Nursing Care of Postoperative Supplementary Surgery for Patients with Positive or High-level CIN after Conization Using CINIII Cold Knife.

Objective: This study aimed to evaluate the effectiveness of personalized nursing care in postoperative supplementary surgery for cervical intraepithelial neoplasia grade III (CIN III) patients with positive or high-grade CIN margins after cold knife conization at the Fourth Hospital of Hebei Medical University in Shijiazhuang, China. The primary objective was to assess the impact of personalized nursing intervention on postoperative outcomes, including psychological well-being, self-care ability, quality of life, and postoperative complications. Methods: A total of 106 patients undergoing additional surgery after CIN III cold knife conization at the Fourth Hospital of Hebei Medical University from January 2020 to April 2023 were randomly allocated into an observation group (n=53) and a control group (n=53) using a random number table method. Detailed information on the randomization process, including stratification factors and blinding procedures, is provided. The observation group received personalized nursing intervention, while the control group received routine nursing. The retreatment methods, including repeat cold knife conization, total hysterectomy, and radical cervical cancer surgery, were analyzed using appropriate statistical methods. Statistical software was employed for data analysis. Results: Pathological results post-cold knife conization revealed positive margins in 76 cases and pathological upgrades in 30 cases. The consistency rate between post-cold knife conization and post-retreatment pathological results was 75.47%. After the intervention, the observation group exhibited significantly lower SAS and SDS scores and significantly higher ESCA and WHO QOL-100 scores compared to the control group (P < .05), indicating improved psychological well-being and quality of life. The total incidence of postoperative complications in the observation group was 5.66%, significantly lower than in the control group (P < .05). Conclusion: Personalized nursing care in postoperative supplementary surgery for CIN III patients with positive or high-grade CIN margins at the Fourth Hospital of Hebei Medical University improves psychological well-being, self-care ability, quality of life, and reduces postoperative complications. The findings underscore the importance of tailored nursing interventions in enhancing patient outcomes. The inclusion of detailed patient demographics and methodological transparency enhances the generalizability and reliability of the study findings beyond the study setting.

Genomic Analysis of the Glutathione S-Transferase Family in Pear (Pyrus communis) and Functional Identification of PcGST57 in Anthocyanin Accumulation.

Anthocyanin accumulation in vacuoles results in red coloration in pear peels. Glutathione S-transferase (GST) proteins have emerged as important regulators of anthocyanin accumulation. Here, a total of 57 PcGST genes were identified in the European pear 'Bartlett' (Pyrus communis) through comprehensive genomic analysis. Phylogenetic analysis showed that PcGST genes were divided into 10 subfamilies. The gene structure, chromosomal localization, collinearity relationship, cis-elements in the promoter region, and conserved motifs of PcGST genes were analyzed. Further research indicated that glutamic acid (Glu) can significantly improve anthocyanin accumulation in pear peels. RNA sequencing (RNA-seq) analysis showed that Glu induced the expression of most PcGST genes, among which PcGST57 was most significantly induced. Further phylogenetic analysis indicated that PcGST57 was closely related to GST genes identified in other species, which were involved in anthocyanin accumulation. Transcript analysis indicated that PcGST57 was expressed in various tissues, other than flesh, and associated with peel coloration at different developmental stages. Silencing of PcGST57 by virus-induced gene silencing (VIGS) inhibited the expression of PcGST57 and reduced the anthocyanin content in pear fruit. In contrast, overexpression of PcGST57 improved anthocyanin accumulation. Collectively, our results demonstrated that PcGST57 was involved in anthocyanin accumulation in pear and provided candidate genes for red pear breeding.

Expression analysis of tissue factor pathway inhibitors TFPI-1 and TFPI-2 in Paralichthys olivaceus and antibacterial and anticancer activity of derived peptides.

