CD155 is essential for skeletal muscle regeneration by regulating satellite cell proliferation and differentiation.

CD155, a member of the immunoglobulin superfamily, is closely related to cell proliferation, adhesion, and migration. CD155 is overexpressed on the surface of cancer cells to promote cell proliferation and is upregulated in damaged tissues as a stress-induced molecule. The process of skeletal muscle regeneration after injury is complex and involves injurious stimulation and subsequent satellite cell proliferation. However, the role of CD155 in this process remains unelucidated. This study aimed to explore the role of CD155 in injured skeletal muscle regeneration and to clarify its effect on satellite cell proliferation and differentiation. Here, quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence results indicated that CD155 expression in satellite cells increased after skeletal muscle injury. CD155 knockout in mice impaired the regeneration of skeletal muscle. A bone marrow transplantation mouse model was constructed and revealed that CD155 on skeletal muscle tissues, not immune cells, affected muscle regeneration. In vitro, CD155 knockdown in myoblasts inhibited their proliferation and differentiation. The transcriptomic analysis also indicated that CD155 absence can impair the biological proliferation and differentiation process of myoblasts. Our research demonstrates that CD155 directly promotes injured muscle regeneration by regulating satellite cell proliferation and differentiation, which may be a potential therapeutic molecule for skeletal muscle injury.

Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration.

BACKGROUND & AIMS: Post-hepatectomy liver failure (PHLF) leads to poor prognosis in patients undergoing hepatectomy, with hepatic vascular reconstitution playing a critical role. However, the regulators of hepatic vascular reconstitution remain unclear. In this study, we aimed to investigate the regulatory mechanisms of hepatic vascular reconstitution and identify biomarkers predicting PHLF in patients undergoing hepatectomy. METHODS: Candidate genes that were associated with hepatic vascular reconstitution were screened using adeno-associated virus vectors in Alb-Cre-CRISPR/Cas9 mice subjected to partial hepatectomy. The biological activities of candidate genes were estimated using endothelial precursor transfusion and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) models. The level of candidates was detected in biopsies from patients undergoing ALPPS. Risk factors for PHLF were also screened using retrospective data. RESULTS: Downregulation of Gata3 and upregulation of Ramp2 in hepatocytes promoted the proliferation of liver sinusoidal endothelial cells and hepatic revascularization. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor A (VEGFA) played opposite roles in regulating the migration of endothelial precursors from bone marrow and the formation of new sinusoids after hepatectomy. Gata3 restricted endothelial cell function in patient-derived hepatic organoids, which was abrogated by a Gata3 inhibitor. Moreover, overexpression of Gata3 led to higher mortality in ALPPS mice, which was improved by a PEDF-neutralizing antibody. The expression of Gata3/RAMP and PEDF/VEGFA tended to have a negative correlation in patients undergoing ALPPS. A nomogram incorporating multiple factors, such as serum PEDF/VEGF index, was constructed and could efficiently predict the risk of PHLF. CONCLUSIONS: The balance of Gata3 and Ramp2 in hepatocytes regulates the proliferation of liver sinusoidal endothelial cells and hepatic revascularization via changes in the expression of PEDF and VEGFA, revealing potential targets for the prevention and treatment of PHLF. IMPACT AND IMPLICATIONS: In this study, we show that the balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution by promoting a shift from pigment epithelium-derived factor (PEDF) to vascular endothelial growth factor A (VEGFA) expression during hepatectomy- or ALLPS (associating liver partition and portal vein ligation for staged hepatectomy)-induced liver regeneration. We also identified serum PEDF/VEGFA index as a potential predictor of post-hepatectomy liver failure in patients who underwent hepatectomy. This study improves our understanding of how hepatocytes contribute to liver regeneration and provides new targets for the prevention and treatment of post-hepatectomy liver failure.

CD226 knockout reduces the development of CD8+ T by impairing the TCR sensitivity of double-positive thymocytes.

