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Citrus leaf blotch virus (CLBV) is a positive-sense single-stranded RNA virus belonging to the genus Citrivirus within the family Betaflexiviridae. It infects a broad range of economically significant fruit crops, including citrus, kiwifruit, and apple. Surveys conducted in the field have documented appreciable incidence rates in several hosts, thereby emphasizing its emerging threat to global pomiculture. Comprehensive surveillance of CLBV genetic diversity is indispensable for predicting strain-specific epidemics and designing durable, broadly protective control strategies. Current surveys of CLBV diversity are still gene-fragment-centric, with whole-genome resolution remaining largely untapped. In this study, an analysis of codon usage bias analysis was performed using all available CLBV full-length genomes. The findings revealed that CLBV exhibits low codon usage bias, with natural selection, rather than mutational drift, being the primary driver. Phylogenetic analysis has been demonstrated to categorize isolates according to their host of origin rather than their geographical location. This observation suggests that host adaptation may supersede spatial structure in CLBV evolution and reinforce natural selection as the dominant force shaping its codon usage landscape. From the perspective of the codon adaptation index, Prunus avium is the host that exerts the greatest influence on the formation of its codon usage bias. The present study provides the first genome-wide portrait of CLBV codon usage bias, offering a robust framework for future investigations into its origin and evolutionary dynamics.

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, and has been pandemic since March 2020 and led to many fatalities. Vaccines represent the most efficient means to control and stop the pandemic of COVID-19. However, currently there is no effective COVID-19 vaccine approved to use worldwide except for two human adenovirus vector vaccines, three inactivated vaccines, and one peptide vaccine for early or limited use in China and Russia. Safe and effective vaccines against COVID-19 are in urgent need. Researchers around the world are developing 213 COVID-19 candidate vaccines, among which 44 are in human trials. In this review, we summarize and analyze vaccine progress against SARS-CoV, Middle-East respiratory syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, including inactivated vaccines, live attenuated vaccines, subunit vaccines, virus like particles, nucleic acid vaccines, and viral vector vaccines. As SARS-CoV-2, SARS-CoV, and MERS-CoV share the common genus, Betacoronavirus , this review of the major research progress will provide a reference and new insights into the COVID-19 vaccine design and development.

Mutations in SPOP , the gene encoding a component of the E3 ubiquitin ligase complex, impair ubiquitination-dependent degradation of BRD2, BRD3 and BRD4 proteins and result in activation of ATK–mTORC1 signaling and resistance to BET inhibitors. Pharmacological blockade of AKT represents a viable strategy to restore the sensitivity of SPOP-mutant prostate tumors to BET inhibitors. These results, together with findings by Dai et al . and Janouskova et al ., uncover a new nongenetic mechanism of resistance to BET inhibition involving cancer-type-specific mutations in SPOP , and support the evaluation of SPOP mutation status to inform the administration of BET inhibitors in the clinic. Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anticancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is the most frequently mutated in primary prostate cancer. Here we demonstrate that wild-type SPOP binds to and induces ubiquitination and proteasomal degradation of BET proteins (BRD2, BRD3 and BRD4) by recognizing a degron motif common among them. In contrast, prostate cancer–associated SPOP mutants show impaired binding to BET proteins, resulting in decreased proteasomal degradation and accumulation of these proteins in prostate cancer cell lines and patient specimens and causing resistance to BET inhibitors. Transcriptome and BRD4 cistrome analyses reveal enhanced expression of the GTPase RAC1 and cholesterol-biosynthesis-associated genes together with activation of AKT–mTORC1 signaling as a consequence of BRD4 stabilization. Our data show that resistance to BET inhibitors in SPOP -mutant prostate cancer can be overcome by combination with AKT inhibitors and further support the evaluation of SPOP mutations as biomarkers to guide BET-inhibitor-oriented therapy in patients with prostate cancer.

Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy. Geminin-Cdt1 plays essential roles in the regulation of DNA replication. Here the authors reveal that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP prevents DNA replication over-firing and genome instability by affecting Geminin ubiquitination.

