B cells constitute a major component of tumor-infiltrating leukocytes. However, the influence of these cells on malignancy is currently under debate, reflecting the heterogeneity of B cell subsets in ...tumors. With recent advances, it becomes apparent that this debate includes not only the evaluation of B cells themselves, but also the underlying immune microenvironment network, which scripts the highly heterogeneous B cell populations in tumors and directs the roles of those sub-populations in disease progression and clinical treatment. In this review, we summarize recent findings on the heterogeneous subset composition of B cells in both human and mouse tumor models and their different impacts on disease progression. We further describe the multidimensional interplays between B cells and other immune cells in the tumor microenvironment, which account for the regulation of B cell differentiation and function in situ. We also assess the potential influences of distinct sub-tumor locations on B cell function in primary tumors during development and those under immunotherapy treatment. Illuminating the heterogeneous nature of B cell subset composition, generation, localization, and related immune network in tumor is of immense significance for comprehensively understanding B cell response in tumor and designing more efficacious cancer immunotherapies.
The authors propose a new technique for parallelizations of tangent linear and adjoint codes, which were applied in the redevelopment for the Weather Research and Forecasting (WRF) model with its ...Advanced Research WRF dynamic core using the automatic differentiation engine. The tangent linear and adjoint codes of the WRF model (WRFPLUS) now have the following improvements: A complete check interface ensures that developers write accurate tangent linear and adjoint codes with ease and efficiency. A new technique based on the nature of duality that existed among message passing interface communication routines was adopted to parallelize the WRFPLUS model. The registry in the WRF model was extended to automatically generate the tangent linear and adjoint codes of the required communication operations. This approach dramatically speeds up the software development cycle of the parallel tangent linear and adjoint codes and leads to improved parallel efficiency. Module interfaces were constructed for coupling tangent linear and adjoint codes of the WRF model with applications such as four-dimensional variational data assimilation, forecast sensitivity to observation, and others.
SINGV‐DA is a convective‐scale numerical weather prediction system with regional data assimilation for Singapore and the surrounding region. This article documents SINGV‐DA's current operational ...configuration and the sensitivity studies that influenced its development. We show that background error covariances derived by bootstrapping (via the lagged National Meteorological Centre method) contain spurious vertical structures at higher model levels that may degrade forecast performance. We found that SINGV‐DA precipitation forecasts are sensitive to horizontal resolution and lateral boundary conditions. Our observing system experiments reveal that satellite radiance assimilation, while clearly beneficial for precipitation forecasts in this region, adversely affected model background temperatures and winds at higher altitudes. Benchmarked against the forecast model in isolation, the regional DA system adds significant value to precipitation forecasts in the nowcasting range, but not at longer lead times. Our findings point to the need for further research and development to improve the system.
The assimilation of satellite radiances, which outnumber all other observations ingested by SINGV‐DA, had the largest positive impact on precipitation forecasts. SINGV‐DA forecasts were also sensitive to background error covariances, horizontal resolution and lateral boundary conditions.
Abstract Achyranthes bidentate Blume (Niuxi) is often employed for treatment of arthritis in Traditional Chinese Medicine and possesses anti-inflammatory properties. Phytochemical and pharmacological ...studies proved the oleanane-type saponins to be the main bioactive principles. In the present study, protective effects of A. bidentata saponins (ABS) on inflammation and apoptosis in interleukine-1β (IL-1β)-induced chondrocytes were investigated. Rat chondrocytes were pretreated with ABS at 3 μg/mL, 10 μg/mL, and 30 μg/mL, and subsequently stimulated with IL-1β (10 ng/mL). Methylthiazolyldiphenyl-tetrazolium bromide assay and annexin V/propidium iodide dual staining demonstrated that ABS could protect IL-1β-induced chondrocyte injury. ABS suppressed IL-1β-induced apoptosis by suppressing the activation of caspase-3, inhibiting levels of proapoptotic proteins Bax and Bad, decreasing p53 protein phosphorylation, and promoting the expression of antiapoptotic protein Bcl-xL and proliferating cell nuclear antigen. IL-1β-induced inflammation and matrix degradation were also alleviated by ABS through the downregulation of the expressions of matrix metalloproteinases 3 and 9 and cyclooxygenase-2. Moreover, ABS inhibited IL-1β-induced nuclear factor κB activation in rat chondrocytes. We demonstrated, for the first time, the protective effects of ABS on IL-1β-stimulated chondrocytes and their molecular mechanisms. Thus, it is suggested that ABS might be a potential drug in the treatment of osteoarthritis.
