Activated mouse CD4+Foxp3−CD4^+Foxp3^− T cells facilitate melanoma metastasis via Qa-1-dependent suppression of NK-cell cytotoxicity

The regulatory activities of mouse $CD^4+Foxp3^+$ T cells on various immune cells, including NK cells, have been well documented. Under some conditions, conventional $CD4^+Foxp3^−$ T cells in the periphery are able to acquire inhibitory function on other T cells, but their roles in controlling innate immune cells are poorly defined. As a potential cellular therapy for cancer, ex vivo activated $CD4^+Foxp3^−$ effector T cells are often infused back in vivo to suppress tumor growth and metastasis. Whether such activated T cells could affect NK-cell control of tumorigenesis is unclear. In the present study, we found that mitogen-activated $CD4^+Foxp3^−$ T cells exhibited potent suppressor function on NK-cell proliferation and cytotoxicity in vitro, and notably facilitated B16 melanoma metastasis in vivo. Suppression of NK cells by activated $CD4^+Foxp3^−$ T cells is cell-cell contact dependent and is mediated by Qa-1:NKG2A interaction, as administration of antibodies blocking either Qa-1 or NKG2A could completely reverse this suppression, and significantly inhibited otherwise facilitated melanoma metastasis. Moreover, activated $CD4^+Foxp3^−$ cells from Qa-1 knockout mice completely lost the suppressor activity on NK cells, and failed to facilitate melanoma metastasis when transferred in vivo. Taken together, our findings indicate that innate anti-tumor response is counter regulated by the activation of adaptive immunity, a phenomenon we term as “activation-induced inhibition”. Thus, the regulatory role of activated $CD4^+Foxp3^−$ T cells in NK-cell activity must be taken into consideration in the future design of cancer therapies

Novel Stability Analysis for Uncertain Neutral-Type Lur’e Systems with Time-Varying Delays Using New Inequality

This paper considers the delay-dependent stability analysis of neutral-type Lur’e systems with time-varying delays and sector bounded nonlinearities. First of all, using constructed function methods, a new Jensen-like inequality is introduced to obtain less conservative results. Second, a new class of Lyapunov-Krasovskii functional (LKF) is constructed according to the characteristic of the considered systems. Third, combining with the new inequality and reciprocal convex approach and some other inequality techniques, the new less conservative robust stability criteria are shown in the form of linear matrix inequalities (LMIs). Finally, three examples demonstrate the feasibility and the superiority of our methods

Revealing the microstructures and seepage characteristics in the uncured rubber-cord composites using micro-computed tomography and lattice Boltzmann approach

The internal microstructure distribution of cord-rubber-air during the processing of uncured rubber-cord composites (URCs) determines the finished product's performance. For the first time, we used computed tomography (CT) and the lattice Boltzmann method (LBM) to establish a geometrical representation model of the real microscopic pore-fracture structures of URCs and investigate the seepage law of fluid in porous URCs, where the reinforced rubber formula was originally designed to reduce CT artifacts of cord. The results showed that the average porosity and pore radius of the original cord (0.2711 and 15.53 μm, respectively) were considerably larger than those of the URCs (0.0509 and 4.46 μm, respectively); the pore number of the cord was the largest when the pore radius was 5–10 μm, accounting for 29.36% of the total number; however, the pore number accounted for 31.36% of the total number of the URCs when the pore radius was 2–3 μm. Moreover, the characteristics of the pore/throat surface area and pore volume/throat length exhibited perfect consistent patterns with those of the pore radius. Furthermore, the fluid flow velocity increased in both cord and URCs as the displacement differential pressure increased, but decreased dramatically as the fluid kinematic viscosity increased. The critical values of displacement differential pressure and kinematic viscosity were different in the cord and URCs samples, presenting 11.1209 Pa/1.3696 × 10−3 m2/s and 14.2984 Pa/2.8869 × 10−4 m2/s, respectively. This phenomenon should be attributed that when the uncured rubber was injected into the original cord sample, its porosity decreased, its pore radius decreased, the number of micro-scale pores increased, and flow resistance became larger, resulting in a higher critical value of displacement differential pressure and a lower critical value of kinematic viscosity

A novel recombinant immunotoxin with the smallest ribosome-inactivating protein Luffin P1: T-cell cytotoxicity and prolongation of allograft survival

Abstract In the creation of stable tolerance to MHC-incompatible allografts, reducing the large mass of donor-reactive cells via apoptosis is often required. Apoptosis induction by immunotoxins targeting surface molecules specifically presented on donor-reactive cytopathic T effector (Teff) cells is a promising strategy. Traditionally, the toxin moieties are bacterial exotoxins or plant-derived ribosome-inactivating proteins (RIPs) with large molecular size and strong immunogenicity, hence causing the problems of tissue penetration, host immune reaction and quick clearance. We have identified a novel class of small molecule RIPs (<10 kD) from the seeds of the plant Luffa cylindrica. The smallest member of this family, Luffin P1, has a molecular weight of 5226.8 Da, yet possessing a highly potent inhibitory activity on cell-free protein synthesis with IC50 of 0.88 nM. We now report a recombinant hIL-2-Luffin P1 immunotoxin, which strongly inhibited T-cell proliferation in mixed lymphocyte reaction and ConA response with IC50 of 1.8–10 nM. In vivo, hIL-2-Luffin P1 significantly prolonged the survival of major MHC-mismatched skin and kidney allografts in animal models. Thus, we demonstrate for the first time the efficacy of the smallest immunotoxin that could be further combined with other pharmacological and immunological reagents for synergistic control of pathogenic lymphocytes in immune-mediated diseases

