In-situ evaluation the fluctuation of hypochlorous acid in acute liver injury mice models with a mitochondria-targeted NIR ratiometric fluorescent probe.

Acute liver injury (ALI) is a frequent and devastating liver disease that has been made more prevalent by the excessive use of chemicals, drugs, and alcohol in modern life. Hypochlorous acid (HClO), an important biomarker of oxidative stress originating mainly from the mitochondria, has been shown to be intimately connected to the development and course of ALI. Herein, a novel BODIPY-based NIR ratiometric fluorescent probe Mito-BS was constructed for the specific recognition of mitochondrial HClO. The probe Mito-BS can rapidly respond to HClO within 20 s with a ratiometric fluorescence response (from 680 nm to 645 nm), 24-fold fluorescence intensity ratio enhancement (I645/I680), a wide pH adaptation range (5-9) and the low detection limit (31 nM). The probe Mito-BS has been effectively applied to visualize endogenous and exogenous HClO fluctuations in living zebrafish and cells based on its low cytotoxicity and prominent mitochondria-targeting ability. Furthermore, the fluorescent probe Mito-BS makes it possible to achieve the non-invasive in-situ diagnosis of ALI through in mice, and provides a feasible strategy for early diagnosis and drug therapy of ALI and its complications.

Learnable Feature Augmentation Framework for Temporal Action Localization.

Temporal action localization (TAL) has drawn much attention in recent years, however, the performance of previous methods is still far from satisfactory due to the lack of annotated untrimmed video data. To deal with this issue, we propose to improve the utilization of current data through feature augmentation. Given an input video, we first extract video features with pre-trained video encoders, and then randomly mask various semantic contents of video features to consider different views of video features. To avoid damaging important action-related semantic information, we further develop a learnable feature augmentation framework to generate better views of videos. In particular, a Mask-based Feature Augmentation Module (MFAM) is proposed. The MFAM has three advantages: 1) it captures the temporal and semantic relationships of original video features, 2) it generates masked features with indispensable action-related information, and 3) it randomly recycles some masked information to ensure diversity. Finally, we input the masked features and the original features into shared action detectors respectively, and perform action classification and localization jointly for model learning. The proposed framework can improve the robustness and generalization of action detectors by learning more and better views of videos. In the testing stage, the MFAM can be removed, which does not bring extra computational costs. Extensive experiments are conducted on four TAL benchmark datasets. Our proposed framework significantly improves different TAL models and achieves the state-of-the-art performances.

Optimizing enzyme properties to enhance dihydroxyacetone production via methylglyoxal biosensor development.

BACKGROUND: Dihydroxyacetone (DHA) stands as a crucial chemical material extensively utilized in the cosmetics industry. DHA production through the dephosphorylation of dihydroxyacetone phosphate, an intermediate product of the glycolysis pathway in Escherichia coli, presents a prospective alternative for industrial production. However, insights into the pivotal enzyme, dihydroxyacetone phosphate dephosphorylase (HdpA), remain limited for informed engineering. Consequently, the development of an efficient tool for high-throughput screening of HdpA hypermutants becomes imperative. RESULTS: This study introduces a methylglyoxal biosensor, based on the formaldehyde-responding regulator FrmR, for the selection of HdpA. Initial modifications involved the insertion of the FrmR binding site upstream of the -35 region and into the spacer region between the -10 and -35 regions of the constitutive promoter J23110. Although the hybrid promoter retained constitutive expression, expression of FrmR led to complete repression. The addition of 350 µM methylglyoxal promptly alleviated FrmR inhibition, enhancing promoter activity by more than 40-fold. The methylglyoxal biosensor system exhibited a gradual increase in fluorescence intensity with methylglyoxal concentrations ranging from 10 to 500 µM. Notably, the biosensor system responded to methylglyoxal spontaneously converted from added DHA, facilitating the separation of DHA producing and non-producing strains through flow cytometry sorting. Subsequently, the methylglyoxal biosensor was successfully applied to screen a library of HdpA mutants, identifying two strains harboring specific mutants 267G > T and D110G/G151C that showed improved DHA production by 68% and 114%, respectively. Expressing of these two HdpA mutants directly in a DHA-producing strain also increased DHA production from 1.45 to 1.92 and 2.29 g/L, respectively, demonstrating the enhanced enzyme properties of the HdpA mutants. CONCLUSIONS: The methylglyoxal biosensor offers a novel strategy for constructing genetically encoded biosensors and serves as a robust platform for indirectly determining DHA levels by responding to methylglyoxal. This property enables efficiently screening of HdpA hypermutants to enhance DHA production.

