Phylogenetic congruence between subtropical trees and their associated fungi.

Recent studies have detected phylogenetic signals in pathogen-host networks for both soil-borne and leaf-infecting fungi, suggesting that pathogenic fungi may track or coevolve with their preferred hosts. However, a phylogenetically concordant relationship between multiple hosts and multiple fungi in has rarely been investigated. Using next-generation high-throughput DNA sequencing techniques, we analyzed fungal taxa associated with diseased leaves, rotten seeds, and infected seedlings of subtropical trees. We compared the topologies of the phylogenetic trees of the soil and foliar fungi based on the internal transcribed spacer (ITS) region with the phylogeny of host tree species based on matK, rbcL, atpB, and 5.8S genes. We identified 37 foliar and 103 soil pathogenic fungi belonging to the Ascomycota and Basidiomycota phyla and detected significantly nonrandom host-fungus combinations, which clustered on both the fungus phylogeny and the host phylogeny. The explicit evidence of congruent phylogenies between tree hosts and their potential fungal pathogens suggests either diffuse coevolution among the plant-fungal interaction networks or that the distribution of fungal species tracked spatially associated hosts with phylogenetically conserved traits and habitat preferences. Phylogenetic conservatism in plant-fungal interactions within a local community promotes host and parasite specificity, which is integral to the important role of fungi in promoting species coexistence and maintaining biodiversity of forest communities

CRISPR accelerates the cancer drug discovery

Emerging cohorts and basic studies have associated certain genetic modifications in cancer patients, such as gene mutation, amplification, or deletion, with the overall survival prognosis, underscoring patients??? genetic background may directly regulate drug sensitivity/resistance during chemotherapies. Understanding the molecular mechanism underpinning drug sensitivity/resistance and further uncovering the effective drugs have been the major ambition in the cancer drug discovery. The emergence and popularity of CRISPR/Cas9 technology have reformed the entire life science research, providing a precise and simplified genome editing tool with unlimited editing possibilities. Furthermore, it presents a powerful tool in cancer drug discovery, which hopefully facilitates us with a rapid and reliable manner in developing novel therapies and understanding the molecular mechanisms of drug sensitivity/resistance. Herein, we summarized the application of CRISPR/Cas9 in drug screening, with the focus on CRISPR/Cas9 mediated gene knockout, gene knock-in, as well as transcriptional modification. Additionally, this review provides the concerns, cautions, and ethnic considerations that need to be taken when applying CRISPR in the drug discovery.Peer reviewe

LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics

Metastasis is the main cause of cancer patients' death despite tremendous efforts invested in developing the related molecular mechanisms. During cancer cell migration, cells undergo dynamic regulation of filopodia, focal adhesion, and endosome trafficking. Cdc42 is imperative for maintaining cell morphology and filopodia, regulating cell movement. Integrin beta1 activates on the endosome, the majority of which distributes itself on the plasma membrane, indicating that endocytic trafficking is essential for this activity. In cancers, high expression of lysosome-associated protein transmembrane 4B (LAPTM4B) is associated with poor prognosis. LAPTM4B-35 has been reported as displaying plasma membrane distribution and being associated with cancer cell migration. However, the detailed mechanism of its isoform-specific distribution and whether it relates to cell migration remain unknown. Here, we first report and quantify the filopodia localization of LAPTM4B-35: mechanically, that specific interaction with Cdc42 promoted its localization to the filopodia. Furthermore, our data show that LAPTM4B-35 stabilized filopodia and regulated integrin beta1 recycling via interaction and cotrafficking on the endosome. In our zebrafish xenograft model, LAPTM4B-35 stimulated the formation and dynamics of focal adhesion, further promoting cancer cell dissemination, whereas in skin cancer patients, LAPTM4B level correlated with poor prognosis. In short, this study establishes an insight into the mechanism of LAPTM4B-35 filopodia distribution, as well as into its biological effects and its clinical significance, providing a novel target for cancer therapeutics development.Peer reviewe

A Conceptual Architecture for Adaptive Human-Computer Interface of a PT Operation Platform Based on Context-Awareness

We present a conceptual architecture for adaptive human-computer interface of a PT operation platform based on context-awareness. This architecture will form the basis of design for such an interface. This paper describes components, key technologies, and working principles of the architecture. The critical contents covered context information modeling, processing, relationship establishing between contexts and interface design knowledge by use of adaptive knowledge reasoning, and visualization implementing of adaptive interface with the aid of interface tools technology

Pore network modeling of thin water film and its influence on relative permeability curves in tight formations

Acknowledgments We acknowledge the Beijing Natural Science Foundation of China (No. 2204093), Science Foundation of China University of Petroleum, Beijing (No.2462018YJRC033) and financial support from China Scholarship Council ((No. 201906440134). Dr. Yingfang Zhou would like to acknowledge the support from State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation (Southwest Petroleum University), PLN201602.Peer reviewedPostprin

Arbuscular mycorrhizal fungi counteract the Janzen-Connell effect of soil pathogens

Soilborne pathogens can contribute to diversity maintenance in tree communities through the Janzen-Connell effect, whereby the pathogenic reduction of seedling performance attenuates with distance from conspecifics. By contrast, arbuscular mycorrhizal fungi (AMF) have been reported to promote seedling performance; however, it is unknown whether this is also distance dependent. Here, we investigate the distance dependence of seedling performance in the presence of both pathogens and AMF. In a subtropical forest in south China, we conducted a four-year field census of four species with relatively large phylogenetic distances and found no distance-dependent mortality for newly germinated seedlings. By experimentally separating the effects of AMF and pathogens on seedling performance of six subtropical tree species in a shade house, we found that soil pathogens significantly inhibited seedling survival and growth while AMF largely promoted seedling growth, and these effects were host specific and declined with increasing conspecific distance. Together, our field and experimental results suggest that AMF can neutralize the negative effect of pathogens and that the Janzen-Connell effect may play a less prominent role in explaining diversity of nondominant tree species than previously thought

S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma

Despite several new therapeutic options, multiple myeloma (MM) patients experience multiple relapses and inevitably become refractory to treatment. Insights into drug resistance mechanisms may lead to the development of novel treatment strategies. The S100 family is comprised of 21 calcium binding protein members with 17 S100 genes located in the 1q21 region, which is commonly amplified in MM. Dysregulated expression of S100 family members is associated with tumor initiation, progression and inflammation. However, the relationship between the S100 family and MM pathogenesis and drug response is unknown. In this study, the roles of S100 members were systematically studied at the copy number, transcriptional and protein level with patients’ survival and drug response. Copy number analysis revealed a predominant pattern of gains occurring in S100 genes clustering in the 1q21 locus. In general, gains of genes encoding S100 family members associated with worse patient survival. However, S100 gene copy number and S100 gene expression did not necessarily correlate, and high expression of S100A4 associated with poor patient survival. Furthermore, integrated analysis of S100 gene expression and ex vivo drug sensitivity data showed significant negative correlation between expression of S100 family members (S100A8, S100A9, and S100A12) and sensitivity to some drugs used in current MM treatment, including proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) and histone deacetylase inhibitor panobinostat. Combined proteomic and pharmacological data exhibited significant negative association of S100 members (S100A4, S100A8, and S100A9) with proteasome inhibitors and panobinostat. Clinically, the higher expression of S100A4 and S100A10 were significantly linked to shorter progression free survival in patients receiving carfilzomib-based therapy. The results indicate an association and highlight the potential functional importance of S100 members on chromosome 1q21 in the development of MM and resistance to established myeloma drugs, including proteasome inhibitors.Peer reviewe