Multifaceted roles of PDCD6 both within and outside the cell.

Programmed cell death protein 6 (PDCD6) is an evolutionarily conserved Ca2+-binding protein. PDCD6 is involved in regulating multifaceted and pleiotropic cellular processes in different cellular compartments. For instance, nuclear PDCD6 regulates apoptosis and alternative splicing. PDCD6 is required for coat protein complex II-dependent endoplasmic reticulum-to-Golgi apparatus vesicular transport in the cytoplasm. Recent advances suggest that cytoplasmic PDCD6 is involved in the regulation of cytoskeletal dynamics and innate immune responses. Additionally, membranous PDCD6 participates in membrane repair through endosomal sorting complex required for transport complex-dependent membrane budding. Interestingly, extracellular vesicles are rich in PDCD6. Moreover, abnormal expression of PDCD6 is closely associated with many diseases, especially cancer. PDCD6 is therefore a multifaceted but pivotal protein in vivo. To gain a more comprehensive understanding of PDCD6 functions and to focus and stimulate PDCD6 research, this review summarizes key developments in its role in different subcellular compartments, processes, and pathologies.

Both intrinsic and microenvironmental factors contribute to the regulation of stem cell quiescence.

Precise regulation of stem cell quiescence is essential for tissue development and homeostasis. Therefore, its aberrant regulation is intimately correlated with various human diseases. However, the detailed mechanisms of stem cell quiescence and its specific role in the pathogenesis of various diseases remain to be determined. Recent studies have revealed that the intrinsic and microenvironmental factors are the potential candidates responsible for the orderly switch between the dormant and activated states of stem cells. In addition, defects in signaling pathways related to internal and external factors of stem cells might contribute to the initiation and development of diseases by altering the dormancy of stem cells. In this review, we focus on the mechanisms underlying stem cell quiescence, especially the involvement of intrinsic and microenvironmental factors. In addition, we discuss the relationship between the anomalies of stem cell quiescence and related diseases, hopefully providing therapeutic insights for developing novel treatments.

Hypoxia-mediated attenuation of EGLN2 inhibition of the NF-κB signaling pathway leads to the formation of a loop between HIF-1α and MUC1-C promoting chemoresistance in bladder cancer.

The expression pattern of MUC1-C in tumors is closely linked to tumor progression; however, its specific mechanism remains unclear. The expression of MUC1-C in cancer and adjacent normal tissues was detected using immunohistochemistry and Western blot. The IC50 of cells to gemcitabine was determined using the CCK8 assay. The effects of hypoxia and MUC1-C on the behavioral and metabolic characteristics of bladder cancer cells were investigated. Gene expression was assessed through Western blot and polymerase chain reaction. The relationship between the genes was analyzed by co-immunoprecipitation, immunofluorescence and Western blot. Finally, the role of the EGLN2 and NF-κB signaling pathways in the interaction between MUC1-C and hypoxia-inducible factor-1α (HIF-1α) was investigated. MUC1-C expression is significantly higher in bladder cancer tissues than in adjacent normal tissues, particularly in large-volume tumors, and is closely correlated with clinical features such as tumor grade. Tumor volume-mediated hypoxia resulted in increased expression of MUC1-C and HIF-1α in bladder cancer cells. Under stimulation of hypoxia, the inhibitory effect of EGLN2 on the NF-κB signaling pathway was weakened, allowing NF-κB to promote the positive feedback formation of MUC1-C and HIF-1α. Simultaneously, EGLN2-mediated degradation of HIF-1α was reduced. This ultimately led to elevated HIF-1α-mediated downstream gene expression, promoting increased glucose uptake and glycolysis, and ultimately resulting in heightened chemotherapy resistance and malignancy.

Superoxide Photoproduction from Wetland Plant-Derived Dissolved Organic Matter: Implications for Biogeochemical Impacts of Plant Invasion.

