Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice.

BACKGROUND: Quercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system. RESULTS: In this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin-CD117+ hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein. CONCLUSIONS: In summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice.

Intravenous administration of IL-12 encoding self-replicating RNA-lipid nanoparticle complex leads to safe and effective antitumor responses.

Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Therapies that can synergistically modulate innate immunity and stimulate adaptive anti-tumor responses are of great interest for cancer immunotherapy. Here we investigated the lipid nanoparticle-encapsulated self-replicating RNA (srRNA) encoding IL-12 (referred to as JCXH-211) for the treatment of cancers. Both local (intratumoral) and systemic (intravenous) administration of JCXH-211 in tumor-bearing mice induced a high-level expression of IL-12 in tumor tissues, leading to modulation of tumor microenvironment and systemic activation of antitumor immunity. Particularly, JCXH-211 can inhibit the tumor-infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). When combined with anti-PD1 antibody, it was able to enhance the recruitment of T cells and NK cells into tumors. In multiple mouse solid tumor models, intravenous injection of JCXH-211 not only eradicated large preestablished tumors, but also induced protective immune memory that prevented the growth of rechallenged tumors. Finally, intravenous injection of JCXH-211 did not cause noticeable systemic toxicity in tumor-bearing mice and non-human primates. Thus, our study demonstrated the feasibility of intravenous administration of JCXH-211 for the treatment of advanced cancers.

Classification of superficial suspected lymph nodes: non-invasive radiomic model based on multiphase contrast-enhanced ultrasound for therapeutic options of lymphadenopathy.

Background: Accurate determination of the types of lymphadenopathy is of great importance in disease diagnosis and treatment and is usually confirmed by pathological findings. Radiomics is a non-invasive tool that can extract quantitative information from medical images. Our study was designed to develop a non-invasive radiomic approach based on multiphase contrast-enhanced ultrasound (CEUS) images for the classification of different types of lymphadenopathy. Methods: A total of 426 patients with superficial suspected lymph nodes (LNs) from three centres were grouped into a training cohort (n=190), an internal testing cohort (n=127), and an external testing cohort (n=109). The radiomic features were extracted from the prevascular phase, vascular phase, and postvascular phase of the CEUS images. Model 1 (the conventional feature model), model 2 (the multiphase radiomics model), and model 3 (the combined feature model) were established for lymphadenopathy classification. The area under the curve (AUC) and confusion matrix were used to evaluate the performance of the three models. The usefulness of the models was assessed in different threshold probabilities by decision curve analysis. Results: There were 139 patients (32.6%) with benign LNs, 110 patients (25.8%) with lymphoma, and 177 patients (41.5%) with metastatic LNs in our population. Finally, twenty features were selected to construct the radiomics models for these three types of lymphadenopathy. Model 2 integrating multiphase images of the CEUS yielded the AUCs of 0.838, 0.739, and 0.733 in the training cohort, internal testing cohort, and external testing cohort, respectively. After the combination of conventional features and radiomic features, the AUCs of model 3 improved to 0.943, 0.823 and 0.785 in the training cohort, internal testing cohort, and external testing cohort. Besides, model 3 had an accuracy of 81.05%, sensitivity of 80%, and specificity of 90.43% in the training cohort. Model performance was further confirmed in the internal testing cohort and external testing cohort. Conclusions: We constructed a combined feature model using a series of CEUS images for the classification of the lymphadenopathies. For patients with superficial suspected LNs, this model can help clinicians make a decision on the LN type noninvasively and choose appropriate treatments.

Insights into substitution strategy towards thermodynamic and property regulation of chemically recyclable polymers.