Mechanisms underlying LncRNA SNHG1 regulation of Alzheimer's disease involve DNA methylation.

Alzheimer's disease (AD) is a neurodegenerative disease associated with long non-coding RNAs and DNA methylation; however, the mechanisms underlying the role of lncRNA small nucleolar RNA host gene 1 (lncRNA SNHG1) and subsequent involvement of DNA methylation in AD development are not known. The aim of this study was to examine the regulatory mechanisms attributed to lncRNA SNHG1 gene utilizing 2 strains of senescence-accelerated mouse prone 8 (SAMP8) model of AD and compared to senescence-accelerated mouse resistant (SAMR) considered a control. Both strains of the mouse were transfected with either blank virus, psLenti-U6-SNHG1(low gene expression) virus, and psLenti-pA-SNHG1(gene overexpression) virus via a single injection into the brains for 2 weeks. At 2 weeks mice were subjected to a Morris water maze to determine any behavioral effects followed by sacrifice to extract hippocampal tissue for Western blotting to measure protein expression of p-tau, DNMT1, DNMT3A, DNMT3B, TET1, and p-Akt. No marked alterations were noted in any parameters following blank virus transfection. In SAMP8 mice, a significant decrease was noted in protein expression of DNMT1, DNMT3A, DNMT3B, and p-Akt associated with rise in p-tau and TET1. Transfection with ps-Lenti-U6-SNHG1 alone in SAMR1 mice resulted in a significant rise in DNMTs and p-Akt and a fall in p-tau and TET1. Transfection of SAMP8 with ps-Lenti-U6-SNHG1 blocked effects on overexpression noted in this mouse strain. However, knockdown of lncRNA SNHG1 yielded the opposite results as found in SAMR1 mice. In conclusion, the knockdown of lncRNA SNHG1 enhanced DNA methylation through the PI3K/Akt signaling pathway, thereby reducing the phosphorylation levels of tau in SAMP8 AD model mice with ameliorating brain damage attributed to p-tau accumulation with consequent neuroprotection.

Part-Object Progressive Refinement Network for Zero-Shot Learning.

Zero-shot learning (ZSL) recognizes unseen images by sharing semantic knowledge transferred from seen images, encouraging the investigation of associations between semantic and visual information. Prior works have been devoted to the alignment of global visual features with semantic information, i.e., attribute vectors, or further mining the local part regions related to each attribute and then simply concatenating them for category decisions. Although effective, these works ignore intrinsic interactions between local parts and the whole object, which enables a more discriminative and representative knowledge transfer for ZSL. In this paper, we propose a Part-Object Progressive Refinement Network (POPRNet), where discriminative and transferable semantics are progressively refined by the cooperation between parts and the whole object. Specifically, POPRNet incorporates discriminative part semantics and object-centric semantics guided by semantic intensity to improve cross-domain transferability. To achieve part-object learning, a semantic-augment transformer (SaT) is proposed to model the part-object relation at the part-level via an encoder and at the object-level via a decoder, generating a comprehensive semantic representation to boost discriminability and transferability. By introducing the prototype updating module embedded with the prototype selection layers, the discriminative ability of the updated category prototype is enhanced to further improve the recognition performance of ZSL. Extensive experiments are conducted to demonstrate the superiority and competitiveness of our proposed POPRNet method on three public benchmark datasets. The code is available at https://github.com/ManLiuCoder/POPRNet.

Isolation, identification and characterization of Aeromonas jandaei from diseased Chinese soft-shell turtles.

