The recent success of immunotherapies has highlighted the power of leveraging the immune system in the fight against cancer. In order for most immune‐based therapies to succeed, T cell subsets with ...the correct tumor‐targeting specificities must be mobilized. When such specificities are lacking, providing the immune system with tumor antigen material for processing and presentation is a common strategy for stimulating antigen‐specific T cell populations. While straightforward in principle, experience has shown that manipulation of the antigen presentation process can be incredibly complex, necessitating sophisticated strategies that are difficult to translate. Herein, the design of a biomimetic nanoparticle platform is reported that can be used to directly stimulate T cells without the need for professional antigen‐presenting cells. The nanoparticles are fabricated using a cell membrane coating derived from cancer cells engineered to express a co‐stimulatory marker. Combined with the peptide epitopes naturally presented on the membrane surface, the final formulation contains the necessary signals to promote tumor antigen‐specific immune responses, priming T cells that can be used to control tumor growth. The reported approach represents an emerging strategy that can be used to develop multiantigenic, personalized cancer immunotherapies.
Cancer cells are genetically engineered to express a co‐stimulatory marker that enables them to directly present their own antigens under an immunostimulatory context. Cell‐membrane‐coated nanoparticles sourced from these modified cells elicit antitumor immunity in vivo while bypassing the need for traditional cell‐mediated antigen presentation. This approach may ultimately enable the facile design of personalized artificial antigen presentation platforms.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking ...given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens. Here, it is reported on the fabrication of a biomimetic, nanoparticulate anticancer vaccine that is capable of delivering autologously derived tumor antigen material together with a highly immunostimulatory adjuvant. The two major components, tumor antigens and adjuvant, are presented concurrently in a fashion that maximizes their ability to promote effective antigen presentation and activation of downstream immune processes. Ultimately, it is demonstrated that the formulation can elicit potent antitumor immune responses in vivo. When combined with additional immunotherapies such as checkpoint blockades, the nanovaccine demonstrates substantial therapeutic effect. Overall, the work represents the rational application of nanotechnology for immunoengineering and can provide a blueprint for the future development of personalized, autologous anticancer vaccines with broad applicability.
A biomimetic, nanoparticulate anticancer vaccine is fabricated by coating membrane derived from cancer cells onto an immunostimulatory core. The resulting nanoformulation can promote immunity against multiple tumor antigens. When the nanovaccine is combined with checkpoint blockade therapy, significant control of tumor growth is achieved. This approach may ultimately be adapted toward designing potent autologous vaccines made from patient‐derived tumor material.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Reduction in methane emissions to the Earth's atmosphere is a critical strategy for tackling climate change. It is well established that anaerobic oxidation of methane (AOM) associated with sulfate ...reduction functions as an important methane sink in marine sediments. However, recent findings show that AOM uses diverse electron acceptors across a range of habitats, prompting examination of the potential role of AOM in mitigation of methane emissions and global climate change in non-marine environments. Methane is also a valuable energy source, widely used for production of electricity. Recent studies suggest that AOM could be used to produce liquid fuels/chemicals. The potential involvement of CO
2
in product formation is particularly exciting as methane bioconversion could act as a net sink of CO
2
. The discovery that AOM is able to transfer electrons to solid electron acceptors suggests that methane may be a suitable source of electrons for a bioelectrochemical, biosynthesis cell. In addition, AOM has been used for pollution control and environmental remediation, such as nitrogen removal from contaminated water. Herein, we review and discuss implications of the latest scientific discoveries in AOM for methane emissions from aquatic and terrestrial environments, and methane as a feedstock for various biotechnology platforms.
Anaerobic oxidation of methane (AOM) is a crucial bioprocess in global methane mitigation. Adoption of AOM in an engineered system provides an opportunity for the development of methane-based biotechnologies.
Aeolian desertification, one of the most serious environmental issues, has hampered socioeconomic development on the Qinghai-Tibet Plateau (QTP). However, research on aeolian desertification in this ...region has been limited. To develop a set of science-based preventive measures to mitigate desertification in this region, it is first necessary to clarify the status, evolution, and driving factors of aeolian desertification. In this study, based on extensive field investigations and a current classification system for aeolian desertification, we established a new system for interpreting aeolian desertified land (ADL) on the plateau using Landsat images from 1977, 1990, 2000, 2010, and 2015 and obtained the distribution of ADL through visual interpretation of the images. The results showed that ADL covered 392,914km2 (15.1% of the study area) in 2015, including gravel ADL, sandy ADL, and aeolian monadnocks. Controlled by climate, landforms, the type of Quaternary deposit, and human activities, ADL is scattered throughout the plateau but is concentrated mostly in the western and northern parts. Aeolian desertification on the plateau expanded from 1977 to 2000 and then began to reverse. The evolution during the study period is the result of the combined effects of natural and human factors. Irrational human activities were the dominant factor responsible for the expansion of ADL prior to 2000, whereas the subsequent reversal was mainly caused by climate change combined with large ecological restoration projects.
