The enchanting Dirac fermions in graphene stimulated us to seek other 2D Dirac materials, and boron monolayers may be a good candidate. So far, a number of monolayer boron sheets have been ...theoretically predicted, and three have been experimentally prepared. However, none of intrinsic sheets possess Dirac electrons near the Fermi level. Herein, by means of density functional theory computations, we identified a new boron monolayer, namely, hr-sB, with two types of Dirac fermions coexisting in the sheet: One type is related to Dirac nodal lines traversing Brillouin zone (BZ) with velocities approaching 106 m/s, and the other is related to tilted semi-Dirac cones with strong anisotropy. This newly predicted boron monolayer consists of hexagon and rhombus stripes. With an exceptional stability comparable to the experimentally achieved boron sheets, it is rather optimistic to grow hr-sB on some suitable substrates such as the Ag (111) surface.
Although changes in alternative splicing have been observed in cancer, their functional contributions still remain largely unclear. Here we report that splice isoforms of the cancer stem cell (CSC) ...marker CD44 exhibit strikingly opposite functions in breast cancer. Bioinformatic annotation in patient breast cancer in The Cancer Genome Atlas (TCGA) database reveals that the CD44 standard splice isoform (CD44s) positively associates with the CSC gene signatures, whereas the CD44 variant splice isoforms (CD44v) exhibit an inverse association. We show that CD44s is the predominant isoform expressed in breast CSCs. Elimination of the CD44s isoform impairs CSC traits. Conversely, manipulating the splicing regulator ESRP1 to shift alternative splicing from CD44v to CD44s leads to an induction of CSC properties. We further demonstrate that CD44s activates the PDGFRβ/Stat3 cascade to promote CSC traits. These results reveal CD44 isoform specificity in CSC and non-CSC states and suggest that alternative splicing provides functional gene versatility that is essential for distinct cancer cell states and thus cancer phenotypes.
Multilayer gradient TiN/Ti (MLG-TiN/Ti) and multilayer TiN/Ti (ML-TiN/Ti) coatings with different layer numbers were deposited on Ti6Al4V alloy by filtered cathodic vacuum arc technique (FCVA) to ...improve the erosion resistance of the substrates. Scan electron microscopy (SEM), energy dispersive spectrometer (EDS), X-ray diffraction (XRD) and nanoindentation were used to examine the microstructural and mechanical properties of the as-deposited coatings. The erosion resistance of these coatings was evaluated with home-made erosion tester. Though the two types of coatings showed similar grain structure, the finer grain sizes and higher hardness were obtained for MLG-TiN/Ti coatings. The structure parameters had a significant influence on erosion resistance. The coating MLG-4 with total thickness 12.09 μm exhibited the lowest erosion rate both among MLG-TiN/Ti and ML-TiN/Ti coatings. It contains two TiN layers, two Ti layers and three gradient layers and the thickness ratio of these three kinds of the layer is 9:1:1. The gradient layers, which can restrain the propagation of lateral cracks, formed in MLG-TiN/Ti coatings made the contribution to the great improvement of the erosion resistance of MLG-TiN/Ti comparing with ML-TiN/Ti coatings.
•The MLG-TiN/Ti coatings have finer grain sizes and higher hardness comparing with the ML-TiN/Ti coatings.•The coating MLG-4 reduces the erosion rate of ML-4 from 0.085 mg/g to 0.007 mg/g under the same erosion condition.•The MLG-TiN/Ti coatings outperformed the corresponding multilayer coatings, showing a better resistance to cracking.•The erosion mechanisms and erosion resistance improvement mechanism of multilayer gradient TiN/Ti coatings were discussed.
The recent results on Charmonium and Charmonium-like states at BESIII are reviewed, including the observation of \rm Z_{cs}(3985) state, the study of the new decay modes of \psi_2(3823) ψ 2 ( 3823 ) ...state, observation of resonance structure in \rm e^+e^- \to \pi^+\pi^-\psi_2(3823) process, the study of the \rm e^+e^- \to K^+K^-J/\psi process, cross section measurement of \rm e^+e^- \to \omega\pi^0 and \omega\eta ω η process, branching fraction measurement of \psi(3686)\to\bar{\Sigma}^0\Lambda + c.c. ψ ( 3686 ) → Σ ‾ 0 Λ + c . c . process. Decay channels for \chi_{cJ} \to \Lambda\bar{\Lambda} χ c J → Λ Λ ‾ , \chi_{cJ} \to \Lambda\bar{\Lambda}\eta χ c J → Λ Λ ‾ η , \psi(3686) \to \Lambda\bar{\Lambda}\omega ψ ( 3686 ) → Λ Λ ‾ ω and \eta_c(2S)\to3(\pi^+\pi^-) η c ( 2 S ) → 3 ( π + π − ) are also discussed. The property of the spin singlet P wave Charmonium state, \rm h_c is also reported.