The development of chemically recyclable polymers serves as an attractive approach to address the global plastic pollution crisis. Monomer design principle is the key to achieving chemical recycling to monomer. Herein, we provide a systematic investigation to evaluate a range of substitution effects and structure-property relationships in the ɛ-caprolactone (CL) system. Thermodynamic and recyclability studies reveal that the substituent size and position could regulate their ceiling temperatures (Tc). Impressively, M4 equipped with a tert-butyl group displays a Tc of 241 °C. A series of spirocyclic acetal-functionalized CLs prepared by a facile two-step reaction undergo efficient ring-opening polymerization and subsequent depolymerization. The resulting polymers demonstrate various thermal properties and a transformation of the mechanical performance from brittleness to ductility. Notably, the toughness and ductility of P(M13) is comparable to the commodity plastic isotactic polypropylene. This comprehensive study is aimed to provide a guideline to the future monomer design towards chemically recyclable polymers.

The preoperative triglyceride-glucose index has a positive effect on predicting the risk of short-term restenosis after carotid artery stenting: a retrospective cohort study.

Background: Increasing evidence suggests that insulin resistance is linked to cardiovascular disease and atherosclerosis. The triglyceride-glucose (TyG) index has proven to be a convincing marker to quantitatively evaluate insulin resistance. However, there is no relevant information about the relationship between the TyG index and restenosis after carotid artery stenting. Methods: A total of 218 patients were enrolled. Carotid ultrasound and computed tomography angiography were used to evaluate in-stent restenosis. A Kaplan-Meier analysis and Cox regression method were performed to analyze the correlation between TyG index and restenosis. Schoenfeld residuals were used to determine the proportional-hazards assumption. A restricted cubic spline method was used to model and visualize the dose-response relationship between the TyG index and the risk of in-stent restenosis. Subgroup analysis was also performed. Results: Thirty-one participants (14.2%) developed restenosis. The preoperative TyG index had a time-varying effect on restenosis. Within 29 months post-surgery, an increasing preoperative TyG index was linked to a significant increased risk of restenosis (hazard ratio: 4.347; 95% confidence interval 1.886-10.023). However, after 29 months, the effect was decreased, although not statistically significant. The subgroup analysis showed that the hazard ratios tended to be higher in the age ≤ 71 years subgroup (p < 0.001) and participants with hypertension (p < 0.001). Conclusion: The preoperative TyG index was significantly associated with the risk of short-term restenosis after CAS within 29 months post-surgery. The TyG index may be employed to stratify patients based on their risk of restenosis after carotid artery stenting.

Predicting the prognosis of primary orbital lymphoma by clinical characteristics and imaging features.

AIM: To analyze the 5-year disease-free survival (DFS) of primary orbital lymphoma (POL) by clinical characteristics and imaging features. METHODS: A total of 72 patients, 43 males and 29 females, with histologically confirmed POL, were retrospectively recruited between January 2012 and May 2017. The information on clinical characteristics, imaging features, and 5-year DFS was obtained. Univariate and multivariate forward logistic regression analyses were used to identify the variables significantly associated with 5-year DFS. Kaplan-Meier was applied for survival analysis. RESULTS: Univariate analysis revealed that uni- or bilateral orbital involvement, single or multiple lesions, treatment methods, and contrast enhancement pattern on images were significant for 5-year DFS (P=0.022, 0.042, <0.001, and 0.028, respectively), while in multivariate logistic regression analysis, only uni- or bilateral orbital involvement, treatment methods and contrast enhancement pattern on images were significant (r=0.453, 0.897, and 0.556, P=0.038, <0.001 and 0.022, respectively). The survival curves for DFS were obtained. CONCLUSION: The majority of POL are B-cell lymphomas. Unilateral orbital involvement, homogeneous contrast enhancement on images, and the appropriate treatment schemes result to be significant factors for a good prognosis for POL.

Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy.