The costimulation molecule CD226 is widely involved in T cell differentiation, activation and immune functional regulation in peripheral immune tissues. CD226-deficient mice have impaired immune response capacity. The function of CD226 in regulating T cell development in the thymus, a central immune organ, is not yet fully understood. We investigated the development of thymocytes using CD226 knockout mice and single-cell sequencing techniques. CD226 began to be expressed in the second half of thymocyte development, with a gradual increase from the double-positive (DP) to single-positive (SP) phase and higher levels of CD226 on CD8+ T cells than on CD4+ T cells from the SP phase to mature T cells. In the thymus of CD226KO mice, the proportion of DPT at the quiescent phase (DPT-Q) increased, of which the Gzma+ cluster that tends to be CD8+ T cells and CD5+ cluster that is undergoing positive selection decreased dramatically. Afterward, the proportion of mature CD8+ T cells reduced dramatically. Depletion of CD226 impaired TCR activation signalling and diminished AKT/ERK/NF-κB/p38 phosphorylation levels. The diminished TCR responsiveness of DPT cells impeded their positive selection process and influenced the maturation of CD8+ T cells. In mechanism, CD226 knockout enhanced DPT cell apoptosis via impairing AKT phosphorylation. These results suggest that CD226 plays a significant role in T cell thymic development via modulation of TCR signalling, affecting CD8+ T cell maturation.

Competitive binding of CD226/TIGIT with poliovirus receptor regulates macrophage polarization and is involved in vascularized skin graft rejection.

End-stage organ failure often requires solid organ transplantation. Nevertheless, transplant rejection remains an unresolved issue. The induction of donor-specific tolerance is the ultimate goal in transplantation research. In this study, an allograft vascularized skin rejection model using BALB/c-C57/BL6 mice was established to evaluate the regulation of the poliovirus receptor signaling pathway using CD226 knockout or T cell immunoglobulin and ITIM domain (TIGIT)-crystallizable fragment (Fc) recombinant protein treatment. In the TIGIT-Fc-treated and CD226 knockout groups, graft survival time prolonged significantly, with a regulatory T cell proportion increase and M2-type macrophage polarization. Donor-reactive recipient T cells became hyporesponsive while responding normally after a third-party antigen challenge. In both groups, serum interleukin (IL)-1ß, IL-6, IL-12p70, IL-17A, tumor necrosis factor-α, interferon gamma, and monocyte chemoattractant protein-1 levels decreased, and the IL-10 level increased. In vitro, M2 markers, such as Arg1 and IL-10, were markedly increased by TIGIT-Fc, whereas iNOS, IL-1ß, IL-6, IL-12p70, tumor necrosis factor-α, and interferon gamma levels decreased. CD226-Fc exerted the opposite effect. TIGIT suppressed TH1 and TH17 differentiation by inhibiting macrophage SHP-1 phosphorylation and enhanced ERK1/2-MSK1 phosphorylation and nuclear translocation of CREB. In conclusion, CD226 and TIGIT competitively bind to poliovirus receptor with activating and inhibitory functions, respectively. Mechanistically, TIGIT promotes IL-10 transcription from macrophages by activating the ERK1/2-MSK1-CREB pathway and enhancing M2-type polarization. CD226/TIGIT-poliovirus receptor are crucial regulatory molecules of allograft rejection.

Dual-function C2H2-type zinc-finger transcription factor GmZFP7 contributes to isoflavone accumulation in soybean.