Aeromonas jandaei is a gram-negative bacterium commonly found in aquatic environments and can induce illnesses in amphibians, reptiles and aquatic animals. In this study, a strain of bacteria was isolated from the diseased Chinese soft-shell turtle (Pelodiscus sinensis), then named strain JDP-FX. This isolate was identified as A. jandaei after analysis of morphological, physiological and biochemical characteristics, as well as 16S rRNA and gyrB gene sequences. Virulence genetic testing further detected temperature-sensitive protease (eprCAI), type III secretion system (TTSS) (ascv), nuclease (nuc), cytotonic enterotoxin (alt) and serine proteinase (ser) in JDP-FX. Compared with healthy Chinese soft-shell turtle, the serum levels of total protein (TP), albumin (ALB) and globulin (GLB) were significantly decreased in the diseased Chinese soft-shell turtle, while, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly increased. Histopathological observations showed that multiple tissues, including intestinal mucosa, liver and kidney, were severely damaged in the diseased Chinese soft-shell turtle. Moreover, the diseased Chinese soft-shell turtle had significant cell degeneration, necrosis, sloughing and interstitial inflammatory cell infiltration. The pathogenicity of JDP-FX was tested via artificial infection. The median lethal dosage (LD50 ) of the strain was 1.05 × 105 colony forming units (CFU/g) per weight of Chinese soft-shell turtle. Drug susceptibility analysis revealed that JDP-FX was susceptible to ceftazidime, minocycline, cefoperazone, ceftriaxone and piperacillin. In addition, JDP-FX was resistant to doxycycline, florfenicol, sulfonamides, gentamicin, ampicillin and neomycin. Therefore, this study may provide guidance for further research into the diagnosis, prevention and treatment of JDP-FX infection.

Isolation and identification of Chryseobacterium indologenes and its pathological changes in Pelodiscus sinensis.

The Chinese revered a species of aquatic reptile known as Pelodiscus sinensis as both an edible and medicinal species. When artificially breeding, many deaths occurred at the farmed P. sinensis, mainly due to excessive breeding density, water contamination, and turtles biting each other secondary to bacterial infections. In this study, an isolate of gram-negative bacteria WH0623 was isolated from the liver and kidney of diseased P. sinensis to trace the potential pathogen of this disease. Based on biochemical characteristics and 16S rRNA gene sequencing analyses, this isolated strain of WH0623 was identified as Chryseobacterium indologenes. The strain's median lethal dose (LD50 ) was 3.3 × 105 colony-forming units (CFU)/g per fish weight tested using artificial infection. Histopathological analysis revealed pathological changes, including cell swelling, hyperaemia, and necrosis in many tissues. Antibiotic susceptibility tests revealed that the bacteria WH0623 was susceptible to doxycycline, sulphonamides, ceftazidime, norfloxacin, and ciprofloxacin. These antibiotics could treat the disease. In conclusion, the pathogen causing the death of farmed P. sinensis was isolated and identified, and a drug-sensitive test was conducted. Our findings contribute to the future diagnosis and treatment of the disease.

Comparison of Different Decompensation Approaches on Facial Profile in Orthodontic-Orthognathic Treatment for Skeletal Class III Patients.

BACKGROUND: The objective of the present study was to assess the hard and soft tissue differences of skeletal Class III malocclusion patients treated with orthodontic-orthognathic surgery treatment between two decompensation approaches including extraction of maxillary premolars in preoperative orthodontics and clockwise rotation of the maxilla in orthognathic surgery. METHODS: 22 skeletal Class III patients with the crowding of maxillary dental arch less than 3mm were included in this study. These patients were divided into two groups: extraction group and non-extraction group. Lateral cephalograms taken before preoperative orthodontic treatment and after postoperative orthodontic treatment were used to analyze the differences of hard and soft tissues between two groups. Independent t test was used to evaluate the differences of variables between extraction group and non-extraction group. RESULTS: After treatment, there was significant difference of Wits between extraction group and non-extraction group (- 4.34 mm vs - 2.82 mm, respectively, P <0.05). Co-Gn was significantly greater in non-extraction group than in extraction group (77.18 mm vs 71.58 mm, P <0.05). U1-SN and L1-MP in extraction group were significantly closer to the normal values than non-extraction group (P <0.05). Regarding the change of variables before and after orthodontic-orthognathic treatment, NLA (7.25° vs 1.46°, P <0.01) and G-Sn-Pog' (8.06° vs 4.62°, P <0.05) were significantly greater in extraction group than in non-extraction group. CONCLUSION: For patients with skeletal Class III malocclusion, extraction of maxillary premolars in preoperative orthodontic treatment can more effectively eliminate the dental compensation and achieve a more harmonious facial profile compared to clockwise rotation of the maxilla in orthognathic surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of Listeria monocytogenes in Melanoma.