Programmed death-1 is a protein found on the surface of immune cells that can interact with its ligand, programmed death-ligand 1 (PD-L1), which is expressed on the plasma membrane, the surface of secreted cellular exosomes, in cell nuclei, or as a circulating soluble protein. This interaction can lead to immune escape in cancer patients. In clinical settings, PD-L1 plays an important role in tumor disease diagnosis, determining therapeutic effectiveness, and predicting patient prognosis. PD-L1 inhibitors are also essential components of tumor immunotherapy. Thus, the detection of PD-L1 levels is crucial, especially in the era of precision cancer therapy. In recent years, innovations have been made in traditional immunoassay methods and the development of new immunoassays for PD-L1 detection. This review aims to summarize recent research progress in tumor PD-L1 detection technology and highlight the clinical applications of PD-L1.

Glycyrrhizic acid inhibits myeloid differentiation of hematopoietic stem cells by binding S100 calcium binding protein A8 to improve cognition in aged mice.

BACKGROUND: Glycyrrhizic acid (GA), a saponin compound often used as a flavoring agent, can elicit anti-inflammatory and anti-tumor effects, and alleviate aging. However, the specific mechanism by which GA alters immune cell populations to produce these beneficial effects is currently unclear. RESULTS: In this study, we systematically analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice. Our in vivo results show that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin-CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to S100 calcium-binding protein 8 (S100A8) protein. Overexpression of S100A8 in Lin- CD117+ hematopoietic stem cells enhanced cognition in aged mice and the immune reconstitution of severely immunodeficient B-NDG (NOD.CB17-Prkdcscid/l2rgtm1/Bcgen) mice. CONCLUSIONS: Collectively, GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.

Saussurea involucrata PIP2;4 improves growth and drought tolerance in Nicotiana tabacum by increasing stomatal density and sensitivity.

Aquaporins, the major facilitators of water transport across membranes, are involved in growth and development and adaptation to drought stress in plants. In this study, a plasma membrane intrinsic protein (SiPIP2;4) was cloned from Saussurea involucrata, a cold-tolerant hardy herb. The expression of SiPIP2;4 increased the stomatal density and sensitivity of tobacco (Nicotiana tabacum), thus, affecting the plant's growth and resistance to the diverse water environment. The higher stomatal density under well-watered conditions effectively promoted the photosynthetic rate, which led to the rapid growth of transgenic lines. The stomata in the transgenic lines responded more sensitively to the vapor pressure deficit than the wild-type under different levels of ambient humidity. Their stomatal apertures positively correlated with the ambient humidity. Under drought conditions, the overexpression of SiPIP2;4 promoted rapid stomatal closure, reduced water dissipation, and enhanced drought tolerance. These results indicate that SiPIP2;4 regulates the density and sensitivity of plant stomata, thus, playing an important role in balancing plant growth and stress tolerance. This suggests that SiPIP2;4 has the potential to serve as a genetic resource for crop improvement.

The diagnostic value of a nomogram based on multimodal ultrasonography for thyroid-nodule differentiation: A multicenter study.

Objective: To establish and verify a nomogram based on multimodal ultrasonography (US) for the assessment of the malignancy risk of thyroid nodules and to explore its value in distinguishing benign from malignant thyroid nodules. Methods: From September 2020 to December 2021, the data of 447 individuals with thyroid nodules were retrieved from the multicenter database of medical images of the National Health Commission's Capacity Building and Continuing Education Center, which includes data from more than 20 hospitals. All patients underwent contrast-enhanced US (CEUS) and elastography before surgery or fine needle aspiration. The training set consisted of three hundred datasets from the multicenter database (excluding Zhejiang Cancer Hospital), and the external validation set consisted of 147 datasets from Zhejiang Cancer Hospital. As per the pathological results, the training set was separated into benign and malignant groups. The characteristics of the lesions in the two groups were analyzed and compared using conventional US, CEUS, and elastography score. Using multivariate logistic regression to screen independent predictive risk indicators, then a nomogram for risk assessment of malignant thyroid nodules was created. The diagnostic performance of the nomogram was assessed utilizing calibration curves and receiver operating characteristic (ROC) from the training and validation cohorts. The nomogram and The American College of Radiology Thyroid Imaging, Reporting and Data System were assessed clinically using decision curve analysis (DCA). Results: Multivariate regression showed that irregular shape, elastography score (≥ 3), lack of ring enhancement, and unclear margin after enhancement were independent predictors of malignancy. During the training (area under the ROC [AUC]: 0.936; 95% confidence interval [CI]: 0.902-0.961) and validation (AUC: 0.902; 95% CI: 0.842-0.945) sets, the multimodal US nomogram with these four variables demonstrated good calibration and discrimination. The DCA results confirmed the good clinical applicability of the multimodal US nomogram for predicting thyroid cancer. Conclusions: As a preoperative prediction tool, our multimodal US-based nomogram showed good ability to distinguish benign from malignant thyroid nodules.

