Diclofenac sodium nanomedicine results in pain-relief and differential expression of the RNA transcriptome in the spinal cord of SNI rats.

Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is one of the most significant areas of clinical medicine and basic research. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. A medicinal preparation is required that relieves the neuropathic pain and prolongs action time, which has not yet been discovered. In this study, MIL-101 (Fe) was employed as a drug carrier to regulate the release of diclofenac sodium, thereby achieving the effect of analgesia and sustained release. The release curves demonstrated that diclofenac sodium could be continuously released from MIL-101 (Fe) for more than 48 h. There was no toxicity in vitro and in vivo, and the safety of MIL-101 (Fe) was confirmed by hematoxylin and eosin as well as ELISA tests in vivo. The results of behavioral testing, pharmacokinetics, and RNA sequencing analysis showed that MIL-101 (Fe) loaded with diclofenac sodium could enhance the mechanical withdrawal threshold and alleviate cold allodynia induced by Spared Nerve Injury, prolonging the work time by three days. The results indicated that MIL-101 (Fe) exhibited excellent biocompatibility, while the MIL-101 (Fe)-DS demonstrated analgesic and controlled-release properties. These findings provide a scientific foundation for the clinical management of neuropathic pain and the development of a novel formulation.

More potential uses of specific perforator flaps in the calf - A cadaveric study on the subdermal vascular structure of the lower leg.

BACKGROUND: The perforator flap has garnered significant interest since its inception due to its advantage of not needing a vascular network at the deep fascial level. Perforator flaps are commonly utilized in different flap transplant surgeries, and the thigh flap is presently the most widely used perforator flap. Is it possible for the calf to replace the thigh as a more suitable site for harvesting materials? Currently, there is a lack of relevant anatomical research. This study aims to address this question from an anatomical and imaging perspective. METHODS: This study used cadavers to observe the branches and courses of perforators on the calf and the distribution of skin branches using microdissection techniques, digital X-ray photography, and micro-computed tomography techniques. RESULTS: The perforators had three main branches: the vertical cutaneous branch, the oblique cutaneous branch, and the superficial fascial branch. The superficial fascial branch traveled in the superficial fascia and connected with the nearby perforators. The vertical and oblique cutaneous branches entered the subdermal layer and connected with each other to create the subdermal vascular network. CONCLUSIONS: We observed an intact calf cutaneous branch chain between the cutaneous nerve and the perforator of the infrapopliteal main artery at the superficial vein site. Utilizing this anatomical structure, the calfskin branch has the potential to serve as a substitute for thigh skin flap transplantation and may be applied to perforator flap transplantation in more locations.

Liquid biopsy biomarkers to guide immunotherapy in breast cancer.

Immune checkpoint inhibitors (ICIs) therapy has emerged as a promising treatment strategy for breast cancer (BC). However, current reliance on immunohistochemical (IHC) detection of PD-L1 expression alone has limited predictive capability, resulting in suboptimal efficacy of ICIs for some BC patients. Hence, developing novel predictive biomarkers is indispensable to enhance patient selection for immunotherapy. In this context, utilizing liquid biopsy (LB) can provide supplementary or alternative value to PD-L1 IHC testing for identifying patients most likely to benefit from immunotherapy and exhibit favorable responses. This review discusses the predictive and prognostic value of LB in breast cancer immunotherapy, as well as its limitations and future directions. We aim to promote the individualization and precision of immunotherapy in BC by elucidating the role of LB in clinical practice.

ALKBH5 Stabilized N6-Methyladenosine-Modified LOC4191 to Suppress E. coli-Induced Apoptosis.

E. coli is a ubiquitous pathogen that is responsible for over one million fatalities worldwide on an annual basis. In animals, E. coli can cause a variety of diseases, including mastitis in dairy cattle, which represents a potential public health hazard. However, the pathophysiology of E. coli remains unclear. We found that E. coli could induce global upregulation of m6A methylation and cause serious apoptosis in bovine mammary epithelial cells (MAC-T cells). Furthermore, numerous m6A-modified lncRNAs were identified through MeRIP-seq. Interestingly, we found that the expression of LOC4191 with hypomethylation increased in MAC-T cells upon E. coli-induced apoptosis. Knocking down LOC4191 promoted E. coli-induced apoptosis and ROS levels through the caspase 3-PARP pathway. Meanwhile, knocking down ALKBH5 resulted in the promotion of apoptosis through upregulated ROS and arrested the cell cycle in MAC-T cells. ALKBH5 silencing accelerated LOC4191 decay by upregulating its m6A modification level, and the process was recognized by hnRNP A1. Therefore, this indicates that ALKBH5 stabilizes m6A-modified LOC4191 to suppress E. coli-induced apoptosis. This report discusses an initial investigation into the mechanism of m6A-modified lncRNA in cells under E. coli-induced apoptosis and provides novel insights into infectious diseases.

