Multi-Omics Study on the Molecular Mechanisms of Tetraodon Nigroviridis Resistance to Exogenous Vibrio Parahaemolyticus Infection

Vibrio parahaemolyticus is an important marine pathogen that causes inflammation and even death in teleost fishes. It has brought significant economic losses to the aquaculture industry as well as high risks to the sustainable development of marine fisheries. In the present study, the fish Tetraodon nigroviridis and the bacterial pathogen Vibrio parahaemolyticus were used to explore the molecular mechanisms underlying the immune response of T. nigroviridis to V. parahaemolyticus exogenous infection. The microRNA (miRNA)–mRNA–protein omics and corresponding experimental validation, followed by comparative analysis, revealed several differentially expressed genes involved in various components of the immune system, including the following: complement system, chemokines, lysosomes, phagocytes, B-cell receptor signaling pathway, T-cell receptor signaling pathway, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, and phospholipid metabolism, among others. Especially, the complements component 3 (C3) gene and protein expression levels were significantly higher after V. parahaemolyticus infection, and miRNAs targeting C3, including mir-6089-y, mir-460-y, and mir-1584-x, were significantly down-regulated. The gene and protein expression levels of complement 1 subunit qA (C1qA) were significantly down-regulated, while mir-203 targeting C1qA was significantly up-regulated. Overall, four complement genes (C1qA, IG, C3, and C5), which are key genes in the classical pathway of complement system activation for inflammatory response, were identified. Evolutionary analysis suggested that T. nigroviridis, acquired an increased ability to recognize pathogens by evolving a more complex complement system than terrestrial vertebrates. In addition, quantitative real-time polymerase chain reaction showed high consistency with the obtained multi-omics results, indicating the reliability of the sequencing data generated in the present study. In summary, our findings can serve as a fundamental basis for further in-depth multi-omics studies on the inflammatory processes of aquatic pathogens hindering fish sustainable production

Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma

This review systematically examines gender differences in hepatocellular carcinoma (HCC), identifying the influence of sex hormones, genetic variance, and environmental factors on the disease’s epidemiology and treatment outcomes. Recognizing the liver as a sexually dimorphic organ, we highlight how gender-specific risk factors, such as alcohol consumption and obesity, contribute differently to hepatocarcinogenesis in men and women. We explore molecular mechanisms, including the differential expression of androgen and estrogen receptors, which mediate diverse pathways in tumor biology such as cell proliferation, apoptosis, and DNA repair. Our analysis underscores the critical need for gender-specific research in liver cancer, from molecular studies to clinical trials, to improve diagnostic accuracy and therapeutic effectiveness. By incorporating a gender perspective into all facets of liver cancer research, we advocate for a more precise and personalized approach to cancer treatment that acknowledges gender as a significant factor in both the progression of HCC and its response to treatment. This review aims to foster a deeper understanding of the biological and molecular bases of gender differences in HCC and to promote the development of tailored interventions that enhance outcomes for all patients

Comparison of upfront haploidentical hematopoietic stem cell transplantation and salvage haploidentical hematopoietic stem cell transplantation after immunosuppressive therapy in children with acquired severe aplastic anemia - a multicenter study

BackgroundFor children with severe aplastic anemia, if the first immunosuppressive therapy (IST) fails, it is not recommended to choose a second IST. Therefore, for patients without matched sibling donor (MSD) and matched unrelated donor (MUD), haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) can be chosen as a salvage treatment. This article aims to explore the comparison between upfront Haplo-HSCT and salvage Haplo-HSCT after IST.Methods29 patients received salvage Haplo-HSCT, and 50 patients received upfront Haplo-HSCT. The two groups received Bu (Busulfan, 3.2mg/kg/d*2d on days -9 to-8), CY (Cyclophosphamide, 60mg/kg/d*2d on days -4 to-3), Flu (fludarabine, 40mg/m2/d*5d on days -9 to -5) and rabbit ATG (Anti-thymocyte globulin, total dose 10mg/kg divided into days -4 to -2).ResultsThe OS of the salvage Haplo-HSCT group showed no difference to the upfront Haplo-HSCT group (80.2 ± 8.0% vs. 88.7 ± 4.8%, p=0.37). The FFS of the salvage Haplo-HSCT group also showed no difference to the frontline Haplo-HSCT group (75 ± 8.2% vs. 84.9 ± 5.3%, p=0.27). There was no significant difference in the incidence of other complications after transplantation between the two groups, except for thrombotic microangiopathy (TMA). In the grouping analysis by graft source, the incidence of II-IV aGVHD in patients using PBSC ± BM+UCB was lower than that in the PBSC ± BM group (p=0.010)ConclusionUpfront Haplo-HSCT and salvage Haplo-HSCT after IST in children with acquired severe aplastic anemia have similar survival outcomes. However, the risk of TMA increases after salvage Haplo-HSCT. This article provides some reference value for the treatment selection of patients. In addition, co-transplantation of umbilical cord blood may reduce the incidence of GVHD

Differential expression profiling of spleen microRNAs in response to two distinct type II interferons in Tetraodon nigroviridis.

