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Finely preserved fossil assemblages (lagerstätten) provide crucial insights into evolutionary innovations in deep time. We report an exceptionally preserved Early Triassic fossil assemblage, the Guiyang Biota, from the Daye Formation near Guiyang, South China. High-precision uranium-lead dating shows that the age of the Guiyang Biota is 250.83 +0.07/–0.06 million years ago. This is only 1.08 ± 0.08 million years after the severe Permian-Triassic mass extinction, and this assemblage therefore represents the oldest known Mesozoic lagerstätte found so far. The Guiyang Biota comprises at least 12 classes and 19 orders, including diverse fish fauna and malacostracans, revealing a trophically complex marine ecosystem. Therefore, this assemblage demonstrates the rapid rise of modern-type marine ecosystems after the Permian-Triassic mass extinction.

IFN-γ-mediated signaling in tumor cells can induce immunosuppressive responses and cause tumor resistance to immunotherapy. Blocking TGF-β promotes T lymphocyte infiltration and turns immunologically cold tumors into hot tumors, thereby improving the efficacy of immunotherapy. Several studies have shown that TGF-β inhibits IFN-γ signaling in immune cells. We thus sought to determine whether TGF-β affects IFN-γ signaling in tumor cells and plays a role in the development of acquired resistance to immunotherapy. TGF-β stimulation of tumor cells increased SHP1 phosphatase activity in an AKT-Smad3-dependent manner, decreased IFN-γ-mediated tyrosine phosphorylation of JAK1/2 and STAT1, and suppressed the expression of STAT1-dependent immune evasion-related molecules, e.g., PD-L1, IDO1, HVEM, and Gal-9. In a lung cancer mouse model, dual blockade of TGF-β and PD-L1 led to superior antitumor activity and prolonged survival compared to anti-PD-L1 therapy alone. However, prolonged combined treatment resulted in tumor resistance to immunotherapy and increased expression of PD-L1, IDO1, HVEM, and Gal-9. Interestingly, after initial anti-PD-L1 monotherapy, dual TGF-β and PD-L1 blockade promoted both immune evasion gene expression and tumor growth compared to that in tumors treated with continuous PD-L1 monotherapy. Alternatively, treatment with JAK1/2 inhibitor following initial anti-PD-L1 therapy effectively suppressed tumor growth and downregulated immune evasion gene expression in tumors, indicating the involvement of IFN-γ signaling in immunotherapy resistance development. These results demonstrate an unappreciated effect of TGF-β on the development of IFN-γ-mediated tumor resistance to immunotherapy.

The TaCN coatings were fabricated on Ti-6Al-4V by reactive magnetron sputtering with different nitrogen partial pressures. The results show that the TaCN coatings have a columnar crystal structure of TaC, TaN nano-crystal and amorphous phases (amorphous carbon and CNx). The crystallinity of TaCN coatings decreases with the increase of N2 flow rate. It is found that hardness and adhesive strength have a downward trend and friction coefficient of TaCN coatings increases with the increase of N2 flow rate. In particular, the TaCN coating with lowest N2 flow rate of 30 sccm has the highest hardness (16.3 GPa), the biggest adhesive strength (74.8 N) and the lowest friction coefficient (~0.19). The TaCN coating exhibits an excellent tribological performances even at high temperature. The lowest friction coefficient at 400 °C could reach below 0.1 thanks to the transfer layer containing graphitic clusters which generated during friction.

Perovskite is of burgeoning interest in catalysis, principally due to such material having high thermal stability, modifiable variability, ferromagnetism, and excellent catalytic performance in peroxomonosulfate (PMS) activation. In this study, the SrCoxMn1−xO3 perovskites with different Mn doping were synthesized by a facile sol-gel method for peroxymonosulfate (PMS) activation to degrade Rhodamine B. The obtained SrCo0.5Mn0.5O3 perovskite exhibited the best catalytic efficiency, as Rhodamine B (40 mg/L) was removed completely within 30 min. In the system of SrCo0.5Mn0.5O3–PMS, several reactive species were produced, among which sulfate radicals and the singlet oxygen mainly contributed to Rhodamine B degradation. The relatively high catalytic performance could be attributed to the coupled redox cycle between Mn and Co, and the abundant oxygen vacancies. Moreover, the SrCo0.5Mn0.5O3 catalyst showed excellent stability and reusability, maintaining a high catalytic activity after several cycling tests. This study demonstrated that the Mn doping of SrCoO3 could not only enhance the B-site activation in SrCo0.5Mn0.5O3 but also enrich the oxygen vacancies, thus improving the efficiency of PMS activation.

