Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

How to boost an obstetrician's confidence in vaginal delivery after high-intensity focused ultrasound: a comparison study on delivery outcomes.

OBJECTIVE: To assess the feasibility of vaginal delivery after HIFU. METHODS: A total of 37 women who met the trial of labor after HIFU (TOLAH) inclusion criteria and 368 women who met the trial of labor after cesarean delivery (TOLAC) inclusion criteria gave birth at Shanghai First Maternity and Infant Hospital between 14th June 2018 and 24th September 2021. The delivery outcomes of the two groups were compared. Multivariable logistic regression analysis was used to estimate the adjusted risk of postpartum hemorrhage (PPH). RESULTS: In the Qualified Candidates for TOLAH group, vaginal delivery is substantially less common (p = 0.000). The prevalence of PPH in the Qualified Candidates for TOLAH group is lower than in the Candidates for TOLAC group (8.82% vs 10.51%, p = 0.534; 0% vs 2.51%, p = 0.418). Hemoglobin drop in the Qualified Candidates for TOLAH group is also lower (7.03 ± 7.39vs 12.11 ± 12.62, p = 0.001). The rate of using more than two types of uterotonic medications to promote contraction is significantly lower in the Qualified Candidates for TOLAH group (54.05% vs 69.84%, p = 0.04), and the percentage of abnormal uterine contraction is lower in the Qualified Candidates for TOLAH group (35.14% vs 49.18%, p = 0.072). PPH is strongly predicted by abnormal uterine contraction (aOR: 17.177, 95% CI:5.046 ∼ 58.472, p = 0.000), but not by HIFU (aOR:1.105; 95% CI:0.240 ∼ 5.087, p = 0.898). No uterine rupture occurred in the cases after HIFU. CONCLUSIONS: No uterine rupture occurred in our study group after HIFU. HIFU is not a risk for PPH. It is promising for those after HIFU to choose vaginal delivery.

Photoresponse-Bias Modulation of a High-Performance MoS2 Photodetector with a Unique Vertically Stacked 2H-MoS2/1T@2H-MoS2 Structure.

Monolayer 2H-phase MoS2-based photodetectors exhibit high photon absorption but suffer from low photoresponse, which severely limits their applications in optoelectronic fields. The metallic 1T phase of MoS2, while transporting carriers faster, shows negligible response to visible light, which limits its usage in photodetectors. Herein, we propose an ultrafast-response MoS2-based photodetector having a channel that consists of a 2H-MoS2 sensitizing monolayer on top of 1T@2H-MoS2. The 1T@2H-MoS2 layer has a thickness of several nanometers and is a mixture of metallic 1T-MoS2 and semiconducting 2H-MoS2, imparting metal-like properties to the photodetector. Compared with the monolayer 2H-MoS2 photodetector, we observed a drastic increase in the photoresponse of the 2H-MoS2/1T@2H-MoS2 vertically stacked photodetector to a value of 1917 A W-1. Owing to the presence of metallic 1T-MoS2 within the metal-like 1T@2H-MoS2, the performance of the 2H-MoS2/1T@2H-MoS2 vertically stacked photodetector is voltage bias-modulated with an external quantum efficiency (EQE) of up to 448,384% and a specific detectivity of up to ∼1011 Jones. The higher carrier density and higher mobility of the 1T@2H-MoS2 layer explain the better bias-modulated performance. In addition, the interface between 2H-MoS2 and 1T@2H-MoS2 ensures fewer dangling bonds and reduced lattice mismatching. Thus, this study presents an exclusive vertically stacked MoS2-based photodetector that lays the foundation for the development of photodetectors exhibiting higher photoresponse.

The Relationship Analysis on Corn Stalk Rot and Ear Rot According to Fusarium Species and Fumonisin Contamination in Kernels.