MicroRNAs are endogenous, small non-coding RNAs approximately 18-26 nucleotides in length that regulate target gene expression at the post-transcription level. Interferon-γ (IFN-γ) is a Th1 cytokine that is involved in both the innate and adaptive immune responses. We previously identified two IFN-γ genes in green-spotted puffer fish (Tetraodon nigroviridis). To determine whether miRNAs participate in IFN-γ-related immune responses, T. nigroviridis spleen cells were treated with recombinant IFN-γ isoforms, and a Solexa high-throughput sequencing method was used to identify miRNAs. In total, 1,556, 1,538 and 1,573 miRNAs were found in the three samples, and differentially expressed miRNAs were determined. In total, 398 miRNAs were differentially expressed after rIFN-γ1 treatment, and 438 miRNAs were differentially expressed after rIFN-γ2 treatment; additionally, 403 miRNAs were differentially expressed between the treatment groups. Ten differentially expressed miRNAs were chosen for validation using qRT-PCR. Target genes for the differentially expressed miRNAs were predicted, and GO and KEGG analyses were performed. This study provides basic knowledge regarding fish IFN-γ-induced miRNAs and offers clues for further studies into the mechanisms underlying fish IFN-γ-mediated immune responses

A new synonym of Enkianthus perulatus (Ericaceae) in East Asia, based on morphological and molecular evidence

Enkianthus calophyllus was once treated as a synonym of E. serrulatus. However, field observations indicate that E. calophyllus is distinct from E. serrulatus but resembles E. perulatus in flowers, leaves, fruits and seeds. Hence, a taxonomic revision of these species was conducted based on morphological comparisons of flowers, leaves, fruits and seeds, as well as molecular analyses of nuclear ribosomal internal transcribed spacer (nrITS) and six plastid DNA markers (psbA-trnH, rpl32-trnL, trnL-trnF, rps16-trnQ, psbJ-petA and matK). The morphological and molecular results reject the synonymization of E. calophyllus with E. serrulatus, and instead show it to be placed in a clade with E. perulatus. Based on molecular evidence and a reassessment of the morphology we synonymize E. calophyllus with the older name E. perulatus

Diabetes Mellitus and COVID-19: Associations and Possible Mechanisms

Coronavirus disease 2019 (COVID-19) is a recently emerged disease with formidable infectivity and high mortality. Emerging data suggest that diabetes is one of the most prevalent comorbidities in patients with COVID-19. Although their causal relationship has not yet been investigated, preexisting diabetes can be considered as a risk factor for the adverse outcomes of COVID-19. Proinflammatory state, attenuation of the innate immune response, possibly increased level of ACE2, along with vascular dysfunction, and prothrombotic state in people with diabetes probably contribute to higher susceptibility for SARS-CoV-2 infection and worsened prognosis. On the other hand, activated inflammation, islet damage induced by virus infection, and treatment with glucocorticoids could, in turn, result in impaired glucose regulation in people with diabetes, thus working as an amplification loop to aggravate the disease. Therefore, glycemic management in people with COVID-19, especially in those with severe illness, is of considerable importance. The insights may help to reduce the fatality in the effort against COVID-19

Small RNA tags matched to the genome by SOAP.

<p>The figure shows the expression and genomic distribution of miRNAs identified in the (A) Sp-con, (B) Sp-γ1, (C) SP-γ2 groups.</p

Normalized read counts for selected miRNAs.

<p>(A): Normalized read counts for miR-124b-3p, miR-142-3p, miR-145b, miR-17, miR-29d-3p, and miR-346 following IFNγ1 treatment, compared to the control group. (B): Normalized read counts of miR-106a-3p, miR-124b-3p, miR-132-3p, miR-17, miR-223-5p, and miR-378 following IFNγ2 treatment, compared to the control group.</p

Log2-ratio scatter plot of the differentially expressed miRNAs between (A) the Sp-con and Sp-γ1 groups, (B) the Sp-con and Sp-γ2 groups, and (C) the Sp-γ1 and SP-γ2 groups.

<p>Each point in the figure represents a miRNA. The X and Y axes show the expression levels in the two samples. The red points represent miRNAs with a ratio >2, the blue points represent miRNAs with a ratio >1/2 and ≤2, and the green points represent miRNAs with a ratio ≤1/2.</p