Abundant algae-sourced dissolved organic matter (A-DOM) is produced during algal blooms in eutrophic lakes. Natural-light-driven photodegradation plays an important role in A-DOM function and its migration in aqueous systems. The photodegradation performance of A-DOM extracted from Chaohu Lake was tested and characterized under UV-A, UV-C irradiation, and dark condition, and the photochemical degradation characteristics and molecular weight changes of A-DOM during degradation were analyzed. A-DOM mainly includes four EEM-PARAFAC components, namely, C1 (protein-like tryptophan), C2 (protein-like tyrosine), C3 (long-wave humus), and C4 (short-wave humus). After irradiation for 168 h under UV-C, the protein-like components C1 and C2 had the highest fluorescence intensity reduction of 95.4% and 100%, respectively. The fluorescence intensities of fulvic-like components, namely C3 and C4, increased. The absorption coefficients (A355) of A-DOM were decreased by 84.46%, 70.83%, and 52.98% with UV-A, UV-C irradiation, and dark condition, respectively. The degradation reaction of C1 and C2 fitted with the first-order kinetic equation with a half-life of 21.59–83.51 h. The SUVA254 value decreased under UV irradiation and increased under dark condition, which is in accordance with the change of molecular weight results. The A-DOM photochemical reaction was driven by UV light irradiation, and the humification rate and molecular weight decreased.

The spatial distribution of microplastics and the factors influencing their distribution in lakes are important aspects of plastics pollution studies. This study investigated the impacts of lake underwater topography on the spatial distribution of microplastics in Dianchi Lake in China. Data on spatial distribution of microplastics were obtained by pump sampling, microscopic examination, and polymer identification. Parameters of underwater topography were extracted from an isobaths map of Dianchi Lake. The relationships between underwater topography and the abundance of microplastics were analyzed. The results showed that for the northern part of the lake, water depth, slope gradient, relief, roughness and surface curvature have significant relationships with the spatial distribution of microplastics. In the southern part, only roughness showed a significant relationship. The roughness is the only important factor which impacts the microplastics distribution in both parts of the lake and the whole lake. These differences between the northern part and the southern part of the lake are related to the stronger circular currents in the southern part of the lake. These results showed that the impacts of underwater topography manifest themselves well when lake currents are weak, and these impacts are reduced or muted when lake currents are strong. Our research results provide a good reference for understanding distribution and migration principle of microplastics in lakes.

OBJECTIVES Electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation is a minimally invasive technology for treating pulmonary lesions. This study analysed the short-term safety and efficacy of ENB-guided microwave ablation in multiple pulmonary nodules (MPNs). METHODS This retrospective study reports a single-centre experience with ENB-guided microwave ablation for MPNs. Clinical, surgical and pathological data were obtained for patients who underwent ENB-guided microwave ablation from 23 December 2019 to 23 June 2021. The primary end points were technical safety and efficiency. RESULTS The study assessed 65 patients who underwent ENB-guided microwave ablation, 57 of whom simultaneously underwent video-assisted thoracic surgery. In total, 216 nodules were treated. Of 96 nodules treated by ENB-guided microwave ablation, 94 nodules had ground-glass opacity. Ablation efficiency was confirmed by hybrid cone-beam computed tomography. Of 120 nodules surgically removed, 106 nodules had ground-glass opacity. The mean nodule size was 7.9 mm in ablated nodules and 10.2 mm in resected nodules. Distance between nodules and pleura or fissure was 17.45 mm in ablated nodules and 7.29 mm in resected nodules. The overall malignancy rate was 47.7% (103/216); the complication rate was low (65 patients). At short-term follow-up, the post-ablation target zone shrank by 1 week and stabilized after 4–6 months. No local recurrence or enlargement of other pulmonary nodules was noted. CONCLUSIONS To treat MPNs, ENB-guided microwave ablation is safe and efficient. The combination of this treatment and video-assisted thoracic surgery is a potential application, which can preserve as much pulmonary function as possible and treat MPNs to the maximum extent.

