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This study aimed to evaluate repression of Klotho on unilateral ureteral obstruction (UUO)-induced renal fibrosis and endothelial-to-mesenchymal transition (EndoMT) in mice. Renal fibrosis model was established by UUO in C57BL/6 male mice. Recombinant Klotho protein was administered to UUO mice as treatment group, and the mice in sham and UUO group were administered with an equal volume of vehicle. EndoMT biomarkers and TGF-β1/Smad2/Snail1 signaling were examined by immunofluorescence, immunohistochemistry, and western blotting assays. UUO deteriorated kidney function and resulted in increased expression of the mesenchymal marker α-smooth muscle actin and decreased expression of vascular endothelial cadherin, an endothelial marker. Moreover, UUO enhanced TGF-β1, phosphorylated Smad2 (p-Smad2), and Snail1 expression. Interestingly, Klotho treatment suppressed UUO-induced TGF-β1, p-Smad3, and Snail1 expression, which was accompanied by alleviation of the EndoMT process. Our findings demonstrated that Klotho significantly ameliorated EndoMT progression by targeting TGF-β1/Smad/Snail1 signaling in UUO mice, which provides the possibility for Klotho-based therapeutic protection against renal fibrosis.

In situ vaccination is a promising strategy to convert the immunosuppressive tumor microenvironment into an immunostimulatory one with limited systemic exposure and side effect. However, sustained clinical benefits require long-term and multidimensional immune activation including innate and adaptive immunity. Here, we develop a probiotic food-grade Lactococcus lactis -based in situ vaccination (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 ligand and co-stimulator OX40 ligand. Intratumoural delivery of FOLactis contributes to local retention and sustained release of therapeutics to thoroughly modulate key components of the antitumour immune response, such as activation of natural killer cells, cytotoxic T lymphocytes, and conventional-type-1-dendritic cells in the tumors and tumor-draining lymph nodes. In addition, intratumoural administration of FOLactis induces a more robust tumor antigen-specific immune response and superior systemic antitumour efficacy in multiple poorly immune cell-infiltrated and anti-PD1-resistant tumors. Specific depletion of different immune cells reveals that CD8 + T and natural killer cells are crucial to the in situ vaccine-elicited tumor regression. Our results confirm that FOLactis displays an enhanced antitumour immunity and successfully converts the ‘cold’ tumors to ‘hot’ tumors. The probiotic Lactococcus lactis has been used for the delivery of therapeutic molecules. Here the authors engineer Lactococcus lactis to express a fusion protein of Flt3L and OX40 ligand, eliciting anti-tumor immune response in preclinical cancer models.

The mechanisms for physiological senescence in bamboo shoots after harvest remain unclear. This study investigated physiological changes in Fargesia yunnanensis shoots during storage at different temperatures. The relationship between morphological and physiological changes in bamboo shoots during storage was also analyzed. The results show that cold storage can reduce weight loss, browning, respiration rates, and sugar degradation in bamboo shoots; decrease related enzymatic activities; and inhibit the increase in lignin and cellulose content. The quality of bamboo shoots declines more during the first 3d after harvesting than it does during subsequent periods. The increase in the degree of lignification and fibrosis is the main reason for senescence and for the decline in quality of bamboo shoots after harvest. The bamboo shoots under RT conditions began browning during the third 3d of storage, with a browning rate of 688gkg −1 even in the upper parts; the increase in shoot browning degrees significantly decreased the quality. Low temperatures had better inhibitory effects on browning than they did on lignification and fibrosis. Nonstructural carbohydrates in bamboo shoots are degraded and flow into sheath and shoot respiration, phenols, and shoot fibrosis and lignification at room temperature, but only flow into sheath respiration, shoot fibrosis, and lignification at cold temperature. Soluble protein and free amino acids are primarily distributed into shoot and sheath respiration and into phenols at room temperature, but that process is well inhibited at cold temperature. Bamboo shoots, once removed from cold storage, should be consumed rapidly because enzyme activity recovers quickly. This research provides new theoretical information on the preservation of bamboo shoots.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease which seriously affects public health. Gut microbiota remains a dynamic balance state in healthy individuals, and its disorder may affect health status and even results in metabolic diseases. Quercetin, a natural flavonoid, has been shown to have biological activities that can be used in the prevention and treatment of metabolic diseases. This study aimed to explore the mechanism of quercetin in alleviating T2DM based on gut microbiota. db/db mice were adopted as the model for T2DM in this study. After 10 weeks of administration, quercetin could significantly decrease the levels of body weight, fasting blood glucose (FBG), serum insulin (INS), the homeostasis model assessment of insulin resistance (HOMA-IR), monocyte chemoattractant protein-1 (MCP-1), D-lactic acid (D-LA), and lipopolysaccharide (LPS) in db/db mice. 16S rRNA gene sequencing and untargeted metabolomics analysis were performed to compare the differences of gut microbiota and metabolites among the groups. The results demonstrated that quercetin decreased the abundance of Proteobacteria, Bacteroides, Escherichia-Shigella and Escherichia_coli. Moreover, metabolomics analysis showed that the levels of L-Dopa and S-Adenosyl-L-methionine (SAM) were significantly increased, but 3-Methoxytyramine (3-MET), L-Aspartic acid, L-Glutamic acid, and Androstenedione were significantly decreased under quercetin intervention. Taken together, quercetin could exert its hypoglycemic effect, alleviate insulin resistance, repair the intestinal barrier, remodel the intestinal microbiota, and alter the metabolites of db/db mice.

