Transgenerational plasticity in morphological characteristics and biomass of the invasive plant Xanthium strumarium.

Transgenerational plasticity (TGP) allows a plant to acclimate to external variable environments and is a potential mechanism that explains the range expansion and invasion success of some exotic plants. Most studies explored the traits of TGP associated with the success of exotic plant invasions by comparison studies among exotic, native, invasive, and noninvasive species. However, studies on the TGP of invasive plants in different resource environments are scarce, and the biological mechanisms involved are not well understood. This study aimed to determine the role of TGP in the invasiveness of Xanthium strumarium in northeast China. We measured the plant morphology of aboveground parts and the growth of three generations of the invader under different environmental conditions. The results showed that the intergenerational plasticity of X. strumarium was stronger under stress conditions. We found that the X. strumarium parent generation (F0) grown under water and/or nutrient deficiency conditions transferred the environmental information to their offspring (F1 and F2). The F1 generation grown under high-resource conditions has greater height with larger crown sizes, thicker basal diameters, and higher biomass. Both water and nutrients can affect the intergenerational transmission of plant plasticity, nutrients play a more important role compared with water. The high morphological intergenerational plasticity of X. strumarium under a pressure environment can help it quickly adapt to the new environment and accelerate the rapid expansion of the population in the short term. The root:shoot ratio and reproductive and nutrient distribution of the X. strumarium F0 and F1 generations showed high stability when the growth environment of the F0 generation differed from that of the F1 generation. The stable resource allocation strategy can ensure that the obtained resources are evenly distributed to each organ to maintain the long-term existence of the community. Therefore, the study of intergenerational transmission plasticity is of great significance for understanding the invasion process, mechanism, and prevention of invasive plants.

Characterization of Immune-Related Alternative Polyadenylation Events in Cancer Immunotherapy.

Alternative polyadenylation (APA) is an important posttranscriptional modification commonly involved in tumor development. However, the functional roles of APA in tumor immunity remain largely unknown. Here, we performed an in-depth analysis of the 3'UTR usage of protein-coding genes and tumor immune response in 10,303 tumor samples across 31 cancer types to develop the immune-related APA event (ImmAPA) score pipeline, an integrated algorithm to characterize the regulatory landscape of APA events in cancer immunity-related pathways. Tumor-specific ImmAPAs that strongly correlate with immune cell infiltration and immune checkpoint blockade (ICB) treatment-related biomarkers were identified. Among these ImmAPAs, the top-ranking COL1A1 3'UTR usage was strongly associated with worse prognosis and tumor immune evasion. Furthermore, a machine learning approach to construct an ICB-related ImmAPA score model predicted immunotherapy efficacy. Overall, the characterization of immune-related APA that corresponds to tumor progression and tumor immunity highlights the clinical utility of APA events as potential biomarkers in cancer immunotherapy. SIGNIFICANCE: Elucidation of the landscape of immune-related alternative polyadenylation in cancer identifies alternative polyadenylation events that may play a role in immune modulation and immunotherapy efficacy.

DjPtpn11 is an essential modulator of planarian (Dugesia japonica) regeneration.

Freshwater planarian Dugesia japonica is an excellent model organism for investigating stem cell behavior during regeneration. Despite studies showing that numerous genetic factors are involved in regeneration, much more research is required to fully understand the molecular mechanisms that orchestrate regeneration. In this study, we identified an evolutionarily conserved gene DjPtpn11(DjShp2). DjPtpn11 transcripts are expressed in neoblasts and some differentiated cells, with a high expression at the newly formed blastema. Its silencing by RNA interference (RNAi) affected anterior regeneration and inhibited the regeneration of posterior regions, including cholinergic and serotonergic neuron regeneration. In adult planarians, DjPtpn11 knockdown did not affect neoblast survival and proliferation but might prevent the stem cell migration and differentiation through ERK signaling. DjPtpn11 was demonstrated to be necessary for the anterior blastema cell differentiation partially via regulating ERK-DjMkpA activity. DjPtpn11 also influenced posterior specification via DjIslet, suggesting that DjPtpn11 may be involved in regulating the Wnt signaling pathway during the development of posterior blastema. Together, these data identified that DjPtpn11 is an essential modulator for the regeneration of planarians, and it may influence the appropriate differentiation of blastema cells.

DjApi5 is required for homeostasis in planarian Dugesia japonica.

Orchestrated apoptosis in planarian Dugesia japonica is very important for its degrowth and regeneration. Apoptosis Inhibitor-5 (API5) is an anti-apoptotic factor that negatively regulates cell apoptosis. We characterized the conserved structure of DjApi5, however, the biological function of DjApi5 in planarians needs further investigation. In this study, we found that DjApi5 and its interacting molecular DjAcinus are required for planarian homeostasis, which may be correlated with their specific localization in neoblasts in addition to their anti-apoptosis functions. We further demonstrated the increased expression of DjApi5 during planarian regeneration, and DjApi5 deficiency affects normal regeneration processes. These results indicated new functions of DjApi5 in development.

Evolution and Structure of API5 and Its Roles in Anti-Apoptosis.