Although the impacts of exotic wetland plant invasions on native biodiversity, landscape features, and carbon-nitrogen cycles are well appreciated, biogeochemical consequences posed by ecological competition, such as the heterogeneity of dissolved organic matter (DOM) from plant detritus and its impact on the formation of reactive oxygen species, are poorly understood. Thus, this study delves into O2•- photogeneration potential of DOM derived from three different parts (stem, leaf, and panicle) of invasive Spartina alterniflora (SA) and native Phragmites australis (PA). It is found that DOM from the leaves of SA and the panicles of PA has a superior ability to produce O2•-. With more stable aromatic structures and a higher proportion of sulfur-containing organic compounds, SA-derived DOM generally yields more O2•- than that derived from PA. UVA exposure enhances the leaching of diverse DOM molecules from plant detritus. Based on the reported monitoring data and our findings, the invasion of SA is estimated to approximately double the concentration of O2•- in the surrounding water bodies. This study can help to predict the underlying biogeochemical impacts from the perspective of aquatic photochemistry in future scenarios of plant invasion, seawater intrusion, wetland degradation, and elevated solar UV radiation.

Comparative evaluation of reproductive organ-preserving versus standard radical cystectomy in female: a meta-analysis and systematic review of perioperative, oncological, and functional outcomes.

BACKGROUND: To evaluate the perioperative, oncological, and functional outcomes of reproductive organ-preserving radical cystectomy (ROPRC) compared to standard radical cystectomy (SRC) in the treatment of female bladder cancer. METHODS: A systematic search was conducted in November 2023 across several scientific databases. We executed a systematic review and cumulative meta-analysis of the primary outcomes of interest, adhering to the PRISMA and AMSTAR guidelines. The study was registered in PROSPERO (CRD42024501522). RESULTS: The meta-analysis included 10 studies with a total of 2015 participants. ROPRC showed a significant reduction in operative time and postoperative fasting period compared to SRC (MD - 45.69, 95% CI - 78.91 ~ - 12.47, p = 0.007, and MD - 0.69, 95% CI - 1.25 ~ - 0.13, p = 0.02, respectively). Functional outcomes, both daytime continence rate (OR 4.94, 95% CI 1.53 ~ 15.91, p = 0.008) and nighttime continence rate (OR 5.91, 95% CI 1.94 ~ 18.01, p = 0.002), and sexual function measured by the Female Sexual Function Index (MD 5.72, 95% CI 0.19 ~ 11.26, p = 0.04), were significantly improved in the ROPRC group. There were no significant differences between ROPRC and SRC in terms of estimated blood loss, length of hospital stay, overall postoperative complications, minor complications or major complications. Oncologically, both procedures showed comparable outcomes with no significant differences in positive surgical margins, tumor recurrence rates, overall survival, cancer-specific survival, recurrence-free survival, or progression-free survival. CONCLUSIONS: ROPRC is a viable and effective alternative to SRC in female bladder cancer patients, offering enhanced functional outcomes and similar oncological safety. These findings suggest that ROPRC can improve the quality of life in female bladder cancer patients without compromising the efficacy of cancer treatment.

Extraperitoneal Versus Intraperitoneal Radical Cystectomy for Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to compare perioperative and oncologic outcomes of extraperitoneal radical cystectomy (EPRC) and transperitoneal radical cystectomy (TPRC). METHODS: A systematical search of multiple scientific databases was performed in September 2022. The systematic review and cumulative meta-analysis of the primary outcomes of interest were performed according to the PRISMA and AMSTAR guidelines and registered in the PROSPERO database (PROSPERO [CRD42022359322]). RESULTS: The review and analysis included eight studies with 989 participants. No significant differences were found between EPRC and TPRC in terms of operation time, estimated blood loss (EBL), hospital length of stay (LOS), or transfusion. A shorter exhaust time (standardized mean difference [SMD] - 0.59; 95 % confidence interval [CI] - 0.97 to 0.21; p = 0.002) and time to liquid intake (SMD, - 0.56; 95 % CI - 1.07 to 0.04; p = 0.03) were associated with EPRC. No clinically meaningful difference was observed in terms of postoperative infection, wound complications, postoperative genitourinary complications, late postoperative complications, early major complications, or late major complications. However, EPRC was related to lower incidences of early postoperative complications (odds ratio [OR], 0.66; 95 % CI 0.51-0.86; p = 0.002), gastrointestinal complications (OR 0.28; 95 % CI 0 0.17-0.46; p < 0.00001), and postoperative ileus (OR 0.38; 95 % CI 0.25-0.59; p < 0.0001). A higher incidence of postoperative lymphocele was associated with EPRC (OR 3.05; 95 % CI 1.13-8.25; p = 0.03). No clinically meaningful difference was found in terms of positive surgical margin (PSM), local recurrence, distant metastasis, or OS. CONCLUSIONS: Although EPRC had a higher incidence of lymphoceles than TPRC, it was found to have similar oncologic outcomes and fewer early complications, particularly in terms of postoperative gastrointestinal complications and ileus. These results suggest that EPRC is a safe option both functionally and oncologically.