Neural-SEIR: A flexible data-driven framework for precise prediction of epidemic disease.

Accurately modeling and predicting epidemic diseases is crucial to prevent disease transmission and reduce mortality. Due to various unpredictable factors, including population migration, vaccination, control efforts, and seasonal fluctuations, traditional epidemic models that rely on prior knowledge of virus transmission mechanisms may not be sufficient to forecast complex epidemics like coronavirus disease 2019(COVID-19). The application of traditional epidemiological models such as susceptible-exposed-infectious-recovered (SEIR) may face difficulties in accurately predicting such complex epidemics. Data-driven prediction approaches lack the ability to generalize and exhibit low accuracy on small datasets due to their reliance on large amounts of data without incorporating prior knowledge. To overcome this limitation, we introduce a flexible ensemble data-driven framework (Neural-SEIR) that "neuralizes" the SEIR model by approximating the core parameters through neural networks while preserving the propagation structure of SEIR. Neural-SEIR employs long short-term memory (LSTM) neural network to capture complex correlation features, exponential smoothing (ES) to model seasonal information, and prior knowledge from SEIR. By incorporating SEIR parameters into the neural network structure, Neural-SEIR leverages prior knowledge while updating parameters with real-world data. Our experimental results demonstrate that Neural-SEIR outperforms traditional machine learning and epidemiological models, achieving high prediction accuracy and efficiency in forecasting epidemic diseases.

Notch signaling pathway: a new target for neuropathic pain therapy.

The Notch gene, a highly evolutionarily conserved gene, was discovered approximately 110 years ago and has been found to play a crucial role in the development of multicellular organisms. Notch receptors and their ligands are single-pass transmembrane proteins that typically require cellular interactions and proteolytic processing to facilitate signal transduction. Recently, mounting evidence has shown that aberrant activation of the Notch is correlated with neuropathic pain. The activation of the Notch signaling pathway can cause the activation of neuroglia and the release of pro-inflammatory factors, a key mechanism in the development of neuropathic pain. Moreover, the Notch signaling pathway may contribute to the persistence of neuropathic pain by enhancing synaptic transmission and calcium inward flow. This paper reviews the structure and activation of the Notch signaling pathway, as well as its potential mechanisms of action, to provide novel insights for future treatments of neuropathic pain.

ERStruct: a fast Python package for inferring the number of top principal components from whole genome sequencing data.

BACKGROUND: Large-scale multi-ethnic DNA sequencing data is increasingly available owing to decreasing cost of modern sequencing technologies. Inference of the population structure with such sequencing data is fundamentally important. However, the ultra-dimensionality and complicated linkage disequilibrium patterns across the whole genome make it challenging to infer population structure using traditional principal component analysis based methods and software. RESULTS: We present the ERStruct Python Package, which enables the inference of population structure using whole-genome sequencing data. By leveraging parallel computing and GPU acceleration, our package achieves significant improvements in the speed of matrix operations for large-scale data. Additionally, our package features adaptive data splitting capabilities to facilitate computation on GPUs with limited memory. CONCLUSION: Our Python package ERStruct is an efficient and user-friendly tool for estimating the number of top informative principal components that capture population structure from whole genome sequencing data.

DeepDetect: Deep Learning of Peptide Detectability Enhanced by Peptide Digestibility and Its Application to DIA Library Reduction.

In tandem mass spectrometry-based proteomics, proteins are digested into peptides by specific protease(s), but generally only a fraction of peptides can be detected. To characterize detectable proteotypic peptides, we have developed a series of methods to predict peptide digestibility and detectability. Here, we propose a bidirectional long short-term memory (BiLSTM)-based algorithm, named DeepDetect, for the prediction of peptide detectability enhanced by peptide digestibility. Compared with existing algorithms, DeepDetect is featured by its improved prediction accuracy for a wide range of commonly used proteases, covering trypsin, ArgC, chymotrypsin, GluC, LysC, AspN, LysN, and LysargiNase. On 11 test data sets from E. coli, yeast, mouse, and human samples, DeepDetect achieved higher prediction accuracies than PepFormer, a state-of-the-art deep-learning-based peptide detectability prediction algorithm. The results further demonstrated that peptide digestibility can substantially enhance the performance of peptide detectability predictors. As an application, DeepDetect was used to reduce the in silico predicted spectral libraries in data-independent acquisition mass spectrometry data analysis. Experiments using DIA-NN software showed that DeepDetect can significantly accelerate the library search without loss of peptide and protein identification sensitivity.