Isoflavones are a class of secondary metabolites produced by legumes and play important roles in human health and plant stress tolerance. The C2H2 zinc-finger transcription factor (TF) functions in plant stress tolerance, but little is known about its function in isoflavone regulation in soybean (Glycine max). Here, we report a C2H2 zinc-finger TF gene, GmZFP7, which regulates isoflavone accumulation in soybean. Overexpressing GmZFP7 increased the isoflavone concentration in both transgenic hairy roots and plants. By contrast, silencing GmZFP7 expression significantly reduced isoflavone levels. Metabolomic and qRT-PCR analysis revealed that GmZFP7 can increase the flux of the phenylpropanoid pathway. Furthermore, dual-luciferase and electrophoretic mobility shift assays showed that GmZFP7 regulates isoflavone accumulation by influencing the expression of Isoflavone synthase 2 (GmIFS2) and Flavanone 3 ß-hydroxylase 1 (GmF3H1). In this study, we demonstrate that GmZFP7 contributes to isoflavone accumulation by regulating the expression of the gateway enzymes (GmIFS2 and GmF3H1) of competing phenylpropanoid pathway branches to direct the metabolic flux into isoflavone. A haplotype analysis indicated that important natural variations were present in GmZFP7 promoters, with P-Hap1 and P-Hap3 being the elite haplotypes. Our findings provide insight into how GmZFP7 regulates the phenylpropanoid pathway and enhances soybean isoflavone content.

Identification of genes for seed isoflavones based on bulk segregant analysis sequencing in soybean natural population.

KEY MESSAGE: We identified four hub genes for isoflavone biosynthesis based on BSA-seq and WGCNA methods and validated that GmIE3-1 positively contribute to isoflavone accumulation in soybean. Soybean isoflavones are secondary metabolites of great interest owing to their beneficial impact on human health. Herein, we profiled the seed isoflavone content by HPLC in 1551 soybean accessions grown in two locations for two years and constructed two extreme pools with high (4065.1 µg g-1) and low (1427.23 µg g-1) isoflavone contents to identify candidate genes involved in isoflavone biosynthesis pathways using bulk segregant analysis sequencing (BSA-seq) approach. The results showed that the average sequencing depths were 50.3× and 65.7× in high and low pools, respectively. A total of 23,626 polymorphic SNPs and 5299 InDels were detected between both pools and 1492 genes with different variations were identified. Based on differential genes in BSA-seq and weighted gene co-expression network analysis (WGCNA), four hub genes, Glyma.06G290400 (designated as GmIE3-1), Glyma.01G239200, Glyma.01G241500, Glyma.13G256100 were identified, encoding E3 ubiquitin-protein ligase, arm repeat protein interacting with ABF2, zinc metallopeptidase EGY3, and dynamin-related protein 3A, respectively. The allelic variation in GmIE3-1 showed a significant influence on isoflavone accumulation. The virus-induced gene silencing (VIGS) and RNAi hairy root transformation of GmIE3-1 revealed partial suppression of this gene could cause a significant decrease (P < 0.0001) of total isoflavone content, suggesting GmIE3-1 is a positive regulator for isoflavones. The present study demonstrated that the BSA-seq approach combined with WGCNA, VIGS and hairy root transformation can efficiently identify isoflavone candidate genes in soybean natural population.

Identification of quantitative trait loci and candidate genes for seed folate content in soybean.

KEY MESSAGE: From 61 QTL mapped, a stable QTL cluster of 992 kb was discovered on chromosome 5 for folate content and a putative candidate gene, Glyma.05G237500, was identified. Folate (vitamin B9) is one of the most essential micronutrients whose deficiencies lead to various health defects in humans. Herein, we mapped the quantitative trait loci (QTL) underlying seed folate content in soybean using recombinant inbred lines developed from cultivars, ZH35 and ZH13, across four environments. We identified 61 QTL on 12 chromosomes through composite interval mapping, with phenotypic variance values ranging from 1.68 to 24.68%. A major-effect QTL cluster (qFo-05) was found on chromosome 5, spanning 992 kb and containing 134 genes. Through gene annotation and single-locus haplotyping analysis of qFo-05 in a natural soybean population, we identified seven candidate genes significantly associated with 5MTHF and total folate content in multiple environments. RNA-seq analysis showed a unique expression pattern of a hemerythrin RING zinc finger gene, Glyma.05G237500, between both parental cultivars during seed development, which suggest the gene might regulate folate content in soybean. This is the first study to investigate QTL underlying folate content in soybean and provides new insight for molecular breeding to improve folate content in soybean.

Autogenous bone block osteotomy in the chin using a robotic system: A clinical report.

