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Fe0.54Mo0.73/Mo2C@Cs are first synthesized by a molybdenum blue preassembly strategy, and not only exhibit excellent low-frequency electromagnetic wave absorption performance, but also have the special function of adjusting the absorption frequency.

Three new aromadendrane-type sesquiterpenoids (1–3) and five known compounds (4–8) were isolated from the stems of Strophanthus divaricatus. Their structures were determined by spectroscopic methods including HR-ESI-MS, 1D and 2D NMR. The absolute configurations of 1–3 was determined by comparison of the experimental and computed ECD spectra. Neridienone A (6) exhibited significant cytotoxicity against human cancer cell lines BEL-7402, SGC-7901, K562, A549, and HeLa with IC50 values of 3.30 ± 0.01, 2.25 ± 0.01, 2.02 ± 0.03, 1.55 ± 0.01, 4.73 ± 0.07 μM, respectively.

As the main exchanger of electroneutral NaCl absorption, sodium-hydrogen exchanger isoform 3 (NHE3) circulates in the epithelial brush border (BB) and intracellular compartments in a multi-protein complex. The size of the NHE3 complex changes during rapid regulation events. Recycling regulation of NHE3 in epithelial cells can be roughly divided into three stages. First, when stimulated by Ca(2+), cGMP, and cAMP-dependent signaling pathways, NHE3 is converted from an immobile complex found at the apical microvilli (MV) into an easily internalized and mobile form that relocates to a compartment near the base of the MV. Second, NHE3 is internalized by clathrin and albumin-dependent pathways into cytoplasmic endosomal compartments, where the complex is reprocessed and reassembled. Finally, NHE3 is translocated from the recycling endosomes (REs) to the apex of epithelial cells, a process that can be stimulated by an increase in sodium-glucose cotransporter 1 (SGLT1) activity, epidermal growth factor receptor (EGFR) signaling, Ca(2+) signaling, and binding to βPix and SH3 and multiple ankyrin repeat domains 2 (Shank2) proteins. This review describes the molecular steps and protein interactions involved in the recycling movement of NHE3 from the apex of epithelial cells, into vesicles, where it is reprocessed and reassembled, and returned to its original location on the plasma membrane, where it exerts its physiological function.

In this study, B4C-TiB2 ceramic composites were manufactured by hot pressing method. The raw materials for the in-situ synthesis of TiB2 were TiO2 and TiC. After being sintered at 1900°C for 60min under a pressure of 30MPa, compact composites samples with a TiB2 volume fraction range from 0 to 11.05% were prepared. The relative density, fracture toughness and flexural strength of different sample were tested. Microstructures on the fracture surface were studied by SEM. The result shows that B4C-TiB2 ceramic composites sintered from B4C-TiC had a better mechanical property than the one sintered from B4C-TiO2. When the content of TiB2 (reacted from TiC) was 11.05vol.%, the strength and toughness of B4C-TiB2 ceramics can reach 598MPa and 6.45MPa·m1/2. The toughening mechanisms of B4C-TiB2 composites include micro-crack toughening and energy consumption by the pulling out process of second phase.

In order to set up a reliable prediction system for the tumor grade and prognosis in glioma patients, we clarify the complicated crosstalk of Annexin A2 (ANXA2) with Glypican 1 (GPC1) and demonstrate whether combined indexes of ANXA2 and GPC1 could improve the prognostic evaluation for glioma patients. We found that ANXA2-induced glioma cell proliferation in a c-Myc-dependent manner. ANXA2 increased the expression of GPC1 via c-Myc and the upregulated GPC1 further promoted the c-Myc level, forming a positive feedback loop, which eventually led to enhanced proliferation of glioma cells. Both mRNA and protein levels of ANXA2 were upregulated in glioma tissues and coincided with the overexpression of GPC1. Besides, we utilized tissue microarrays (TMAs) and immunohistochemistry to demonstrate that glioma patients with both high expression of ANXA2 and GPC1 tended to have higher rate of tumor recurrence and shorter overall survival (OS). In conclusion, the overexpression of ANXA2 promotes proliferation of glioma cells by forming a GPC1/c-Myc positive feedback loop, and ANXA2 together with its downstream target GPC1 could be a potential “combination biomarker” for predicting prognosis of glioma patients.