EPR Evidence for Mechanistic Diversity of Cu(II)/Peroxygen Oxidation Systems by Tracing the Origin of DMPO Spin Adducts.

Electron paramagnetic resonance (EPR) has been extensively used for the identification of free radicals that are generated from advanced oxidation processes (AOPs) so as to establish the reaction mechanism. However, some misinterpretations or controversies on the identity of detected EPR signals remain in the literature. This study, with Cu(II)-based AOPs as examples, comprehensively investigated the origin of 5,5-dimethyl-l-pyrroline N-oxide (DMPO) adducts in Cu(II) alone, Cu(II)/H2O2, Cu(II)/peroxymonosulfate (PMS), and Cu(II)/peroxydisulfate (PDS) systems. In most Cu(II) systems, DMPO-OH signals can be detected even without any peroxygens, indicating the presence of other origins of this adduct in addition to the genuine spin trapping of •OH by DMPO. According to the formed secondary radical adducts (DMPO-OCH3 from a nonradical process or DMPO-CH2OH from a radical oxidation) derived from methanol quenching, we propose that CuO+, instead of free radicals, is involved in the Cu(II)/PMS system, while •OH is indeed generated in the Cu(II)/H2O2 and Cu(II)/PDS systems under neutral conditions. Notably, 17O-incorporation experiments demonstrate that -OH in the detected DMPO-OH adduct originates 100% from water in the Cu(II) alone system but the amount of -OH is over 99.8% from the oxidant while peroxygens are added. In addition, DMPO-O2- appears only in the Cu(II)/PDS system under highly alkaline conditions and H2O is not involved in superoxide formation.

A prognosis marker MUC1 correlates with metabolism and drug resistance in bladder cancer: a bioinformatics research.

BACKGROUND: MUC1 is a type I transmembrane protein that plays an important role in tumor cell signal transduction. Although current studies have shown that MUC1 is upregulated in bladder cancer (BC), the specific mechanism is still unclear. METHODS: We performed expression analysis, gene set enrichment analysis, survival analysis, immune infiltration analysis, drug sensitivity analysis, and metabolism-related gene expression analysis on TCGA-BLCA, GES31684 and GSE13507. RESULTS: The expression of MUC1 in the tumor and lymphatic metastasis positive samples was significantly increased. Genes related to MUC1 expression were significantly enriched in immune response, ribosomes, exosomes, and energy metabolism. The results of the immune infiltration analysis showed that M1 macrophages in BC with high MUC1 expression were significantly decreased. Expression of MUC1 increases drug resistance in BC patients. In addition, MUC1 increases glycolysis, glucose uptake, and lactate production by inducing metabolic reprogramming. CONCLUSION: MUC1 has a significant effect on the metabolism and immune cell infiltration of BC, which may be the cause of increased drug resistance, and can be used as a molecular target for the diagnosis and treatment of BC.

The Microbial Mechanisms of a Novel Photosensitive Material (Treated Rape Pollen) in Anti-Biofilm Process under Marine Environment.

