Phototherapy has emerged to eradicate recalcitrant bacteria without causing drug resistance, but it is often accompanied by considerable limitations owing to a high tolerance of recalcitrant bacteria to heat and oxidative damage, leading to low efficiency of monotherapy and unwanted side effects. Assuming that employing antimicrobial peptides (AMPs) to disrupt bacterial membranes could reduce bacterial tolerance, a multifunctional "on-demand" nanosystem based on zeolitic imidazolate framework-8 (ZIF-8) with metal ions for intrinsic antibacterial activity was constructed to potently kill methicillin-resistant (MRSA). Then, microneedles (MNs) were used to transdermally deliver the ZIF-8-based nanosystem for localized skin infection.
View Article and Find Full Text PDFImmunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy.
View Article and Find Full Text PDFHere, we reported the complete profiling of the crotonylation proteome in common wheat. Through a combination of crotonylation and multi-omics analysis, we identified a TaPGK associated with wheat cold stress. Then, we confirmed the positive role of TaPGK-modulating wheat cold tolerance.
View Article and Find Full Text PDFDespite vaccination having the potency to revolutionize disease treatments, some critical issues including lack of safe and effective delivery system, insufficient internalization and ineffective antigen cross-presentation by dendritic cells (DCs) severely hamper its extensive clinical applications. Herein, we developed a whole cell-encapsulated antitumor vaccine microneedle patch (TCV-DMNs) potentiated with transdermal co-delivery of granulocyte-macrophage colony-stimulating factor (GM-CSF) and autophagy promoter (Tat-beclin 1). After transdermal vaccination with TCV-DMNs, GM-CSF released from DMNs serves as a potent adjuvant to recruit and promote the phagocytosis of antigens by DCs.
View Article and Find Full Text PDFIntegrating dissolving microneedles (DMNs) and nanocarriers (NC) holds great potential in transdermal drug delivery because it can simultaneously overcome the stratum corneum barrier and achieve efficient and controlled drug delivery. However, different skin sites with different thicknesses and compositions can affect the transdermal diffusion of NC-loaded DMNs. There are few reports on the biological fate (especially transdermal diffusion) of NC-loaded DMNs, and inaccurate bioimaging information of intact NC limits the accurate understanding of the in vivo fate of NC-loaded DMNs.
View Article and Find Full Text PDFMolecular manipulation of susceptibility (S) genes that are antipodes to resistance (R) genes has been adopted as an alternative strategy for controlling crop diseases. Here, we show the S gene encoding Triticum aestivum mA methyltransferase B (TaMTB) is identified by a genome-wide association study and subsequently shown to be a positive regulator for wheat yellow mosaic virus (WYMV) infection. TaMTB is localized in the nucleus, is translocated into the cytoplasmic aggregates by binding to WYMV NIb to upregulate the mA level of WYMV RNA1 and stabilize the viral RNA, thus promoting viral infection.
View Article and Find Full Text PDFViruses manipulate the cells they infect in order to replicate and spread. Due to strict size restrictions, viral genomes have reduced genetic space; how the action of the limited number of viral proteins results in the cell reprogramming observed during the infection is a long-standing question. Here, we explore the hypothesis that combinatorial interactions may expand the functional landscape of the viral proteome.
View Article and Find Full Text PDFSpinal muscular atrophy (SMA) is one of the most common and severe genetic diseases. SMA carrier screening is an effective way to identify couples at risk of having affected children. Next-generation sequencing (NGS)-based expanded carrier screening could detect SMN1 gene copy number without extra experiment and with high cost performance.
View Article and Find Full Text PDFUnclear biological fate hampers the clinical translation of nanoparticles for biomedical uses. In recent years, it is documented that the formation of protein corona upon nanoparticles is a critical factor leading to the ambiguous biological fate. Efforts have been made to explore the protein corona forming behaviors on nanoparticles, and rearrangement of the relevant studies will help to understand the current trend of such a topic.
View Article and Find Full Text PDFThe excessive colonization of () is responsible for the genesis of acne vulgaris, a common inflammatory disease of skin. However, the conventional anti-acne therapies are always limited by various side effects, drug resistance, and poor skin permeability. Microneedles (MNs) are emerging topical drug delivery systems capable of noninvasively breaking through the skin stratum corneum barrier to efficiently enhance the transdermal drug penetration.
View Article and Find Full Text PDFPlants rely on cell surface receptors to integrate developmental and environmental cues into behaviour adapted to the conditions. The largest group of these receptors, leucine-rich repeat receptor-like kinases, form a complex interaction network that is modulated and extended by receptor-like proteins. This raises the question of how specific outputs can be generated when receptor proteins are engaged in a plethora of promiscuous interactions.