Tissue factor pathway inhibitors (TFPI), including TFPI-1 and TFPI-2, are Kunitz-type serine protease inhibitors that mainly inhibit the blood coagulation induced by tissue factors. Previous reports on teleost proved TFPI play important roles in innate immunity. In this study, two TFPI (PoTFPI-1 and PoTFPI-2) molecules from Japanese flounder (Paralichthys olivaceus) were analyzed and characterized for their expression patterns, antibacterial and anticancer activities of the C-terminal derived peptides. Quantitative real time RT-PCR analysis shows that constitutive PoTFPI-1 expression occurred, in increasing order, in the brain, muscle, spleen, gills, head kidney, blood, intestine, heart, and liver; PoTFPI-2 was expressed, in increasing order, in the brain, gills, head kidney, muscle, intestine, spleen, liver, heart, and blood. Under the stimulation of fish pathogens, both PoTFPI-1 and PoTFPI-2 expressions increased significantly in a manner that depended on the pathogens, tissue type, and infection stage. Furthermore, C-terminal peptides TP25 and TP26, derived from PoTFPI-1 and PoTFPI-2, respectively, were synthesized and proved to be active against Micrococcus luteus (for TP25 and TP26) and Staphylococcus aureus (for TP25) via retardation effects on bacterial nucleic acids. In addition, TP25 and TP26 also displayed significant inhibitory effects on human colon cancer cell line HT-29. These results reveal that both PoTFPI-1 and PoTFPI-2 play important roles in host innate immunity. The antibacterial activity and anticancer cells function of TP25 and TP26 will add new insights into the roles of teleost TFPI.

Prediction model for the onset risk of impaired fasting glucose: a 10-year longitudinal retrospective cohort health check-up study.

BACKGROUND: Impaired fasting glucose (IFG) is a prediabetic condition. Considering that the clinical symptoms of IFG are inconspicuous, these tend to be easily ignored by individuals, leading to conversion to diabetes mellitus (DM). In this study, we established a prediction model for the onset risk of IFG in the Chongqing health check-up population to provide a reference for prevention in a health check-up cohort. METHODS: We conducted a retrospective longitudinal cohort study in Chongqing, China from January 2009 to December 2019. The qualified subjects were more than 20 years old and had more than two health check-ups. After following the inclusion and exclusion criteria, the cohort population was randomly divided into a training set and a test set at a ratio of 7:3. We first selected the predictor variables through the univariate generalized estimation equation (GEE), and then the training set was used to establish the IFG risk model based on multivariate GEE. Finally, the sensitivity, specificity, and receiver operating characteristic curves were used to verify the performance of the model. RESULTS: A total of 4,926 subjects were included in this study, with an average of 3.87 check-up records, including 2,634 males and 2,292 females. There were 442 IFG cases during the follow-up period, including 286 men and 156 women. The incidence density was 26.88/1000 person-years for men and 18.53/1000 person-years for women (P<0.001). The predictor variables of our prediction model include male (relative risk (RR) =1.422, 95 % confidence interval (CI): 0.923-2.193, P=0.3849), age (RR=1.030, 95 %CI: 1.016-1.044, P<0.0001), waist circumference (RR=1.005, 95 %CI: 0.999-1.012, P=0.0975), systolic blood pressure (RR=1.004, 95 %CI: 0.993-1.016, P=0.4712), diastolic blood pressure (RR=1.023, 95 %CI: 1.005-1.041, P=0.0106), obesity (RR=1.797, 95 %CI: 1.126-2.867, P=0.0140), triglycerides (RR=1.107, 95 %CI: 0.943-1.299, P=0.2127), high-density lipoprotein cholesterol (RR=0.992, 95 %CI: 0.476-2.063, P=0.9818), low-density lipoprotein cholesterol (RR=1.793, 95 %CI: 1.085-2.963, P=0.0228), blood urea (RR=1.142, 95 %CI: 1.022-1.276, P=0.0192), serum uric acid (RR=1.004, 95 %CI: 1.002-1.005, P=0.0003), total cholesterol (RR=0.674, 95 %CI: 0.403-1.128, P=0.1331), and serum creatinine levels (RR=0.960, 95 %CI: 0.945-0.976, P<0.0001). The area under the receiver operating characteristic curve (AUC) in the training set was 0.740 (95 %CI: 0.712-0.768), and the AUC in the test set was 0.751 (95 %CI: 0.714-0.817). CONCLUSIONS: The prediction model for the onset risk of IFG had good predictive ability in the health check-up cohort.

TC26, a teleost TFPI-1 derived antibacterial peptide that induces degradation of bacterial nucleic acids and inhibits bacterial infection in vivo.