A dearomatization/deiodination/rearomatization strategy for the [3 + 2] cyclization of

The current natural environment is unpredictable with heavy rains and floods happening from time to time. In order to ensure the safety of underground workers, infrastructure, and rail transit, a mobile and expandable underground flood control wall was optimized and designed. The use of mortise-and-tenon structure splicing and modular extension design effectively increases the stability and useable area of the flood wall. The finite element analysis software was used to simulate and study the force of each component under combined loads, such as static water, dynamic water, and impact, to analyze the stability performance of the assembly such as anti-sliding, anti-tilting, and internal stress. The verification results show that when the designed and studied underground flood control wall equipment is fully deployed, the maximum stress is 220.762 MPa, and the maximum offset distance is 32.334 mm, which are all within the safe range. It provides innovative ideas for the optimization of the related flood control wall structure.

In a satellite network, the inter-satellite link can facilitate the information transmission and exchange between satellites, and the packet routing of the inter-satellite link is the key development direction of satellite communication systems. Aiming at the complex topology and dynamic change in LEO satellite networks, the traditional single shortest path algorithm can no longer meet the optimal path requirement. Therefore, this paper proposes a multi-path routing algorithm based on an improved breadth-first search. First, according to the inter-satellite network topology information, the improved breadth-first search algorithm is used to obtain all the front hop node information of the destination node. Second, all the shortest paths are obtained by backtracking the path through the front hop node. Finally, according to the inter-satellite network, the bandwidth capacity of the traffic and nodes determines the optimal path from multiple shortest paths. However, due to the high dynamics of low-orbit satellite networks, the topology changes rapidly, and the global topology of the network is often not available. At this time, in order to enhance the adaptability of the algorithm, this paper proposes an inter-satellite network dynamic routing algorithm based on reinforcement learning. Verified by simulation experiments, the proposed algorithm can improve the throughput of the inter-satellite network, reduce the time delay, and the packet loss rate.

Neopterygii is the largest clade of ray-finned fishes, including Teleostei, Holostei, and their closely related fossil taxa. This clade was first documented in the Early Carboniferous and underwent rapid evolutionary radiation during the Early to Middle Triassic. This article describes a new perleidid neopterygian species, Teffichthys elegans sp. nov., based on 13 well-preserved specimens from the lower Daye Formation (Dienerian, Induan) in Guizhou, China. The new species documents one of the oldest perleidids, providing insights into the early diversification of this family. The results of a phylogenetic analysis recover Teffichthys elegans sp. nov. as the sister taxon to Teffichthys madagascariensis within the Perleididae. T. elegans sp. nov. shares three derived features of Perleididae: the length of the anteroventral margin of the dermohyal nearly half the length of the anterodorsal margin of the preopercle; the anteroventral margin of the preopercle nearly equal to the anterior margin of the subopercle in length; and the anteroventral margin of the preopercle one to two times as long as the anterodorsal margin of the preopercle. It possesses diagnostic features of Teffichthys but differs from T. madagascariensis by the following features: presence of three supraorbitals; six pairs of branchiostegal rays; relatively deep anterodorsal process of subopercle; absence of spine on the posterior margin of the jugal; and pterygial formula of D26/P14, A22, C36/T39-41. The Perleidiformes are restricted to include only the Perleididae, and other previously alleged ‘perleidiform’ families (e.g., Hydropessidae and Gabanellidae) are excluded to maintain the monophyly of the order. Similar to many other perleidids, T. elegans sp. nov. was likely a durophagous predator with dentition combining grasping and crushing morphologies. The new finding also may indicate a relatively complex trophic structure of the Early Triassic marine ecosystem in South China.

3D human pose estimation plays important roles in various human-machine interactive applications, but lacking diversity in existing labeled 3D human posture dataset restricts the generalization ability of deep learning based models. Data augmentation is therefore an important method to solve this problem. However, data augmentation and pose estimation network training are usually treated as two isolated processes, limiting the performance of pose estimation network. In this paper, we developed an improved data augmentation method which jointly performs pose network estimation and data augmentation by designing a reward/penalty strategy for effective joint training, making model training and data augmentation improve each other. In particular, an improved evolutionary data augmentation method is proposed to generate the distribution of nodes in crossover and rotation angles in mutation through the process of the evolution. Extensive experiments show that our approach not only significantly improves state-of-the-art models without additional data efforts but also is extremely competitive with other advanced methods.

