An improvement of sufficient condition for kk-leaf-connected graphs

For integer $k\geq2,$ a graph $G$ is called $k$-leaf-connected if $|V(G)|\geq k+1$ and given any subset $S\subseteq V(G)$ with $|S|=k,$ $G$ always has a spanning tree $T$ such that $S$ is precisely the set of leaves of $T.$ Thus a graph is $2$-leaf-connected if and only if it is Hamilton-connected. In this paper, we present a best possible condition based upon the size to guarantee a graph to be $k$-leaf-connected, which not only improves the results of Gurgel and Wakabayashi [On $k$-leaf-connected graphs, J. Combin. Theory Ser. B 41 (1986) 1-16] and Ao, Liu, Yuan and Li [Improved sufficient conditions for $k$-leaf-connected graphs, Discrete Appl. Math. 314 (2022) 17-30], but also extends the result of Xu, Zhai and Wang [An improvement of spectral conditions for Hamilton-connected graphs, Linear Multilinear Algebra, 2021]. Our key approach is showing that an $(n+k-1)$-closed non-$k$-leaf-connected graph must contain a large clique if its size is large enough. As applications, sufficient conditions for a graph to be $k$-leaf-connected in terms of the (signless Laplacian) spectral radius of $G$ or its complement are also presented.Comment: 15 pages, 2 figure

Non-Coding Transcriptome Provides Novel Insights into the Escherichia coli F17 Susceptibility of Sheep Lamb

SIMPLE SUMMARY: Diarrhea and vomiting caused by Escherichia coli (E. coli) F17 are considered significant threats to animal farming. In the present study, RNA-Seq was performed to investigate the potential circRNA and miRNA biomarkers for E. coli F17-antagonism (AN) and -sensitive (SE) lambs. The results indicated that circRNA and miRNA expression is closely associated with the susceptibility of E. coli F17 in lambs. Numbers of circRNAs and miRNAs may serve as potential biomarkers for intestinal inflammatory response against E. coli F17 infection. Our study can provide a preliminary understanding of the underlying mechanisms of intestinal immunity. ABSTRACT: It has long been recognized that enterotoxigenic Escherichia coli (ETEC) is the major pathogen responsible for vomiting and diarrhea. E. coli F17, a main subtype of ETEC, is characterized by high morbidity and mortality in young livestock. However, the transcriptomic basis underlying E. coli F17 infection has not been fully understood. In this study, RNA sequencing was performed to explore the expression profiles of circRNAs and miRNAs in the jejunum of E. coli F17-antagonism (AN) and -sensitive (SE) lambs. A total of 16,534 circRNAs and 271 miRNAs (125 novel miRNAs and 146 annotated miRNAs) were screened, and 214 differentially expressed (DE) circRNAs and 53 DE miRNAs were detected between the AN and SE lambs (i.e., novel_circ_0025840, novel_circ_0022779, novel_miR_107, miR-10b). Functional enrichment analyses showed that source genes of DE circRNAs were mainly involved in metabolic-related pathways, while target genes of DE miRNAs were mainly enriched in the immune response pathways. Then, a two-step machine learning approach combining Random Forest (RF) and XGBoost (candidates were first selected by RF and further assessed by XGBoost) was performed, which identified 44 circRNAs and 39 miRNAs as potential biomarkers (i.e., novel_circ_0000180, novel_circ_0000365, novel_miR_192, oar-miR-496-3p) for E. coli infection. Furthermore, circRNA-related and lncRNA-related ceRNA networks were constructed, containing 46 circRNA-miRNA-mRNA competing triplets and 630 lncRNA-miRNA-mRNA competing triplets, respectively. By conducting a serious of bioinformatic analyses, our results revealed important circRNAs and miRNAs that could be potentially developed as candidate biomarkers for intestinal inflammatory response against E. coli F17 infection; our study can provide novel insights into the underlying mechanisms of intestinal immunity

Defining ovine dermal papilla cell markers and identifying key signaling pathways regulating its intrinsic properties

Dermal papilla cell (DPC), one of the key cell types during hair follicle development and regeneration, specifies hair size, shape and cycling. It is also an important in vitro screening model for hair growth. Although some characteristics of DPCs, such as agglutinative growth and marker genes, have been studied in mice and humans, the intrinsic properties of ovine DPCs and the regulatory mechanism of the intrinsic properties during continued culture in vitro remained unknown. In this study, based on our previous single-cell transcriptome sequencing on sheep lambskin, we verified SOX18 and PDGFRA as the novel marker genes of ovine DPCs through immunofluorescence staining on skin sections and cultured DPCs. Using continued cell culture and alkaline phosphatase staining, we found that different from mice and humans, ovine DPCs exhibit particularly robust and stable aggregation with unbated alkaline phosphatase activity till 30 passages during continued culture in vitro. Also, we found that the expression of some marker genes and the activity of Wnt/β-catenin signaling differ between early passaged DPCs and multiple passaged DPCs. Further, using Wnt/β-catenin agonist and antagonist, we demonstrated that Wnt/β-catenin signaling could regulate cell aggregation and alkaline phosphatase activity of ovine DPCs through regulating FGF and IGF signaling. This study provides the basis for isolating ovine DPCs and defines their intrinsic properties, which contribute to improving wool performance and medicine of hair regeneration

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Promises and challenges of adoptive T-cell therapies for solid tumours

