Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3-CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases.

OBJECTIVE: To develop a multi-modal deep learning method for automatic classification of immune-mediated glomerular diseases based on images of optical microscopy (OM), immunofluorescence microscopy (IM), and transmission electron microscopy (TEM).
METHODS: We retrospectively collected the pathological images from 273 patients and constructed a multi-modal multi- instance model for classification of 3 immune-mediated glomerular diseases, namely immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN). This model adopts an instance-level multi-instance learning (I-MIL) method to select the TEM images for multi-modal feature fusion with the OM images and IM images of the same patient. By comparing this model with unimodal and bimodal models, we explored different combinations of the 3 modalities and the optimal methods for modal feature fusion.
RESULTS: The multi-modal multi-instance model combining OM, IM, and TEM images had a disease classification accuracy of (88.34±2.12)%, superior to that of the optimal unimodal model [(87.08±4.25)%] and that of the optimal bimodal model [(87.92±3.06)%].
CONCLUSIONS: This multi- modal multi- instance model based on OM, IM, and TEM images can achieve automatic classification of immune-mediated glomerular diseases with a good classification accuracy.

Levamisole (LVM) is considered an immunomodulatory agent that has the potential to treat various cancer and inflammation diseases. However, there is still much debate surrounding the toxicokinetic and toxicological information of LVM. Therefore, it is crucial to assess its toxicity to provide useful data for future human LVM risk assessments. In this study, a barrier environment was established under the guidance of good laboratory practice (GLP) at the Fujian Center for New Drug Safety Evaluation. Male beagle dogs were orally administered with 5, 15, and 30 mg/kg of LVM daily for four weeks. Toxicity assessment was based on various factors such as mortality, clinical signs, food and water consumption, body weight, body temperature, electrocardiogram, ophthalmological examination, hematology, serum biochemistry, organ/body coefficients, histopathological study, and toxicokinetic analysis. The results of this study showed that LVM did not exhibit any significant toxicological effects on beagle dogs at the exposure levels tested. A no observed adverse effect level (NOAEL) of LVM was set at 30 mg/kg/day for male beagle dogs, which is equivalent to a 12-fold clinical dose in humans. Moreover, the repeated exposure to LVM for four weeks did not lead to any bioaccumulation. These findings provide valuable insights for future human LVM risk assessments.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer.
METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence.
RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups.
CONCLUSIONS: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

UNASSIGNED: Immune-related lncRNA is involved in tumor initiation and progression, while its effect in glioblastoma (GBM) is still unknown.
UNASSIGNED: We sought to investigate the association between immune-related lncRNA (ir-lncRNA) and GBM.
UNASSIGNED: Transcriptomic and clinical data were obtained from the TCGA dataset, and we found 2008 ir-lncRNA differentially expressed between GBM and adjacent brain tissues.
UNASSIGNED: Appling the univariate Cox and Lasso regression model, we found 30 prognosis-related ir-lncRNA pairs to construct a Cox regression risk model to associate the outcome of GBM patients. Furthermore, with this risk model, we can identify the tumor immune infiltration status, the expression of immunosuppressive biomarkers, and chemical sensitivity in GBM patients.
UNASSIGNED: We constructed an immunologic risk model with lncRNA to associate the survival outcome of GBM patients, which can provide useful biomarkers.

BACKGROUND: The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease, metabolites, and microbes can provide efficient and targeted solutions towards understanding the mechanism of complex disease and development of new markers and drugs.
RESULTS: We developed Gut Microbial Metabolite Association with Disease (GMMAD), a manually curated database of associations among human diseases, gut microbes, and metabolites of gut microbes. Here, this initial release (i) contains 3,836 disease-microbe associations and 879,263 microbe-metabolite associations, which were extracted from literatures and available resources and then experienced our manual curation; (ii) defines an association strength score and a confidence score. With these two scores, GMMAD predicted 220,690 disease-metabolite associations, where the metabolites all belong to the gut microbes. We think that the positive effective (with both scores higher than suggested thresholds) associations will help identify disease marker and understand the pathogenic mechanism from the sense of gut microbes. The negative effective associations would be taken as biomarkers and have the potential as drug candidates. Literature proofs supported our proposal with experimental consistence; (iii) provides a user-friendly web interface that allows users to browse, search, and download information on associations among diseases, metabolites, and microbes. The resource is freely available at http://guolab.whu.edu.cn/GMMAD .
CONCLUSIONS: As the online-available unique resource for gut microbial metabolite-disease associations, GMMAD is helpful for researchers to explore mechanisms of disease- metabolite-microbe and screen the drug and marker candidates for different diseases.