Discovery of novel targets and mechanisms of MEK inhibitor Selumetinib for LGG treatment based on molecular docking and molecular dynamics simulation.

Based on molecular docking and molecular dynamics simulation, to find a new target and mechanism of MEK inhibitor Selumetinib in the treatment of low-grade glioma (LGG), and to provide theoretical guidance for its clinical medication. All possible targets of Selumetinib were fished through the compound target prediction database. New targets of Selumetinib in the treatment of LGG were found and its mechanism was evaluated employing molecular docking, gene difference analysis, molecular dynamics simulation, and protein subcellular localization prediction. A total of 100 Selumetinib targets and 85 LGG-related targets were screened in this study. There were 7 active targets at the intersection of the two. Through protein interaction (PPI), gene enrichment analysis, and gene difference analysis, one effective target of Selumetinib was finally screened, CDK2 mainly existing in the cytoplasm, endoplasmic reticulum, and plasma membrane; the target plays a role in the treatment of LGG by inhibiting the signal pathways of PI3K Akt and participating in biological processes such as peptide amino acid modification, regulation of intracellular signal transduction, and positive regulation of cell metabolism. CDK2 may be a new direction of Selumetinib in the clinical treatment of LGG.

Screening the components of Saussurea involucrata for novel targets for the treatment of NSCLC using network pharmacology.

BACKGROUND: Saussurea involucrata (SAIN), also known as Snow lotus (SI), is mainly distributed in high-altitude areas such as Tibet and Xinjiang in China. To identify novel targets for the prevention or treatment of lung adenocarcinoma and lung squamous cell carcinoma (LUAD&LUSC), and to facilitate better alternative new drug discovery as well as clinical application services, the therapeutic effects of SAIN on LUAD&LUSC were evaluated by gene differential analysis of clinical samples, compound target molecular docking, and GROMACS molecular dynamics simulation. RESULTS: Through data screening, alignment, analysis, and validation it was confirmed that three of the major active ingredients in SAIN, namely quercetin (Q), luteolin (L), and kaempferol (K), mainly act on six protein targets, which mainly regulate signaling pathways in cancer, transcriptional misregulation in cancer, EGFR tyrosine kinase inhibitor resistance, adherens junction, IL-17 signaling pathway, melanoma, and non-small cell lung cancer. In addition, microRNAs in cancer exert preventive or therapeutic effects on LUAD&LUSC. Molecular dynamics (MD) simulations of Q, L, or K in complex with EGFR, MET, MMP1, or MMP3 revealed the presence of Q in a very stable tertiary structure in the human body. CONCLUSION: There are three active compounds of Q, L, and K in SAIN, which play a role in the treatment and prevention of non-small cell lung cancer (NSCLC) by directly or indirectly regulating the expression of genes such as MMP1, MMP3, and EGFR.

Rapid Progress in Intelligent Radiotherapy and Future Implementation.

Radiotherapy is one of the major approaches to cancer treatment. Artificial intelligence in radiotherapy (shortly, Intelligent radiotherapy) mainly involves big data, deep learning, extended reality, digital twin, radiomics, Internet plus and Internet of Things (IoT), which establish an automatic and intelligent network platform consisting of radiotherapy preparation, target volume delineation, treatment planning, radiation delivery, quality assurance (QA) and quality control (QC), prognosis judgment and post-treatment follow-up. Intelligent radiotherapy is an interdisciplinary frontier discipline in infancy. The review aims to summary the important implements of intelligent radiotherapy in various areas and put forward the future of unmanned radiotherapy center.