Along with the progress of natural language processing technology and deep learning, the subjectivity, slow feedback, and long grading time of traditional English essay grading have been addressed. Intelligent English automatic scoring has been widely concerned by scholars. Given the limitations of topic relevance feature extraction methods and traditional automatic grading methods for English compositions, a topic decision model is proposed to calculate the topic relevance score of the topic richness in English composition. Then, based on the Score of Relevance Based on Topic Richness (TRSR) calculation method, an intelligent English composition scoring method combining artificial feature extraction and deep learning is designed. From the findings, the Topic Decision (TD) model achieved the best effect only when it was iterated 80 times. The corresponding accuracy, recall and F1 value were 0.97, 0.93 and 0.95 respectively. The model training loss finally stabilized at 0.03. The Intelligent English Composition Grading Method Integrating Deep Learning (DLIECG) method has the best overall performance and the best performance on dataset P. To sum up, the intelligent English composition scoring method has better effectiveness and reliability.

Temporomandibular disorders (TMD) intelligent diagnosis promises to elevate clinical efficiency and facilitate timely TMD management for patients. However, development of TMD intelligent diagnostic tools with high accuracy and sensitivity presents challenges, particularly in sensing minute deformations and ensuring rapid self-recovery. Here we report a biocompatible hydrogel electronic sensor with instantaneous self-recovery (within 2.1 s) and ultra-low detection limit (0.005% strain). It could efficiently diagnose disc displacement with reduction (DDwR) with satisfactory accuracy of 90.00%, and also had a clear indication of the typical clinical manifestations of DDwR and the timing of temporomandibular joint (TMJ) clicking, with a sensitivity of up to 100% in human compared to the diagnostic criteria for TMD (DC/TMD). Furthermore, a predictive model based on waveform features achieved 84.4% accuracy and 86% sensitivity, reducing dependence on physicians. In summary, the hydrogel sensor is expected to become a radiation-free, non-invasive, practical and effective tool for future TMD diagnosis. Clinical diagnosis of temporomandibular joint (TMJ) disorders is complex and requires evaluation by a qualified physician. Here, Yan et al. develop a hydrogel electronic sensor to detect TMJ movement, able to accurately detect and classify disc displacement with reduction, a common TMJ disorder.

A multi-drug delivery platform is needed as the intra-tumoral heterogeneity of cancer leads to different drug susceptibility. Cancer stem cells (CSCs), a small population of tumor cells responsible for tumor seeding and recurrence, are considered chemotherapy-resistant and have been reported to be sensitive to salinomycin (Sal) instead of paclitaxel (Ptx). Here we report a novel silk fibroin (SF) hydrogel-loading Sal and Ptx by incorporating drug-loaded silk fibroin nanoparticles (SF-NPs) to simultaneously kill CSCs and non-CSCs. Using the method we have previously reported to prepare Ptx-loaded SF-NPs (Ptx-SF-NPs), Sal-loaded SF-NPs (Sal-SF-NPs) were fabricated under mild and non-toxic conditions. The drug-loaded SF-NPs were dispersed in the ultrasound processed SF solution prior to gelation. The resulting SF hydrogel (Sal-Ptx-NP-Gel) retained its injectable properties, exhibited bio-degradability and demonstrated homogeneous drug distribution compared to the non-NP incorporated hydrogel. Sal-Ptx-NP-Gel showed superior inhibition of tumor growth compared to single drug-loaded hydrogel and systemic dual drug administration in the murine hepatic carcinoma H22 subcutaneous tumor model. Sal-Ptx-NP-Gel also significantly reduced CD44 CD133 tumor cells and demonstrated the least tumor formation in the in vivo tumor seeding experiment, indicating superior inhibition of cancer stem cells. These results suggest that SF-NPs incorporated SF hydrogel is a promising drug delivery platform, and Sal-Ptx-NP-Gel could be a novel and powerful locoregional tumor treatment regimen in the future.