Fusarium diseases, including corn root rot, sheath rot, stalk rot, and ear rot are frequently occurring in maize producing areas of China. Fusarium stalk rot and ear rot are the most serious diseases and often occur at the same time, but it is unclear whether there is a correlation between Fusarium composition and disease occurrence. This study was conducted to clarify the relationship between the two diseases. A total of 49 corn stalk rot samples were collected from 15 regions of eight provinces in China from 2016 to 2018. The pathogens were isolated and identified separately from stalks, ear stems, and kernels. The contents of the fumonisins (FB1 and FB2) were detected in kernels. The results showed that the main Fusarium species were found in corn kernels, ear stems and stalks at the same time. The results showed that 1201 strains of Fusarium verticillioides, 668 strains of Fusarium oxysporum, 574 strains of Fusarium graminearum species complex (FGSC), 318 strains of Fusarium equiseti, 95 strains of Fusarium proliferatum, and 40 strains of Fusarium subglutinans were isolated from 1470 corn kernels, 245 ear stems, and 1225 stalks randomly selected from 49 samples. The contamination rate of fumonisins in the 49 samples was 57.1% with an average content of 1.9 µg/g, of which four samples exhibited higher levels as set by the European Commission (4.0 µg/g). These results provide a certain association between stalk rot and ear rot and lay a foundation to study the relationships among Fusarium maize diseases.

A simple computer vision pipeline reveals the effects of isolation on social interaction dynamics in Drosophila.

Isolation profoundly influences social behavior in all animals. In humans, isolation has serious effects on health. Drosophila melanogaster is a powerful model to study small-scale, temporally-transient social behavior. However, longer-term analysis of large groups of flies is hampered by the lack of effective and reliable tools. We built a new imaging arena and improved the existing tracking algorithm to reliably follow a large number of flies simultaneously. Next, based on the automatic classification of touch and graph-based social network analysis, we designed an algorithm to quantify changes in the social network in response to prior social isolation. We observed that isolation significantly and swiftly enhanced individual and local social network parameters depicting near-neighbor relationships. We explored the genome-wide molecular correlates of these behavioral changes and found that whereas behavior changed throughout the six days of isolation, gene expression alterations occurred largely on day one. These changes occurred mostly in metabolic genes, and we verified the metabolic changes by showing an increase of lipid content in isolated flies. In summary, we describe a highly reliable tracking and analysis pipeline for large groups of flies that we use to unravel the behavioral, molecular and physiological impact of isolation on social network dynamics in Drosophila.

Spatial-Resolution Cell Type Proteome Profiling of Cancer Tissue by Fully Integrated Proteomics Technology.

Increasing attention has been focused on cell type proteome profiling for understanding the heterogeneous multicellular microenvironment in tissue samples. However, current cell type proteome profiling methods need large amounts of starting materials which preclude their application to clinical tumor specimens with limited access. Here, by seamlessly combining laser capture microdissection and integrated proteomics sample preparation technology SISPROT, specific cell types in tumor samples could be precisely dissected with single cell resolution and processed for high-sensitivity proteome profiling. Sample loss and contamination due to the multiple transfer steps are significantly reduced by the full integration and noncontact design. H&E staining dyes which are necessary for cell type investigation could be selectively removed by the unique two-stage design of the spintip device. This easy-to-use proteome profiling technology achieved high sensitivity with the identification of more than 500 proteins from only 0.1 mm2 and 10 µm thickness colon cancer tissue section. The first cell type proteome profiling of four cell types from one colon tumor and surrounding normal tissue, including cancer cells, enterocytes, lymphocytes, and smooth muscle cells, was obtained. 5271, 4691, 4876, and 2140 protein groups were identified, respectively, from tissue section of only 5 mm2 and 10 µm thickness. Furthermore, spatially resolved proteome distribution profiles of enterocytes, lymphocytes, and smooth muscle cells on the same tissue slices and across four consecutive sections with micrometer distance were successfully achieved. This fully integrated proteomics technology, termed LCM-SISPROT, is therefore promising for spatial-resolution cell type proteome profiling of tumor microenvironment with a minute amount of clinical starting materials.

Loss of Asxl2 leads to myeloid malignancies in mice.