Low-temperature severely affects the growth and development of chrysanthemum which is one kind of ornamental plant well-known and widely used in the world. Lysine crotonylation is a recently ...identified post-translational modification (PTM) with multiple cellular functions. However, lysine crotonylation under low-temperature stress has not been studied.
Proteome-wide and lysine crotonylation of chrysanthemum at low-temperature was analyzed using TMT (Tandem Mass Tag) labeling, sensitive immuno-precipitation, and high-resolution LC-MS/MS. The results showed that 2017 crotonylation sites were identified in 1199 proteins. Treatment at 4 °C for 24 h and - 4 °C for 4 h resulted in 393 upregulated proteins and 500 downregulated proteins (1.2-fold threshold and P < 0.05). Analysis of biological information showed that lysine crotonylation was involved in photosynthesis, ribosomes, and antioxidant systems. The crotonylated proteins and motifs in chrysanthemum were compared with other plants to obtain orthologous proteins and conserved motifs. To further understand how lysine crotonylation at K136 affected APX (ascorbate peroxidase), we performed a site-directed mutation at K136 in APX. Site-directed crotonylation showed that lysine decrotonylation at K136 reduced APX activity, and lysine complete crotonylation at K136 increased APX activity.
In summary, our study comparatively analyzed proteome-wide and crotonylation in chrysanthemum under low-temperature stress and provided insights into the mechanisms of crotonylation in positively regulated APX activity to reduce the oxidative damage caused by low-temperature stress. These data provided an important basis for studying crotonylation to regulate antioxidant enzyme activity in response to low-temperature stress and a new research ideas for chilling-tolerance and freezing-tolerance chrysanthemum molecular breeding.
Glucocorticoids (GCs) are the important stress hormones and widely prescribed as drugs. Although stress has been suggested as a promoter of tumor progression, the direct influence of GCs on ...metastasis of tumor is not fully understood. Metastasis is a major cause of death in pancreatic cancer patients. In the present study, we investigated the effect of GCs on progression of pancreatic cancer and elucidated the underlying mechanism. It was found that GCs significantly promote cell adhesion, migration, and invasion of pancreatic cancer cells in vitro and their lung metastasis in vivo. Further mechanistic studies showed that GCs notably up-regulate the expression of a trans-membrane glycoprotein, mucin 1 (MUC1) and increase the activation of AKT. Inhibiting MUC1 expression not only attenuates the activation of AKT, but also significantly reduces the promoting effects of GCs on cell adhesion, migration, invasion, and lung metastasis of pancreatic cancer cells. Moreover, GCs not only significantly up-regulate expression of Rho-associated kinase 1/2 (ROCK1/2) and matrix metalloproteinase 3 and 7 (MMP3/7), but also activate ROCK2, which are also involved in the pro-migratory and pro-invasive effects of GCs in pancreatic cancer cells. Taken together, our findings reveal that GCs promote metastasis of pancreatic cancer cells through complex mechanism. MUC1-PI3K/AKT pathway, ROCK1/2 and MMP3/7 are involved in the promoting effect of GCs on cell migration, invasion and metastasis in pancreatic cancer cells. These results suggest the importance of reducing stress and GCs administration in patients with pancreatic cancer to avoid an increased risk of cancer metastasis.