We used an enhanced recognition strategy to fabricate a novel levamisole-detecting chiral electrochemical sensor featuring a metal-organic framework (MOF) combined with a molecularly imprinted polymer (MIP). We first synthesised a Cu/Zn-[benzene-1,3,5-tricarboxylic acid] (Cu/Zn-BTC) MOF as the molecular immobilisation and signal-amplifying unit, and then prepared the MIP (molecular recognition unit) using levamisole as the template on a glassy carbon electrode modified with Cu/Zn-BTC. We obtained a composite chiral sensor with enhanced recognition capability for levamisole after template removal. Using the templated sites as the switch and K3[Fe(CN)6]/K4[Fe(CN)6] as a probe, we established a new method for detecting levamisole in meat products and water bodies. The linear detection range and detection limit of our chiral sensor are 5 to 6000 × 10-11 mol/L and 1.65 × 10-12 mol/L, respectively. Moreover, the sensor exhibited 93.8-109.0% recovery in the detection of levamisole in chicken and other real samples.

Imidazothiazole derivatives are becoming increasingly important in therapeutic use due to their outstanding physiological activities. Recently, applying imidazothiazole as the core, researchers have synthesized a series of derivatives with biological effects such as antitumor, anti-infection, anti-inflammatory and antioxidant effects. In this review, we summarize the main pharmacological effects and pharmacological mechanisms of imidazothiazole derivates; the contents summarized herein are intended to advance the research and rational development of imidazothiazole-based drugs in the future.

Datura stramonium L. (Solanaceae) is used traditionally in west Africa to treat asthma, epilepsy, rheumatoid arthritis, filariasis microbial infections and conjunctivitis. This study investigated the immunomodulatory effects of aqueous seed extract of D. stramonium L. (ASEDS) on Wistar rats.
Thirty Wistar albino rats (180-200 g) were randomized into 6 groups (n = 5). Group 1 received distilled water only. Rats in groups 2-6 were pretreated with 10 mg/kg body weight (b.w.) Cyclophosphamide orally for 27-days to induce immunosuppression. Thereafter, they received treatment orally for 28 days as follows: Group 2 (distilled water), group 3 (5 mg/kg b.w. Levamisole), groups 4-6 (60, 90 and 120 mg/kg b.w. ASEDS, respectively). HPLC was used to determine major compounds in ASEDS. The effects of ASEDS on immune cells, immunoglobulins A, G and M levels, lipoproteins, and antioxidant status of rats were evaluated.
ASEDS indicated high content of Acutumine, Quinine, Catechin, Chlorogenic acid, Gallic acid, Quercetin, Vanillic acid, Luteolin, Formosanin C, Saponin, Cyanidin, Tannic acid, 3-Carene, Limonene and α-terpineol. Cyclophosphamide triggered significant (p < 0.05) reduction in total leucocyte count and differentials, IgA, IgG, high-density lipoproteins (HDL), catalase, superoxide dismutase, glutathione peroxidase, vitamins A, C and E levels of untreated rats. Administration of ASEDS led to significant (p < 0.05) improvement in immune cell counts, immunoglobulin synthesis, high-density lipoprotein concentration, and antioxidant status of rats in the treated groups.
The results obtained from the study showed the immunomodulatory activity of ASEDS, thereby indicating its potential in immunostimulatory drug discovery.

Levamisole (LEV) is a veterinary drug that often remains in animal food. Consuming products containing high levels of LEV will cause a series of harmful reactions to human health. This work describes the Capture-SELEX (Capture-systematic evolution of ligands by exponential enrichment) screening strategy of LEV aptamers, using streptavidin modified agarose beads as a solid phase medium to separate target-bound and unbound ssDNA. The affinity and specificity of candidate aptamers were determined by SYBR Green I (SGI) dye and isothermal titration calorimetry (ITC), in which LEV-5 showed good binding affinity and specificity, and the dissociation constant was 66.15 ± 11.86 nM. Circular dichroism (CD) was used to characterize aptamer conformational changes before and after target binding, including increased helicity and enhanced base stacking. To evaluate whether this aptamer can be used for LEV detection, a colorimetric-surface-enhanced Raman spectroscopy (colorimetric-SERS) dual-mode aptasensor was constructed based on the peroxidase-like activity and SERS effect of AuNPs/Cu-TCPP(Fe) nanosheets. The detection limits of this dual-mode aptasensor for LEV were 5 nM and 1.12 nM, respectively. This aptamer-based method was further successfully used to detect LEV in milk, with recoveries ranging from 94.95% to 111.2%, providing a potential application for the detection of harmful substances in food.