virus (ASFV) in China, since 2018 have caused significant economic losses to the pig farming industry. The complexity of ASFV has impeded the development of effective vaccines, and with no commercial vaccines currently available in China, highlighting the urgent need for safe and efficacious vaccine candidates. In this study, we utilized a highly immunogenic quadruple‐gene‐deleted recombinant pseudorabies virus (PRV) strain (rPRV SX‐10ΔUL24/TK/gI/gE) as a vector to construct two recombinant viral strains expressing ASFV p54, p72, CD2v, and pp62 proteins using the HDR‐CRISPR/Cas9 system. These strains, rPRV‐p54+p72 and rPRV‐CD2v+pp62, demonstrated stable genetic characteristics and efficiently expressed and delivered heterologous proteins while maintaining biological properties similar to their parental strain. Safety evaluation revealed that both recombinant strains exhibited favorable safety profiles in immunized mice and piglets. Furthermore, the strains induced robust humoral and cellular immune responses, as evidenced by specific antibody enzyme‐linked immunosorbent assay (ELISA), lymphocyte proliferation assays, and analysis of CD3+, CD4+, and CD8+ T lymphocytes. These findings suggest that rPRV‐p54+p72 and rPRV‐CD2v+pp62 are promising bivalent vaccine candidates for protecting against both PRV and ASFV infections.

Utilizing DNA’s molecular programmability, massive parallelism, and minimal energy requirements, it emerges as a transformative medium for secure data storage and encryption. However, practical implementation is limited by technical challenges, particularly the development of robust, programmable systems for flexible data encoding, precise molecular operations, and reliable encryption. Here, we present a molecular information storage and encryption platform that integrates hierarchical core–shell DNA condensates with biomolecular computing networks. It allows programmable and rapid execution of core operations such as information encoding, erasure, rewriting, replication, and repair within readily accessible and readable DNA-based condensates. Moreover, programmable biomolecular computing circuits endowed the system with unprecedented encryption capabilities, including multi-level logic encryption, time-dependent dynamic encryption, living system-driven encryption and fine-grained access control of information. Together, this work represents a meaningful advancement in molecular information storage and encryption, with notable advantages in dynamic editability and system scalability. DNA is a transformative storage medium, but flexible encoding and secure encryption remain challenging. Here, the authors present a DNA condensate-based system capable of writing, erasing, rewriting, replicating, and repairing information, while supporting versatile encryption.

In the era of big data, data-driven methods mainly based on deep learning have been widely used in the field of intelligent fault diagnosis. Traditional neural networks tend to be more subjective when classifying fault time-frequency graphs, such as pooling layer, and ignore the location relationship of features. The newly proposed neural network named capsules network takes into account the size and location of the image. Inspired by this, capsules network combined with the Xception module (XCN) is applied in intelligent fault diagnosis, so as to improve the classification accuracy of intelligent fault diagnosis. Firstly, the fault time-frequency graphs are obtained by wavelet time-frequency analysis. Then the time-frequency graphs data which are adjusted the pixel size are input into XCN for training. In order to accelerate the learning rate, the parameters which have bigger change are punished by cost function in the process of training. After the operation of dynamic routing, the length of the capsule is used to classify the types of faults and get the classification of loss. Then the longest capsule is used to reconstruct fault time-frequency graphs which are used to measure the reconstruction of loss. In order to determine the convergence condition, the three losses are combined through the weight coefficient. Finally, the proposed model and the traditional methods are, respectively, trained and tested under laboratory conditions and actual wind turbine gearbox conditions to verify the classification ability and reliable ability.

Ignition electrodes have an immense impact on the accurate measurement of the flame propagation spherical radius. In this study, a flame-radius calculation method is designed. The method is able to eliminate effects due to the ignition electrodes. The adaptability and optimization effects of the proposed method are analyzed. The results show that the ratio of the angle is affected by the ignition electrodes under the Han II method. There are three obvious divisions include a high-value area, a sharp-variation area, and a mild-variation area. The ratio of the angle affected by the ignition electrodes is only applicable to the mild-variation region when the flame presents respective convex and concave distributions. For these distributions, the increment rate of the mean radius is 0.4–0.85% and 0.42–3.19%. The reduced rate of the standard deviation of the radius extraction value is 11.91–22.1% and 5.13–17.99%, and the reduced rate of the radius extraction value range is 20.32–39.51% and 0.32–8.09%.

