Melanin-like nanoparticles alleviate ischemia-reperfusion injury in the kidney by scavenging reactive oxygen species and inhibiting ferroptosis.

Kidney transplantation is essential for patients with end-stage renal disease; however, ischemia-reperfusion injury (IRI) during transplantation can lead to acute kidney damage and compromise survival. Recent studies have reported that antiferroptotic agents may be a potential therapeutic strategy, by reducing production of reactive oxygen species (ROS). Therefore, we constructed rutin-loaded polydopamine nanoparticles (PEG-PDA@rutin NPs, referred to as PPR NPs) to eliminate ROS resulting from IRI. Physicochemical characterization showed that the PPR NPs were ∼100 nm spherical particles with good ROS scavenging ability. Notably, PPR NPs could effectively enter lipopolysaccharide (LPS)-treated renal tubular cells, then polydopamine (PDA) released rutin to eliminate ROS, repair mitochondria, and suppress ferroptosis. Furthermore, in vivo imaging revealed that PPR NPs efficiently accumulated in the kidneys after IRI and effectively protected against IRI damage. In conclusion, PPR NPs demonstrated an excellent ability to eliminate ROS, suppress ferroptosis, and protect kidneys from IRI.

An analysis of lncRNAs related to fiber quality and the discovery of their target genes in a Gossypium hirsutum line with Gossypium mustelinum introgression.

KEY MESSAGE: Analysis of fiber quality lncRNAs and their target genes from a pair of Gossypium mustelinum near-isogenic lines provide new prospects for improving the fiber quality of Upland cotton. Long noncoding RNAs (lncRNAs) are an important part of genome transcription and play roles in a wide range of biological processes in plants. In this research, a pair of near-isogenic cotton lines, namely, a Gossypium mustelinum introgression line (IL9) with outstanding fiber quality and its recurrent Upland cotton parent (PD94042), were used as the experimental materials. Cotton fibers were selected for lncRNA sequencing at 17 and 21 days post-anthesis. A total of 2693 differentially expressed genes were identified. In total, 5841 lncRNAs were ultimately screened, from which 163 differentially expressed lncRNAs were identified. Target genes of the lncRNAs were predicted by two different methods: cis and trans. Some of the target genes were related to cell components, membrane components, plant hormone signal transduction and catalytic metabolism, and the results indicated that there might also be important effects on the development of fiber. Four differentially expressed target genes related to fiber quality (Gomus.D05G015100, Gomus.A05G281300, Gomus.A12G023400 and Gomus.A10G226800) were screened through gene function annotation, and the functions of these four genes were verified through virus-induced gene silencing (VIGS). Compared to the negative controls, plants in which any of these four genes were silenced showed significant reductions in fiber strength. In addition, the plants in which the Gomus.A12G023400 gene was silenced showed a significant reduction in fiber uniformity, whereas the plants in which Gomus.A05G281300 was silenced showed a significant increase in fiber fineness as measured via micronaire. Our results showed that these genes play different roles during fiber development, impacting fiber quality.

Tumor-targeting hydroxyapatite nanoparticles for remodeling tumor immune microenvironment (TIME) by activating mitoDNA-pyroptosis pathway in cancer.