At present, several reports have indicated that the C-terminal peptides of tissue factor pathway inhibitor 1 (TFPI-1) were active antibacterial peptides. However, the functions of TFPI-1 C-terminal peptides in teleost are still very limited. In this study, a C-terminal peptide, TC26 (with 26 amino acids), derived from common carp (Cyprinus carpio) TFPI-1, was synthesized and investigated for its antibacterial spectrum, action mechanism, as well as the in vivo effects on bacterial invasion. Our results showed that TC26 was active against Gram-positive bacteria Micrococcus luteus and Staphylococcus aureus, as well as Gram-negative bacterium Vibrio vulnificus. TC26 treatment facilitated the bactericidal process of erythromycin by enhancing the out-membrane permeability of V. vulnificus. During the bactericidal process, TC26 killed the target bacterial cells Vibrio vulnificus, by destroying cell membrane integrity, penetrating into the cytoplasm and inducing degradation of genomic DNA and total RNA. In vivo study showed that administration of turbot with TC26 before bacterial infection significantly reduced pathogen dissemination and replication in tissues. These results indicated that TC26 is a novel and active antibacterial peptide and may play a vital role in fighting pathogenic infection in aquaculture.

Serum biochemistry, liver histology and transcriptome profiling of bighead carp Aristichthys nobilis following different dietary protein levels.

Dietary protein plays a major role in determining the rate of fish growth and overall health. Given that the liver is an important organ for metabolism and detoxification, we hypothesized that optimal dietary protein levels may benefit liver function. Herein, we investigated the effects of dietary protein level on serum biochemistry, liver histology and transcriptome profiling of juvenile bighead carp Aristichthys nobilis fed for 8 weeks on a diet supplemented with high protein (HP, 40%), low protein (LP, 24%) or optimal protein (OP, 32%; controls). The results revealed a significant change in liver morphology in LP and HP groups compared with the OP group, coupled with increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity. RNA sequencing (RNA-Seq) analysis of the liver transcriptome yielded 47 million high-quality reads using an Illumina platform, which were de novo assembled into 80,777 unique transcript fragments (unigenes) with an average length of 1021 bp. Subsequent bioinformatics analysis identified 878 and 733 differentially expressed unigenes (DEGs) in liver in response to LP and HP diets, respectively. KEGG enrichment analysis of DEGs identified immune and metabolism-related pathways, including Toll-like receptor signaling, PI3K-Akt signaling, NF-κB signaling, complement and coagulation, peroxisome, nitrogen metabolism, PPAR signaling, and glycolysis and gluconeogenesis pathways. Transcriptome profiling results were validated by quantitative real-time PCR for 16 selected DEGs. The findings expand our understanding of the molecular mechanisms underlying the effects of dietary protein level on liver function in bighead carp.

Chromosome instability drives phenotypic switching to metastasis.

Chromosome instability (CIN) is the most striking feature of human cancers. However, how CIN drives tumor progression to metastasis remains elusive. Here we studied the role of chromosome content changes in generating the phenotypic dynamics that are required for metastasis. We isolated epithelial and mesenchymal clones from human carcinoma cell lines and showed that the epithelial clones were able to generate mesenchymal variants, which had the potential to further produce epithelial revertants autonomously. The successive acquisition of invasive mesenchymal and then epithelial phenotypes recapitulated the steps in tumor progression to metastasis. Importantly, the generation of mesenchymal variants from clonal epithelial populations was associated with subtle changes in chromosome content, which altered the chromosome transcriptome and influenced the expression of genes encoding intercellular junction (IJ) proteins, whereas the loss of chromosome 10p, which harbors the ZEB1 gene, was frequently detected in epithelial variants generated from mesenchymal clones. Knocking down these IJ genes in epithelial cells induced a mesenchymal phenotype, whereas knocking down the ZEB1 gene in mesenchymal cells induced an epithelial phenotype, demonstrating a causal role of chromosome content changes in phenotypic determination. Thus, our studies suggest a paradigm of tumor metastasis: primary epithelial carcinoma cells that lose chromosomes harboring IJ genes acquire an invasive mesenchymal phenotype, and subsequent chromosome content changes such as loss of 10p in disseminated mesenchymal cells generate epithelial variants, which can be selected for to generate epithelial tumors during metastatic colonization.

Genome-wide characterization of simple sequence repeats in Pyrus bretschneideri and their application in an analysis of genetic diversity in pear.