View Article and Find Full Text PDFBackground: Due to its reduced cost and incomparable advantages, WGS is likely to lead to changes in clinical diagnosis of rare and undiagnosed diseases. However, the sensitivity and breadth of coverage of clinical WGS as a diagnostic test for genetic disorders has not been fully evaluated.
Methods: Here, the performance of WGS in NA12878, the YH cell line, and the Chinese trios were measured by assessing their sensitivity, PPV, depth and breadth of coverage using MGISEQ-2000.
The ubiquitin-proteasome system (UPS) is an important post-translational regulatory mechanism that controls many cellular functions in eukaryotes. Here, we show that stable expression of P3 protein encoded by Rice grassy stunt virus (RGSV), a negative-strand RNA virus in the Bunyavirales, causes developmental abnormities similar to the disease symptoms caused by RGSV, such as dwarfing and excess tillering, in transgenic rice plants. We found that both transgenic expression of P3 and RGSV infection induce ubiquitination and UPS-dependent degradation of rice NUCLEAR RNA POLYMERASE D1a (OsNRPD1a), one of two orthologs of the largest subunit of plant-specific RNA polymerase IV (Pol IV), which is required for RNA-directed DNA methylation (RdDM).
View Article and Find Full Text PDFMicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in plant development and abiotic stresses. To date, studies have mainly focused on the roles of individual miRNAs, however, a few have addressed the interactions among multiple miRNAs. In this study, we investigated the interplay and regulatory circuit between miR160 and miR165/166 and its effect on leaf development and drought tolerance in Arabidopsis using Short Tandem Target Mimic (STTM).
View Article and Find Full Text PDFBackground: The extensive adaptability of polyploidy wheat is attributed to its complex genome, and accurately controlling heading stage is a prime target in wheat breeding process. Wheat heading stage is an essential growth and development processes since it starts at a crucial point in the transition from vegetative phase to reproductive phase.
Main Body: Heading stage is mainly decided by vernalization, photoperiod, hormone (like gibberellic acid, GA), and earliness per se (Eps).
Virus inoculation is a basic experimental procedure to evaluate the resistance of a rice variety or a transgenic material upon virus infection. We recently demonstrated that (RRSV), an that is transmitted by brown planthopper (BPH), can suppress jasmonic acid-mediated antiviral defense through the induction of microRNA319 and facilitate virus infection in rice. To verify this, we performed virus inoculation experiments on wild-type rice plants and miR319-TCP21-associated transgenic rice plants through a modified group inoculation method.
View Article and Find Full Text PDFHeading date is one of the most important traits in wheat breeding as it affects adaptation and yield potential. A genome-wide association study (GWAS) using the 90 K iSelect SNP genotyping assay indicated that a total of 306 loci were significantly associated with heading and flowering dates in 13 environments in Chinese common wheat from the Yellow and Huai wheat region. Of these, 105 loci were significantly correlated with both heading and flowering dates and were found in clusters on chromosomes 2, 5, 6, and 7.
View Article and Find Full Text PDFHigh-throughput sequencing was employed to investigate the expression of miRNAs and their target genes in superior and inferior seeds of Aikang 58. Small RNA sequencing revealed 620 conserved and 64 novel miRNAs in superior grains, and 623 conserved and 66 novel miRNAs in inferior grains. Among these, 97 known miRNAs, and eight novel miRNAs showed differential expression between the superior and inferior seeds.
View Article and Find Full Text PDFCrops are often subjected to a combination of stresses in the field. To date, studies on the physiological and molecular responses of common wheat to a combination of osmotic and cold stresses, however, remain unknown. In this study, wheat seedlings exposed to osmotic-cold stress for 24 h showed inhibited growth, as well as increased lipid peroxidation, relative electrolyte leakage, and soluble sugar contents.
View Article and Find Full Text PDFProtein ubiquitination, which is a major post-translational modifications that occurs in eukaryotic cells, is involved in diverse biological processes. To date, large-scale profiling of the ubiquitome in common wheat has not been reported, despite its status as the major cereal crop in the world. Here, we performed the first ubiquitome analysis of the common wheat (Triticum aestivum L.
View Article and Find Full Text PDFMicroRNAs (miRNAs) are small regulatory RNAs processed from primary miRNA transcripts, and plant miRNAs play important roles in plant growth, development, and response to infection by microbes. Microbial infections broadly alter miRNA biogenesis, but the underlying mechanisms remain poorly understood. In this study, we report that the Rice stripe virus (RSV)-encoded nonstructural protein 3 (NS3) interacts with OsDRB1, an indispensable component of the rice (Oryza sativa) miRNA-processing complex.
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