In recent years, immunotherapy has emerged as a promising strategy for treating solid tumors, although its efficacy remains limited to a subset of patients. Transforming non-responsive "cold" tumor types into immuno-responsive "hot" ones is critical to enhance the efficacy of immune-based cancer treatments. Pyroptosis, a programmed cell death mechanism, not only effectively eliminates tumor cells but also triggers a potent inflammatory response to initiate anti-tumor immune activities. This sheds light on the potential of pyroptosis to sensitize tumors to immune therapy. Hence, it is urgent to explore and develop novel treatments (e.g., nanomedicines) which are capable of inducing pyroptosis. In this study, we constructed tumor-targeting nanoparticles (CS-HAP@ATO NPs) by loading atorvastatin (ATO) onto chondroitin sulfate (CS) modified hydroxyapatite (HAP) nanoparticles (CS-HAP). CS was strategically employed to target tumor cells, while HAP exhibited the capacity to release calcium ions (Ca2+) in response to the tumor microenvironment. Moreover, ATO disrupted the mitochondrial function, leading to intracellular energy depletion and consequential changes in mitochondrial membrane permeability, followed by the influx of Ca2+ into the cytoplasm and mitochondria. CS and HAP synergetically augmented mitochondrial calcium overload, inciting the production of substantial amount of reactive oxygen species (ROS) and the subsequent liberation of oxidized mitochondrial DNA (OX-mitoDNA). This intricate activation process promoted the assembly of inflammasomes, most notably the NLRP3 inflammasome, followed by triggering caspase-1 activation. The activated caspase-1 was able to induce gasderminD (GSDMD) protein cleavage and present the GSDM-N domain, which interacted with phospholipids in the cell membrane. Then, the cell membrane permeability was raised, cellular swelling was observed, and abundant cell contents and inflammatory mediators were released. Ultimately, this orchestrated sequence of events served to enhance the anti-tumor immunoresponse within the organism.

Genome-wide analysis of the LAZ1 gene family in Gossypium hirsutum.

BACKGROUND: As the world's leading fiber crop and a major oil-producing crop, cotton fiber yield and fiber quality are affected by environmental stresses, especially heat, drought and salinity. The LAZ1 (Lazarus 1) family genes are responsive to abscisic acid, drought, and salt treatments. Currently, mining and functional analyses of LAZ1 family genes in cotton have not been reported. METHODS AND RESULTS: In this study, 20 GhLAZ1 genes, designated GhLAZ1-1 - GhLAZ1-20, were identified in the genome of Gossypium hirsutum through the construction of an HMM model, and their molecular properties, chromosomal localization, phylogeny, gene structure, evolutionary selection pressure, promoter cis elements and gene expression under salt stress were analyzed. With the exception of GhLAZ1-17 and GhLAZ1-20, the remaining 18 GhLAZ1 genes were unevenly localized on 13 chromosomes in G. hirsutum; evolutionary analysis showed that these genes could be divided into three subfamilies; and evolutionary selection pressure analysis demonstrated that the GhLAZ1 genes were all under purifying selection. Many elements related to light responses, hormone responses, and abiotic stresses were predicted on the GhLAZ1 family gene promoters, and real-time quantitative PCR results showed that GhLAZ1-2, GhLAZ1-8, and GhLAZ1-18 were upregulated significantly in salt-treated cotton leaves. CONCLUSIONS: Our results suggested that GhLAZ1 genes were involved in the salt tolerance mechanism in G. hirsutum and provided a reference for further exploring the function and molecular mechanism of LAZ1 genes.

Genome-wide identification and expression analysis of terpene synthases in Gossypium species in response to gossypol biosynthesis.

Cottonseed is an invaluable resource, providing protein, oil, and abundant minerals that significantly contribute to the well-being and nutritional needs of both humans and livestock. However, cottonseed also contains a toxic substance called gossypol, a secondary metabolite in Gossypium species that plays an important role in cotton plant development and self-protection. Herein, genome-wide analysis and characterization of the terpene synthase (TPS) gene family identified 304 TPS genes in Gossypium. Bioinformatics analysis revealed that the gene family was grouped into six subgroups TPS-a, TPS-b, TPS-c, TPS-e, TPS-f, and TPS-g. Whole-genome, segmental, and tandem duplication contributed to the evolution of TPS genes. According to the analysis of selection pressure, it was predicted that TPS genes experience predominantly negative selection, with positive selection occurring subsequently. RT-qPCR analysis in TM-1 and CRI-12 lines revealed GhTPS48 gene as the candidate gene for silencing experiments. To summarize, comprehensive genome-wide studies, RT-qPCR, and gene silencing experiments have collectively demonstrated the involvement of the TPS gene family in the biosynthesis of gossypol in cotton.

Genome-wide identification of the geranylgeranyl pyrophosphate synthase (GGPS) gene family involved in chlorophyll synthesis in cotton.