Improving the Electrochemical Performance of LiNi0.80Co0.15Al0.05O2 in Lithium Ion Batteries by LiAlO2 Surface Modification

LiNi0.80Co0.15Al0.05O2 (NCA) as a lithium ion battery cathode material has received attention for its highly specific capacity and excellent low temperature performance. However, the disadvantages of its high surface lithium compound residues and high pH value have influenced its processing performance and limited its application. This paper uses a facile method to modify NCA through LiAlO2 coating. The results showed that when the molar ratio of Al(NO3)3·9H2O and lithium compound residues at the surface of NCA cathode material was 0.25:1, the pH of the cathode material decreased from 12.70 to 11.80 and the surface lithium compound residues decreased from 3.99% to 1.48%. The NCA cell was charged and discharged for 100 cycles at 1 C in the voltage range of 3.0–4.3 V, to test the capacity retention of NCA. It was found to be as high as 94.67%, which was 5.36% higher than the control NCA cell. The discharge capacity of NCA-0.25-500 °C was 139.8 mAh/g even at 8 C rate, which was 15% higher than the raw NCA. Further research indicated that Al(NO3)3·9H2O reacted with the surface lithium compound residues of NCA and generated LiAlO2, which improved the NCA electrochemical performance

Carbon Dioxide Retrieval from TanSat Observations and Validation with TCCON Measurements

In this study we present the retrieval of the column-averaged dry air mole fraction of carbon dioxide (XCO2) from the TanSat observations using the ACOS (Atmospheric CO2 Observations from Space) algorithm. The XCO2 product has been validated with collocated ground-based measurements from the Total Carbon Column Observing Network (TCCON) for 2 years of TanSat data from 2017 to 2018. Based on the correlation of the XCO2 error over land with goodness of fit in three spectral bands at 0.76, 1.61 and 2.06 μm, we applied an a posteriori bias correction to TanSat retrievals. For overpass averaged results, XCO2 retrievals show a standard deviation (SD) of ~2.45 ppm and a positive bias of ~0.27 ppm compared to collocated TCCON sites. The validation also shows a relatively higher positive bias and variance against TCCON over high-latitude regions. Three cases to evaluate TanSat target mode retrievals are investigated, including one field campaign at Dunhuang with measurements by a greenhouse gas analyzer deployed on an unmanned aerial vehicle and two cases with measurements by a ground-based Fourier-transform spectrometer in Beijing. The results show the retrievals of all footprints, except footprint-6, have relatively low bias (within ~2 ppm). In addition, the orbital XCO2 distributions over Australia and Northeast China between TanSat and the second Orbiting Carbon Observatory (OCO-2) on 20 April 2017 are compared. It shows that the mean XCO2 from TanSat is slightly lower than that of OCO-2 with an average difference of ~0.85 ppm. A reasonable agreement in XCO2 distribution is found over Australia and Northeast China between TanSat and OCO-2

Electron cryo-microscopy structure of the mechanotransduction channel NOMPC.

Mechanosensory transduction for senses such as proprioception, touch, balance, acceleration, hearing and pain relies on mechanotransduction channels, which convert mechanical stimuli into electrical signals in specialized sensory cells. How force gates mechanotransduction channels is a central question in the field, for which there are two major models. One is the membrane-tension model: force applied to the membrane generates a change in membrane tension that is sufficient to gate the channel, as in the bacterial MscL channel and certain eukaryotic potassium channels. The other is the tether model: force is transmitted via a tether to gate the channel. The transient receptor potential (TRP) channel NOMPC is important for mechanosensation-related behaviours such as locomotion, touch and sound sensation across different species including Caenorhabditis elegans, Drosophila and zebrafish. NOMPC is the founding member of the TRPN subfamily, and is thought to be gated by tethering of its ankyrin repeat domain to microtubules of the cytoskeleton. Thus, a goal of studying NOMPC is to reveal the underlying mechanism of force-induced gating, which could serve as a paradigm of the tether model. NOMPC fulfils all the criteria that apply to mechanotransduction channels and has 29 ankyrin repeats, the largest number among TRP channels. A key question is how the long ankyrin repeat domain is organized as a tether that can trigger channel gating. Here we present a de novo atomic structure of Drosophila NOMPC determined by single-particle electron cryo-microscopy. Structural analysis suggests that the ankyrin repeat domain of NOMPC resembles a helical spring, suggesting its role of linking mechanical displacement of the cytoskeleton to the opening of the channel. The NOMPC architecture underscores the basis of translating mechanical force into an electrical signal within a cell