Neutral/negatively charged nanoparticles are beneficial to reduce plasma protein adsorption and prolong their blood circulation time, while positively charged nanoparticles easily transverse the blood vessel endothelium into a tumor and easily penetrate the depth of the tumor via transcytosis. Γ-Glutamyl transpeptidase (GGT) is overexpressed on the external surface of endothelial cells of tumor blood vessels and metabolically active tumor cells. Nanocarriers modified by molecules containing γ-glutamyl moieties (such as glutathione, G-SH) can maintain a neutral/negative charge in the blood, as well as can be easily hydrolyzed by the GGT enzymes to expose the cationic surface at the tumor site, thus achieving good tumor accumulation via charge reversal. In this study, DSPE-PEG2000-GSH (DPG) was synthesized and used as a stabilizer to generate paclitaxel (PTX) nanosuspensions for the treatment of Hela cervical cancer (GGT-positive). The obtained drug-delivery system (PTX-DPG nanoparticles) was 164.6 ± 3.1 nm in diameter with a zeta potential of −9.85 ± 1.03 mV and a high drug-loaded content of 41.45 ± 0.7%. PTX-DPG NPs maintained their negative surface charge in a low concentration of GGT enzyme (0.05 U/mL), whereas they showed a significant charge-reversal property in the high-concentration solution of GGT enzyme (10 U/mL). After intravenous administration, PTX-DPG NPs mainly accumulated more in the tumor than in the liver, achieved good tumor-targetability, and significantly improved anti-tumor efficacy (68.48% vs. 24.07%, tumor inhibition rate, p < 0.05 in contrast to free PTX). This kind of GGT-triggered charge-reversal nanoparticle is promising to be a novel anti-tumor agent for the effective treatment of such GGT-positive cancers as cervical cancer.

Refining the land use structure can boost land utilization efficiency and curtail regional carbon emissions. Nevertheless, prior research has predominantly concentrated on static linear planning analysis. It has failed to account for how future dynamic alterations in driving factors (such as GDP and population) affect simulation outcomes and how the land use spatial configuration impacts the attainment of the carbon-neutrality goal. In this research, 1 km spatial resolution LULC products were employed to meticulously simulate multiple land use scenarios across China at the national level from 2030 to 2060. This was performed by taking into account the dynamic changes in driving factors. Subsequently, an analysis was carried out on the low-carbon land use spatial structure required to reach the carbon-neutrality target. The findings are as follows: (1) When employing the PLUS (Patch—based Land Use Simulation) model to conduct simulations of various land use scenarios in China by taking into account the dynamic alterations in driving factors, a high degree of precision was attained across diverse scenarios. The sustainable development scenario demonstrated the best performance, with kappa, OA, and FoM values of 0.9101, 93.15%, and 0.3895, respectively. This implies that the simulation approach based on dynamic factors is highly suitable for national-scale applications. (2) The simulation accuracy of the PLUS and GeoSOS-FLUS (Systems for Geographical Modeling and Optimization, Simulation of Future Land Utilization) models was validated for six scenarios by extrapolating the trends of influencing factors. Moreover, a set of scenarios was added to each model as a control group without extrapolation. The present research demonstrated that projecting the trends of factors having an impact notably improved the simulation precision of both the PLUS and GeoSOS-FLUS models. When contrasted with the GeoSOS-FLUS model, the PLUS model attained superior simulation accuracy across all six scenarios. The highest precision indicators were observed in the sustainable development scenario, with kappa, OA, and FoM values reaching 0.9101, 93.15%, and 0.3895, respectively. The precise simulation method of the PLUS model, which considers the dynamic changes in influencing factors, is highly applicable at the national scale. (3) Under the sustainable development scenario, it is anticipated that China’s land use carbon emissions will reach their peak in 2030 and achieve the carbon-neutrality target by 2060. Net carbon emissions are expected to decline by 14.36% compared to the 2020 levels. From the perspective of dynamic changes in influencing factors, the PLUS model was used to accurately simulate China’s future land use. Based on these simulations, multi-scenario predictions of future carbon emissions were made, and the results uncover the spatiotemporal evolution characteristics of China’s carbon emissions. This study aims to offer a solid scientific basis for policy-making related to China’s low-carbon economy and high-quality development. It also intends to present Chinese solutions and key paths for achieving carbon peak and carbon neutrality.

Oleic acid (OA) is a kind of monounsaturated omega-3 fatty acid that abounds in plants and animals which can induce apoptosis and has broad-spectrum inhibitory activity against a variety of tumor cell lines. However, OA is quite insoluble and thus inconvenient to be efficiently delivered in vivo. In this work, OA was fabricated into nanoparticles to generate OA elastic nanoparticles (OA-ENPs) with a particle size of 185.6 nm and good stability in various physiological media. OA-ENPs alone achieved a high tumor inhibition rate of 60.3% without significant side effect. More surprisingly, the resultant OA-ENPs displayed dose-dependent tumor targetability. Low dose of OA-ENPs (10 mg/kg) mainly distributed in the liver after intravenous injection, while high dose of OA-ENPs mainly distributed in tumor. At the high dose of 90 mg/kg, OA-ENPs accumulation in tumor reached nearly twice as that in the liver. Here we provide a simple but effective way to achieve excellent tumor targetability without the need of any surface modification of nanoparticles.