Cerebral venous sinus thrombosis (CVST) typically presents as headache, papilledema, and seizures. A dural arteriovenous fistula (DAVF) is a rare intracranial vascular malformation, and common ...symptoms include headache, pulsatile tinnitus, and stroke. The occurrence of CVST as a complication of DAVF is infrequent. Moreover, optic neuropathy presenting as the initial symptom of CVST and secondary DAVF is also unusual. We present a case of a patient with optic neuropathy and persistent intracranial hypertension who underwent head magnetic resonance imaging, which indicated CVST. She received normative anticoagulant and dehydration therapy; however, a repeated lumbar puncture showed dramatically increased intracranial pressure. Further digital subtraction angiography revealed an intracranial DAVF. The patient was finally diagnosed with a DAVF and secondary CVST. This case indicates that intractable optic neuropathy could be an uncommon indicator for CVST and secondary DAVF. Early diagnosis and early treatment are essential for visual rehabilitation and prognosis improvement.
Research shows that entrepreneurial activities significantly promote economic development, which enhances the importance of the innovative entrepreneurial potential of college students. This study ...analyzes the effect of entrepreneurship education on entrepreneurial intention from the perspective of planned behavior theory. By examining the significant role of entrepreneurship education at colleges and universities on economic and social development, we established a conceptual model. To understand the relationship between entrepreneurship education and entrepreneurial intention, the hypotheses propose the intermediary role of entrepreneurial ability, and the study provides evidence from China the relationship between entrepreneurship education and entrepreneurial intention. Improving entrepreneurial intention and encouraging college students to establish businesses through entrepreneurship education in universities is crucial. This study proposes a hypothetical model of the relationship between entrepreneurial competence and entrepreneurial intention in entrepreneurship education at universities. Using a questionnaire survey of college students with practical experience in the Yangtze River Delta of China, the bootstrap method in the SPSS macro program process software verifies the hypotheses. The results show that entrepreneurial teaching, business plan competition, and entrepreneurial practice support positively affect entrepreneurial competence. In addition, entrepreneurial competence plays an intermediary role in the relationship between entrepreneurial teaching, business plan competition, entrepreneurship practice support, and entrepreneurial intention. Entrepreneurship education improves the ability to establish a business in the present and in entrepreneurial activities in the future. Entrepreneurial competence obtained through entrepreneurship education continuously affects entrepreneurial intention.
In the field of surface plasmon-mediated photocatalysis, the coupling reactions of p-aminothiophenol (PATP) and p-nitrothiophenol (PNTP) to produce p,p′-dimercaptoazobenzene (DMAB) are the most ...widely investigated systems. However, a clear understanding of the structure–function relationship is still required. Here, we used tip-enhanced Raman spectroscopy (TERS) to study the coupling reactions of PATP and PNTP on well-defined Ag(111) and Au(111) surfaces using 632.8 and 532 nm lasers. On Au(111), the oxidative coupling of PATP can proceed under irradiation by a 632.8 nm laser, and the reductive coupling of PNTP can only occur under irradiation by a 532 nm laser. Neither wavelength of laser light can induce the coupling reactions of these two molecules on Ag(111). Density functional theory (DFT) was used to calculate the stable adsorption configurations of PATP and PNTP on Ag(111) and Au(111). Both the adsorption configurations of the two molecules on the surfaces and laser energies were, experimentally and theoretically, found to determine whether the coupling reactions can occur on different substrates. These results may help the rational design of photocatalysts with enhanced reactivity.
A novel exopolysaccharide (EPS) from Paenibacillus polymyxa PYQ1 was extracted, well purified and characterized. This EPS was homogeneous glucomannan-type polysaccharide with the average molecular ...weight of 4.38 × 106 Da. Structural characterization indicated that the monosaccharides of EPS were pyranoses connected by β-glycosidic linkages. Furthermore, our results showed the protective benefits of EPS against UVC induced cytotoxicity in HaCaT cells through scavenging excessive reactive oxygen species, mitigating the decrease of mitochondrial membrane potential, improving catalase activity and maintaining membrane integrity. Taken together, this study qualified EPS from P. polymyxa PYQ1 was a promising natural polymer which worth further investigation as a skin-care agent.
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