The Role of N6-Methyladenosine in Inflammatory Diseases.

N6-Methyladenosine (m6A) is the most abundant epigenetic RNA modification in eukaryotes, regulating RNA metabolism (export, stability, translation, and decay) in cells through changes in the activity of writers, erasers, and readers and ultimately affecting human life or disease processes. Inflammation is a response to infection and injury in various diseases and has therefore attracted significant attention. Currently, extensive evidence indicates that m6A plays an essential role in inflammation. In this review, we focus on the mechanisms of m6A in inflammatory autoimmune diseases, metabolic disorder, cardio-cerebrovascular diseases, cancer, and pathogen-induced inflammation, as well as its possible role as targets for clinical diagnosis and treatment.

A simple mesoporous silica Nanoparticle-based aptamers SERS sensor for the detection of acetamiprid.

In this study, we developed a novel, rapid, simple, and sensitive nano sensor based on the controlled release of 4-Aminothiophenol (4-ATP) signal molecules from aptamers (Apts) modified aminated mesoporous silica nanoparticles (MSNs-NH2) for the quantitative detection of acetamiprid (ACE). Firstly, we synthesized the positively charged MSNs-NH2 by one-pot method, then loaded 4-ATP signal molecules into the pore, and finally electrostatically adsorbed the Apts onto the MSNs-NH2, which acts as a gate to control the release of signal molecules. When ACE is added to the system, ACE preferentially and specifically binds to Apts, so the gate opens and 4-ATP signal molecules are released from the pore. Meanwhile, the silver-loaded mesoporous silica nanoparticles (Ag@SiO2) were prepared by one-pot method as surface-enhanced Raman spectroscopy (SERS) substrate to amplify the signal. The intensity of 4-ATP signal molecules at 1433 cm-1 position was observed to has a linear relationship with the concentration of ACE by SERS detection. Under the optimized detection conditions, a linear correlation was observed in the range of 5-60 ng/mL (R2 = 0.99749), and the limit of detection (LOD) was 2.66 ng/mL. The method has high sensitivity, good selectivity and reproducibility, and can be used for actual sample analysis with the recovery rate of 96.24-103.6 %. This study provides a reference for the rapid and convenient detection of ACE in agricultural products.

Fluorescent aptamer-modified mesoporous silica nanoparticles for quantitative acetamiprid detection.

Acetamiprid (ACE) is widely used to control aphids, brown planthoppers, and other pests in agricultural production. However, ACE is difficult to degrade in the environment, resulting in excessive residue, which causes acute and chronic toxicity to human beings and non-target organisms. Therefore, the development of a rapid, convenient, and highly sensitive method to quantify ACE is essential. In this study, aminated mesoporous silica nanoparticles (MSNs-NH2) were synthesized by one-pot method, and 6-carboxyl fluorescein modified aptamers (FAM-Apt) of ACE were adsorbed on the surface of MSNs-NH2 by electrostatic interaction. Finally, a simple and sensitive fluorescence analysis method for the rapid detection of ACE was established. In the absence of ACE, the negatively charged FAM-Apt was electrostatically bound to the positively charged MSNs-NH2, followed by centrifugation to precipitate MSNs-NH2@FAM-Apt, and no fluorescent signal was detected in the supernatant. In the presence of ACE, the specific combination of FAM-Apt with ACE was greater than its electrostatic interaction with MSNs-NH2, so that FAM-Apt was separated from MSNs-NH2, and the supernatant had strong fluorescence signal after centrifugation. For ACE detection, the linear concentration range was 50-1100 ng/mL, and the detection limit (LOD) was 30.26 ng/mL. The method exhibited high sensitivity, selectivity and reproducibility, which is suitable for practical sample analysis and provides guidance for rapid detection of pesticide residues.

Regularity of Toll-Like Receptors in Bovine Mammary Epithelial Cells Induced by Mycoplasma bovis.