An autogenous bone block osteotomy in the chin assisted by a robotic system is described. The size of the required bone graft was designed in the robotic system before surgery, and a precise bone block osteotomy was achieved with the assistance of the robotic system in a visualized, safe, and accurate surgical approach.

CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype.

Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adipose tissue macrophages (ATMs) would switch to pro-inflammatory M1 state during obesity, causing local and systemic inflammation. However, the regulatory mechanism of ATMs has not yet been well described within this process. Using a high-fat diet (HFD)-induced mouse obesity model, we found that the costimulatory molecule CD226 was highly expressed on ATMs and knockout (KO) of CD226 alleviated obesity caused by HFD. Loss of CD226 reduced the accumulation of ATMs and hindered macrophage M1 polarization, with lower serum proinflammatory cytokine levels. Furthermore, deficiency of CD226 on ATMs decreased the phosphorylation levels of VAV1, AKT, and FOXO1 and thereby upregulated PPAR-γ. Further administration of PPAR-γ inhibitor restored M1 phenotype in CD226KO ATMs. In summary, loss of CD226 alleviates the HFD-induced obesity and systemic inflammation through inhibition of the accumulation and M1 polarization of ATMs in which PPAR-γ-dependent signaling pathway is involved, suggesting that CD226 may be identified as a potential molecular target for the clinical treatment of obesity.

Inhaled vitamin A is more effective than intramuscular dosing in mitigating hyperoxia-induced lung injury in a neonatal rat model of bronchopulmonary dysplasia.

Prevention of bronchopulmonary dysplasia (BPD) in premature-birth babies continues to be an unmet medical need. Intramuscular vitamin A is currently employed in preterm neonates to prevent BPD but requires intramuscular injections in fragile neonates. We hypothesized that noninvasive inhaled delivery of vitamin A, targeted to lung, would be a more effective and tolerable strategy. We employed our well-established hyperoxia-injury neonatal rat model, exposing newborn rats to 7 days of constant extreme (95% O2) hyperoxia, comparing vitamin A dosed every 48 h via either aerosol inhalation or intramuscular injection with normoxic untreated healthy animals and vehicle-inhalation hyperoxia groups as positive and negative controls, respectively. Separately, similar vitamin A dosing of normoxia-dwelling animals was performed. Analyses after day 7 included characterization of alveolar histomorphology and protein biomarkers of alveolar maturation [surfactant protein C (SP-C), peroxisome proliferator-activated receptor (PPAR) γ, cholinephosphate cytidylyl transferase, vascular endothelial growth factor and its receptor, FLK-1, and retinoid X receptors (RXR-α, -ß, and -γ], apoptosis (Bcl2 and Bax) key injury repair pathway data including protein markers (ALK-5 and ß-catenin) and neutrophil infiltration, and serum vitamin A levels. Compared with intramuscular dosing, inhaled vitamin A significantly enhanced biomarkers of alveolar maturation, mitigated hyperoxia-induced lung damage, and enhanced surfactant protein levels, suggesting that it may be more efficacious in preventing BPD in extremely premature infants than the traditionally used IM dosing regimen. We speculate lung-targeted inhaled vitamin A may also be an effective therapy against other lung damaging conditions leading to BPD or, more generally, to acute lung injury.

Association of patient factors with time to treatment for breast cancer.