Forest spatial structure (FSS) directly reflects resource competition and growth space distribution among different trees. The characteristics of FSS play an important role in mastering the growth status of ecological forest, formulating stand structure regulation measures, and improving forest quality and ecological services. In this study, seven plain ecological plantations including林分空间结构直接反映林木间资源竞争情况和生长空间分配状况,对掌握生态林生长状况、制定林分结构调控措施,提升森林质量和生态服务具有重要作用。本文以北京市通州区油松林、白蜡林、旱柳林、毛白杨林、国槐林、刺槐林和垂柳林7种平原生态林为对象,采用聚集度、角尺度、大小比数、开敞度、树冠指数、竞争指数、边缘效益和空间结构综合指数评价了平原生态林的空间结构特征。结果表明: 研究区林分水平分布格局良好,聚集度处于0.32～1.41,角尺度都分布在0.4左右,大小比数主要分布在0.5附近。林分垂直分布格局有待改善,开敞度介于0.19～0.52,大部分树冠指数在0.7左右,竞争指数均大于50,整体居于高位状态。除刺槐林空间结构综合评价指数为Ⅲ级外,其他6种林分均为Ⅱ级,林分开阔程度较低,生活力一般,各林分空间结构综合评价指数从大到小为刺槐林垂柳林油松林旱柳林白蜡林国槐林毛白杨林。.

Background Programmed cell death protein 1 (PD-1) blockade is a major advance in the treatment of malignancies, but there remain many problems in efficacy evaluation. The aim of this study was to determine whether dynamic monitoring of serum specific tumor markers (SSTMs) could predict the response to PD-1 blockade and prognosis in patients with malignancies. Methods The dynamic changes in SSTMs in 27 patients between January 1, 2018 and July 31, 2019 were analyzed retrospectively. The association between the SSTM response and the radiological response was evaluated using the χ2 test and Spearman’s correlation analysis. Kaplan-Meier estimates and the log rank test were used to explore the correlation of SSTM dynamics with progression-free survival (PFS) and overall survival (OS). Results In this study, 85.3% of patients with malignant tumors had detectable SSTM. According to the changes of SSTM within the first 12 weeks of treatment, the patients were divided into a tumor marker increased group and a tumor marker decreased group. The change in SSTM was strongly associated with the change in target lesions (χ2=15.326, P≤0.001), and there was a positive correlation between them (Pearson Correlation r=0.727, P

Hypertensive cardiac remodeling is a constellation of abnormalities that includes cardiomyocyte hypertrophy and death and tissue fibrosis. Adenosine is a long-known vasodilator, through interacting with its four cell surface receptor subtypes in cardiovascular system. However, it is unclear that whether adenosine A2A receptor (A2AR) activation is involved in the cardiac remodeling in hypertension. WT mice were utilized to induce DOCA-salt sensitive hypertension and received A2AR agonist CGS21680 or antagonist KW6002 treatment. Cardiac functional phenotyping measurement by echocardiography showed that CGS21680 improved cardiac dysfunction in DOCA-salt mice. Moreover, CGS21680 reduced cardiomyocyte hypertrophy, cardiac inflammation and fibrosis. However, iBAT depletion surgery induces dramatic cardiac remodeling in DOCA-salt mice, and the protective function of CGS21680 was blocked without intact iBAT. Mechanistically, A2AR agonist CGS21680 increased iBAT-derived fibroblast growth factor 21 (FGF21). Our data suggest that activation of A2AR could be a potential therapeutic strategy in preventing heart damage in hypertension.