BACKGROUND: Pear (Pyrus spp.) is an economically important temperate fruit tree worldwide. In the past decade, significant progress has been made in pear molecular genetics based on DNA research, but the number of molecular markers is still quite limited, which hardly satisfies the increasing needs of geneticists and breeders. RESULTS: In this study, a total of 156,396 simple sequence repeat (SSR) loci were identified from a genome sequence of Pyrus bretschneideri 'Dangshansuli'. A total of 101,694 pairs of SSR primers were designed from the SSR loci, and 80,415 of the SSR loci were successfully located on 17 linkage groups (LGs). A total of 534 primer pairs were synthesized and preliminarily screened in four pear cultivars, and of these, 332 primer pairs were selected as clear, stable, and polymorphic SSR markers. Eighteen polymorphic SSR markers were randomly selected from the 332 polymorphic SSR markers in order to perform a further analysis of the genetic diversity among 44 pear cultivars. The 14 European pears and their hybrid materials were clustered into one group (European pear group); 29 Asian pear cultivars were clustered into one group (Asian pear group); and the Zangli pear cultivar 'Deqinli' from Yunnan Province, China, was grouped in an independent group, which suggested that the cultivar 'Deqinli' is a distinct and valuable germplasm resource. The population structure analysis partitioned the 44 cultivars into two populations, Pop 1 and Pop 2. Pop 2 was further divided into two subpopulations. Results from the population structure analysis were generally consistent with the results from the UPGMA cluster analysis. CONCLUSIONS: The results of the present study showed that the use of next-generating sequencing to develop SSR markers is fast and effective, and the developed SSR markers can be utilized by researchers and breeders for future pear improvement.

Chromosome level high-density integrated genetic maps improve the Pyrus bretschneideri 'DangshanSuli' v1.0 genome.

BACKGROUND: Chromosomal level reference genomes provide a crucial foundation for genomics research such as genome-wide association studies (GWAS) and whole genome selection. The chromosomal-level sequences of both the European (Pyrus communis) and Chinese (P. bretschneideri) pear genomes have not been published in public databases so far. RESULTS: To anchor the scaffolds of P. bretschneideri 'DangshanSuli' (DS) v1.0 genome into pseudo-chromosomes, two genetic maps (MH and YM maps) were constructed using half sibling populations of Chinese pear crosses, 'Mantianhong' (MTH) × 'Hongxiangsu' (HXS) and 'Yuluxiang' (YLX) × MTH, from 345 and 162 seedlings, respectively, which were prepared for SNP discovery using genotyping-by-sequencing (GBS) technology. The MH and YM maps, each with 17 linkage groups (LGs), were constructed from 2606 and 2489 SNP markers and spanned 1847 and 1668 cM, respectively, with average marker intervals of 0.7. The two maps were further merged with a previously published genetic map (BD) based on the cross 'Bayuehong' (BYH) × 'Dangshansuli' (DS) to build a new integrated MH-YM-BD map. By using 7757 markers located on the integrated MH-YM-BD map, 898 scaffolds (400.57 Mb) of the DS v1.0 assembly were successfully anchored into 17 pseudo-chromosomes, accounting for 78.8% of the assembled genome size. About 88.31% of them (793 scaffolds) were directionally anchored with two or more markers on the pseudo-chromosomes. Furthermore, the errors in each pseudo-chromosome (especially 1, 5, 7 and 11) were manually corrected and pseudo-chromosomes 1, 5 and 7 were extended by adding 19, 12 and 14 scaffolds respectively in the newly constructed DS v1.1 genome. Synteny analyses revealed that the DS v1.1 genome had high collinearity with the apple genome, and the homologous fragments between pseudo-chromosomes were similar to those found in previous studies. Moreover, the red-skin trait of Asian pear was mapped to an identical locus as identified previously. CONCLUSIONS: The accuracy of DS v1.1 genome was improved by using larger mapping populations and merged genetic map. With more than 400 MB anchored to 17 pseudo-chromosomes, the new DS v1.1 genome provides a critical tool that is essential for studies of pear genetics, genomics and molecular breeding.

Identification of candidate genes involved in the sugar metabolism and accumulation during pear fruit post-harvest ripening of 'Red Clapp's Favorite' (Pyrus communis L.) by transcriptome analysis.

