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Since 2011, the emergence of Pseudorabies virus (PRV) variants has led to significant vaccine failures, resulting in severe economic losses in China’s swine industry. Conventional PRV vaccines have shown limited efficacy against these emergent variants, underscoring the urgent need for novel immunization strategies. This study aimed to develop and evaluate a novel recombinant PRV vaccine candidate with improved safety and immunogenicity profiles. Utilizing the homology-directed repair (HDR)-CRISPR/Cas9 system, we generated a recombinant PRV strain, designated PRV SX-10ΔgI/gE/TK/UL24, with deletions in the gI, gE, TK, and UL24 genes. In vitro analyses demonstrated that the recombinant virus exhibited similar replication kinetics and growth curves comparable to the parental strain. The immunological properties of the recombinant PRV were assessed in murine and porcine models. All animals inoculated with PRV SX-10ΔgI/gE/TK/UL24 survived without exhibiting significant clinical signs or pathological alterations. Immunological assays revealed that PRV SX-10ΔgI/gE/TK/UL24 elicited significantly higher levels of gB-specific antibodies, neutralizing antibodies, and cytokines (including IFN-γ, IL-2, and IL-4) compared to both the Bartha-K61 and PRV SX-10ΔgI/gE/TK strains. Notably, both murine and porcine subjects immunized with PRV SX-10ΔgI/gE/TK/UL24 demonstrated enhanced protection against challenges with the variant PRV SX-10 strain, compared to other vaccine strains. These findings suggest that PRV SX10ΔgI/gE/TK/UL24 represents a promising PRV vaccine candidate strain, offering valuable insights for the prevention and control of PRV in clinical applications. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to reveal the current knowledge map, research hotspots of functional magnetic resonance imaging (fMRI) studies on depression, as well as identify the brain regions associated with depression. Methods: CiteSpace was conducted to analyze the publication outputs, country, institution, cited journals, author and cited author, references, keyword cocurrence and burst keywords of fMRI studies in depression from 2010 to 2024. And a meta-analysis of fMRI was used to identify brain regions associated with depression using Neurosynth. Results: A total of 4,049 publications were included, and Gong Qiyong was the most prolific authors. Neuroimage, Biological Psychiatry, and Human Brain Mapping were prominent journals. Default mode network (DMN), prefrontal cortex, amygdala, and anterior cingulate cortex were the popular keywords. The fMRI studies on depression have mainly focused on major depression, especially the DMN. Functional connectivity and regional homogeneity of brain regions were research hotspots. The meta-analysis revealed significant differences in brain regions between patients with depression and healthy controls, including the Amygdala_L, Insula_R, Frontal_Inf_Oper_R, Cingulum_Post_L, Putamen_L, Thalamus_R, Angular_L, Precuneus_R, Frontal_Sup_R, Occipital_Inf_L. Conclusions: This study sheds light on key issues and future directions in fMRI research on depression, elucidating the brain regions related to depression. [ABSTRACT FROM AUTHOR]

Liver cancer has been reported to be one of the most malignant diseases in the world. It is late diagnosis consequently leads to a difficult treatment, as the cancer reached an advanced stage. Hepatocellular carcinoma (HCC) is the primary type of cancer diagnosed in the liver, with deadly characteristics and a poor prognosis. The first‐in‐line treatment for advanced HCC is sorafenib. Sorafenib acts by inhibiting cell proliferation and by inducing apoptosis as well as blocks receptors associated with these mechanisms. Due to its constant use, sorafenib resistance has been described, especially to proteins of the Bcl‐2 family, and their overexpression of Bcl‐XL and Mcl‐1. This review focuses on the role of the Bcl‐2 proteins in relation to sorafenib resistance as a consequence of first‐in‐line treatment in HCC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the feasibility of 11C-CFT PET brain imaging in Parkinson's Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice. Methods: Thirty-two patients with Parkinson's disease (PD) performing 11C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference. Results: The overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P < 0.05). However, all G300 image quality was clinically acceptable (≥ 3 points). As the scan duration reduced, the SUVmean and DAT binding of caudate nucleus and putamen decreased progressively, while there were no statistically significant variations in the SUVmean of the background among the different groups. Moreover, the changes in the lesion DAT binding (ΔDAT-binding) between the full-time reference G900 image and other reconstructed group G720 to G30 images generally increased along with the reduced scan time. Conclusion: Sufficient image quality and lesion conspicuity could be achieved at 600-s scan duration for 11C-CFT PET brain imaging in PD assessment using a total-body PET/CT scanner, while the image quality of G300 was acceptable to meet clinical diagnosis, contributing to improve patient compliance and throughput of PET brain imaging. [ABSTRACT FROM AUTHOR]

ctive: In this study, we further explored the discovery of novel PARP-1 inhibitors based on previous studies. We designed and synthesized 6 compounds with different structures, which further enriched the structural types of novel PARP-1 inhibitors. Methods: Firstly, the structures of all target compounds were determined by 1H NMR, 13C NMR, and high resolution MS. Next, the target compounds were evaluated for enzyme activity in vitro. Finally, ADMET prediction and molecular docking studies were used for experimental analysis. Results and Discussion: Compound (S10a) (IC50 = 23.74 nM) was found to have PARP-1 enzyme inhibitory activity similar to Rucaparib (IC50 = 23.88 nM). We also predicted the ADMET activity of all compounds, and their corresponding index values were similar to those of the reference drug Rucaparib. The molecular docking studies showed that compounds (X10a) and (S10a) could penetrate deep into the active pocket. Conclusions: Overall, based on the above analysis, the compounds reported in this paper have better research potential, and are expected to be the lead compounds for the discovery of novel PARP-1 inhibitors. [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors (iHDACs) have been extensively studied as enhancers of therapeutic protein production in recombinant Chinese hamster ovary (CHO) (rCHO) cell cultures. However, the addition of iHDACs reduces the viable cell concentration (VCC) in rCHO cell cultures, thereby reducing their potential to enhance therapeutic protein production. To mitigate the negative effects of iHDACs on VCC, screening using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based single-gene knockout (KO) library in rCHO cells was performed in the presence of CI994, a member of iHDACs, and 10 potential KO genes that enhanced the VCC of CI994-treated rCHO cells were identified. Among these, Bcor was validated as a promising KO target that improved VCC without negatively affecting the specific productivity in the presence of CI994. Bcor KO increased the VCC and therapeutic protein concentrations in both batch and fed-batch cultures in the presence of CI994. Taken together, these findings highlight the potential of the whole-genome CRISPR/Cas9-based single-gene KO cell library to identify KO target genes for the development of iHDAC-resistant rCHO cells for enhanced therapeutic protein production., (© 2023 Wiley Periodicals LLC.)