Mastitis is one of the most common and significant infectious diseases in dairy cattle and is responsible for significant financial losses for the dairy industry globally. An important pathogen of bovine mastitis, Mycoplasma bovis (M. bovis) has a high infection rate, requires a long course of treatment, and is difficult to cure. Bovine mammary epithelial cells (BMECs) are the first line of defense of the mammary gland, and their natural immune system plays a critical role in resisting M. bovis infection. This study aimed to explore and demonstrate the regularity of Toll-like receptors (TLRs) activation during M. bovis infection and their function during M. bovis mastitis. An in vitro model of M. bovis-induced mastitis showed that the expression of IL-6, IL-8, and TNF-α increased significantly following infection. M. bovis infection also upregulated the expression of TLR1/2/6 on the cell membrane and TLR3/9 in the cytoplasm. There is a crosstalk effect between TLR1-TLR2 and TLR2-TLR6. Furthermore, M. bovis infection was found to activate the TLR1/2/6/9/MyD88/NF-κB and TLR3/TRIF/IRF signal transduction pathways, which in turn activate inflammatory factors. These findings lay the theoretical foundation for understanding the pathogenesis of M. bovis, permitting the development of effective measures for preventing and controlling M. bovis mastitis.

N6-Methyladenosine-Modified circRNA in the Bovine Mammary Epithelial Cells Injured by Staphylococcus aureus and Escherichia coli.

Mastitis is a common disease that hinders the development of dairy industry and animal husbandry. It leads to the abuse of antibiotics and the emergence of super drug-resistant bacteria, and poses a great threat to human food health and safety. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common pathogens of mastitis in dairy cows and usually cause subclinical or clinical mastitis. CircRNAs and N6-methyladenosine (m6A) play important roles in immunological diseases. However, the mechanisms by which m6A modifies circRNA in bovine mammary epithelial cells remain poorly understood. The aim of our study was to investigate m6A-modified circRNAs in bovine mammary epithelial cells (MAC-T cells) injured by S. aureus and E. coli. The profile of m6A-modified circRNA showed a total of 1,599 m6A peaks within 1,035 circRNAs in the control group, 35 peaks within 32 circRNAs in the S. aureus group, and 1,016 peaks within 728 circRNAs in the E. coli group. Compared with the control group, 67 peaks within 63 circRNAs were significantly different in the S. aureus group, and 192 peaks within 137 circRNAs were significantly different in the E. coli group. Furthermore, we found the source genes of these differentially m6A-modified circRNAs in the S. aureus and E. coli groups with similar functions according to GO and KEGG analyses, which were mainly associated with cell injury, such as inflammation, apoptosis, and autophagy. CircRNA-miRNA-mRNA interaction networks predicted the potential circRNA regulation mechanism in S. aureus- and E. coli-induced cell injury. We found that the mRNAs in the networks, such as BCL2, MIF, and TNFAIP8L2, greatly participated in the MAPK, WNT, and inflammation pathways. This is the first report on m6A-modified circRNA regulation of cells under S. aureus and E. coli treatment, and sheds new light on potential mechanisms and targets from the perspective of epigenetic modification in mastitis and other inflammatory diseases.

Facile pathway to construct mesoporous silica nanoparticles loaded with pyraclostrobin: Physicochemical properties, antifungal activity, and biosafety.

BACKGROUND: A controlled-release formulation based on mesoporous silica nanoparticles (MSNs) provides an effective way for reducing pesticide use and protecting the ecological environment. In this study, MSNs loaded with pyraclostrobin (PYR@MSNs) were prepared using a one-pot method. RESULTS: The characteristics of PYR@MSNs were systematically investigated, including morphology, loading content, ultraviolet (UV) resistance, release behavior, control effects against pathogens, and safety to nontarget organisms. The results show that the prepared PYR@MSNs presented characteristics of regular spherical shapes, uniform particle size (200 nm), high drug loading (38.9%), and enhanced UV resistance. Compared with traditional formulation, PYR@MSNs exhibited improved control effects against Fusarium graminearum, an extended control period, and lower toxicity to zebrafish, earthworms and BEAS-2B cells. CONCLUSIONS: This research will facilitate the development of efficient and safe pesticide delivery systems. The PYR@MSNs has showed its potential as a new controlled-release formulation with increased efficacy and is expected to benefit the sustainable development of agriculture. © 2022 Society of Chemical Industry.

Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice.