BACKGROUND: Pear (Pyrus spp.) is a popular fruit that is commercially cultivated in most temperate regions. In fruits, sugar metabolism and accumulation are important factors for fruit organoleptic quality. Post-harvest ripening is a special feature of 'Red Clapp's Favorite'. RESULTS: In this study, transcriptome sequencing based on the Illumina platform generated 23.8 - 35.8 million unigenes of nine cDNA libraries constructed using RNAs from the 'Red Clapp's Favorite' pear variety with different treatments, in which 2629 new genes were discovered, and 2121 of them were annotated. A total of 2146 DEGs, 3650 DEGs, 1830 DEGs from each comparison were assembled. Moreover, the gene expression patterns of 8 unigenes related to sugar metabolism revealed by qPCR. The main constituents of soluble sugars were fructose and glucose after pear fruit post-harvest ripening, and five unigenes involved in sugar metabolism were discovered. CONCLUSIONS: Our study not only provides a large-scale assessment of transcriptome resources of 'Red Clapp's Favorite' but also lays the foundation for further research into genes correlated with sugar metabolism.

The genetic locus underlying red foliage and fruit skin traits is mapped to the same location in the two pear bud mutants 'Red Zaosu' and 'Max Red Bartlett'.

BACKGROUND: Red-skinned pears are attractive to consumers because of their aesthetic appeal and the antioxidant-associated health benefits provided by the anthocyanins in their red skin. In China, the 'Red Zaosu' (RZS) red bud mutation of the Zaosu (ZS) pear has been used as a parent in Asian pear breeding to generate new cultivars with crispy red fruit and red tender shoots resembling those of the 'Max Red Bartlett' (MRB) pears. RESULTS: In this study, a segregation ratio of 1:1 was observed between plants with red or green shoots in four families with RZS as the only red shoot gene donor parent, suggesting that the red shoot trait of RZS is associated with a dominant gene. Three markers, In1400-1, In1579-1 and In1579-3, were chosen from 22 pairs of indel primers targeting regions in the vicinity of the previously identified red fruit skin locus of MRB and were able to effectively distinguish the eight red shoot plants from the eight green shoot plants. Linkage analysis indicated that the genetic distance between the two marker loci (In1579-1 and In1579-3) and the red shoot locus of RZS were both 1.4 cM, while the genetic distance between the In1400-1 marker and the red shoot locus was 2.1 cM. The physical position of the red locus in RZS should be in the 368.6 kb candidate interval at the bottom of LG4. CONCLUSIONS: The genetic locus responsible for the red tender shoots of RZS was located in the same interval of the red fruit skin gene of MRB, meaning that the bud mutation loci of RZS and MRB may be the same or adjacent to each other, and the red shoot trait and the red fruit skin trait in RZS may be controlled by the same, or a closely linked locus. As a result, breeders could use red shoots as a morphological marker to select for the red-skinned hybrids from RZS families.

Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent.

Binding of hepatocyte growth factor (HGF) to the receptor tyrosine kinase MET is implicated in the malignant process of multiple cancers, making disruption of this interaction a promising therapeutic strategy. However, targeting MET with bivalent antibodies can mimic HGF agonism via receptor dimerization. To address this limitation, we have developed onartuzumab, an Escherichia coli-derived, humanized, and affinity-matured monovalent monoclonal antibody against MET, generated using the knob-into-hole technology that enables the antibody to engage the receptor in a one-to-one fashion. Onartuzumab potently inhibits HGF binding and receptor phosphorylation and signaling and has antibody-like pharmacokinetics and antitumor activity. Biochemical data and a crystal structure of a ternary complex of onartuzumab antigen-binding fragment bound to a MET extracellular domain fragment, consisting of the MET Sema domain fused to the adjacent Plexins, Semaphorins, Integrins domain (MET Sema-PSI), and the HGF ß-chain demonstrate that onartuzumab acts specifically by blocking HGF α-chain (but not ß-chain) binding to MET. These data suggest a likely binding site of the HGF α-chain on MET, which when dimerized leads to MET signaling. Onartuzumab, therefore, represents the founding member of a class of therapeutic monovalent antibodies that overcomes limitations of antibody bivalency for targets impacted by antibody crosslinking.

Macroscopic and Strong Ribbons of Functionality-Rich Metal Oxides from Highly Ordered Assembly of Unilamellar Sheets.