Cancer immunotherapy has made unprecedented breakthrough in the fields of chimeric antigen receptor-redirected T (CAR T) cell therapy and immune modulation. Combination of CAR modification and the ...disruption of endogenous inhibitory immune checkpoints on T cells represent a promising immunotherapeutic modality for cancer treatment. However, the potential for the treatment of hepatocellular carcinoma (HCC) has not been explored. In this study, the gene expressing the programmed death 1 receptor (PD-1) on the Glypican-3 (GPC3)-targeted second-generation CAR T cells employing CD28 as the co-stimulatory domain was disrupted using the CRISPR/Cas9 gene-editing system. It was found that,
, the CAR T cells with the deficient PD-1 showed the stronger CAR-dependent anti-tumor activity against native programmed death 1 ligand 1-expressing HCC cell PLC/PRF/5 compared with the wild-type CAR T cells, and meanwhile, the CD4 and CD8 subsets, and activation status of CAR T cells were stable with the disruption of endogenous PD-1. Additionally, the disruption of PD-1 could protect the GPC3-CAR T cells from exhaustion when combating with native PD-L1-expressing HCC, as the levels of Akt phosphorylation and anti-apoptotic protein Bcl-xL expression in PD-1 deficient GPC3-CAR T cells were significantly higher than those in wild-type GPC3-CAR T cells after coculturing with PLC/PRF/5. Furthermore, the
anti-tumor activity of the CAR T cells with the deficient PD-1 was investigated using the subcutaneous xenograft tumor model established by the injection of PLC/PRF/5 into NOD-scid-IL-2Rγ-/- (NSG) mice. The results indicated that the disruption of PD-1 enhanced the
anti-tumor activity of CAR T cells against HCC, improved the persistence and infiltration of CAR T cells in the NSG mice bearing the tumor, and strengthened the inhibition of tumor-related genes expression in the xenograft tumors caused by the GPC3-CAR T cells. This study indicates the enhanced anti-tumor efficacy of PD-1-deficient CAR T cells against HCC and suggests the potential of precision gene editing on the immune checkpoints to enhance the CAR T cell therapies against HCC.
We measured the levels of High-Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the ...peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child-care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme-linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)-17, IL-6, transforming growth factor β (TGF-β), IL-10, and NT-proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL-17, and IL-6 and was negatively correlated with TGF-β and IL-10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.
The peripheral nerve system has an intrinsic regenerative capacity in response to traumatic injury. To better understand the molecular events occurring after peripheral nerve injury, in the current ...study, a rat model of sciatic nerve crush injury was used. Injured nerves harvested at 0, 1, 4, 7, and 14 days post injury were subjected to deep RNA sequencing for examining global gene expression changes. According to the temporally differential expression patterns of a huge number of genes, 3 distinct phases were defined within the post-injury period of 14 days: the acute, sub-acute, and post-acute stages. Each stage showed its own characteristics of gene expression, which were associated with different categories of diseases and biological functions and canonical pathways. Ingenuity pathway analysis revealed that genes involved in inflammation and immune response were significantly up-regulated in the acute phase, and genes involved in cellular movement, development, and morphology were up-regulated in the sub-acute stage, while the up-regulated genes in the post-acute phase were mainly involved in lipid metabolism, cytoskeleton reorganization, and nerve regeneration. All the data obtained in the current study may help to elucidate the molecular mechanisms underlying peripheral nerve regeneration from the perspective of gene regulation, and to identify potential therapeutic targets for the treatment of peripheral nerve injury.