Previous studies have implicated that the transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) effectively alleviates systemic lupus erythematosus (SLE) primarily due to immunomodulatory effects. However, little is known about the role of hUC-MSC-derived exosomes in SLE. This study is carried out to investigate the modifying effects of hUC-MSC-exosomes on the differentiation and function of immune cells in SLE. hUC-MSC-derived exosomes were extracted from the cultural supernatant of hUC-MSCs by ultrahigh speed centrifugation. Quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and flow cytometry were performed to estimate the effect of hUC-MSC-derived exosomes on macrophage and regulatory T cell (Treg) polarization. In vivo, hUC-MSC-exosomes were injected intravenously into 28-week-old MRL/lpr mice. We had found that exosomes derived from hUC-MSC restrained the proliferation and inflammation of macrophages in vitro. Besides, MSC-exosomes inhibited CD68+M1 and HLA-DR+M1 but promoted CD206+M2 and CD163+M2 in vitro. Moreover, MRL/lpr mice administrated by intravenous injection of MSC-exosomes had less infiltration of CD14+CD11c+M1 cells but more CD14+CD163+M2 cells as well as Tregs in spleens compared with those in MRL/lpr mice treated by PBS. Additionally, MSC-exosomes could alleviate nephritis, liver and lung injuries of MRL/lpr mice. The survival of lupus mice could be improved after MSC-exosome treatment. This study has suggested that MSC-derived exosomes exert anti-inflammatory and immunomodulatory effects in SLE. MSC-exosomes ameliorate nephritis and other key organ injuries by inducing M2 macrophages and Tregs polarization. As natural nanocarriers, MSC-exosomes may serve as a promising cell-free therapeutic strategy for SLE.Abbreviations: SLE: Systemic lupus erythematosus; hUC-MSCs: Human umbilical cord mesenchymal stem cells; MSCs: Mesenchymal stem cells; qRT-PCR: Quantitative real-time polymerase chain reaction; ELISA: Enzyme-linked immunosorbent assay; Tregs: Regulatory cells; TNF-α: Tumor necrosis factor alfa; IL: Interleukin; COVID-19: Coronavirus disease 2019; pTHP-1: PMA-induced THP-1 macrophages; TEM: Transmission electron microscopy; LPS: Lipopolysaccharide; EVs: Extracellular vesicles; TRAF1: Tumor necrosis factor receptor-associated factor 1; IRAK1: Interferon-α-interleukin-1 receptor-associated kinase 1; NF-κB: Nuclear factor-κB; BLyS: B lymphocyte stimulator; APRIL: A proliferation-inducing ligand.

Mechanism and effects of STING-IFN-I pathway on nociception: A narrative review.

Since the discovery of STING in 2008, numerous studies have investigated its functions in immunity, inflammation, and cancer. STING activates downstream molecules including IFN-I, NLRP3, and NF-κB. The STING-IFN-I pathway plays a vital role in nociception. After receiving the upstream signal, STING is activated and induces the expression of IFN-I, and after paracrine and autocrine signaling, IFN-I binds to IFN receptors. Subsequently, the activity of ion channels is inhibited by TYK2, which induces an acute antinociceptive effect. JAK activates PIK3 and MAPK-MNK-eIF4E pathways, which sensitize nociceptors in the peripheral nervous system. In the mid-late stage, the STING-IFN-I pathway activates STAT, increases pro-inflammatory and anti-inflammatory cytokines, inhibits ER-phagy, and promotes microglial M1-polarization in the central nervous system, leading to central sensitization. Thus, the STING-IFN-I pathway may exert complex effects on nociception at various stages, and these effects require further comprehensive elucidation. Therefore, in this review, we systematically summarized the mechanisms of the STING-IFN-I pathway and discussed its function in nociception.

Relationship between Different Degrees of Compression and Clinical Symptoms in Patients with Myocardial Bridge and the Risk Factors of Proximal Atherosclerosis.