The strong interest in macroscopic graphene and/or carbon nanotube (CNT) fiber has highlighted that anisotropic nanostructured materials are ideal components for fabricating fiber assemblies. Prospectively, employing two-dimensional (2D) crystals or nanosheets of functionality-rich transition metal oxides would notably enrich the general knowledge for desirable fiber constructions and more importantly would greatly broaden the scope of functionalities. However, the fibers obtained up to now have been limited to carbon-related materials, while those made of 2D crystals of metal oxides have not been achieved, probably due to the intrinsically low mechanical stiffness of a molecular sheet of metal oxides, which is only few hundredths of that for graphene. Here, using 2D titania sheets as an illustrating example, we present the first successful fabrication of macroscopic fiber of metal oxides composed of highly aligned stacking sheets with enhanced sheet-to-sheet binding interactions. Regardless of the intrinsically weak Ti-O bond in molecular titania sheets, the optimal fiber manifested mechanical performance comparable to that documented for graphene or CNTs. This work provided important hints for devising optimized architecture in macroscopic assemblies, and the rich functionalities of titania promises fibers with limitless promise for a wealth of innovative applications.

Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma.

Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development against several types of cancer, including glioblastoma, it is important to identify predictive markers that indicate patient subgroups suitable for such therapies. We investigated in vivo glioblastoma models characterized by hepatocyte growth factor (HGF) autocrine or paracrine activation, or by MET or EGFR amplification, for their susceptibility to MET inhibitors. HGF autocrine expression correlated with high phospho-MET levels in HGF autocrine cell lines, and these lines showed high sensitivity to MET inhibition in vivo. An HGF paracrine environment may enhance glioblastoma growth in vivo but did not indicate sensitivity to MET inhibition. EGFRvIII amplification predicted sensitivity to EGFR inhibition, but in the same tumor, increased copies of MET from gains of chromosome 7 did not result in increased MET activity and did not predict sensitivity to MET inhibitors. Thus, HGF autocrine glioblastoma bears an activated MET signaling pathway that may predict sensitivity to MET inhibitors. Moreover, serum HGF levels may serve as a biomarker for the presence of autocrine tumors and their responsiveness to MET therapeutics.

Studies of the in vitro antibacterial activities of several polyphenols against clinical isolates of methicillin-resistant Staphylococcus aureus.

In this study, we report the antibacterial activities of six polyphenols (i.e., luteolin, quercetin, scutellarin, apigenin, chlorogenic acid, and resveratrol) against 29 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), and in vitro antibacterial activities of two-drug combinations. All of the MRSA strains evaluated were clinical isolates from patients with MRSA bacteremia. The antibacterial activities were determined by agar dilution method, and the two-drug antibacterial activities were determined by the checkerboard agar dilution method. It was found that luteolin, quercetin and resveratrol show obvious antibacterial activities against MRSA, and the results of two-drug antibacterial activity show either synergy or additivity, without evidences of antagonistic effects.

Evolutionarily conserved Otub1 suppresses antiviral immune response by promoting Irf3 proteasomal degradation in miiuy croaker, Miichthys miiuy.

Increasing evidence has been shown that OTUB1, a member of OTU deubiquitinases, is of importance in regulating the immune system. However, its molecular identification and functional characterization in teleosts are still rarely known. In this work, we cloned the otub1 of miiuy croaker (Miichthys miiuy), analyzed its sequence, structure, and evolution at genetic and protein levels, and determined its function in the antiviral immune response. The complete open reading frame (ORF) of miiuy croaker otub1 is 843 bp in length, encoding 280 amino acids. Miiuy croaker Otub1 has an OTU domain at the carboxyl terminus, which is a common functional domain that exists in OTU deubiquitinases. Molecular characteristics and evolution analysis results indicated that miiuy croaker Otub1, especially its functional domain, is highly conserved during evolution. The luciferase reporter assays showed that miiuy croaker Otub1 could significantly inhibit the poly(I:C) and Irf3-induced IFN1 and IFN-stimulated response element (ISRE) activation. Further experiments showed that miiuy croaker Otub1 decreases Irf3 protein abundance by promoting its proteasomal degradation. These data suggest that the evolutionarily conserved Otub1 acts as a suppressor in controlling antiviral immune response by promoting Irf3 proteasomal degradation in miiuy croaker.