ASXL2 is frequently mutated in acute myeloid leukaemia patients with t(8;21). However, the roles of ASXL2 in normal haematopoiesis and the pathogenesis of myeloid malignancies remain unknown. Here we show that deletion of Asxl2 in mice leads to the development of myelodysplastic syndrome (MDS)-like disease. Asxl2-/- mice have an increased bone marrow (BM) long-term haematopoietic stem cells (HSCs) and granulocyte-macrophage progenitors compared with wild-type controls. Recipients transplanted with Asxl2-/- and Asxl2+/- BM cells have shortened lifespan due to the development of MDS-like disease or myeloid leukaemia. Paired daughter cell assays demonstrate that Asxl2 loss enhances the self-renewal of HSCs. Deletion of Asxl2 alters the expression of genes critical for HSC self-renewal, differentiation and apoptosis in Lin-cKit+ cells. The altered gene expression is associated with dysregulated H3K27ac and H3K4me1/2. Our study demonstrates that ASXL2 functions as a tumour suppressor to maintain normal HSC function.

ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis.

ASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice; however, the underlying molecular mechanisms remain unclear. We report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromatid segregation and regulate gene expression. Loss of Asxl1 impairs the cohesin function, as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. Chromatin immunoprecipitation followed by DNA sequencing data revealed that ASXL1, RAD21, and SMC1A share 93% of genomic binding sites at promoter regions in Lin-cKit+ (LK) cells. We have shown that loss of Asxl1 reduces the genome binding of RAD21 and SMC1A and alters the expression of ASXL1/cohesin target genes in LK cells. Our study underscores the ASXL1-cohesin interaction as a novel means to maintain normal sister chromatid separation and regulate gene expression in hematopoietic cells.

Cytoplasmic Drosha activity generated by alternative splicing.

RNase III enzyme Drosha interacts with DGCR8 to form the Microprocessor, initiating canonical microRNA (miRNA) maturation in the nucleus. Here, we re-evaluated where Drosha functions in cells using Drosha and/or DGCR8 knock out (KO) cells and cleavage reporters. Interestingly, a truncated Drosha mutant located exclusively in the cytoplasm cleaved pri-miRNA effectively in a DGCR8-dependent manner. In addition, we demonstrated that in vitro generated pri-miRNAs when transfected into cells could be processed to mature miRNAs in the cytoplasm. These results indicate the existence of cytoplasmic Drosha (c-Drosha) activity. Although a subset of endogenous pri-miRNAs become enriched in the cytoplasm of Drosha KO cells, it remains unclear whether pri-miRNA processing is the main function of c-Drosha. We identified two novel in-frame Drosha isoforms generated by alternative splicing in both HEK293T and HeLa cells. One isoform loses the putative nuclear localization signal, generating c-Drosha. Further analysis indicated that the c-Drosha isoform is abundant in multiple cell lines, dramatically variable among different human tissues and upregulated in multiple tumors, suggesting that c-Drosha plays a unique role in gene regulation. Our results reveal a new layer of regulation on the miRNA pathway and provide novel insights into the ever-evolving functions of Drosha.

Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands.

Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response to Haemonchus infection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 × 10(-4)). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair, and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed.

RNA-seq analysis of glycosylation related gene expression in STZ-induced diabetic rat kidney inner medulla.