Efficacy and safety of recombinant human endostatin during peri-radiotherapy period in advanced non-small-cell lung cancer.

Background: This study aimed to retrospectively investigate the efficacy and safety of recombinant human endostatin (Rh-endostatin) combined with radiotherapy in advanced non-small-cell lung cancer (NSCLC). Methods: Patients with unresectable stage III and IV NSCLC who treated with radiotherapy were enrolled. Patients who received Rh-endostatin infusion throughout the whole peri-radiotherapy period formed the Endostar group, and those who received no Rh-endostatin infusion were the control group. Results: The median progression-free survival was 8.0 and 4.4 months (hazard ratio: 0.53; 95% CI: 0.32-0.90; p = 0.019) and median overall survival was 40.0 and 13.1 months (hazard ratio: 0.53; 95% CI: 0.28-0.98; p = 0.045) for the Endostar and control groups, respectively. The Endostar group exhibited a numerically lower rate of radiation pneumonitis relapse, radiation pneumonitis death and pulmonary fibrosis. Conclusion: Rh-endostatin infusion throughout the peri-radiotherapy period enhanced radiosensitivity and showed better survival outcomes and a tendency toward fewer radiation-related pulmonary events in patients with NSCLC.

Recombinant human endostatin (Rh-endostatin/Endostar) combined with chemotherapy has been approved as first-line standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) in China. This study aimed to retrospectively investigate the efficacy and safety of Rh-endostatin combined with radiotherapy in advanced NSCLC. Patients with unresectable stage III and IV NSCLC who treated with radiotherapy were enrolled. Patients who received Rh-endostatin infusion throughout the whole peri-radiotherapy period were the Endostar group, and those receiving no Rh-endostatin infusion were the control group. Results showed that the median progression-free survival was 8.0 and 4.4 months, and median overall survival was 40.0 and 13.1 months, for the Endostar and control groups, respectively. The Endostar group had a lower rate of radiation pneumonitis relapse, radiation pneumonitis death and pulmonary fibrosis. In conclusion, Rh-endostatin infusion throughout the peri-radiotherapy period enhanced radiosensitivity and showed better survival outcomes and a tendency toward fewer radiation-related pulmonary events in patients with NSCLC.

Licochalcone A activation of glycolysis pathway has an anti-aging effect on human adipose stem cells.

Licochalcone A (LA) is a chalcone flavonoid of Glycyrrhiza inflata, which has anti-cancer, antioxidant, anti-inflammatory, and neuroprotective effects. However, no anti-aging benefits of LA have been demonstrated in vitro or in vivo. In this study, we explored whether LA has an anti-aging effect in adipose-derived stem cells (ADSCs). We performed ß-galactosidase staining and measured reactive oxygen species, relative telomere lengths, and P16ink4a mRNA expression. Osteogenesis was assessed by Alizarin Red staining and adipogenesis by was assessed Oil Red O staining. Protein levels of related markers runt-related transcription factor 2 and lipoprotein lipase were also examined. RNA sequencing and measurement of glycolysis activities showed that LA significantly activated glycolysis in ADSCs. Together, our data strongly suggest that the LA have an anti-aging effect through activate the glycolysis pathway.

Evaluation of the immunomodulatory effects of C9-13-CPs in macrophages.