Marine biofouling is a worldwide problem in coastal areas and affects the maritime industry primarily by attachment of fouling organisms to solid immersed surfaces. Biofilm formation by microbes is the main cause of biofouling. Currently, application of antibacterial materials is an important strategy for preventing bacterial colonization and biofilm formation. A natural three-dimensional carbon skeleton material, TRP (treated rape pollen), attracted our attention owing to its visible-light-driven photocatalytic disinfection property. Based on this, we hypothesized that TRP, which is eco-friendly, would show antifouling performance and could be used for marine antifouling. We then assessed its physiochemical characteristics, oxidant potential, and antifouling ability. The results showed that TRP had excellent photosensitivity and oxidant ability, as well as strong anti-bacterial colonization capability under light-driven conditions. Confocal laser scanning microscopy showed that TRP could disperse pre-established biofilms on stainless steel surfaces in natural seawater. The biodiversity and taxonomic composition of biofilms were significantly altered by TRP (p < 0.05). Moreover, metagenomics analysis showed that functional classes involved in the antioxidant system, environmental stress, glucose−lipid metabolism, and membrane-associated functions were changed after TRP exposure. Co-occurrence model analysis further revealed that TRP markedly increased the complexity of the biofilm microbial network under light irradiation. Taken together, these results demonstrate that TRP with light irradiation can inhibit bacterial colonization and prevent initial biofilm formation. Thus, TRP is a potential nature-based green material for marine antifouling.

A Novel Approach To Display Structural Proteins of Hepatitis C Virus Quasispecies in Patients Reveals a Key Role of E2 HVR1 in Viral Evolution.

Hepatitis C virus (HCV) infection remains a major worldwide health problem despite development of highly effective direct-acting antivirals. HCV rapidly evolves upon acute infection and generates multiple viral variants (quasispecies), leading to immune evasion and persistent viral infection. Identification of epitopes of broadly neutralizing anti-HCV antibodies (nAbs) is critical to guide HCV vaccine development. In this study, we developed a new reverse genetics system for HCV infection based on trans-complementation of viral structural proteins. The HCV genome (JFH1 strain) lacking the structural protein-coding sequence can be efficiently rescued by ectopic expression of core-E1-E2-p7-NS2 (core-NS2) or core-E1-E2-p7 (core-p7) in trans, leading to production of single-round infectious virions designated HCVΔS. JFH1-based HCVΔS can be also rescued by expressing core-NS2 of other HCV genotypes, rendering it an efficient tool to display the structural proteins of HCV strains of interests. Furthermore, we successfully rescued HCVΔS with structural proteins from clinical isolates. Multiple viral structural proteins with different sensitivities to nAbs were identified from a same patient serum, demonstrating the genetic diversity of HCV quasispecies in vivo Interestingly, the structural protein-coding sequences of highly divergent viral quasispecies from the same patient can be clustered based on their hypervariable region 1 (HVR1) in viral envelope protein E2, which critically dictates the sensitivity to neutralizing antibodies. In summary, we developed a novel reverse genetics system that efficiently displays viral structural proteins from HCV clinical isolates, and analysis of quasispecies from the same patient using this system demonstrated that E2 HVR1 is the major determinant of viral evolution in vivoIMPORTANCE A cell culture model that can recapitulate the diversity of HCV quasispecies in patients is important for analysis of neutralizing epitopes and HCV vaccine development. In this study, we developed a new reverse genetics system for HCV infection based on trans-complementation of viral structural proteins (HCVΔS). This system can be used to display structural proteins of HCV strains of multiple genotypes as well as clinical isolates. By using this system, we showed that multiple different HCV structural proteins from a same patient were displayed on HCVΔS. Interestingly, these variant structural proteins within the same patient can be classified according to the sequence of HVR1in E2, which dictates viral sensitivity to nAbs and viral evolution in vivo Our work provided a new tool to study highly divergent HCV quasispecies and shed light on underlying mechanisms driving HCV evolution.

BAG6 is a novel microtubule-binding protein that regulates ciliogenesis by modulating the cell cycle and interacting with γ-tubulin.