Listeria monocytogenes has been shown to exhibit antitumor effects. However, the mechanism remains unclear. Autophagy is a cellular catabolic process that mediates the degradation of unfolded proteins and damaged organelles in the cytosol, which is a double-edged sword in tumorigenesis and treatment outcome. Tumor cells display lower levels of basal autophagic activity than normal cells. This study examined the role and molecular mechanism of autophagy in the antitumor effects induced by LM, as well as the combined antitumor effect of LM and the autophagy inhibitor chloroquine (CQ). We investigated LM-induced autophagy in B16F10 melanoma cells by real-time PCR, immunofluorescence, Western blotting, and transmission electron microscopy and found that autophagic markers were increased following the infection of tumor cells with LM. The autophagy pathway in B16F10 cells was blocked with the pharmacological autophagy inhibitor chloroquine, which led to a significant increase in intracellular bacterial multiplication in tumor cells. The combination of CQ and LM enhanced LM-mediated cancer cell death and apoptosis compared with LM infection alone. Furthermore, the combination of LM and CQ significantly inhibited tumor growth and prolonged the survival time of mice in vivo, which was associated with the increased colonization and accumulation of LM and induced more cell apoptosis in primary tumors. The data indicated that the inhibition of autophagy by CQ enhanced LM-mediated antitumor activity in vitro and in vivo and provided a novel strategy to improving the anticancer efficacy of bacterial treatment.

Integrating highly active graphite nanosheets into microspheres for enhanced lithium storage properties of silicon.

Integrating silicon (Si) and graphitic carbon into micron-sized composites by spray-drying holds great potential in developing advanced anodes for high-energy-density lithium-ion batteries (LIBs). However, common graphite particles as graphitic carbon are always too large in three-dimensional size, resulting in inhomogeneous hybridization with nanosized Si (NSi); in addition, the rate capability of graphite is poor owing to sluggish intercalation kinetics. Herein, we integrated graphite nanosheets (GNs) with NSi to prepare porous NSi-GN-C microspheres by spray-drying and subsequent calcination with the assistance of glucose. Two-dimensional GNs with average thickness of ∼80 nm demonstrate superior lithium storage capacity, high conductivity, and flexibility, which could improve the electronic transfer kinetics and structural stability. Moreover, the porous structure buffers the volume expansion of Si during the lithiation process. The obtained NSi-GN-C microspheres manifest excellent electrochemical performance, including high initial coulombic efficiency of 85.9%, excellent rate capability of 94.4% capacity retention after 50 repeated high-rate tests, and good cyclic performance for 500 cycles at 1.0 A g-1. Kinetic analysis and in situ impedance spectra reveal dominant pseudocapacitive behavior with rapid and stable Li+ insertion/extraction processes. Ex situ morphology characterization demonstrates the ultra-stable integrated structure of the NSi-GN-C. The highly active GN demonstrates great potential to improve the lithium storage properties of Si, which provides new opportunity for constructing high-performance anodes for LIBs.

A Small Object Detection Algorithm Based on Modulated Deformable Convolution and Large Kernel Convolution.