Short-chain chlorinated paraffins (SCCPs) have been listed as a new class of persistent organic pollutants by the Stockholm Convention. SCCPs exhibit carcinogenic-, endocrine-, and metabolism-disrupting effects. However, the knowledge of the immunomodulatory effects of SCCPs and their underlying mechanisms, especially in specific immune cells, remains limited. In addition to SCCPs, C9-13-CPs have also been detected in humans. In this study, murine RAW264.7 macrophages were exposed to C9-13-CPs at environmentally relevant concentrations to investigate whether or how C9-13-CPs exhibit immunomodulatory effects. The results showed that the exposure of RAW264.7 cells to C9-13-CPs increased cell viability, as assayed by MTT analysis at 490 nm, and also promoted cell proliferation, as indicated by EdU uptake assay, which was measured at excitation and emission wavelengths of 488 and 512 nm, respectively. In addition, exposure to C9-13-CPs not only led to elevated ATP level and intracellular Ca2+ level but also caused AMPK signaling activation and NF-κB signaling inhibition. Moreover, molecular docking showed that the ß2-AR receptor could bind to C9-13-CPs. Taken together, these results suggest that the immune dysfunction of RAW264.7 cells caused by C9-13-CPs is closely related to the ß2-AR/AMPK/NF-κB signaling axis.

A randomized, controlled phase II trial of maxillofacial and oral massage in attenuating severe radiotherapy-induced oral mucositis and lipid metabolite changes in nasopharyngeal carcinoma.

PURPOSE: This randomized controlled phase II study investigated the efficacy, safety and underlying mechanism of maxillofacial and oral massage (MOM) in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy. METHODS: A total of 158 NPC patients were randomly assigned 1:1 to routine oral care and medication (the control group) or that with additional MOM (the treatment group). The primary endpoint was the incidence of severe radiotherapy-induced oral mucositis (SRTOM). In addition, the time of initiation and duration of RTOM and SRTOM, adverse events, dynamic changes of lipid metabolites in peripheral blood were analyzed. RESULTS: Seventy-six patients in the treatment group and seventy-nine in the control group completed the trial. The incidence of SRTOM in the treatment group was lower than the control (26.3% vs. 46.8%, P = 0.008). The median initiation time to RTOM and SRTOM was significantly longer in the treatment group than the control (RTOM:12 vs 10 days, hazard ratio [HR] 0.52, P < 0.001; SRTOM: 28.5 vs 19 days, HR 0.5579, P = 0.002). While the median duration time of RTOM and SRTOM in the treatment group was shorter (RTOM: 20.7 vs 24.7 days, P = 0.001; SRTOM: 8.05 vs 13.08 days, P < 0.001). Only 1.3% of patients obtained grade 3 or higher adverse events during MOM. The anti-inflammatory lipids increased significantly after MOM, especially with 10.6 Gy or higher. CONCLUSION: MOM significantly attenuated the incidence of SRTOM in NPC patients. The adverse events of MOM were slight and tolerant. MOM enhanced anti-inflammatory lipid metabolites, which might be an underlying mechanism.

Licochalcone A improves the cognitive ability of mice by regulating T- and B-cell proliferation.

Licochalcone A (LA), a flavonoid found in licorice, has anticancer, antioxidant, anti-inflammatory, and neuroprotective properties. Here, we explored the effect of injecting LA into the tail vein of middle-aged C57BL/6 mice on their cognitive ability as measured by the Morris water maze (MWM) test and cerebral blood flow (CBF). The related mechanisms were assessed via RNA-seq, and T (CD3e+) and B (CD45R/B220+) cells in the spleen and whole blood were quantified via flow cytometry. LA improved the cognitive ability, according to the MWM test results, and upregulated the CBF level of treated mice. The RNA-seq results indicate that LA affected the interleukin (IL)-17 signaling pathway, which is related to T- and B-cell proliferation, and the flow cytometry data suggest that LA promoted T- and B-cell proliferation in the spleen and whole blood. We also performed immune reconstruction via a tail vein injection of lymphocytes into B-NDG (NOD-PrkdcscidIl2rgtm1/Bcge) mice before treating them with LA. We tested cognitive ability by subjecting these animals to new object recognition tests and quantified the splenic and whole blood T and B cells. Cognitive ability improved after immune reconstruction and LA treatment, and LA promoted T- and B-cell proliferation in the spleen and whole blood. This study demonstrates that LA, by activating the IL-17 signaling pathway, promotes T- and B-cell proliferation in the spleen and whole blood of mice and improves cognitive ability. Thus, LA may have immune-modulating therapeutic potential for improving cognition.