Microtubule-binding proteins provide an alternative and vital pathway to the functional diversity of microtubules. Considerable work is still required to understand the complexities of microtubule-associated cellular processes and to identify novel microtubule-binding proteins. In this study, we identify Bcl2-associated athanogene cochaperone 6 (BAG6) as a novel microtubule-binding protein and reveal that it is crucial for primary ciliogenesis. By immunofluorescence we show that BAG6 largely colocalizes with intracellular microtubules and by co-immunoprecipitation we demonstated that it can interact with α-tubulin. Additionally, both the UBL and BAG domains of BAG6 are indispensable for its interaction with α-tubulin. Moreover, the assembly of primary cilia in RPE-1 cells is significantly inhibited upon the depletion of BAG6. Notably, BAG6 inhibition leads to an abnormal G0/G1 transition during the cell cycle. In addition, BAG6 colocalizes and interactes with the centrosomal protein γ-tubulin, suggesting that BAG6 might regulate primary ciliogenesis through its action in centrosomal function. Collectively, our findings suggest that BAG6 is a novel microtubule-bindng protein crucial for primary ciliogenesis.

A Nanoparticle-Based Hepatitis C Virus Vaccine With Enhanced Potency.

Despite the emergence of new direct-acting antivirals, hepatitis C virus (HCV) chronic infection and its consequent fibrosis and hepatocarcinoma remain a significant burden for public health, thus requiring an effective preventive vaccine. Our group previously showed that a subunit vaccine based on recombinant soluble E2 (sE2) can induce broadly neutralizing antibodies. To improve the immunogenicity of sE2, we designed and produced a fusion protein (sE2-ferritin) comprising sE2 and a ferritin unit in Drosophila S2 cells, which self-assembled into a nanoparticle with sE2 displayed on the surface. The sE2 moiety on the sE2-ferritin nanoparticle not only had nearly natural conformation but also had better affinities than the unfused sE2 to neutralizing antibodies, receptor, and patient serum. Mouse immunization studies showed that sE2-ferritin was more potent than sE2 in inducing anti-HCV broadly neutralizing antibodies. Our results demonstrate that sE2-ferritin is a vaccine candidate superior to previously developed sE2, providing a new possibility for controlling HCV.

Genetic Analysis of Serum-Derived Defective Hepatitis C Virus Genomes Revealed Novel Viral cis Elements for Virus Replication and Assembly.

Defective viral genomes (DVGs) of hepatitis C virus (HCV) exist, but their biological significances have not been thoroughly investigated. Here, we analyzed HCV DVGs circulating in patient sera that possess deletions in the structural protein-encoding region. About 30% of 41 HCV clinical isolates possess DVGs that originated from the full-length genome in the same patients. No correlation between DVGs, viremia, and alanine aminotransferase (ALT) levels was found. Sequencing analysis of DVGs revealed the existence of deletion hot spots, with upstream sites in E1 and downstream sites in E2 and NS2. Interestingly, the coding sequences for the core protein and the C-terminal protease domain of NS2 were always intact in DVGs despite the fact that both proteins are dispensable for HCV genome replication. Mechanistic studies showed that transmembrane segment 3 (TMS3) of NS2, located immediately upstream of its protease domain, was required for the cleavage of NS2-NS3 and the replication of DVGs. Moreover, we identified a highly conserved secondary structure (SL750) within the core domain 2-coding region that is critical for HCV genome packaging. In summary, our analysis of serum-derived HCV DVGs revealed novel viral cis elements that play important roles in virus replication and assembly.IMPORTANCE HCV DVGs have been identified in vivo and in vitro, but their biogenesis and physiological significances remain elusive. In addition, a conventional packaging signal has not yet been identified on the HCV RNA genome, and mechanisms underlying the specificity in the encapsidation of the HCV genome into infectious particles remain to be uncovered. Here, we identified new viral cis elements critical for the HCV life cycle by determining genetic constraints that define the boundary of serum-derived HCV DVGs. We found that transmembrane segment 3 of NS2, located immediately upstream of its protease domain, was required for the cleavage of NS2-NS3 and the replication of DVGs. We identified a highly conserved secondary structure (SL750) within the core-coding region that is critical for HCV genome packaging. In summary, our analysis of serum-derived HCV DVGs revealed previously unexpected novel cis elements critical for HCV replication and morphogenesis.

A novel strategy to develop a robust infectious hepatitis C virus cell culture system directly from a clinical isolate.

Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases. Progress in the HCV field was greatly enhanced by constructing infectious cDNA clone of JFH-1. Since then, JFH-1-based intra- and intergenotypic recombinants have been developed, and this permitted the study of vaccines and antiviral inhibitors for all genotypes. Recently, highly efficient HCV culture systems have been established by using consensus sequence-based clones. We developed a novel strategy to construct infectious HCV cDNA clone by combining functional screening of sequences directly from a genotype 2a clinical isolate (PR63) and cell culture adaptation. Using JFH-1 cDNA as the starting backbone, we sequentially replaced the JFH-1 fragments with a sequence from the pools of PR63 sequences. Through engineering adaptive mutations that improve HCV infectivity, we finally established a full-length cell culture-derived infectious clone of PR63, named PR63cc, that could efficiently produce virus particles in Huh7-derived cells, with peak titers of 1.6 × 10(5) focus-forming units/ml. The PR63cc could be neutralized by an anti-E2 antibody and inhibited by antiviral agents but appeared more resistant to an NS5A inhibitor than JFH-1. In summary, we developed a new approach to construct an infectious HCV cDNA clone that can produce viruses efficiently in cell culture. This approach could be applied to other viral isolates, with potential implications for individualized treatments of HCV patients.

Formation and function of multiciliated cells.

In vertebrates, multiciliated cells (MCCs) are terminally differentiated cells that line the airway tracts, brain ventricles, and reproductive ducts. Each MCC contains dozens to hundreds of motile cilia that beat in a synchronized manner to drive fluid flow across epithelia, the dysfunction of which is associated with a group of human diseases referred to as motile ciliopathies, such as primary cilia dyskinesia. Given the dynamic and complex process of multiciliogenesis, the biological events essential for forming multiple motile cilia are comparatively unelucidated. Thanks to advancements in genetic tools, omics technologies, and structural biology, significant progress has been achieved in the past decade in understanding the molecular mechanism underlying the regulation of multiple motile cilia formation. In this review, we discuss recent studies with ex vivo culture MCC and animal models, summarize current knowledge of multiciliogenesis, and particularly highlight recent advances and their implications.

Effect of n-C-S-H on Hydration and Reinforcement of Mineral Powder-Cement System at Low Temperatures.

This paper investigated the effect of nano-calcium silicate hydrate (n-C-S-H) on the early compressive strength of mineral powder-cement systems under low-temperature curing conditions (5 °C). The hydration mechanism of n-C-S-H in the mineral powder-cement system at different dosages was analyzed by combining it with XRD, DSC-TG, MIP, and other techniques. The results show that n-C-S-H significantly enhances the early compressive strength of the mineral powder-cement system under low-temperature curing conditions, with optimal results observed at a dosage of 1.0% (mass fraction). The XRD, DSC-TG, and MIP tests reveal that n-C-S-H promotes the hydration of the mineral powder cement, accelerates the generation rate of hydration products, reduces the porosity of the hardened mineral powder-cement slurry, and improves the system's density.

Device-assisted intravesical chemotherapy versus bacillus Calmette-Guerin for intermediate or high-risk non-muscle invasive bladder cancer: a systematic reviewer and meta-analysis.

PURPOSE: To investigate the effectiveness and safety of device-assisted intravesical chemotherapy compared to Bacillus Calmette-Guerin (BCG) in the treatment of patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: In February 2023, a systematic search was conducted on the PubMed, Cochrane, and Embase databases. Following the PRISMA guidelines, a systematic review and meta-analysis of the primary outcomes of interest were performed. The review was prospectively registered on PROSPERO under the registration number CRD42023398559. RESULTS: A total of 10 studies involving 1160 patients were included. The results of the meta-analysis showed that compared to BCG, device-assisted chemotherapy had a lower recurrence rate (OR: 0.63, 95% CI: 0.48-0.84, p = 0.001), longer recurrence-free survival (OR: 0.64, 95% CI: 0.47-0.88, p = 0.006), and lower incidence of fever (OR: 0.18, 95% CI: 0.08-0.44, p = 0.0002). However, no significant differences were observed between the two groups in terms of progression, overall survival, progression-free survival, disease-free survival, overall adverse events, serious adverse events, hematuria, allergy, and general discomfort. Subgroup analysis revealed that neither chemohyperthermia (CHT) nor electromotive drug administration (EMDA) showed statistically significant differences in oncological outcomes compared to BCG. Regarding adverse events, both CHT and EMDA groups showed lower rates of fever compared to the BCG group (OR: 0.26, 95% CI: 0.10-0.67, p = 0.005, and OR: 0.14, 95% CI: 0.05-0.37, p < 0.0001, respectively). No significant differences were observed in the remaining adverse events between either the CHT or EMDA group and the BCG group. CONCLUSION: Device-assisted intravesical chemotherapy appears to be a safe and viable alternative to BCG for patients with intermediate and high-risk NMIBC, showing comparable oncological outcomes and adverse events.