Object detection is one of the most critical areas in computer vision, and it plays an essential role in a variety of practice scenarios. However, small object detection has always been a key and difficult problem in the field of object detection. Therefore, considering the balance between the effectiveness and efficiency of the small object detection algorithm, this study proposes an improved YOLOX detection algorithm (BGD-YOLOX) to improve the detection effect of small objects. We present the BigGhost module, which combines the Ghost model with a modulated deformable convolution to optimize the YOLOX for greater accuracy. At the same time, it can reduce the inference time by reducing the number of parameters and the amount of computation. The experimental results show that BGD-YOLOX has a higher average accuracy rate in terms of small target detection, with mAP0.5 up to 88.3% and mAP0.95 up to 56.7%, which surpasses the most advanced object detection algorithms such as EfficientDet, CenterNet, and YOLOv4.

Magnetodielectric Properties of Ordered Microstructured Polydimethylsiloxane-Based Magnetorheological Elastomer with Fe3O4@rGO Nanoparticles.

Magnetodielectric properties of prepared ordered microstructured polydimethylsiloxane-based magnetorheological elastomer with the Fe3O4@rGO (Fe3O4@rGO/PDMS-MRE) were investigated to expand the application of magnetorheological elastomer (MRE) in magnetic sensing fields by improving the magnetodielectric effect. Five types of Fe3O4@rGO electromagnetic biphasic composite particles were synthesized by the solvothermal method, and their characterization and magnetic properties were also tested. Microstructurally ordered Fe3O4@rGO/PDMS-MRE samples with different Fe3O4@rGO concentrations were obtained through the magnetic field orientation technique, an experimental platform for magnetodielectric properties was built, and the relative permittivity of the samples was tested under magnetic flux density from 0 to 500 mT. The results show when the ratio of modified Fe3O4 to GO reaches 10:1, the Fe3O4@rGO composite particles exhibit uniform distribution with a flaky structure and strong magnetic properties and have the best bonding effect of composite particles. The relative permittivity of Fe3O4@rGO/PDMS-MRE increases with the rise of Fe3O4@rGO concentration and applied magnetic flux density. The relative permittivity of Fe3O4@rGO/PDMS-MRE with Fe3O4@rGO concentration of 60 wt% reaches 12.934 under the action of 500 mT magnetic flux density, and the magnetodielectric effect is as high as 92.4%. A reasonable mechanism for improving the magnetodielectric effect of ordered microstructured Fe3O4@rGO/PDMS-MRE is proposed.

Overexpression of ST7-AS1 Enhances Apoptosis and Inhibits Proliferation of Papillary Thyroid Carcinoma Cells Via microRNA-181b-5p-Dependent Inhibition Tripartite Motif Containing 3.

Long non-coding RNAs (lncRNAs) are of great significance in the pathogenesis and progression of papillary thyroid carcinoma (PTC). LncRNA tumorigenicity 7 antisense RNA 1 (ST7-AS1) is a newly identified lncRNA serving as an oncogene or tumor suppressor in different tumors; however, the role of ST7-AS1 in PTC remains completely unknown. In this study, ST7-AS1 was mainly distributed in the cytoplasm of PTC cells and presented reduced expression in THCA tumors and PTC cell lines. Functional experiments revealed that overexpressed ST7-AS1 inhibited the viability and proliferation of PTC cells, whereas accelerated the apoptosis of PTC cells. The expression of miR-181b-5p was upregulated and it bound with ST7-AS1 in PTC cells. Moreover, TRIM3 exhibited downregulated expression level in PTC cells and ST7-AS1 elevated TRIM3 expression via harboring miR-181b-5p. Rescue experiments illuminated that knockdown of TRIM3 reversed ST7-AS1 overexpression-induced promotion on PTC cell proliferation and suppression on PTC cell apoptosis. Overall, overexpression of ST7-AS1 enhances apoptosis and represses proliferation of PTC cells via targeting the miR-181b-5p/TRIM3 axis, which may help broaden the horizon and establish the foundation to develop therapeutic strategies for PTC in the future.

Analysis of the transcriptomic profiles of Mandarin fish (Siniperca chuatsi) infected with red sea bream iridovirus (RSIV).