Cytotoxic CD8

Blocking PD-1/PD-L1 signaling transforms cancer therapy and is assumed to unleash exhausted tumor-reactive CD8

Transmissible gastroenteritis coronavirus (TGEV) is enteropathogenic coronavirus that causes diarrhea in pigs, and is associated with high morbidity and mortality in sucking piglets. The TGEV membrane (M) protein is a decisive protein for the proliferation of viral proteins, and is associated with virus assembly and budding. To identify the cellular proteins that interact with the TGEV M protein, yeast two-hybrid screening was employed, and seven cellular proteins were identified M-binding partners. Using the GST pull-down approach and a CO-IP assay, the M protein was found to interact with porcine intestinal cells via eukaryotic translation initiation factor 4-alpha (EIF4A2), an essential component of the cellular translational machinery. Additionally, confocal microscopy revealed that EIF4A2 and M were colocalized in the cytoplasm. Furthermore, the function of EIF4A2 in intestinal cells during TGEV infection was examined. A knockdown of EIF4A2 by siRNA markedly decreased M protein proliferation and TGEV replication in target cells. Thus demonstrating that EIF4A2 plays a significant role in TGEV replication. The present study provides mechanistic insight into the interaction between the TGEV M protein and intestinal cells which contributes to the understanding of coronavirus replication and may be useful for the development of novel therapeutic strategies for TGEV infection., Highlights • Yeast two-hybrid system identified seven proteins to interact with TGEV M protein. • EIF4A2 was confirmed to interact with and TGEV M protein via GST-pull down and CO-IP. • Immunofluorescence revealed colocalization of EIF4A2 and M protein in the cytoplasm. • EIF4A2 siRNA knockdown reduced TGEV replication in porcine IECs. • EIF4A2 may be associated with TGEV replication in porcine intestinal cells.

Obesity-induced secretory disorder of adipose tissue–derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)–infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow–specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.

Transmissible gastroenteritis (TGE) and porcine epidemic diarrhea (PED) are highly transmissible intestinal infections caused by transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), respectively. They are clinically associated with vomiting, diarrhea, and dehydration in piglets. An imbalance in Na+ uptake by intestinal epithelial cells causes TGEV/PEDV-induced diarrhea. However, the mechanism by which TGEV/PEDV-infection in piglets causes Na+ imbalance diarrhea has not been elucidated. In the present study, we demonstrated that specific inhibition of NHE3 activity caused small intestinal bulging, intestinal wall thinning and severe diarrhea in piglets, consistent with the signs of TGEV/PEDV infection. This study further elucidated the role of NHE3 in TGEV/PEDV-induced diarrhea. In this study, small intestinal epithelial cells (IPEC-J2) were used as a model of infection. The results showed that TGEV/PEDV infection reduced NHE3 activity and Na+ uptake in IPEC-J2 cells. Further studies revealed that the use of NHE3-specific inhibitors could reduce the amount of cell membrane NHE3, thereby decreasing Na+ uptake and ultimately leading to diarrhea. Transcriptomic studies performed on obtained jejunal tissues were also consistent with pre-laboratory results. This study will provide a basis for understanding Na+ imbalance diarrhea caused by TGEV/PEDV, as well as for elucidating the diarrheal pathogenesis of other members of α-animal coronaviruses.

Follicular regulatory T cells (Tfrs), a specialized subset of regulatory T cells (Tregs), have a particular role in the control of follicular helper T cell-driven germinal center (GC) responses. Following differentiation signals similar to those received by follicular helper T cells (Tfhs), Tfrs gain expression of characteristic chemokine receptors and transcription factors, such as CXCR5 and Bcl-6, allowing them to migrate into the B-cell follicle and perform in situ suppression. Thus, together with Tfhs, Tfrs help maintaining an optimized GC-reaction. However, the mechanism underlying the Treg-to-Tfr transition remains obscure. Here, we established a highly reproducible protocol for investigating the differentiation of Tregs into Tfrs by constructing spleen-chimeric mice combined with retrovirus transduction. We demonstrated that using this strategy, over 4 folds of Tregs could differentiate into Tfrs in Bcl-6 overexpression group compared to control counterparts (Migr1), and Bcl-6 could efficiently promote Tfr differentiation during acute viral infection. Hence, this method provides us an easy access to investigate the factors that regulate the differentiation program that converts Tregs into Tfrs, which will enhance our understanding of the networks regulating GC-reaction and shed new light on the molecular basis of immune homeostasis.