Interferon-gamma (IFN-γ) is a major effector molecule of immunity and a common feature of tumors responding to immunotherapy. Active IFN-γ signaling can directly trigger apoptosis and cell cycle arrest in human cancer cells. However, the mechanisms underlying these actions remain unclear. Here, we report that IFN-γ rapidly increases protein synthesis and causes the unfolded protein response (UPR), as evidenced by the increased expression of glucose-regulated protein 78, activating transcription factor-4, and c/EBP homologous protein (CHOP) in cells treated with IFN-γ. The JAK1/2-STAT1 and AKT-mTOR signaling pathways are required for IFN-γ-induced UPR. Endoplasmic reticulum (ER) stress promotes autophagy and restores homeostasis. Surprisingly, in IFN-γ-treated cells, autophagy was impaired at the step of autophagosome-lysosomal fusion and caused by a significant decline in the expression of lysosomal membrane protein-1 and −2 (LAMP-1/LAMP-2). The ER stress inhibitor 4-PBA restored LAMP expression in IFN-γ-treated cells. IFN-γ stimulation activated the protein kinase-like ER kinase (PERK)-eukaryotic initiation factor 2a subunit (eIF2α) axis and caused a reduction in global protein synthesis. The PERK inhibitor, GSK2606414, partially restored global protein synthesis and LAMP expression in cells treated with IFN-γ. We further investigated the functional consequences of IFN-γ-induced ER stress. We show that inhibition of ER stress significantly prevents IFN-γ-triggered apoptosis. CHOP knockdown abrogated IFN-γ-mediated apoptosis. Inhibition of ER stress also restored cyclin D1 expression in IFN-γ-treated cells. Thus, ER stress and the UPR caused by IFN-γ represent novel mechanisms underlying IFN-γ-mediated anticancer effects. This study expands our understanding of IFN-γ-mediated signaling and its cellular actions in tumor cells.

Background The repetitive antigen stimulation during chronic infection often leads to the accumulation of CD8+CD57+ T cells. These cells express high levels of interferon-γ, granzyme B and perforin with elevated cytolytic effect, and are considered as the most potent cells for combating chronical viral infection. The status of CD8+CD57+ T cells in non-small cell lung cancer (NSCLC) has not been well defined. Methods We used flow cytometry and undertook a systemic approach to examine the frequency, immunophenotyping and functional properties of CD8+CD57+ T cells in the peripheral blood, tumor tissue and the corresponding normal tissue, as well as lung draining lymph nodes, of patients with NSCLC. Results CD57+ T cells expressed high levels of programmed cell death-1 (PD-1) in all tested compartments and were predominantly CD8+ T cells. These cells in the peripheral blood displayed a terminally differentiated phenotype as defined by loss of CD27 and CD28 while expressing KLRG1. CD8+CD57+ T cells exhibited enhanced cytotoxic potencies and impaired proliferative capability. Unlike CD57+ T cells in the peripheral blood, a significant proportion of CD57+ T cells in the primary tumors expressed CD27 and CD28. CD8+CD57+ T cells in tumors lacked cytotoxic activity. The proliferative activity of these cells was also impaired. CD8+CD57+ T cells in the corresponding normal lung tissues shared similarities with their counterparts in peripheral blood rather than their counterparts in tumors. The vast majority of CD8+CD57+ T cells in lung draining lymph nodes were positive for CD27 and CD28. These cells were unable to produce perforin and granzyme B, but their proliferative activity was preserved. CD8+CD57+ T cells in tumors displayed an inferior response to PD-1 blockade compared with their CD8+CD57- counterparts. Interleukin (IL)-15 preferentially restored the effector function of these cells. Additionally, IL-15 was able to restore the impaired proliferative activity of CD8+CD57+ T cells in tumors and peripheral blood. Conclusions Our data indicate that the failure of the immune system to fight cancer progression could be a result of impaired CD8+ T-cell functional maturation into fully differentiated effector T cells within the tumor microenvironment. Boosting IL-15 activity might promote tumor-reactive CD8+ T-cell functional maturation while preserving their proliferative activity.