Globally, natural wetlands have suffered severe ecological degradation (vegetation, soil, and biotic community) due to multiple factors. Understanding the spatiotemporal dynamics and driving forces ...of natural wetlands is the key to natural wetlands’ protection and regional restoration. In this study, we first investigated the spatiotemporal evolutionary trends and shifting characteristics of natural wetlands in the Northeast Plain of China from 1990 to 2020. A dataset of driving-force evaluation indicators was constructed with nine indirect (elevation, temperature, road network, etc.) and four direct influencing factors (dryland, paddy field, woodland, grassland). Finally, we built the driving force analysis model of natural wetlands changes to quantitatively refine the contribution of different driving factors for natural wetlands’ dynamic change by introducing the sparrow search algorithm (SSA) and extreme gradient boosting algorithm (XGBoost). The results showed that the total area of natural wetlands in the Northeast Plain of China increased by 32% from 1990 to 2020, mainly showing a first decline and then an increasing trend. Combined with the results of transfer intensity, we found that the substantial turn-out phenomenon of natural wetlands occurred in 2000–2005 and was mainly concentrated in the central and eastern parts of the Northeast Plain, while the substantial turn-in phenomenon of 2005–2010 was mainly located in the northeast of the study area. Compared with a traditional regression model, the SSA-XGBoost model not only weakened the multicollinearity of each driver but also significantly improved the generalization ability and interpretability of the model. The coefficient of determination (R2) of the SSA-XGBoost model exceeded 0.6 in both the natural wetland decline and rise cycles, which could effectively quantify the contribution of each driving factor. From the results of the model calculations, agricultural activities consisting of dryland and paddy fields during the entire cycle of natural wetland change were the main driving factors, with relative contributions of 18.59% and 15.40%, respectively. Both meteorological (temperature, precipitation) and topographic factors (elevation, slope) had a driving role in the spatiotemporal variation of natural wetlands. The gross domestic product (GDP) had the lowest contribution to natural wetlands’ variation. This study provides a new method of quantitative analysis based on machine learning theory for determining the causes of natural wetland changes; it can be applied to large spatial scale areas, which is essential for a rapid monitoring of natural wetlands’ resources and an accurate decision-making on the ecological environment’s security.
Cancer immunotherapy relies on the insight that the immune system can be used to defend against malignant cells. The aim of cancer immunotherapy is to utilize, modulate, activate, and train the ...immune system to amplify antitumor T-cell immunity. In parallel, the immune system response to damaged tissue is also crucial in determining the success or failure of an implant. Due to their extracellular matrix mimetics and tunable chemical or physical performance, hydrogels are promising platforms for building immunomodulatory microenvironments for realizing cancer therapy and tissue regeneration. However, submicron or nanosized pore structures within hydrogels are not favorable for modulating immune cell function, such as cell invasion, migration, and immunophenotype. In contrast, hydrogels with a porous structure not only allow for nutrient transportation and metabolite discharge but also offer more space for realizing cell function. In this review, the design strategies and influencing factors of porous hydrogels for cancer therapy and tissue regeneration are first discussed. Second, the immunomodulatory effects and therapeutic outcomes of different porous hydrogels for cancer immunotherapy and tissue regeneration are highlighted. Beyond that, this review highlights the effects of pore size on immune function and potential signal transduction. Finally, the remaining challenges and perspectives of immunomodulatory porous hydrogels are discussed.
Periodic groundwater table fluctuations are found frequently in natural aquifers due to sea tides or seasonal recharge. However, their impact on the transport of volatile organic compounds in the ...vadose zone released from a groundwater contaminant source (i.e., vapor intrusion) has not been well known. A 2D numerical model was developed to explore vapor intrusion processes in the sandy vadose zone, subject to a fluctuating groundwater table with a range of fluctuation amplitudes and periods. A carcinogenic compound, Trichloroethylene (TCE), was chosen as the groundwater contaminant of interest in the current study and assumed to transport into the dwelling through a crack at the corner of the basement. Results showed that the resistant effect caused by high soil moisture contents in the thin capillary fringe is weakened by periodic groundwater table fluctuations, resulting in a higher concentration of gaseous TCE at the building foundation crack, in comparison with that under a static groundwater table. The increase of the gaseous TCE concentration was induced by the enhancement of diffusion and advection due to groundwater table fluctuations. Sensitivity analyses indicated that a higher amplitude and frequency of fluctuations lead to a higher TCE concentration at the crack under the dynamic equilibrium condition. Specifically, compared with the static groundwater table condition, the TCE concentration at the crack increased by one order of magnitude under the condition of groundwater table fluctuations with an amplitude of 0.2 m and a period of one day. The results obtained could provide insights into the importance of the amplitude and frequency of groundwater table fluctuations on vapor intrusion.
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