Transcriptome analysis of differentially expressed genes in rice seedling leaves under different nitrate treatments on resistance to bacterial leaf blight.

Nitrogen (N), as one of the most abundant mineral elements in rice, not only is the primary limiting factor for rice yield, but also impacts plant disease resistance by modulating plant morphology, regulating biochemical characteristics, as well as enhancing metabolic processes. Bacterial blight, a severe bacterial disease caused by Xanthomonas oryzae pv. oryzae (Xoo), significantly impairing rice yield and quality. Previous studies have shown that moderate application of nitrate nitrogen can improve plant disease resistance. However, further exploration is urgently required to investigate the involvement of the nitrate nitrogen signaling pathway in conferring resistance against bacterial leaf blight. In this study, we employed transcriptome sequencing to analyze the differentially expressed genes under various concentrations of nitrate supply duringrice bacterial blight infection. Our research reveals that nitrate nitrogen supply influences rice resistance to bacterial leaf blight. Through transcriptomic profiling of rice leaves inoculated under different nitrate nitrogen concentrations, we identified 4815 differentially expressed genes (DEGs) among four comparison groups, with notable differences in DEG enrichment between low and high nitrate nitrogen conditions, with some members of the NPF family implicated and we preliminarily elucidated the molecular regulatory network in which nitrate nitrogen participates in bacterial leaf blight resistance. Our findings provide a novel insight into a mechanism involving the nitrate nitrogen drive wider defense in rice.

HER2 Affects the Biological Behaviours of Bladder Cancer Cells and is Closely Associated with the Progression and Prognosis of Bladder Cancer.

OBJECTIVE: Given the growing recognition of molecular targets in oncology, this study aimed to examine the expression pattern and prognostic significance of human epidermal growth factor receptor-2 (HER2) in bladder cancer (BC) and the effects of HER2 knockdown on the biological behaviours of BC cells. METHODS: A total of 126 BC tissue samples and 20 samples of normal bladder mucosa were collected for immunohistochemical staining. The clinicopathological data were obtained from patients with BC. HER2 was knocked down in two BC cell lines (T24 and 5637) using lentiviral delivery of short hairpin RNA (shRNA), referred to as shHER2, with a blank control group (shCtrl) for comparison. A range of assays, including cell counting kit-8, colony formation, transwell, wound healing, and flow cytometry, were performed to assess the effects of HER2 knockdown on the proliferation, migration, cell cycle entry, and apoptosis of BC cells. RESULTS: The study revealed a notable overexpression rate of HER2 in BC tissues (57.1%) than in normal bladder mucosa (0%) (p < 0.001). HER2 overexpression was associated with tumour number (p < 0.0001), pathological grade (p < 0.0001), lymph node metastasis (p = 0.040), distant metastasis (p = 0.037), overall survival (p = 0.0006), and recurrence-free survival (RFS) (p < 0.0001). In contrast, no significant association was identified between HER2 overexpression and demographic factors such as sex (p = 0.687), age (p = 0.430), tumour size (p = 0.053), or T stage (p = 0.134). Furthermore, the experimental knockdown of HER2 in BC cells inhibited the proliferation and migration and promoted their apoptosis and cell cycle arrest in the G1 phase. CONCLUSIONS: The findings suggest HER2 as a potential therapeutic target for BC and underscore the promise of developing anti-HER2-targeting strategies for BC management.