BACKGROUND: Studies have shown that in the United States, there is an increasing time from breast cancer diagnosis to first treatment (time to treatment or "TTT"), with concern that such delays may worsen oncologic outcomes. A component of TTT is the time from the initial diagnosis to initial surgical consultation (SC). We sought to identify patient-related factors associated with time to initial SC, and evaluate how this interval is associated with overall total time to treatment (TTT). METHODS: A prospective database of women diagnosed with breast cancer at our institution from 2015 to 2016 was reviewed. Time from initial breast cancer diagnosis to SC and overall TTT was collected from the electronic medical record. Documented patient-identified preferences regarding scheduling the first surgical appointment were reviewed. A multivariate analysis was performed to determine clinical and patient factors associated with TTT. RESULTS: Of 553 breast cancer patients included in the study, 27% of women opted for the earliest appointment while 73% chose a later date. The median time from diagnosis to SC was 8.5 ± 4.7 days. Patients who accepted a first available SC waited an average of 5.6 ± 3.4 days, while those who deferred waited 9.5 ± 4.6 days (P < .001). Patients who deferred the earliest available SC were older, with a median age of 67 versus 63 years, (P = .018), and had a preference for a specific location in the geographical hospital region (P = .003). Patients who deferred the first available SC also had a longer TTT (33 vs. 28 days, P = .027). DISCUSSION: Among newly diagnosed breast cancer patients, there is a substantial population that defers the first available SC. These patients are also more likely to have a prolonged TTT. Future follow-up of this cohort is necessary to determine the delays on TTT affect cancer outcomes and overall survival.

Electroacupuncture Improves Cognitive Function in Senescence-Accelerated P8 (SAMP8) Mice via the NLRP3/Caspase-1 Pathway.

Background. Clinically, electroacupuncture (EA) is the most common therapy for aging-related cognitive impairment (CI). However, the underlying pathomechanism remains unidentified. The aims of this study were to observe the effect of EA on cognitive function and explore the potential mechanism by which EA acts on the NLRP3/caspase-1 signaling pathway. Main Methods. Thirty male SAMP8 mice were randomly divided into the model, the 2 Hz EA and 10 Hz EA groups. Ten male SAMR1 mice were assigned to the control group. Cognitive function was assessed through the Morris water maze test. Hippocampal morphology and cell death were observed by HE and TUNEL staining, respectively. The serum IL-1ß, IL-6, IL-18, and TNF-α levels were measured by ELISA. Hippocampal NLRP3, ASC, caspase-1, GSDM-D, IL-1ß, IL-18, Aß, and tau proteins were detected by Western blotting. Key Findings. Cognitive function, hippocampal morphology, and TUNEL-positive cell counts were improved by both EA frequencies. The serum IL-1ß, IL-6, IL-18, and TNF-α levels were decreased by EA treatment. However, 10 Hz EA reduced the number of TUNEL-positive cells in the CA1 region and serum IL-1ß and IL-6 levels more effectively than 2 Hz EA. NLRP3/caspase-1 pathway-related proteins were significantly downregulated by EA, but 2 Hz EA did not effectively reduce ASC protein expression. Interestingly, both EA frequencies failed to reduce the expression of Aß and tau proteins. Significance. The effects of 10 Hz EA at the GV20 and ST36 acupoints on the NLRP3/caspase-1 signaling pathway may be a mechanism by which this treatment relieves aging-related CI in mice.

Protective effect of electro-acupuncture at maternal different points on perinatal nicotine exposure-induced pulmonary dysplasia in offspring based on HPA axis and signal transduction pathway.

Perinatal nicotine exposure can not only lead to lung dysplasia in offspring, but also cause epigenetic changes and induce transgenerational asthma. Previous studies have shown that electro-acupuncture (EA) applied to "Zusanli" (ST 36) can improve the lung morphology and correct abnormal expression of lung development-related protein in perinatal nicotine exposure offspring. However, it is still unclear whether ST 36 has a specific therapeutic effect and how maternal acupuncture can protect the offspring from pulmonary dysplasia. In this study, we compared the different effect of ST 36 and "Fenglong" (ST 40), which belong to the same meridian, in terms of lung pulmonary function and morphology, PPARγ, ß-catenin, GR levels in the lung tissues and CORT in the serum of perinatal nicotine exposure offspring, and explored the mechanism of acupuncture based on the maternal hypothalamus-pituitary-adrenal (HPA) axis. It is shown that EA applied to ST 36 could restore the normal function of maternal HPA axis and alleviate maternal glucocorticoid overexposure in offspring, thereby it can up-regulate the PTHrP/PPARγ and down-regulate the Wnt/ß-catenin signaling pathways, and protects perinatal nicotine exposure-induced pulmonary dysplasia in offspring. Its effect is better than that of ST 40. These results are of great significance in preventing perinatal nicotine exposure-induced pulmonary dysplasia in offspring.