The graphite-like carbon (GLC) based nanocomposite coating have attracted great attention in tribology, however, its high-temperature tribological behavior is not well investigated. In this study, the GLC-based nanocomposite coatings with different target power by direct current magnetron sputtering were fabricated, and the influence of target power on microstructure, tribological property of these coatings was investigated. The results indicates that these coatings show the graphite-like carbon (with doped nitrogen atom)/amorphous-(Si3N4, TiO2, Ti2O3)/nanocrystalline-TiC structure. With the target power increasing, the content of TiC nanocrstallines fluctuates, yet the carbon content basically is unchanged. The hardness and wear resistance are related to the ratio of nanocrystallines to amorphous phase. The maximum hardness of as-deposited coatings is about 18 GPa. The minimum COF (coefficient of friction) of coatings sliding against Al2O3 was 0.22, and the lowest wear rate is 3.2 × 10−5 mm3/(N·m). At elevated temperature, due to the cracks and the transformation in graphite-like carbon from the sp2 bond carbon clusters (sp2-C) to sp3 bond carbon clusters (sp3-C), the load-bearing capacity becomes worse, and the carbon clusters deteriorate with increasing temperature, resulting in higher COF and wear rate.

The traditional MCrAlY coatings face severe hot corrosion issue under the effect of NaCl. Therefore, Al-gradient NiSiAlY coatings were obtained by multi-arc ion plating and a following annealing. With a further pre-oxidation, a thin layer of dense α-Al2O3 was formed on the coating. Subsequently, hot corrosion test was performed on the as-annealed and pre-oxidized coatings at 750 °C. The dense α-Al2O3 layer formed by pre-oxidation could effectively protect the underlying coating from NaCl-induced hot corrosion and improve the hot corrosion resistance of the coatings. By pre-oxidation, the total mass gain was reduced by 75% from 2.1 mg/cm2 to 0.4 mg/cm2 after 168 h of hot corrosion test.

Objective Prolonged exposure to hand-transmitted vibration (HTV) is associated with an increased risk of hand-arm vibration syndrome (HAVS). This study aimed to identify the signs and symptoms associated with coal workers using hand-held vibrating tools in a northern China coal mine, and to determine the risk factors for HAVS. Methods A cross-sectional survey was conducted of 167 male workers with part-time exposure to HTV. A structured questionnaire was administered to the workers along with a series of function tests. The frequency-weighted vibration acceleration of hand-held tools was measured. The prevalence ratio and symptom correlation to HAVS among the different subgroups were evaluated. Results The prevalence of hand numbness, carpal tunnel syndrome, hand ache, tinnitus, memory loss, dizziness and headache showed significant differences in the longer-exposure groups (working years > 3 years or the daily-exposure duration > 2 h), compared with the control group ( P 0.05). Function tests showed abnormal findings only in vibration sensation and the X-ray examination of the longer-exposure groups ( P 0.05). The logistic regression analysis showed that longer working years, higher daily exposure and alcohol consumption were risk factors, while wearing anti-vibration gloves showed protective effects for hand numbness. Conclusions This study has identified the main signs and symptoms of HAVS among coal workers exposed to HTV in China. More information related to occupational safety and health programs are required to reduce the risk of HAVS.

Monitoring of interfacial electron transfer (ET) in situ is important to understand the ET mechanism and designing efficient photocatalysts. We describe herein a mass spectrometric approach to investigate the ultrafast transfer of photoelectrons that are generated by ultraviolet irradiation on surfaces of semiconductor nanoparticles or crystalline facets. The mass spectrometric approach can not only untargetedly detect various intermediates but also monitor their reactivity through associative or dissociative photoelectron capture dissociation, as well as electron detachment dissociation of adsorbed molecules. Proton-coupled electron transfer and proton-uncoupled electron transfer with radical initiated polymerization or hydroxyl radical abstraction have been unambiguously demonstrated with the mass spectrometric approach. Active crystalline facets of titanium dioxide for photocatalytic degradation of juglone and organochlorine dichlorodiphenyltrichloroethane are visualized with mass spectrometry imaging based on ion scanning and spectral reconstruction. This work provides a new technique for studying photo-electric properties of various materials., Monitoring interfacial electron transfer in photocatalytic systems is fundamentally important but experimentally challenging. Here the authors use mass spectrometry to detect and monitor intermediates formed through photoelectron transfer and to image active crystalline facets of semiconductor photocatalysts.