Colorectal cancer has one of the highest mortality rates among malignant tumors, and most patients with non-microsatellite instability-high (MSI-H) colorectal cancer do not benefit from targeted therapy or immune checkpoint inhibitors. Identification of immunogenic neoantigens is a promising strategy for inducing specific antitumor T cells for cancer immunotherapy. Here, we screened potential high-frequency neoepitopes from non-MSI-H colorectal cancer and tested their abilities to induce tumor-specific cytotoxic T cell responses. Three HLA-A2-restricted neoepitopes (P31, P50, and P52) were immunogenic and could induce cytotoxic T lymphocytes in peripheral blood mononuclear cells from healthy donors and colorectal cancer patients. Cytotoxic T lymphocytes induced in HLA-A2.1/Kb transgenic mice could recognize and lyse mutant neoepitope-transfected HLA-A2+ cancer cells. Adoptive transfer of cytotoxic T lymphocytes induced by the peptide pool of these three neoepitopes effectively inhibited tumor growth and increased the therapeutic effects of anti-PD-1 antibody. These results revealed the potential of high-frequency mutation-specific peptide-based immunotherapy as a personalized treatment approach for patients with non-MSI-H colorectal cancer. The combination of adoptive T cell therapy based on these neoepitopes with immune checkpoint inhibitors, such as anti-PD-1, could provide a promising treatment strategy for non-MSI-H colorectal cancer.

Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus; it causes diarrhea in pigs and is associated with high morbidity and mortality in sucking piglets. In this study, we performed in vitro and in vivo experiments to determine the inhibitory effects of Lactobacillus plantarum metabolites (LPM) on PEDV replication. Gas chromatography–mass spectrometry revealed exopolysaccharides to be one of the main components of LPM. We then determine whether L. plantarum exopolysaccharides (LPE) have an antiviral effect and also detected the expression levels of the apoptosis-related genes Bax and Bcl-2 and of the pro-apoptotic protein caspase-3. Further, we assessed the transcription levels of an immune-related protein (STAT1) and antiviral factors (MX1, MX2, ISG15, ZAP, PKR, and OAS1). Our results showed that the most effective method was to pretreat cells with LPM and that the optimal dose of LPM that could be safely administered to Vero cells was 1/8 times of the stock solution. LPE had a strong inhibitory effect on PEDV; the most effective method of administration was to co-incubate cells with LPE and PEDV, and the optimal concentration of LPE was 1.35 mg/mL. To conclude, LPE prevented PEDV adsorption and also alleviated inflammatory responses and induced early apoptosis of injured cells, but it could not regulate the immune function of cells.

Porcine epidemic diarrhea virus (PEDV; family Coronaviridae, genus Alphacoronavirus) causes acute diarrhea and vomiting, dehydration, and high mortality in neonatal piglets. Despite extensive research focusing on the pathogenesis of PEDV infection, the molecular pathogenesis of PEDV-induced diarrhea in piglets remains unclear. Na

Phenolic pollutants as highly toxic and hazardous organics are widely generated from industrial and domestic process. Phenolic pollutants with different hydroxyl position (catechol, resorcinol, hydroquinone, phenol) were preferentially and efficiently oxidized in photocatalytic process (PC) by designing boron-doped TiO2 (B-TiO2).The key role for enhancing the photocatalytic activity of B-TiO2 was the formation of abundant Ti3+ species. The formation of Ti3+-O weakened the competitive adsorption of H2O in aqueous solution and favored the formation of cooperative hydrogen bond on the surface of B-TiO2, leading to enhanced adsorption of phenolic pollutants. The degradation rate constant of B-TiO2 (kB-TiO2) was regardless of the corresponding oxidation potential of phenolic pollutants. The kB-TiO2 for catechol in photocatalytic process was as high as 3.46 min-1, which was 18.2, 1.6 times higher than that of biodegradation and ozonation methods, respectively. Of note, the preferential removal mechanism of phenolic pollutants was elucidated by in-situ attenuated total reflectance (ATR)-IR and density functional theory calculation (DFT). The results were helpful for developing new preferential oxidation technologies in HO∙-mediated process for selectively removing low concentration but highly toxic pollutants.