From Springer Nature via Jisc Publications RouterHistory: received 2020-11-09, rev-recd 2021-02-22, accepted 2021-03-04, registration 2021-03-04, pub-electronic 2021-03-29, online 2021-03-29, pub-print 2021-05-25Publication status: PublishedFunder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272; Grant(s): RCF18/046Funder: Ovarian Cancer Action; doi: https://doi.org/10.13039/501100000299; Grant(s): HER000762Abstract: Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous or allogeneic transplant of tumour-infiltrating lymphocytes or genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors, has shown promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. Technological advances in genomics, computational biology, immunology and cell manufacturing have brought the aspiration of individualised therapies for cancer patients closer to reality. This new era of cell-based individualised therapeutics challenges the traditional standards of therapeutic interventions and provides opportunities for a paradigm shift in our approach to cancer therapy. Invited speakers at a 2020 symposium discussed three areas—cancer genomics, cancer immunology and cell-therapy manufacturing—that are essential to the effective translation of T-cell therapies in the treatment of solid malignancies. Key advances have been made in understanding genetic intratumour heterogeneity, and strategies to accurately identify neoantigens, overcome T-cell exhaustion and circumvent tumour immunosuppression after cell-therapy infusion are being developed. Advances are being made in cell-manufacturing approaches that have the potential to establish cell-therapies as credible therapeutic options. T-cell therapies face many challenges but hold great promise for improving clinical outcomes for patients with solid tumours

Promises and challenges of adoptive T-cell therapies for solid tumours.

Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous or allogeneic transplant of tumour-infiltrating lymphocytes or genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors, has shown promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. Technological advances in genomics, computational biology, immunology and cell manufacturing have brought the aspiration of individualised therapies for cancer patients closer to reality. This new era of cell-based individualised therapeutics challenges the traditional standards of therapeutic interventions and provides opportunities for a paradigm shift in our approach to cancer therapy. Invited speakers at a 2020 symposium discussed three areas-cancer genomics, cancer immunology and cell-therapy manufacturing-that are essential to the effective translation of T-cell therapies in the treatment of solid malignancies. Key advances have been made in understanding genetic intratumour heterogeneity, and strategies to accurately identify neoantigens, overcome T-cell exhaustion and circumvent tumour immunosuppression after cell-therapy infusion are being developed. Advances are being made in cell-manufacturing approaches that have the potential to establish cell-therapies as credible therapeutic options. T-cell therapies face many challenges but hold great promise for improving clinical outcomes for patients with solid tumours

miR-143 Targeting CUX1 to Regulate Proliferation of Dermal Papilla Cells in Hu Sheep

Wool curvature is the determining factor for lambskin quality of Hu lambs. However, the molecular mechanism of wool curvature formation is not yet known. miRNA has been proved to play an important role in hair follicle development, and we have discovered a differentially expressed miRNA, miR-143, in hair follicles of different curl levels. In this study, we first examined the effects of miR-143 on the proliferation and cell cycle of dermal papilla cells using CCK8, EdU and flow cytometry and showed that miR-143 inhibited the proliferation of dermal papilla cells and slowed down the cell cycle. Bioinformatics analysis was performed to predict the target genes KRT71 and CUX1 of miR-143, and both two genes were expressed at significantly higher levels in small waves than in straight lambskin wool (p < 0.05) as detected by qPCR and Western blot (WB). Then, the target relationships between miR-143 and KRT71 and CUX1 were verified through the dual-luciferase assay in 293T cells. Finally, after overexpression and suppression of miR-143 in dermal papilla cells, the expression trend of CUX1 was contrary to that of miR-143. Meanwhile, KRT71 was not detected because KRT71 was not expressed in dermal papilla cells. Therefore, we speculated that miR-143 can target CUX1 to inhibit the proliferation of dermal papilla cells, while miR-143 can target KRT71 to regulate the growth and development of hair follicles, so as to affect the development of hair follicles and ultimately affect the formation of wool curvature

Isolation and Classification of Fungal Whitefly Entomopathogens from Soils of Qinghai-Tibet Plateau and Gansu Corridor in China

<div><p>Qinghai-Tibet Plateau and Gansu Corridor of China with distinct geographic and climatic conditions are remote and less disturbed by humans, in which are likely to find some new strains of fungal entomopathogens against B-biotype whiteflies that is a very important invading pest worldwide. In this research, nineteen strains among six species of entomogenous fungi were isolated from the soil samples collected from 32 locations in Qinghai-Tibet Plateau and Gansu Corridor. From the data of isolation rates, it was indicated that the good biodiversity of entomogenous fungi was found in the soil covered good vegetations. On the contrary, no strains were isolated from the desert areas. In addition, the dominant species, <i>Isaria fumosorosea</i> and <i>Metarhizium anisopliae</i> var. <i>anisopliae</i> in the Qinghai-Tibet Plateau are different from the strains of other places based on ITS genetic homology analysis. It was verified that the Qinghai-Tibet Plateau area was less disturbed by human, and the fungi in this place exchanged less compared with other regional species. All of these strains showed the pathogenicity against the B-biotype whitefly with the mortality of more than 30%. However, a few strains of <i>Paecilomyces lilacinus</i>, <i>Lecanicillium psalliotae</i>, <i>Aspergillus ustus</i>, <i>I</i>. <i>fumosorosea</i> and <i>M</i>. <i>anisopliae</i> var. <i>anisopliae</i> had better virulence with LC₅₀s of 0.36–26.44×10⁶ spores/mL on post-treatment day 6–7. Especially, the <i>L</i>. <i>psalliotae</i> strain LpTS01 was the greatest virulence with LC₅₀ of 0.36×10⁶spores/mL and LT₅₀ of 4.23d. Our research thus presents some new insights to discover new entomopathogenic fungal strains used for B-biotype whitefly biocontrol.</p></div

The 19 fungal strains isolated from the soil of the Qinghai-Tibet plateau and Gansu Corridor.

<p>The 19 fungal strains isolated from the soil of the Qinghai-Tibet plateau and Gansu Corridor.</p