Display omitted
•Desertification from 1977 to 2015 in QTP was monitored using Landsat images.•The spatial-temporal distribution of ADL in different stages was identified.•The spatial distribution of ADL was controlled by natural and human factors.•Human activities were responsible for the expansion of ADL before 2000.•Ecological protection projects and climate change contributed to the reversal of ADL.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR ...in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression.
Materials and Methods
We examined the expression of HOTAIR in 110 HCC samples using real-time reverse transcription-polymerase chain reaction and analyzed its correlation with clinical parameters and prognosis in 60 HCC patients that have undergone liver transplantation (LT). Suppression of HOTAIR using siRNA was performed to explore its roles in tumor progression.
Results
The expression level of HOTAIR in cancer tissues was higher than in adjacent noncancerous tissues. High expression level of HOTAIR was an independent prognostic factor for predicting HCC recurrence in LT patients (
P
= .001, hazard ratio, 3.564). Furthermore, in patients exceeding the Milan criteria, those with a high expression level of HOTAIR revealed a significantly shorter recurrence-free survival. Moreover, siRNA suppression of HOTAIR in a liver cancer cell line reduced cell viability and cell invasion, sensitized TNF-α induced apoptosis, and increased the chemotherapeutic sensitivity of cancer cells to cisplatin and doxorubicin.
Conclusions
The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The biology-inspired intelligent computing system for the neuromorphic hardware implementation is useful in high-speed parallel information processing. However, the traditional Von Neumann computer ...architecture and the unsatisfactory signal transmission approach have jointly limited the overall performance of the specific hardware implementation. In this paper, a compact extreme learning machine (ELM) architecture synthesized with the spintronic memristor-based synaptic circuit, the biasing circuit, and the activation function circuit is presented. Notably, due to the threshold characteristic of the memristive device, the synaptic circuit has a bimodal behavior. Namely, it is capable to provide the constant and adjustable network weights between the adjacent layers in the ELM. Furthermore, two major limitations (process variations and sneak path issue) are taken into account for the detailed robustness analysis of the whole network. Finally, the entire scheme is verified with case studies in single image super-resolution (SR) reconstruction.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Soil wind erosion of farmland in a large area was mapped using SWEEP.•Soil loss obtained using limited wind data was compared with measurements.•SWEEP estimated wind erosion over a large area well ...at intermediate wind velocities.•SWEEP underestimated erosion at low winds mainly due to threshold friction velocity.
Farmland especially dry farmland managed in traditional ways has high wind erosion risk and contributes mainly to dust emission in arid area. Modeling predicting provides a general view to soil erosion susceptibility, and is very helpful for the understanding of potential spatial source of wind erosion. This study applied the Single-event Wind Erosion Evaluation Program (SWEEP) to predict soil wind erosion of farmland in the study area. SWEEP is a standalone version of the erosion sub-model from the Wind Erosion Prediction System (WEPS). It needs fewer calculation parameters than WEPS and is often used for single erosion events of limited size. The objective of this study was to test the feasibility of using SWEEP to estimate annual wind erosion of farmland over large areas (downwind distance >1600m) with limited wind data (2005–2011) from weather stations. We validated the simulation results by comparing them with field measurements and wind tunnel data for the same soils. The soil material eroded by wind included PM10, suspension, saltation, and creep particles. Suspension particles were the main component involved in the soil loss (averaged 61.8%). However, saltation and creep particles dominate the particle clouds for fields with a downwind length of less than 550m (averaged 56.6%), and the mass flux dominated by suspension particles stabilizes when this length is longer than 1000m (averaged 83.4%). PM 10 always has very low proportion (<2.3%). Our validation results suggest that it is feasible to use SWEEP for large areas with limited wind data. However, SWEEP could not simulate the small soil losses that occur especially at low wind velocities well. Many factors contribute to this problem, but the main one is overestimation of the threshold wind velocity. Previous research suggest that it will be difficult to replace SWEEP’s calculation algorithms for the threshold wind velocity, but both these algorithms and some SWEEP parameters must be improved to provide accurate predictions of soil erosion.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Effective treatments for patients suffering from heat hypersensitivity are lacking, mostly due to our limited understanding of the pathogenic mechanisms underlying this disorder. In the nervous ...system, activating transcription factor 4 (ATF4) is involved in the regulation of synaptic plasticity and memory formation. Here, we show that ATF4 plays an important role in heat nociception. Indeed, loss of ATF4 in mouse dorsal root ganglion (DRG) neurons selectively impairs heat sensitivity. Mechanistically, we show that ATF4 interacts with transient receptor potential cation channel subfamily M member-3 (TRPM3) and mediates the membrane trafficking of TRPM3 in DRG neurons in response to heat. Loss of ATF4 also significantly decreases the current and KIF17-mediated trafficking of TRPM3, suggesting that the KIF17/ATF4/TRPM3 complex is required for the neuronal response to heat stimuli. Our findings unveil the non-transcriptional role of ATF4 in the response to heat stimuli in DRG neurons.