Background To explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis. Methods The results of chromosome karyotype analysis and CMA of 477 cases undergoing amniocentesis were analyzed. The results of the no ultrasound abnormality group and the ultrasound abnormality group were compared separately. Within the ultrasound abnormality group, the results of the ultrasound structural malformation group, the ultrasound soft index abnormality group, and other ultrasound abnormality (including abnormal amniotic fluid volume and fetal growth restriction) groups were compared. Results Abnormal chromosome and CMA results were found in a total of 71 cases (15.88%, 71/447), which can be broken down into a total of 23 karyotype abnormalities (5.15%, 23/447), consisting of 18 cases of aneuploidy (4.03%, 18/447), 2 cases of unbalanced chromosome rearrangements (0.44%, 2/447), and 3 cases of chimerism (0.67%, 3/447); 17 cases with detection of pathogenic copy number variations (pCNVs) (3.80%, 17/447); and 31 cases of detection of clinical variants of unknown significance (VOUS) (6.93%, 31/447). CMA detected 3.8% more genetic abnormalities than karyotype analysis (in addition to the abnormalities detected simultaneously by karyotype analysis). Between the no ultrasound abnormality group and the ultrasound abnormality group, there was an extremely significant difference in the detection rate of an abnormal chromosomal karyotype ( P  < 0.01) and of VOUS ( P  < 0.01), but there was no significant difference in the detection rate of pCNV ( P > 0.05). Comparing the ultrasound structural malformation group, the ultrasound soft index abnormality group, and the other ultrasound abnormality group, there were no significant differences in the detection rate of abnormal chromosomal karyotypes ( P > 0.05), pCNV ( P > 0.05) or VOUS ( P > 0.05). Conclusions The detection rate of chromosomal karyotype abnormalities in prenatal diagnosis in cases with no ultrasound abnormalities was higher. For cases with fetal ultrasound structural abnormalities, when compared with traditional karyotype analysis, CMA can improve the detection rate of fetal genetic abnormalities. However, the no ultrasound abnormality group also had a high VOUS abnormality detection rate, so it is necessary to strictly define the CMA indications.

Pseudosasa subsolida belongs to the Pseudosasa genus within the Poaceae family. Due to its unique flowering cycle and the physiological traits associated with asexual reproduction, acquiring floral material from P . subsolida is particularly challenging. To investigate the causes of the low seed set rate in P. subsolida, floral organs and the development of male and female gametes were examined using conventional paraffin sectioning. The results revealed that the spikelet of P . subsolida exhibited the characteristics of a pseudospikelet with a latent bud, while the inflorescence displayed traits of an infinite inflorescence. Each spikelet contained approximately 10–16 florets and was accompanied by two bracts at its base. The fundamental structure of the florets comprised one lemma, one palea, three lodicules, three stamens, and one pistil. At the later stages of anther development, some abnormalities were observed, including the failure of pollen grains to form, deformation and shrinkage of the cells in the anther sac and tapetum, loss of the cells in the middle layer, cavitation of the microspores, and no identifiable contents The study concluded that the primary factor contributing to the low seed setting rate of P . subsolida was the aberrant development of male gametophytes. The significance of this study lay in its pioneering exploration of the reproductive structure of P . subsolida , and provide a theoretical reference for the fundamental examination of flower structure.

Red blood cell membrane-coated nanoparticle (RBCm-NP) platform, which consist of natural RBCm and synthetic polymeric core, can extend circulation time in vivo with an improved biocompatibility and stability of this biomimetic nanocarrier. To achieve better bioavailability of antitumor drugs that were loaded in RBCm-NPs, the functionalization of coated RBCm with specific targeting ability is essential. Bispecific recombinant protein anti-EGFR-iRGD, containing both tumor penetrating peptide (internalizing RGD peptide) and EGFR single-domain antibody (sdAb), seems to be an optimal targeting ligand for RBCm-NPs in the treatment of multiple tumors, especially colorectal cancer with high EGFR expression. We modified the anti-EGFR-iRGD recombinant protein on the surface of RBCm-NPs by lipid insertion method to construct iE-RBCm-PLGA NPs and confirmed the presentation of active tumor-targeting ability in colorectal cancer models with high EGFR expression when compared with RBCm-PLGA NPs. In addition, potential anti-tumor drug gambogic acid (GA) was loaded into the NPs to endow the antitumor efficiency of iE-RBCm-GA/PLGA NPs. It was simultaneously evaluated whether GA can reach better biocompatibility benefiting from the improved antitumor efficiency of iE-RBCm-GA/PLGA NPs in colorectal cancer models. We successfully modified anti-EGFR-iRGD proteins on the surface of biomimetic NPs with integrated and stable \"shell-core\" structure. iE-RBCm-PLGA NPs showed its improved targeting ability in vitro (multicellular spheroids [MCS]) and in vivo (nude mice bearing tumors). Besides, no matter on short-term cell apoptosis at tumor site (terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) and long-term tumor inhibition, iE-RBCm-GA/PLGA NPs achieved better antitumor efficacy than free GA in spite of the similar effects of cytotoxicity and apoptosis to GA in vitro. We expect that the bispecific biomimetic nanocarrier can extend the clinical application of many other potential antitumor drugs similar to GA and become a novel drug carrier in the colorectal cancer treatment.