A new HP-PRRSV strain (SD2020) was isolated from pigs with suspected highly pathogenic porcine reproductive and respiratory syndrome disease in a pig farm in Shandong Province, China, and its genome was sequenced. This pig farm has been using the VR-2332 vaccine strain to immunize pigs for a long time. The phylogenic and single nucleotide polymorphisms (SNPs) analysis of the viruses isolated from dead pigs showed that SD2020 was a natural recombinant virus of the VR-2332 vaccine strain and the JXA1 similar strain, and that two splicing fragments highly homologous to JXA1 in the virus genome were probably derived from the JXA1 wild strain and JXA1-R vaccine strain, respectively. Therefore, the possible recombination events of SD2020 and its mutation site might be related to high pathogenicity.

Dysregulation of the cell cycle is one of the fundamental mechanisms underlying tumorigenesis, making cell cycle-related regulators potential antitumor therapeutic targets. Despite significant advances in understanding cell cycle regulatory networks, there is still a lack of a comprehensive and up-to-date synthesis that integrates the latest mechanistic insights with their translational potential in oncology. This review first systematically outlines the pivotal role of the cyclin-cyclin-dependent kinase (CDK)-cyclin-dependent kinase inhibitor (CKI) axis in driving aberrant cell cycle progression in tumors. Then the complex regulatory mechanisms of the tumor cell cycle were explored from various perspectives, including transcriptional control, post-translational modifications, checkpoint mechanisms, crosstalk with cellular processes, and integration with key signaling pathways. Furthermore, we highlight a series of clinically relevant biomarkers tightly linked to cell cycle dysregulation. Focusing on approved therapeutic agents and natural compounds in clinical trials, current treatment approaches that target the cell cycle and related metabolic pathways were also comprehensively assessed, and their prospects in precision oncology were elaborated. Finally, we discuss persistent challenges, including the incomplete understanding of tumor-specific cell cycle networks and the barriers to the clinical translation of targeted therapies. We advocate for future research to leverage multi-omics integration and systems biology approaches to facilitate more precise and effective cell cycle-directed interventions. This work offers a comprehensive framework that connects the fundamental mechanisms of cell cycle dysregulation in tumors with clinical translation, aiming to accelerate biomarker discovery and the development of next-generation precision oncology strategies.

Colorectal cancer (CRC), which develops from the gradual evolution of tubular adenomas and serrated polyps in the colon and rectum, has a poor prognosis and a high mortality rate. In addition to genetics, lifestyle, and chronic diseases, intestinal integrity and microbiota (which facilitate digestion, metabolism, and immune regulation) could promote CRC development. For example, enterotoxigenic Bacteroides fragilis, genotoxic Escherichia coli (pks+ E. coli), and Fusobacterium nucleatum, members of the intestinal microbiota, are highly correlated in CRC. This review describes the roles and mechanisms of these three bacteria in CRC development. Their interaction during CRC initiation and progression has also been proposed. Our view is that in the precancerous stage of colorectal cancer, ETBF causes inflammation, leading to potential changes in intestinal ecology that may provide the basic conditions for pks+ E. coli colonization and induction of oncogenic mutations, when cancerous intestinal epithelial cells can further recruit F. nucleatum to colonise the lesion site and F. nucleatum may contribute to CRC advancement by primarily the development of cancer cells, stemization, and proliferation, which could create new and tailored preventive, screening and therapeutic interventions. However, there is the most dominant microbiota in each stage of CRC development, not neglecting the possibility that two or even all three bacteria could be engaged at any stage of the disease. The relationship between the associated gut microbiota and CRC development may provide important information for therapeutic strategies to assess the potential use of the associated gut microbiota in CRC studies, antibiotic therapy, and prevention strategies.

Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored. Suppression subtractive hybridization (SSH) technique was applied to identify genes differentially expressed in the ORFV-infected MDBK cells at an early phase of infection. Cellular CypB was confirmed to be significantly up-regulated by quantitative reverse transcription-PCR (qRT-PCR) analysis and Western blotting. The role of CypB in ORFV infection was further determined using Cyclosporin A (CsA) and RNA interference (RNAi). Effect of CypB gene silencing on ORFV replication by 50% tissue culture infectious dose (TCID50) assay and qRT-PCR detection. In the present study, CypB was found to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection. Cyclosporin A (CsA) exhibited suppressive effects on ORFV replication through the inhibition of CypB. Silencing of CypB gene inhibited the replication of ORFV in MDBK cells. In conclusion, these data suggest that CypB is critical for the efficient replication of the ORFV genome. Cellular CypB was confirmed to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection, which could effectively facilitate the replication of ORFV.

The occurrence and development of colorectal cancer (CRC) is an incredibly long process that involves continuous changes in the tumor microenvironment. These constant changes may ultimately result in genetic alterations and changes in the metabolic processes of some symbiotic bacteria as a way to adapt to the changing environment. Patients with CRC exhibit an altered abundance of Bacteroides fragilis (B. fragilis) as indicated by several studies. To better understand the genomic characteristics and virulence spectrum of B. fragilis strains in tumor tissues, B. fragilis strains were isolated from tumor and paracancerous tissues of CRC patients. The isolates were identified using 16 S rRNA sequencing, morphological analysis, physiological and biochemical characterization and PCR, and they were then subjected to whole genome sequencing (WGS) analysis. A strain of B. fragilis enterotoxin (BFT) bft1-producing ZY0302 and a non-enterotoxin-producing B. fragilis ZY0804 were isolated from cancerous and paraneoplastic tissues, respectively. Analysis based on the core and nonessential genes showed that the genomic profiles of the isolates, ZY0302 and ZY0804, differed from those of B. fragilis from other tissue sources. This core and the co-evolution of non-essential genes may be the result of their adaptation to fluctuations in the tumor microenvironment and enhancing their survival. In addition, the ZY0302 and ZY0804 genomes underwent extensive horizontal gene transfer and varying degrees of genomic rearrangements, inversions, insertions, and deletion events, which may favor the enhancement of bacteria’s ability to adapt to environmental changes. For instance, the virulence factors, such as the capsular biosynthesis gene clusters and components of the type IV secretion system, acquired through horizontal gene transfer, may facilitated B. fragilis in evading immune responses and managing oxidative stress. Moreover, our analysis revealed that multiple virulence factors identified in the isolates were mainly involved in bacterial adhesion and colonization, oxidative stress, iron acquisition, and immune evasion. This observation is worth noting given that enzymes such as neuraminidase, lipase, hemolysin, protease, and phosphatase, along with genes responsible for LPS biosynthesis, which are recognized for their association with the virulence of B. fragilis, were prevalent among the isolates. In summary, it is our assertion that the alterations observed in both core and nonessential genes of B. fragilis, which have been isolated from tissues of colorectal cancer patients, along with significant instances of horizontal gene transfer to the genome, are likely intended to enhance adaptation to the evolving conditions of the tumor microenvironment. This study may provide new insights into the interaction between B. fragilis and the CRC microenvironment.