[Effects of Sagacious Confucius' Pillow Elixir on cognitive function in type 2 diabetic rats].

Type 2 diabetes mellitus (T2DM) is the leading threat to human health in China, and severe cognitive impairment often occurs in most T2DM patients. Although Sagacious Confucius' Pillow Elixir is a type of classical traditional Chinese medicine for cognitive impairment in clinic, the mechanism has not yet been completely defined. In this study, an experimental model of type 2 diabetes mellitus (T2DM) was established by injecting Sprague Dawley (SD) rats with streptozocin (STZ), so as to compare the learning and memory ability, hippocampal neurons pathological changes, beta amyloid protein (A beta) content, degree of Tau protein phosphorylation, blood glucose and insulin level. The results showed that the Sagacious Confucius' Pillow Elixir could improve the learning and memory ability of STZ injected rats, reduce the level of A beta content both in hippocampus and serum, effectively reduce Tau protein phosphorylation degree, and also significantly alleviate hippocampal pathological injury, blood glucose, insulin and other basic indicators. The results showed that Sagacious Confucius' Pillow Elixir can alleviate the hippocampal pathological damage caused by STZ, and is expected to provide a theoretical basis for human T2DM patients in clinical adjuvant therapy.

Fertility in Women of Reproductive Age After Breast Cancer Treatment: Practice Patterns and Outcomes.

BACKGROUND: Breast cancer is the most frequently occurring cancer in women of reproductive age, and systemic treatments may adversely affect childbearing plans. Use of assisted reproductive technologies and therapies for ovarian protection improve fertility prospects. We evaluated whether patients had a documented fertility discussion (FD) with their oncology physician prior to therapy, what options were chosen, and if pregnancy was achieved. METHODS: A retrospective chart review from 2006 to 2014 was performed to evaluate women aged 40 years and younger who were diagnosed with breast cancer and treated with chemotherapy and/or antihormonal therapy. Patient demographics, treatment regimens, presence or absence of FD, in vitro fertilization (IVF) consultation, gonadotropin-releasing hormone (GnRH) agonist use, and subsequent successful pregnancy were analyzed. RESULTS: Among 303 patients meeting the inclusion criteria, 80 (26 %) had an FD with their physician documented; 71 of these 80 women (89 %) sought further fertility consultation and options. Sixteen (20 %) women were prescribed a GnRH agonist only for ovarian protection during chemotherapy, 50 (63 %) underwent IVF consultation only, and 5 (6 %) had both a GnRH agonist prescribed and an IVF consultation. The overall pregnancy rate was 7 % at a mean of 3 years post breast cancer treatment. Pregnancy after treatment was more common among those pursuing IVF consultation or prescribed a GnRH agonist. CONCLUSIONS: In treating young breast cancer patients, it is important to assess fertility desire, discuss treatment risks relating to fertility, and discuss preservation options. Although not every woman in this group desired pregnancy, 71/80 (89 %) women having a documented FD sought further fertility consultation and options.

[Expression of CD226 in the small intestinal group 3 innate lymphoid cells (ILC3) in mice].

Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.

Anti-inflammatory discovery of sesquiterpenoids and a jasmonic acid derivative from Artemisia stolonifera.

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.

Preparation and Performance Evaluation of a Plugging Agent with an Interpenetrating Polymer Network.

