Complete genome analysis of a novel hypovirus in the phytopathogenic fungus Monilinia fructicola.

Monilinia fructicola is one of the most devastating fungal diseases of rosaceous fruit crops, both in the field and postharvest, causing significant yield losses. Here, we report the discovery of a novel positive single-stranded RNA virus, Monilinia fructicola hypovirus 3 (MfHV3), in a strain (hf-1) of the phytopathogenic fungus Monilinia fructicola. The complete genome of MfHV3 is 9259 nucleotides (nt) in length and contains a single large open reading frame (ORF) from nt position 462 to 8411. This ORF encodes a polyprotein with three conserved domains, namely UDP-glycosyltransferase, RNA-dependent RNA polymerase (RdRp), and DEAD-like helicase. The MfHV3 polyprotein shares the highest similarity with Colletotrichum camelliae hypovirus 1. Phylogenetic analysis indicated that MfHV3 clustered with members of the genus Betahypovirus within the family Hypoviridae. Taken together, the results of genomic organization comparisons, amino acid sequence alignments, and phylogenetic analysis convincingly show that MfHV3 is a new member of the genus Betahypovirus, family Hypoviridae.

Functional hyaluronic acid microneedles for skin photoaging based on collagen induction and oxidative stress regulation strategies.

Photoaging holds remarkable importance for skin health and senescence. Ultraviolet (UV) irradiation results in the disruption of the extracellular matrix (ECM) microenvironment, the degradation of collagen, and the generation of oxidative stress. Traditional hyaluronic acid (HA) exhibits a diminished capacity to stimulate collagen regeneration, and hampered by its poor permeability as a macromolecule, ultimately resulting in constrained therapeutic outcomes for the treatment of photoaging. In this study, HA/PX was prepared by functional modification of HA with sulfonate-rich or phosphatidylcholine-rich polymers, which could complement the loss of ECM and ameliorate the senescence of human fibroblasts (HDFs) and hairless mouse models subjected to UVB-induced photoaging. The results indicate that HA/PX exhibits superior abilities in delaying cellular aging, promoting collagen regeneration, and resisting reactive oxygen species (ROS) compared to HA. Furthermore, HA/PX shows good biocompatibility both in vivo and in vitro, without causing allergic reactions or other adverse effects. We also demonstrated that the transdermal delivery of HA/PX via microneedle arrays (MNs) can significantly mitigate wrinkles and skin damage in photoaged nude mice, and achieve the treatment of skin photoaging by enhancing epidermal thickness, promoting collagen deposition, and reducing oxidative stress. Therefore, our research offers a novel possibility for future anti-aging therapeutic strategies.

Report on the diagnosis and treatment of 3 cases of emphysematous pyelonephritis with two different outcomes.

Background: Emphysematous pyelonephritis (EPN) is a rare acute severe necrotising infection of the kidneys in clinical practice. It is characterized by the presence of gas in the renal parenchyma, collecting system, or perirenal tissue. The prognosis is poor, with a high nephrectomy rate and a mortality rate of up to 20-40%. Methods: Retrospective analysis of 3 cases of emphysematous pyelonephritis with two different outcomes. Results: Three patients who we described were all female with diabetes mellitus, and their blood sugar was poorly controlled. One patient with the advanced age and poor general health died due to the patient's family choosing to terminate therapy. Two patients underwent surgical procedures achieved an excellent clinical recovery. Both of them underwent percutaneous nephrostomy and perinephric abscess puncture drainage before nephrectomy. Escherichia coli were the microorganisms implicated. Conclusion: EPN is a rare and severe urinary system infection. Computed tomography (CT) and microbiological culture confirmed the diagnosis. Control of diabetes, sensitive antibiotic therapy, fluid resuscitation and prompt surgical intervention are crucial.

Genome-wide and functional analysis of late embryogenesis abundant (LEA) genes during dormancy and sprouting periods of kernel consumption apricots (P. armeniaca L. × P. sibirica L.).

Late embryogenesis abundant (LEA) proteins play a crucial role in protecting cells from stress, making them potential contributors to abiotic stress tolerance. This study focuses on apricot (P. armeniaca L. × P. sibirica L.), where a comprehensive genome-wide analysis identified 54 LEA genes, categorized into eight subgroups based on phylogenetic relationships. Synteny analysis revealed 14 collinear blocks containing LEA genes between P. armeniaca × P. sibirica and Arabidopsis thaliana, with an additional 9 collinear blocks identified between P. armeniaca × P. sibirica and poplar. Examination of gene structure and conserved motifs indicated that these subgroups exhibit consistent exon-intron patterns and shared motifs. The expansion and duplication of LEA genes in P. armeniaca × P. sibirica were driven by whole-genome duplication (WGD), segmental duplication, and tandem duplication events. Expression analysis, utilizing RNA-seq data and quantitative real-time RT-PCR (qRT-PCR), indicated induction of PasLEA2-20, PasLEA3-2, PasLEA6-1, Pasdehydrin-3, and Pasdehydrin-5 in flower buds during dormancy and sprouting phases. Coexpression network analysis linked LEA genes with 15 cold-resistance genes. Remarkably, during the four developmental stages of flower buds in P. armeniaca × P. sibirica - physiological dormancy, ecological dormancy, sprouting period, and germination stage - the expression patterns of all PasLEAs coexpressed with cold stress-related genes remained consistent. Protein-protein interaction networks, established using Arabidopsis orthologs, emphasized connections between PasLEA proteins and cold resistance pathways. Overexpression of certain LEA genes in yeast and Arabidopsis conferred advantages under cold stress, including increased pod length, reduced bolting time and flowering time, improved survival and seed setting rates, elevated proline accumulation, and enhanced antioxidative enzymatic activities. Furthermore, these overexpressed plants exhibited upregulation of genes related to flower development and cold resistance. The Y1H assay confirmed that PasGBF4 and PasDOF3.5 act as upstream regulatory factors by binding to the promoter region of PasLEA3-2. PasDOF2.4, PasDnaJ2, and PasAP2 were also found to bind to the promoter of Pasdehydrin-3, regulating the expression levels of downstream genes. This comprehensive study explores the evolutionary relationships among PasLEA genes, protein interactions, and functional analyses during various stages of dormancy and sprouting in P. armeniaca × P. sibirica. It offers potential targets for enhancing cold resistance and manipulating flower bud dormancy in this apricot hybrid.

Novel therapeutic perspectives for wet age-related macular degeneration: RGD-modified liposomes loaded with 2-deoxy-D-glucose as a promising nanomedicine.

Choroidal neovascularization (CNV), characterized as a prominent feature of wet age-related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide-modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2-DG interfered with N-glycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.