Mannheimia bovis sp. nov., Isolated from a Dead Cow with Hemorrhagic Pneumonia.

Strain ZY190616T was isolated from lung of a dead cow with hemorrhagic pneumonia in Yunnan Province, China. The strain was Gram-stain-negative, facultatively anaerobic bacterium. Phylogenetic analysis based on 16S rRNA gene sequence indicated that the strain was closely related to species of the genus Mannheimia and formed an independent clade with M.varigena CCUG 38462 T (97.0% similarity). Phylogenetic analysis based on recN gene indicated that the strain formed a clade with M.caviae CCUG 59995 T (87.8% similarity). Phylogenetic analysis based on rpoB gene indicated that the strain formed a clade with M.varigena CCUG 38462 T (94.7% similarity). The genomic OrthoANI values between strain ZY190616T and M. ovis, M.haemolytica and M.granulomatis were 84.5%, 82.7% and 81.9%, respectively. The genomic G + C content was 39.8 mol%. The predominant fatty acids (> 5%) of the strain were C16:0, C14:0, C18:1ω7c, summed feature 3 (C16:1 ω7c and/ or C16:1ω6c) and summed feature 2 (C14:0 3OH/ C16:1 Iso). The major polar lipids were phosphatidylglycerol (PG), phosphatidylethanolamine (PE), monophosphatidylglycerol (MGDG), triacylglycerol (TAG) and diphosphatidylglycerol (DLCL). The sole respiratory quinone was CoQ-7. Based on evidence from the taxonomic study, strain ZY190616T represents a novel species of the genus Mannheimia, for which the name Mannheimia bovis sp. nov. is proposed. The type strain is ZY190616T (= CCTCC AB 2020168 T = KCTC 25018 T).

Mannheimia ovis sp. nov., Isolated from Dead Sheep with Hemorrhagic Pneumonia.

Two Gram-stain-negative, facultatively anaerobic bacteria, designated ZY170218T and ZY180512, were isolated from lungs of dead sheep with hemorrhagic pneumonia in Yunnan Province, China and their taxonomic positions were studied by a polyphasic approach. The two isolates grew optimally at 37 °C, pH 9.0 and 1.0% NaCl (w/v), and showed identical 16S rRNA, recN and rpoB gene sequences. Phylogenetic analysis based on 16S rRNA gene sequence showed that the two strains fell within the cluster of species in the genus Mannheimia and formed a separated lineage with comparatively low similarity to the closest related species M. granulomatis (96.5%). Phylogenetic analysis based on rpoB gene indicated that the strains formed a monophyletic evolutionary lineage, with low sequence similarity ≤ 89.0% to the species of the genus Mannheimia. The genomic OrthoANI values between strain ZY170218T and M. granulomatis and M. haemolytica were 80.4% and 83.1%, respectively. The genomic G + C content of strain ZY170218T was 39.1 mol%. The predominant fatty acids (> 5%) of the two strains were C16:0, C14:0, C18:1ω7c, summed feature 3 (C16:1 ω7c and/ or C16:1ω6c) and summed feature 2 (C14:0 3OH/ C16:1 Iso). The major polar lipids of strain ZY170218T were phosphatidylglycerol, phosphatidylcholine, monogalactosyldiacylglycerol, bis(monoacylglycero)phosphate and diacylglycerols. The sole respiratory quinone of the two strains was CoQ-7. On the basis of phylogenetic, phenotypic and chemotaxonomic features, strain ZY170218T and ZY180512 clearly represents a novel species of the genus Mannheimia, for which the name Mannheimia ovis sp. nov. is proposed. The type strain is ZY170218T (= CGMCC 1.13620 T = KCTC 15731 T).