In view of the problems of polymer cross-linked elastic particle plugging agents commonly used in oilfields, including easy shear, poor temperature resistance, and weak plugging strength for large pores, the introduction of particles with certain rigidity and network structure, and cross-linking with a polymer monomer can improve the structural stability, temperature resistance, and plugging effect, and the preparation method is simple and low-cost. An interpenetrating polymer network (IPN) gel was prepared in a stepwise manner. The conditions of IPN synthesis were optimized. The IPN gel micromorphology was analyzed by SEM and the viscoelasticity, temperature resistance, and plugging performance were also evaluated. The optimal polymerization conditions included a temperature of 60 °C, a monomer concentration of 10.0-15.0%, a cross-linker concentration of 1.0-2.0% of monomer content, and a first network concentration of 20%. The IPN showed good fusion degree with no phase separation, which was the prerequisite for the formation of high-strength IPN, whereas particle aggregates reduced the strength. The IPN had better cross-linking strength and structural stability, with a 20-70% increase in the elastic modulus and a 25% increase in temperature resistance. It showed better plugging ability and erosion resistance, with the plugging rate reaching 98.9%. The stability of the plugging pressure after erosion was 3.8 times that of a conventional PAM-gel plugging agent. The IPN plugging agent improved the structural stability, temperature resistance, and plugging effect of the plugging agent. This paper provides a new method for improving the performance of a plugging agent in an oilfield.

Identification of hub genes regulating isoflavone accumulation in soybean seeds via GWAS and WGCNA approaches.

Introduction: Isoflavones are the secondary metabolites synthesized by the phenylpropanoid biosynthesis pathway in soybean that benefits human and plant health. Methods: In this study, we have profiled seed isoflavone content by HPLC in 1551 soybean accessions grown in Beijing and Hainan for two consecutive years (2017 and 2018) and in Anhui for one year (2017). Results: A broad range of phenotypic variations was observed for individual and total isoflavone (TIF) content. The TIF content ranged from 677.25 to 5823.29 µg g-1 in the soybean natural population. Using a genome-wide association study (GWAS) based on 6,149,599 single nucleotide polymorphisms (SNPs), we identified 11,704 SNPs significantly associated with isoflavone contents; 75% of them were located within previously reported QTL regions for isoflavone. Two significant regions on chromosomes 5 and 11 were associated with TIF and malonylglycitin across more than 3 environments. Furthermore, the WGCNA identified eight key modules: black, blue, brown, green, magenta, pink, purple, and turquoise. Of the eight co-expressed modules, brown (r = 0.68***), magenta (r = 0.64***), and green (r = 0.51**) showed a significant positive association with TIF, as well as with individual isoflavone contents. By combining the gene significance, functional annotation, and enrichment analysis information, four hub genes Glyma.11G108100, Glyma.11G107100, Glyma.11G106900, and Glyma.11G109100 encoding, basic-leucine zipper (bZIP) transcription factor, MYB4 transcription factor, early responsive to dehydration, and PLATZ transcription factor respectively were identified in brown and green modules. The allelic variation in Glyma.11G108100 significantly influenced individual and TIF accumulation. Discussion: The present study demonstrated that the GWAS approach, combined with WGCNA, could efficiently identify isoflavone candidate genes in the natural soybean population.

Ablation of CD226 on CD4+ T cells modulates asthma progress associated with altered IL-10 response and gut microbiota.

To investigate the role of the costimulatory molecule CD226 in asthma pathogenesis, we produced a CD4+ T-cell-specific CD226 knockout mice model (Cd226ΔCD4) and induced airway allergic inflammation by administering ovalbumin (OVA). Our results revealed alleviated lung inflammation, decreased levels of OVA-specific IgE, and increased levels of IL-10 in the serum of Cd226ΔCD4 mice (P < 0.05). Moreover, IL-10 levels in CD4+ T cells were significantly elevated in the mediastinal lymph node, spleen, and Peyer's patches in the Cd226ΔCD4 mice compared with those in controls (P < 0.05 to P < 0.01). Notably, there was a significantly higher IL-10 mRNA levels in the large intestine of the mice (P < 0.05). The protective effect of CD226 deficiency is also associated with the accumulation of gut TCRγδ+ intraepithelial lymphocytes and reversion of the gut microbiome dysbiosis. The Bacteroidetes-to-Firmicutes ratio and the abundance of Akkermansia increased in the absence of CD226 after OVA treatment. Our data reveal the synchronous changes in the lung and intestine in OVA-treated CD226-knockout mice, supporting the gut-lung axis concept and providing evidence for novel therapeutic approaches for asthma.