UNLABELLED: The UT-A1 urea transporter is crucial to the kidney's ability to generate concentrated urine. Native UT-A1 from kidney inner medulla (IM) is a heavily glycosylated protein with two glycosylation forms of 97 and 117 kDa. In diabetes, UT-A1 protein abundance, particularly the 117 kD isoform, is significantly increased corresponding to an increased urea permeability in perfused IM collecting ducts, which plays an important role in preventing the osmotic diuresis caused by glucosuria. However, how the glycan carbohydrate structure change and the glycan related enzymes regulate kidney urea transport activity, particularly under diabetic condition, is largely unknown. In this study, using sugar-specific binding lectins, we found that the carbohydrate structure of UT-A1 is changed with increased amounts of sialic acid, fucose, and increased glycan branching under diabetic conditions. These changes were accompanied by altered UT-A1 association with the galectin proteins, ß-galactoside glycan binding proteins. To explore the molecular basis of the alterations of glycan structures, the highly sensitive next generation sequencing (NGS) technology, Illumina RNA-seq, was employed to analyze genes involved in the process of UT-A1 glycosylation using streptozotocin (STZ)-induced diabetic rat kidney. Differential gene expression analysis combining with quantitative PCR revealed that expression of a number of important glycosylation related genes were changed under diabetic conditions. These genes include the glycosyltransferase genes Mgat4a, the sialylation enzymes St3gal1 and St3gal4 and glycan binding protein galectin-3, -5, -8, and -9. In contrast, although highly expressed in kidney IM, the glycosyltransferase genes Mgat1, Mgat2, and fucosyltransferase Fut8, did not show any changes. CONCLUSIONS: In diabetes, not only is UT-A1 protein abundance increased but the protein's glycan structure is also significantly changed. UT-A1 protein becomes highly sialylated, fucosylated and branched. Consistently, a number of crucial glycosylation related genes are changed under diabetic conditions. The alteration of these genes may contribute to changes in the UT-A1 glycan structure and therefore modulate kidney urea transport activity and alleviate osmotic diuresis caused by glucosuria in diabetes.

RNASeqMetaDB: a database and web server for navigating metadata of publicly available mouse RNA-Seq datasets.

UNLABELLED: Gene targeting is a protocol for introducing a mutation to a specific gene in an organism. Because of the importance of in vivo assessment of gene function and modeling of human diseases, this technique has been widely adopted to generate a large number of mutant mouse models. Due to the recent breakthroughs in high-throughput sequencing technologies, RNA-Seq experiments have been performed on many of these mouse models, leading to hundreds of publicly available datasets. To facilitate the reuse of these datasets, we collected the associated metadata and organized them in a database called RNASeqMetaDB. The metadata were manually curated to ensure annotation consistency. We developed a web server to allow easy database navigation and data querying. Users can search the database using multiple parameters like genes, diseases, tissue types, keywords and associated publications in order to find datasets that match their interests. Summary statistics of the metadata are also presented on the web server showing interesting global patterns of RNA-Seq studies. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://rnaseqmetadb.ece.tamu.edu.

Changes of blood-brain barrier permeability following intracerebral hemorrhage and the therapeutic effect of minocycline in rats.

OBJECTIVE: to investigate the changes of blood-brain barrier (BBB) permeability and expressions of VEGF, NGF and HPS70 in brain at different time points following intracerebral hemorrhage (ICH) in rats, and observe therapeutic effect of minocycline (MC). METHODS: rat ICH model was induced with Type IV collagenase. Early MC treatment was administrated via intraperitoneal injection. BBB permeability was evaluated by Evans blue (EB) amount exuded out of cerebral vessels. VEGF, NGF, and HPS70 expressions were determined with immunohistochemical staining. RESULTS: EB exudation amount in MC treatment group was less than the ICH group (P < 0.05). The former showed a transient EB exudation peak only 1 h after modeling and then gradually decreased, while the latter showed two EB exudation peaks 1 and 4 days after modeling, respectively. The number of VEGF-positive cells in MC treatment group was less than the ICH group (P < 0.05), whereas the number of NGF- and HSP70-positive cells were more than the ICH group (P < 0.05). All three were mainly expressed in neurons and gitter cells, but there were only few expressions in the control group. CONCLUSION: after ICH, the BBB permeability was destroyed, with neuron function affected. In the early stage, VEGF increased BBB permeability, while NGF and HSP70 showed protective effects on nerve cells. Early intraperitoneal injection with MC could reduce the damage of BBB and increase the protective effect on nerve cells, the mechanism of which may be achieved by reducing VEGF expression and enhancing NGF and HSP70 expressions.