Mutations in SPOP E3 ligase gene are reportedly associated with genome-wide DNA hypermethylation in prostate cancer (PCa) although the underlying mechanisms remain elusive. Here, we demonstrate that SPOP binds and promotes polyubiquitination and degradation of histone methyltransferase and DNMT interactor GLP. SPOP mutation induces stabilization of GLP and its partner protein G9a and aberrant upregulation of global DNA hypermethylation in cultured PCa cells and primary PCa specimens. Genome-wide DNA methylome analysis shows that a subset of tumor suppressor genes (TSGs) including FOXO3 , GATA5 , and NDRG1 , are hypermethylated and downregulated in SPOP-mutated PCa cells. DNA methylation inhibitor 5-azacytidine effectively reverses expression of the TSGs examined, inhibits SPOP-mutated PCa cell growth in vitro and in mice, and enhances docetaxel anti-cancer efficacy. Our findings reveal the GLP/G9a-DNMT module as a mediator of DNA hypermethylation in SPOP-mutated PCa. They suggest that SPOP mutation could be a biomarker for effective treatment of PCa with DNA methylation inhibitor alone or in combination with taxane chemotherapeutics. The molecular mechanism underlying the DNA hypermethylation phenotype observed in the SPOP-mutant prostate cancers is unclear. Here, the authors show that mutant SPOP induces global aberrant DNA methylation patterns through GLP/G9a and renders prostate cancer cells susceptible to DNA demethylating agents.

DNA‐binding proteins, including transcription factors (TFs), play essential roles in various cellular processes and pathogenesis of diseases, deeming to be potential therapeutic targets. However, these proteins are generally considered undruggable as they lack an enzymatic catalytic site or a ligand‐binding pocket. Proteolysis‐targeting chimera (PROTAC) technology has been developed by engineering a bifunctional molecule chimera to bring a protein of interest (POI) to the proximity of an E3 ubiquitin ligase, thus inducing the ubiquitination of POI and further degradation through the proteasome pathway. Here, the development of oligonucleotide‐based PROTAC (O'PROTACs), a class of noncanonical PROTACs in which a TF‐recognizing double‐stranded oligonucleotide is incorporated as a binding moiety of POI is reported. It is demonstrated that O'PROTACs of lymphoid enhancer‐binding factor 1 (LEF1) and ETS‐related gene (ERG), two highly cancer‐related transcription factors, successfully promote degradation of these proteins, impede their transcriptional activity, and inhibit cancer cell growth in vitro and in vivo. The programmable nature of O'PROTACs indicates that this approach is also applicable to destruct other TFs. O'PROTACs not only can serve as a research tool but also can be harnessed as a therapeutic arsenal to target DNA binding proteins for effective treatment of diseases such as cancer. DNA binding proteins including transcription factors remain as challenging targets in drug discovery. oligonucleotide‐based proteolysis‐targeting chimeras (O'PROTACs), which employ unique DNA sequences as natural “ligand” of targeting proteins, are developed to effectively destruct lymphoid enhancer‐binding factor 1 (LEF1) and ETS‐related gene (ERG) and inhibit prostate cancer cell growth. O'PROTAC represents an attractive approach for treatment of diseases including cancer.

The measurement matrix used influences the performance of image reconstruction in compressed sensing. To enhance the performance of image reconstruction in compressed sensing, two different Gaussian random matrices were orthogonalized via Gram–Schmidt orthogonalization, respectively. Then, one was used as the real part and the other as the imaginary part to construct a complex-valued Gaussian matrix. Furthermore, we sparsified the proposed measurement matrix to reduce the storage space and computation. The experimental results show that the complex-valued Gaussian matrix after orthogonalization has better image reconstruction performance, and the peak signal-to-noise ratio and structural similarity under different compression ratios are better than the real-valued measurement matrix. Moreover, the sparse measurement matrix can effectively reduce the amount of calculation.