Red sea bream iridovirus (RSIV) belongs to the family Iridoviridae, genus Megalocytivirus, which could widely infect marine fish, causing diseases and huge economic losses. Now it has been reported that RSIV was also detected in diseased mandarin fish. Transmission electron microscopy and immunohistochemistry showed that spleen was the main target organ in mandarin fish infected with RSIV. To investigate the immune response mechanism of mandarin fish to RSIV infection, transcriptomics of RSIV-infected mandarin fish was analyzed. A total of 53,040 unigenes were obtained, and there were 21,576 and 17,904 unigenes had significant hit the Nr and SwissProt databases, respectively. In RSIV-infected and non-infected spleen tissues, there were 309 differentially expressed genes (DEGs), including 100 up-regulated genes and 209 down-regulated genes. Gene Ontology database (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed to reveal the function information and give a better understanding of the signal transduction pathways of DEGs. Further analysis of the cytokine-cytokine receptor interactions pathway exhibited that the expression of cytokines was widely activated after viral infection. In addition, ten DEGs were randomly selected and verified by quantitative real-time PCR, which revealed a similar expression tendency as the high-throughput sequencing data. These findings present valuable information that will benefit for better understanding of RSIV infection in mandarin fish.

Rescue of an enterotropic Newcastle disease virus strain ZM10 from cloned cDNA and stable expressing an inserted foreign gene.

BACKGROUND: Newcastle disease virus (NDV) strain ZM10, a typical enterotropic avirulent vaccine strain, has been widely used in China for chickens against Newcastle disease. To elucidate its enterotropic mechanism and develop recombiant multivalent vaccines based on it, the reverse genetics system for NDV ZM10 is an indispensable platform. RESULTS: A full-length cDNA clone of NDV ZM10 and three supporting plasmids were constructed using the ligation-independent cloning method. Recombinant NDV rZM10 was successfully rescued after these plasmids were co-transfected into BHK-21 cells. Besides, the recombinant virus rZM10-RFP encoding the red fluorescent protein was generated by inserting the RFP gene into the full-length clone of NDV between the P and M genes. These rescued viruses were genetically and biologically identical to the parental strain and showed similar growth kinetics. CONCLUSION: The recovery system of NDV ZM10 strain was established, and can be used as a foundation for research on the enterotropic mechanism and development of multivalent vaccines against viral diseases of livestock and poultry.

5'-Nucleotidase is dispensable for the growth of Salmonella Typhimurium but inhibits the bactericidal activity of macrophage extracellular traps.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic pathogen that causes severe gastroenteritis. The 5'-nucleotidases of pathogens can dephosphorylate adenosine phosphates, boost adenosine levels and suppress the pro-inflammatory immune response. In our previous study, an extracellular nuclease, 5'-nucleotidase, was identified in the extracellular proteins of S. Typhimurium. However, the nuclease activity and the function of the 5'-nucleotidase of S. Typhimurium have not been explored. In the present study, deletion of the 5'-nucleotidase gene is dispensable for S. Typhimurium growth, even under environmental stress. Fluorescence microscopy revealed that the 5'-nucleotidase mutant induced more macrophage extracellular traps (METs) than the wild type did. Furthermore, recombinant 5'-nucleotidase protein (r5Nuc) could degrade λDNA, and the nuclease activity of r5Nuc was optimum at 37 °C and pH 6.0-7.0. The Mg2+ enhanced the nuclease activity of r5Nuc, whereas Zn2+ inhibited it. Meanwhile, deletion of the 5'-nucleotidase gene increased the bactericidal activity of METs, and r5Nuc could degrade METs and inhibit the bactericidal activity of METs. In conclusion, S. Typhimurium growth was independent of 5'-nucleotidase, but the nuclease activity of 5'-nucleotidase assisted S. Typhimurium to evade macrophage-mediated extracellular killing through degrading METs.

Exemplar-Based, Semantic Guided Zero-Shot Visual Recognition.