To meet the real-time requirement and data fast processing has become a significant challenge in the Internet of Things platform. In an attempt to design and implement new reactive paradigm, this paper presents an innovative Actor model to design and implement IoT platform using Akka Actor, Akka Stream, Akka Cluster, Akka-MQTT Connector, Kafka, MQTT, Angular technologies to process high speed and super mass monitoring data from IoT devices in real-tine. In this IoT platform system the actor model based on Akka with functional reactive approach was used in both the platform back-end and the front-end to meet the performance requirement of IoT platform. Future research will focus on the practice validation of this work by implementing this IoT platform into a big data system and artificial intelligence application.

17 pages; International audience; The biotic recovery following the Permian/Triassic boundary mass extinction was influenced by several secondary extinctions during the Early Triassic, of which the late Smithian crisis is the most severe known for some nekto-pelagic organisms such as ammonoids. The Smithian-Spathian transition is characterized by successive global biotic and environmental changes, including a dramatic positive carbon isotopic excursion, oceanic anoxia and a cooling event beginning in the late Smithian. However, the tempo, modalities and the causal relationships among these various events remain poorly constrained. Here we synthesized paleontological, sedimentological, and geochemical data from three sections (Motianling, Nafang, and Shanggang) within the Nanpanjiang Basin, representing platform slop to basinal deposits spanning the Smithian/Spathian boundary. High-resolution analyses of thin sections show a sudden decrease in richness and abundance of fossil grains at the middle/upper Smithian boundary in all three sections, coinciding with the onset of a positive shift in δ13Ccarb. It also slightly precedes the beginning of the late Smithian cooling. At Shanggang, a change in dominance from bivalve-rich to ostracod-rich strata is also recorded at the middle/upper Smithian boundary. Overall, our results therefore indicate that a first major biotic crisis and turnover happened during the beginning of the late Smithian in the Nanpanjiang Basin, rather than around the Smithian/Spathian boundary. Complementary analyses on pyrite framboid size indicate that these observed biotic changes are concurrent with oxygen depletion in the studied sections, supporting the hypothesis that oceanic anoxia also played an important role in the late Smithian crisis in combination with climate cooling and oceanic acidification.

The TiN coating and Ti/TiN multilayer coatings were successfully fabricated on Ti6Al4V alloy by multi-arc ion plating. The Ti/TiN multilayer coatings with a total thickness of 4.6 μm and the TiN coating were prepared with a thickness of 5.6 μm. The XRD results indicate that the TiN phase of Ti/TiN multilayer coatings has a face-centered cubic crystal with the strong preferred orientation of (111) while the TiN coating has the face-centered cubic crystal structure with a preferred orientation of (200). For TiN coating, the hardness is (27.5 ± 1.9) GPa, the load-bearing capacity is (19.0 ± 3.6) N. For Ti/TiN multilayer coating, the hardness is (26.8 ± 1.7) GPa and the load-bearing capacity is (60.4 ± 4.0) N. The Ti/TiN multilayer coatings have excellent tribocorrosion resistance and lower coefficient of friction in simulated body fluid at 37 °C, compared with Ti6Al4V alloy and TiN coating, the tribocorrosion resistance of the multilayer coatings increased by approximately 58 and two times, respectively. The material loss which arises from tribocorrosion is not simply the summation of pure corrosion and pure wear loss, the synergism between corrosion and wear takes a large proportion of the total volume loss.