Splenic abscess caused by Streptococcus gallolyticus subsp. pasteurianus as presentation of a pancreatic cancer.

Splenic abscesses caused by Streptococcus bovis are rarely reported in the literature and are mainly seen in patients with endocarditis and associated colonic neoplasia/carcinoma. We report the first case of splenic abscess caused by Streptococcus gallolyticus subsp. pasteurianus (Streptococcus bovis biotype II/2) as presentation of a pancreatic cancer.

Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis.

The objective was to examine the pooled effects of antibiotic-probiotic combinations by examining the cure rate and recurrence rate for bacterial vaginosis (BV). A systematic literature search was conducted from electronic databases. All parallel randomized controlled trials (RCTs) that focused on the effects of antibiotics combined with intravaginal probiotics were included. Cure rate and recurrence rate were the primary and secondary outcomes to be analyzed. Meta-analysis was conducted following the Cochrane handbook for Systematic Reviews of Interventions. As a result, of 923 studies identified, 11 articles involving 1,493 BV patients met the inclusion criteria and nine were available for meta-analysis. A meta-analysis of two studies evaluated the recurrence rate 12-16 weeks after treatment. Results showed a statistically significant difference favoring the antibiotics plus probiotics group vs the antibiotics plus placebo group (relative risk 0.62, 95% confidence interval [CI]: 0.45-0.85). The narrative review in one study indicated that the cure rate was higher in the antibiotics plus probiotics group, giving a significant HR ratio of 0.73 (95% CI 0.54-0.98) (p = 0.042). In conclusion, vaginal application of Lactobacillus in combination with antibiotics for the treatment of BV could be a promising method for both reducing the recurrence rate and relieving symptoms of BV.

Transcriptome and Physiological Analysis Highlight Lignin Metabolism of the Fruit Dots Disordering during Postharvest Cold Storage in 'Danxiahong' Pear.

Pear (Pyrus L.) is one of the most important fruits in the world. Fruit dots are an important trait that affects pear quality. Abnormal fruit dots usually reduce the merchantability of pears. In this research, during cold storage, 'Danxiahong' pear fruit exhibited protrudent fruit dots on the peels. Microscopy system measurement showed that fruit dots size and height on the abnormal fruit peel were bigger and higher than the normal ones. Likewise, scanning electron microscopy observations indicated that the abnormal fruit peel, in contrast to the normal pear peel, exhibited an abnormal cell structure and fruit dots. Physiological analysis showed that the lignin content in abnormal fruit peel was significantly higher than in normal fruit peel. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the top-enriched pathways were mainly associated with lignin synthesis and metabolism. The transcripts of lignin biosynthesis-associated genes were analyzed, and the results showed that the expression of a cascade of structural genes, including PpyPAL, PpyCCR, PpyC3H, PpyC4H, PpyHCT, PpyCAD, PpyLAC, and PpyPOD, was significantly induced in the protrudent peels. Furthermore, the expression of regulatory genes involved in lignin biosynthesis, especially the NAC-MYB-based gene regulatory network, was significantly upregulated in the abnormal peels. Real-time quantitative PCR (RT-qPCR) analysis confirmed the induction of lignin biosynthesis genes. Overall, this research revealed that the abnormal fruit surface was caused by fruit dots disorder during cold storage. This research provides insights into the fine regulation pathways in the prevention of fruit dots protrusion, especially in modulating lignin synthesis and metabolism during postharvest storage.

Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer.

Understanding the signaling pathways that drive aggressive breast cancers is critical to the development of effective therapeutics. The oncogene MET is associated with decreased survival in breast cancer, yet the role that MET plays in the various breast cancer subtypes is unclear. We describe a knockin mouse with mutationally activated Met (Met(mut)) that develops a high incidence of diverse mammary tumors with basal characteristics, including metaplasia, absence of progesterone receptor and ERBB2 expression, and expression of cytokeratin 5. With gene expression and tissue microarray analysis, we show that high MET expression in human breast cancers significantly correlated with estrogen receptor negative/ERBB2 negative tumors and with basal breast cancers. Few treatment options exist for breast cancers of the basal or trastuzumab-resistant ERBB2 subtypes. We conclude from these studies that MET may play a critical role in the development of the most aggressive breast cancers and may be a rational therapeutic target.