The Hippo tumor suppressor pathway plays an important role in tissue homeostasis that ensures development of functional organs at proper size. The YAP transcription coactivator is a major effector of ...the Hippo pathway and is phosphorylated and inactivated by the Hippo pathway kinases Lats1/2. It has recently been shown that YAP activity is regulated by G-protein-coupled receptor signaling. Here we demonstrate that cyclic adenosine monophosphate (cAMP), a second messenger downstream from Gαs-coupled receptors, acts through protein kinase A (PKA) and Rho GTPases to stimulate Lats kinases and YAP phosphorylation. We also show that inactivation of YAP is crucial for PKA-induced adipogenesis. In addition, PKA activation in Drosophila inhibits the expression of Yorki (Yki, a YAP ortholog) target genes involved in cell proliferation and death. Taken together, our study demonstrates that Hippo-YAP is a key signaling branch of cAMP and PKA and reveals new insight into mechanisms of PKA in regulating a broad range of cellular functions.
Zircon is a versatile mineral for geochemical studies. The slow diffusion of water in zircon makes it reliable to record the original water content of magma during the zircon crystallization. ...However, the application of water-in-zircon in Earth Sciences is hampered by the ambiguity in the hydrogen incorporation mechanism. In this study, we measured the zircon water and trace element contents on ten natural megacrystic zircons from different magmatic settings (incl. Reference zircon Plešovice, KIM-G, D15395, and SA01) with secondary ion mass spectrometry (SIMS), Fourier transform infrared spectroscopy (FTIR) and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS), in order to explore the hydrogen-trace elements coupling mechanism in zircon. Our results show that water content in zircon from various magmatic settings conspicuously surpasses the amount required to charge balancing with excess REY (REE and Y). This implies that the H-REY charge balance is not the sole mechanism for H incorporation into zircon as supposed previously. This conclusion is also supported by FTIR analysis, which shows multiple OH stretching bands, especially at ∼ 3100, ∼ 3200, ∼ 3385 cm−1 (E//a), and ∼ 3420 cm−1 (E//c). The 3100 cm−1 absorption band is most probably related to the H-compensated REY cations, as suggested by the corresponding water content with that required to the charge balance of excess REY. The hydrogrossular-type substitution at the Si or Zr vacancy SiO4 or ZrO4 = (OH)4 is indicated by the pair of oriented OH absorption bands at 3420 cm−1 (E//c) and 3385 cm−1 (E//a) or 3200 and 3180 cm−1, respectively, which accounts for the large H excess (>62% H2O, unrelated to extrinsic cations). This indicates that vacancy substitution dominates the zircon water uptaking in our samples. Furthermore, we show that the zircon water content is correlated negatively with P/REY, likely implying that the magma water content may also affect the partitioning of P and REY between zircon and melt. Integrating various published zircon water content datasets from different geological backgrounds, we posit that the water content in igneous zircon can reflect that in its parental magma, similar to other nominally anhydrous minerals (e.g., olivine, pyroxene, and plagioclase) used for this purpose.
•Hydrogen is incorporated into zircon by multi-coupling mechanisms.•Water in zircon can characterize water content of its parental magma.•Water is the controlling factor for distribution of trace elements in zircon.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