Apoptosis, also named programmed cell death, is a highly conserved physiological mechanism. Apoptosis plays crucial roles in many life processes, such as tissue development, organ formation, homeostasis maintenance, resistance against external aggression, and immune responses. Apoptosis is regulated by many genes, among which Apoptosis Inhibitor-5 (API5) is an effective inhibitor, though the structure of API5 is completely different from the other known Inhibitors of Apoptosis Proteins (IAPs). Due to its high expression in many types of tumors, API5 has received extensive attention, and may be an effective target for cancer treatment. In order to comprehensively and systematically understand the biological roles of API5, we summarized the evolution and structure of API5 and its roles in anti-apoptosis in this review.

Characterization of Corosolic Acid as a KPC-2 Inhibitor That Increases the Susceptibility of KPC-2-Positive Bacteria to Carbapenems.

The emergence of KPC-producing Gram-negative bacteria in clinical practice highlights the need to search for novel antimicrobials and new anti-infection strategies. In this study, we constructed a laboratory KPC-2-positive strain, E. coli BL21(DE3) (pET28a-KPC-2) and identified the activity of KPC-2 in this strain. Using enzyme inhibition assays, checkerboard MIC assays, growth curves, time-killing assays and combined disk test, we found that the natural compound corosolic acid (CA) significantly inhibited the activity of the class A ß-lactamase KPC-2, which is common among clinical isolates. CA treatment increased the antibacterial or bactericidal activity of imipenem and meropenem against E. coli BL21(DE3) (pET28a-KPC-2) in vitro (FIC index = 0.17 ± 0.03 for both carbapenems). In addition, the mouse intraperitoneal infection model confirmed that the combination therapy significantly reduced the bacterial load in the livers and spleens following subcutaneous administration. Our results showed that CA can be used to extend the life of carbapenems, providing a viable strategy for severe infections caused by KPC-2-positive bacteria.

Protein arginine methyltransferase 1 mediates regeneration in Dugesia japonica.

As a typical organism of platyhelminth, Dugesia japonica attracts more and more attention for its strong regenerative ability. Protein arginine methyltransferase (PRMT) family is composed of a class of enzymes with methyltransferase activities, which play fundamental roles in vivo in many important physiological processes. PRMT1 is a predominant type Ⅰ PRMT, which has been reported to be expressed in Schmidtea mediterranea. Nevertheless, the existence and the specific biological functions of PRMT1 in Dugesia japonica need further investigation. In this study, we acquired the full-length sequence of DjPRMT1 and confirmed it was a conserved protein. Thereafter, whole-mount in situ hybridization results showed DjPRMT1 was mainly expressed in neoblasts of adult worms, and obvious aggregation of DjPRMT1 was observed at the wound site in early stages of regeneration. Silencing of the DjPRMT1 gene retarded the movement of planarians with decreased DjPIWI-A expression, and DjPRMT1 knockdown also affected planarian regeneration with slightly attenuated proliferation around the blastema of posterior-facing wounds regeneration. In summary, these preliminary results demonstrated DjPRMT1 was involved in the regeneration of planarian.

PEGylated Polyurea Bearing Hindered Urea Bond for Drug Delivery.

In recent years, polyureas with dynamic hindered urea bonds (HUBs), a class of promising biomedical polymers, have attracted wide attention as a result of their controlled hydrolytic properties. The effect of the chemical structures on the properties of polyureas and their assemblies has rarely been reported. In this study, four kinds of polyureas with different chemical groups have been synthesized, and the polyureas from cyclohexyl diisocyanate and tert-butyl diamine showed the fastest hydrolytic rate. The amphiphilic polyurea composed of hydrophobic cyclohexyl-tert-butyl polyurea and hydrophilic poly(ethylene glycol) (PEG) was synthesized for the controlled delivery of the antitumor drug paclitaxel (PTX). The PTX-loaded PEGylated polyurea micelle more effectively entered into the murine breast cancer 4T1 cells and inhibited the corresponding tumor growth in vitro and in vivo. Therefore, the PEGylated polyurea with adjustable degradation might be a promising polymer matrix for drug delivery.

Rapid purification of bacteriophage endolysin TSPphg and its exogenous treatment could act as an alternative bacterial cell disruption method.

Bacteriophage endolysins have long been demonstrated to be effective enzybiotics, and have the potential value in the areas of food, agricultural, and industrial science. Traditionally, extraction of recombinant proteins from bacterium E. coli is achieved by chemical, biological or mechanical disruption methods. Here, we present heat treatment, a simple and highly effective method that differs from the conventional ones, for disruption of E. coli cells to extract recombinant TSPphg, an endolysin originated from thermophilic bacteriophage TSP4. In addition, we found that exogenous TSPphg treatment is able to disrupt E. coli cell and release its intracellular proteins, suggesting its great potentiality to be developed as an alternative bacterial cell disruption method. Moreover, the large scale purification of TSPphg by heat treatment can be carried out directly in fermentation broth in situ without complex downstream processing, which may make it a more applicable approach for commercial scale processes. Our findings shed light on recovery of recombinant thermostable proteins and strategy of bacterial cell disruption.