OBJECTIVE: To explore the relationship between different degrees of compression and clinical symptoms in patients with the myocardial bridge and the risk factors of proximal atherosclerosis. METHODS: The clinical data of 156 patients with the myocardial bridge who underwent selective coronary angiography in our hospital from December 2010 to December 2015 were collected. The patients were divided into Noble grade I group (102 cases) and Noble grades II-III group (54 cases) according to the degree of mural coronary artery systolic stenosis. According to the results of coronary angiography, 156 patients with the myocardial bridge were divided into an atherosclerosis group (the myocardial bridge combined with atherosclerosis at the proximal end of the myocardial bridge of simple wall coronary artery), 91 cases, and a control group (isolated myocardial bridge), 65 cases. The relationship between different degrees of compression and clinical symptoms in patients with the myocardial bridge was observed, and the logistic regression model was used to analyze the risk factors of proximal atherosclerosis in patients with the myocardial bridge. RESULTS: The incidence of atherosclerotic stenosis, angina pectoris, and myocardial infarction in the proximal part of the myocardial bridge in the Noble grades II-III group was higher than that in the Noble grade I group (P < 0.05). The differences in age, hypertension, and Noble classification between the two groups were statistically significant (P < 0.05). The differences of total cholesterol (TC) and C-reactive protein (CRP) between the two groups were statistically significant (P < 0.05). Multivariate analysis showed that age, hypertension, Noble grade, and CRP were all risk factors for proximal atherosclerosis in patients with the myocardial bridge (P < 0.05). CONCLUSION: The more severe the compression of the myocardial bridge, the greater the risk of cardiovascular events for patients and the higher the incidence of atherosclerotic stenosis in the proximal part of the myocardial bridge. In addition, the occurrence of atherosclerosis in the proximal coronary artery of the myocardial bridge may be affected by age, hypertension, Noble grade, and CRP level.

Fabrication and Characterization of Prochloraz Nanoemulsion against Penicillium citrinum for the Postharvest Storage of Navel Oranges.

Nanoemulsions have become extremely popular water-insoluble pesticide delivery systems in recent years. In this study, prochloraz nanoemulsions were obtained by selecting the mixing ratio of surfactants (6:1, 3:1, 2:1, 1:1, 1:2, 1:3, and 1:6), surfactant concentration, and shearing time. The optimal formula was 10 wt % prochloraz, 6 wt % surfactant (2 wt % CO-100 + 4 wt % CO-360) dissolved in 6 wt % hydrocarbon solvent (S-100A), and deionized water replenished to 100 wt %. This formula meets the quality index standards of the Food and Agriculture Organization. Compared with oil-in-water emulsion (EW), the prochloraz nanoemulsion exhibited higher antifungal activity against Penicillium citrinum in vitro (lower LC50 of 1.17 mg L-1) and in vivo (fewer lesions). In addition, the L02 cells treated with the nanoemulsion had a higher survival rate and lower apoptosis rate at the same concentration. Results showed that the toxicity of the prochloraz nanoemulsion on L02 cells was lower than that of EW. The findings provide an important method for developing an efficient, safe, and environment-friendly nanoemulsion for postharvest fruit storage.

Immunomodulatory Effect of MSCs and MSCs-Derived Extracellular Vesicles in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a common autoimmune connective tissue disease with unclear etiology and pathogenesis. Mesenchymal stem cell (MSC) and MSC derived extracellular vesicles (EVs) play important roles in regulating innate and adaptive immunity, which are involved in many physiological and pathological processes and contribute to the immune homeostasis in SLE. The effects of MSCs and EVs on SLE have been drawing more and more attention during the past few years. This article reviews the immunomodulatory effects and underlying mechanisms of MSC/MSC-EVs in SLE, which provides novel insight into understanding SLE pathogenesis and guiding the biological therapy.

Genome-Wide Analysis of LncRNA in Bovine Mammary Epithelial Cell Injuries Induced by Escherichia Coli and Staphylococcus Aureus.

Escherichia coli and Staphylococcus aureus are two common pathogenic microorganisms that cause mastitis in dairy cows. They can cause clinical mastitis and subclinical mastitis. In recent studies, lncRNAs have been found to play an important role in the immune responses triggered by microbial inducers. However, the actions of lncRNAs in bovine mastitis remain unclear. The purpose of this study was to investigate the effects of bovine mammary epithelial cell injuries induced by treatment with E. coli and S. aureus, and to explore the lncRNA profile on cell injuries. The lncRNA transcriptome analysis showed a total of 2597 lncRNAs. There were 2234 lncRNAs differentially expressed in the E. coli group and 2334 in the S. aureus group. Moreover, we found that the E. coli and S. aureus groups of maternal genes targeted signaling pathways with similar functions according to KEGG and GO analyses. Two lncRNA-miRNA-mRNA interaction networks were constructed in order to predict the potential molecular mechanisms of regulation in the cell injuries. We believe that this is the first report demonstrating the dysregulation of lncRNAs in cells upon E. coli and S. aureus infections, suggesting that they have the potential to become important diagnostic markers and to provide novel insights into controlling and preventing mastitis.