Cannabidiol (CBD), a nonpsychoactive major component derived from Cannabis sativa, widely used in neurodegenerative diseases, has now been proven to have growth inhibitory effects on many tumor cell lines, including breast tumors. Meanwhile CBD can effectively alleviate cancer-associated pain, anxiety, and depression, especially tumor cachexia, thus it is very promising as an anti-tumor drug with unique advantages. 20(S)-Protopanaxadiol (PPD) derived from the best-known tonic Chinese herbal medicine Ginseng was designed to be co-loaded with CBD into liposomes to examine their synergistic tumor-inhibitory effect. The CBD-PPD co-loading liposomes (CP-liposomes) presented a mean particle size of 138.8 nm. Further glycosyl-modified CP-liposomes (GMCP-liposomes) were prepared by the incorporation of n-Dodecyl β-D-maltoside (Mal) into the liposomal bilayer with glucose residue anchored on the surface to act as a ligand targeting the GLUT1 receptor highly expressed on tumor cells. In vivo studies on murine breast tumor (4T1 cells)-bearing BALB/c mice demonstrated good dose dependent anti-tumor efficacy of CP-liposomes. A high tumor inhibition rate (TIR) of 82.2% was achieved with good tolerance. However, glycosylation modification failed to significantly enhance TIR of CP-liposomes. In summary, combined therapy with PPD proved to be a promising strategy for CBD to be developed into a novel antitumor drug, with characteristics of effectiveness, good tolerance, and the potential to overcome tumor cachexia.

Background Most intravenously administered drug-loaded nanoparticles are taken up by liver Kupffer cells, and only a small portion can accumulate at the tumor, resulting in an unsatisfactory therapeutic efficacy and side effects for chemotherapeutic agents. Tumor-targeted drug delivery proves to be the best way to solve this problem; however, the complex synthesis, or surface modification process, together with the astonishing high cost make its clinical translation nearly impossible. Methods Referring to Ouyang’s work and over-threshold dosing theory in general, blank PEGylated liposomes (PEG-Lipo) were prepared and used as tumor delivery enhancers to determine whether they could significantly enhance the tumor accumulation and in vivo antitumor efficacy of co-injected liposomal ACGs (PEG-ACGs-Lipo), a naturally resourced chemotherapeutic. Here, the phospholipid dose was used as an indicator of the number of liposomes particles with similar particle sizes, and the liposomes was labelled with DiR, a near-red fluorescent probe, to trace their in vivo biodistribution. Two mouse models, 4T1-bearing and U87-bearing, were employed for in vivo examination. Results PEG-Lipo and PEG-ACGs-Lipo had similar diameters. At a low-threshold dose (12 mg/kg equivalent phospholipids), PEG-Lipo was mainly distributed in the liver rather than in the tumor, with the relative tumor targeting index (RTTI) being ~ 0.38 at 72 h after administration. When over-threshold was administered (50 mg/kg or 80 mg/kg of equivalent phospholipids), a much higher and quicker drug accumulation in tumors and a much lower drug accumulation in the liver were observed, with the RTTI increasing to ~ 0.9. The in vivo antitumor study in 4T1 tumor-bearing mice showed that, compared to PEG-ACGs-Lipo alone (2.25 mg/kg phospholipids), the co-injection of a large dose of blank PEG-Lipo (50 mg/kg of phospholipids) significantly reduced the tumor volume of the mice by 22.6% ( P  < 0.05) and enhanced the RTTI from 0.41 to 1.34. The intravenous injection of a low drug loading content (LDLC) of liposomal ACGs (the same dose of ACGs at 50 mg/kg of equivalent phospholipids) achieved a similar tumor inhibition rate (TIR) to that of co-injection. In the U87 MG tumor-bearing mouse model, co-injection of the enhancer also significantly promoted the TIR (83.32% vs. 66.80%, P < 0.05) and survival time of PEG-ACGs-Lipo. Conclusion An over-threshold dosing strategy proved to be a simple and feasible way to enhance the tumor delivery and antitumor efficacy of nanomedicines and was benefited to benefit their clinical result, especially for liposomal drugs. Graphical Abstract