In the search for a highly active bulk material for the hydrogen evolution reaction (HER) under acidic conditions, we developed a simple solvothermal approach to synthesize Pd2B nanosheets supported on carbon, which achieves a low overpotential for the HER, 15.3 mV at 10 mA cm−2, a small Tafel slope of 22.5 mV dec−1 and a high exchange current density (j0) of 2.84 mA cm−2. The atomic structure evolution from Pd to Pd2B catalyst during synthesis is analyzed in detail via experimental and theoretical calculations, which shows that the slow insertion of B is assisted by the layer-by-layer fcc-to-hcp phase transition. Theoretical calculations further revealed that both the subsurface B and the lattice expansion after the hcp lattice formation play a key role to boost the HER activity. Since the Pd2B crystal is the global minimum in the Pd–B alloy, the success in the synthesis and demonstration of high HER activity paves the way towards further exploration of the catalytic performance for this stable metal boride material.

Highlights • Decreased of apical of NHE3 protein expression and Na+/H+ exchange activity after TGEV infected IPEC-J2. • SGLT1 can regulation the trafficking of NHE3 by p38MAPK/AKt2 singal pathway and show a corporate relationship. • TGEV infection causes an increase in the expression of total SGLT1 protein. • TGEV infection attenuates the translocation and exchange activity of NHE3 via the p38MAPK/AKt2 signaling pathway., Transmissible gastroenteritis virus (TGEV) primarily replicates in intestinal epithelial cells and causes severe damage to host cells, resulting in diarrhea. Surface NHE3 serves as the key regulatory site controlling electroneutral Na+ absorption. In this study, our results showed that the surface NHE3 content was significantly reduced following TGEV infection, whereas the total level of protein expression was not significantly changed, and NHE3 activity gradually decreased with prolonged infection time. We then inhibited SGLT1 expression by lentiviral interference and drug inhibition, respectively. Inhibition studies showed that the level of phosphorylation of the downstream key proteins, MAPKAPK-2 and EZRIN, in the SGLT1-mediated p38MAPK/AKt2 signaling pathway was significantly increased. The surface NHE3 expression was also significantly increased, and NHE3 activity was also significantly enhanced. These results demonstrate that a TGEV infection can inhibit NHE3 translocation and attenuates sodium-hydrogen exchange activity via the SGLT1-mediated p38MAPK/AKt2 signaling pathway, affecting cellular electrolyte absorption leading to diarrhea.

Obesity increases the risk of vascular diseases, including aortic aneurysm (AA). Perivascular adipose tissue (PVAT) surrounding arteries are altered during obesity. However, the underlying mechanism of adipose tissue, especially PVAT, in the pathogenesis of AA is still unclear. Here we showed that angiotensin II (AngII) infusion increases the incidence of AA in leptin-deficient obese mice (ob/ob) and high-fat diet–induced obese mice with adventitial inflammation. Furthermore, transcriptome analysis revealed that platelet-derived growth factor-D (PDGF-D) was highly expressed in the PVAT of ob/ob mice. Therefore, we hypothesized that PDGF-D mediates adventitial inflammation, which provides a direct link between PVAT dysfunction and AA formation in AngII-infused obese mice. We found that PDGF-D promotes the proliferation, migration, and inflammatory factors expression in cultured adventitial fibroblasts. In addition, the inhibition of PDGF-D function significantly reduced the incidence of AA in AngII-infused obese mice. More importantly, adipocyte-specific PDGF-D transgenic mice are more susceptible to AA formation after AngII infusion accompanied by exaggerated adventitial inflammatory and fibrotic responses. Collectively, our findings reveal a notable role of PDGF-D in the AA formation during obesity, and modulation of this cytokine might be an exploitable treatment strategy for the condition.