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the world. Elevated glucose metabolism in the availability of oxygen, a phenomenon called the Warburg effect, is important for cancer cell growth. Fructose-1,6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis and is frequently lost in various types of cancer. Here, we demonstrated that expression of FBP1 was downregulated in HCC patient specimens and decreased expression of FBP1 associated with poor prognosis. Low expression of FBP1 correlated with high levels of histone deacetylase 1 (HDAC1) and HDAC2 proteins in HCC patient tissues. Treatment of HCC cells with HDAC inhibitors or knockdown of HDAC1 and/or HDAC2 restored FBP1 expression and inhibited HCC cell growth. HDAC-mediated suppression of FBP1 expression correlated with decreased histone H3 lysine 27 acetylation (H3K27Ac) in the FBP1 enhancer. Restored expression of FBP1 decreased glucose reduction and lactate secretion and inhibited HCC cell growth in vitro and tumor growth in mice. Our data reveal that loss of FBP1 due to histone deacetylation associates with poor prognosis of HCC and restored FBP1 expression by HDAC inhibitors suppresses HCC growth. Our findings suggest that repression of FBP1 by HDACs has important implications for HCC prognosis and treatment.

Background Infection is the cause of diarrhoea, and rotaviruses and adenoviruses are important pathogens in children. Methods A retrospective study was conducted on 144,067 children with diarrhoea between 2014 and 2023 in China. We used the colloidal gold method to detect intestinal adenovirus and rotavirus A antigens in faeces. The epidemiological characteristics of these viruses and the impact of meteorological factors on them were analysed before and after coronavirus disease 2019 (COVID-19) pandemic. Results During this decade, the positive rate of adenovirus infection was 6.41%, while the positive rate of rotavirus A infection was 11.81%, higher than that of adenovirus infection. The positive rate of adenovirus and rotavirus A coinfection was 1.92%. The positive rates of adenovirus, rotavirus A and coinfection showed a fluctuating trend, and suddenly decreased in 2020. There was an apparent decrease of positive rate of rotavirus A, with a decrease of 57.27%, during 2020 – 2023. Surprisingly, the positive rate of adenovirus infection exceeded that of rotavirus A infection in 2021 and 2023. During the COVID-19 pandemic, the proportion of female patients and children over two years of age infected with adenovirus or rotavirus A increased, while the proportion of cases in winter decreased. In addition, we found that the positive rate of rotavirus A infection was related to average temperature and sunshine, and the positive rate of adenovirus and rotavirus A coinfection was only related to sunshine. However, these correlations disappeared during the COVID-19 pandemic. Conclusions This study revealed the recent prevalence of adenovirus and rotavirus A infections in children with diarrhoea in south-central China and provided a theoretical basis for the prevention and control of viral diarrhoea.

The objective of this meta-epidemiological study was to develop a rating that captures participants’ motivation at the study level in digital health intervention (DHI) randomised controlled trials (RCTs). The rating was used to investigate whether participants’ motivation is associated with the effect estimates in DHI RCTs for cancer patients. The development of the rating was based on a bottom-up approach involving the collection of information that captures participants’ baseline motivation in empirical studies from the Smartphone-RCCT Database. We specified three indicators for rating: indicator 1 captures whether the study team actively selects or enhances the motivation of the potential study participants; indicator 2 captures the study participants’ active engagement before the treatment allocation; and indicator 3 captures the potential bond and trust between the study participants and the person/institution referring to the study. The rating of each indicator and the overall rating varies between high motivation, moderate motivation, and low motivation. We applied the rating across 27 DHI RCTs with cancer patients. We performed meta-regression analysis to examine the effect of patient motivation on quality of life (QoL), psychological outcomes, and attrition. The intraclass correlation coefficient (ICC) indicated moderate to poor inter-rater reliability. The meta-regression showed that cancer patients’ overall motivation before engaging in the intervention was associated with the treatment effect of QoL. Patient motivation was not found to be associated with psychological outcomes or attrition. Subgroup analyses revealed that the clinical effects of DHIs were more prevalent in the high-motivation subgroups, whereas the low-motivation subgroups were unlikely to show intervention benefits. The likelihood of dropouts from DHIs seems to be especially high among the low-bond (indicator 3) subgroup. We suggest using single indicators since they reflect specific content. Better reporting about baseline motivation is required to enable meaningful interpretations in not only primary studies but also in evidence syntheses.