Zero-shot recognition has been a hot topic in recent years. Since no direct supervision is available, researchers use semantic information as the bridge instead. However, most zero-shot recognition methods jointly model images on the class level without considering the distinctive character of each image. To solve this problem, in this paper, we propose a novel exemplar-based, semantic guided zero-shot recognition method (EBSG). Both visual and semantic information of each image is used. We train visual sub-model to separate each image from the other images of different classes. We also train semantic sub-model to separate this image from the other images described with different semantics. We concatenate the outputs of visual and semantic sub-models to represent images. Image classification model is then learned by measuring visual similarity and semantic consistency of both source and target images. We conduct zero-shot recognition experiments on four widely used datasets. Experimental results show the effectiveness of the proposed EBSG method.

Effects of Koumiss on Intestinal Immune Modulation in Immunosuppressed Rats.

Koumiss is a traditional fermented dairy product with health and medicinal benefits. It is very popular in the Inner Mongolia Autonomous Region of China. The results of relevant studies have shown that koumiss can regulate the gastrointestinal environment, improve the absorption of nutrients, improve the body's intolerance to lactose, enhance the body's immunity, prevent scurvy and atherosclerosis, and aid in the treatment of tuberculosis. However, there are no systematic reports on the effects of koumiss on immunity. In this study, we aimed to decipher the effects of koumiss on intestinal immune modulation. We used liquid chromatography-tandem mass spectrometry (LC-MS) analysis to determine the composition of Koumiss. Using Compound Discoverer software, we compared the mass spectrometry data with the compound information in the online databases ChemSpider and mzCloud to intelligently identify the main chemical components of koumiss. Additionally, we used Mass Frontier small molecule fragmentation libraryTM to determine the structure of fragment ions. A total of 21 components were identified, which clarified the chemical basis of koumiss. These 21 compounds were then used to perform molecular docking with immune-related targets, such as TNF, IL2, IL10, etc. The results indicated good docking activity between most of the compounds and the targets. Then, an immunosuppressive rat model was used to determine the therapeutic effect of koumiss. The results of this study showed that koumiss could, to a certain extent, correct the atrophy of the thymus and spleen in immunosuppressed model rats. The number of leukocytes, lymphocytes, and the CD4+/CD8+ ratio of peripheral blood lymphocytes was also increased. In addition, it could effectively improve the structure of the small intestinal mucosa, which shows that koumiss has a positive effect on the intestinal immune function of immunosuppressed rats. These findings provide an experimental basis for the development and utilization of koumiss as a therapeutic product.

CTBP1-AS2 promoted non-small cell lung cancer progression via sponging the miR-623/MMP3 axis.

Mounting evidence indicates that lncRNAs (long noncoding RNAs) are involved in the initiation and development of tumors, including non-small cell lung cancer (NSCLC). However, the involvement of C-terminal binding protein-antisense RNA 2 (CTBP1-AS2) in NSCLC remains to be studied. RT-qPCR was carried out to detect CTBP1-AS2 and miR-623 expression in NSCLC cells and tissues. CCK-8 and flow cytometry were performed to measure cell proliferation and cell cycle progression. Luciferase reporter analysis was performed to study the potential target of CTBP1-AS2. We found that CTBP1-AS2 expression was upregulated in NSCLC cells (SPC-A1, A549, H23, and H1299) compared to 16HBE cells. We demonstrated that the CTBP1-AS2 level was higher in NSCLC specimens than in paired non-tumor specimens. Elevated expression of CTBP1-AS2 increased cell growth and induced cell cycle progression and epithelial-mesenchymal transition (EMT). We also found that ectopic expression of CTBP1-AS2 inhibited miR-623 expression. MMP3 was a direct target of miR-623, and luciferase reporter assays suggested that miR-623 overexpression suppressed the luciferase expression driven by the MMP3 wild-type reporter but not the mutant reporter. Overexpression of miR-623 suppressed MMP3 expression in A549 cells, and overexpression of CTBP1-AS2 increased MMP3 expression in A549 cells. Moreover, the miR-623 level was lower in NSCLC specimens than in paired non-tumor specimens, and CTBP1-AS2 expression was negatively correlated with miR-623 expression in NSCLC samples. Furthermore, overexpression of CTBP1-AS2 enhanced cell growth, cell cycle progression, and EMT progression by modulating MMP3 expression.