BACKGROUND: Geranylgeranyl pyrophosphate synthase (GGPS) is a structural enzyme of the terpene biosynthesis pathway that is involved in regulating plant photosynthesis, growth and development, but this gene family has not been systematically studied in cotton. RESULTS: In the current research, genome-wide identification was performed, and a total of 75 GGPS family members were found in four cotton species, Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum and Gossypium raimondii. The GGPS genes were divided into three subgroups by evolutionary analysis. Subcellular localization prediction showed that they were mainly located in chloroplasts and plastids. The closely related GGPS contains a similar gene structure and conserved motif, but some genes are quite different, resulting in functional differentiation. Chromosome location analysis, collinearity and selection pressure analysis showed that many fragment duplication events occurred in GGPS genes. Three-dimensional structure analysis and conservative sequence analysis showed that the members of the GGPS family contained a large number of α-helices and random crimps, and all contained two aspartic acid-rich domains, DDxxxxD and DDxxD (x is an arbitrary amino acid), suggesting its key role in function. Cis-regulatory element analysis showed that cotton GGPS may be involved in light response, abiotic stress and other processes. A GGPS gene was silenced successfully by virus-induced gene silencing (VIGS), and it was found that the chlorophyll content in cotton leaves decreased significantly, suggesting that the gene plays an important role in plant photosynthesis. CONCLUSIONS: In total, 75 genes were identified in four Gossypium species by a series of bioinformatics analysis. Gene silencing from GGPS members of G. hirsutum revealed that GGPS plays an important regulatory role in photosynthesis. This study provides a theoretical basis for the biological function of GGPS in cotton growth and development.

Classification of breast cancer histology images using MSMV-PFENet.

Deep learning has been used extensively in histopathological image classification, but people in this field are still exploring new neural network architectures for more effective and efficient cancer diagnosis. Here, we propose multi-scale, multi-view progressive feature encoding network (MSMV-PFENet) for effective classification. With respect to the density of cell nuclei, we selected the regions potentially related to carcinogenesis at multiple scales from each view. The progressive feature encoding network then extracted the global and local features from these regions. A bidirectional long short-term memory analyzed the encoding vectors to get a category score, and finally the majority voting method integrated different views to classify the histopathological images. We tested our method on the breast cancer histology dataset from the ICIAR 2018 grand challenge. The proposed MSMV-PFENet achieved 93.0[Formula: see text] and 94.8[Formula: see text] accuracies at the patch and image levels, respectively. This method can potentially benefit the clinical cancer diagnosis.

Uncovering candidate genes responsive to salt stress in Salix matsudana (Koidz) by transcriptomic analysis.

Salix matsudana, a member of Salicaceae, is an important ornamental tree in China. Because of its capability to tolerate high salt conditions, S. matsudana also plays an important ecological role when grown along Chinese coastal beaches, where the salinity content is high. Here, we aimed to elucidate the mechanism of higher salt tolerance in S. matsudana variety '9901' by identifying the associated genes through RNA sequencing and comparing differential gene expression between the S. matsudana salt-tolerant and salt-sensitive samples treated with 150 mM NaCl. Transcriptomic comparison of the roots of the two samples revealed 2174 and 3159 genes responsive to salt stress in salt-sensitive and salt-tolerant sample, respectively. Real-time polymerase chain reaction analysis of 9 of the responsive genes revealed a strong, positive correlation with RNA sequencing data. The genes were enriched in several pathways, including carbon metabolism pathway, plant-pathogen interaction pathway, and plant hormone signal transduction pathway. Differentially expressed genes (DEGs) encoding transcription factors associated with abiotic stress responses and salt stress response network were identified; their expression levels differed between the two samples in response to salt stress. Hub genes were also revealed by weighted gene co-expression network (WGCNA) analysis. For functional analysis of the DEG encoding sedoheptulose-1,7-bisphosphatase (SBPase), the gene was overexpressed in transgenic Arabidopsis, resulting in increased photosynthetic rates, sucrose and starch accumulation, and enhanced salt tolerance. Further functional characterization of other hub DEGs will reveal the molecular mechanism of salt tolerance in S. matsudana and allow the application of S. matsudana in coastal afforestation.