BackgroundThe repetitive antigen stimulation during chronic infection often leads to the accumulation of CD8+CD57+ T cells. These cells express high levels of interferon-γ, granzyme B and perforin with elevated cytolytic effect, and are considered as the most potent cells for combating chronical viral infection. The status of CD8+CD57+ T cells in non-small cell lung cancer (NSCLC) has not been well defined.MethodsWe used flow cytometry and undertook a systemic approach to examine the frequency, immunophenotyping and functional properties of CD8+CD57+ T cells in the peripheral blood, tumor tissue and the corresponding normal tissue, as well as lung draining lymph nodes, of patients with NSCLC.ResultsCD57+ T cells expressed high levels of programmed cell death-1 (PD-1) in all tested compartments and were predominantly CD8+ T cells. These cells in the peripheral blood displayed a terminally differentiated phenotype as defined by loss of CD27 and CD28 while expressing KLRG1. CD8+CD57+ T cells exhibited enhanced cytotoxic potencies and impaired proliferative capability. Unlike CD57+ T cells in the peripheral blood, a significant proportion of CD57+ T cells in the primary tumors expressed CD27 and CD28. CD8+CD57+ T cells in tumors lacked cytotoxic activity. The proliferative activity of these cells was also impaired. CD8+CD57+ T cells in the corresponding normal lung tissues shared similarities with their counterparts in peripheral blood rather than their counterparts in tumors. The vast majority of CD8+CD57+ T cells in lung draining lymph nodes were positive for CD27 and CD28. These cells were unable to produce perforin and granzyme B, but their proliferative activity was preserved. CD8+CD57+ T cells in tumors displayed an inferior response to PD-1 blockade compared with their CD8+CD57- counterparts. Interleukin (IL)-15 preferentially restored the effector function of these cells. Additionally, IL-15 was able to restore the impaired proliferative activity of CD8+CD57+ T cells in tumors and peripheral blood.ConclusionsOur data indicate that the failure of the immune system to fight cancer progression could be a result of impaired CD8+ T-cell functional maturation into fully differentiated effector T cells within the tumor microenvironment. Boosting IL-15 activity might promote tumor-reactive CD8+ T-cell functional maturation while preserving their proliferative activity.

Side-channel attacks are effective attacks against modern cryptographic schemes, which exploit the leaking information besides input and output to the algorithm. As one of the cache-based side-channel attacks, Flush+Reload features high resolution, low noise, and virtual machine compatibility. However, a state-of-the-art Flush+Reload attack only reveals whether the memory address is accessed or not. This paper presents differential Flush+Reload attack that can recover the access sequence of memory addresses, which could lead to new vulnerabilities. The idea is to analyze statistical difference among multiple Flush+Reload results. Specifically, we add controlled delay between the start of victim calculation and the memory flush. Multiple Flush+Reload results with different delays are measured to determine the memory access sequence. Under this concept, we demonstrate the details of a successful recovery of T-table access sequences for an AES implementation from MatrixSSL version 3.9.3 on an Intel CPU.

Polyacrylamide gel electrophoresis (PAGE) coupled with mass spectrometry has been well established for separating, identifying and quantifying protein mixtures from cell lines, tissues or other biological samples. The copolymerization process of acrylamide and bis-acrylamide is the key to mastering this powerful technique. In general, this is a vinyl addition reaction initiated by free radical-generating reagents such as ammonium persulfate (APS) and tetramethylethylenediamine (TEMED) under basic pH and degassing experimental condition. We report herein a photocatalytic polymerization approach that is based on photo-generated hydroxyl radicals with nanoparticles of titanium dioxide. It was shown that the polymerization process is greatly accelerated in acidic condition when ultraviolet light shots on the gel solution containing TiO2 nanoparticles without degassing. This feature makes it very useful in preparing Triton X-100 acid urea (TAU) gel that has been developed for separating basic proteins such as histones and variants in acidic experimental condition. Additionally, the presence of titanium dioxide in the gel not only improves mechanistic property of gels but also changes the migration pattern of different proteins that have different affinities to titanium dioxide.

The wild type avian pathogenic Escherichia coli (APEC) isolate A2 (Serotype O2:K89) was selected as the prototype of the (APEC) Type I Fimbriae. Based on the original sequences of Type I Fimbriae operon gene clusters in the GenBank,we generated PCR products by using primers with the homologies extension of fimH gene to be deleted and template plasmid pKD3 carrying selectable antibiotic chloramphenicol resistance (cat) gene that is flanked by FRT (FLP recognition target) sites. By using the PCR products, the A2 deltafimH::Cat deletion mutant from A2 isolate was constructed by lambdaRed-mediated recombination system in the flanking homologies. After selection, the resistance gene located in the A2deltafimH::Cat mutant was eliminated in the second recombination, by using a helper plasmid pCP20, a temperature-sensitive one encoding and expressing the FLP recombinase, which acts on the directly repeated FRT sites flanking the resistance gene. The A2deltafimH mutant obtained was further confirmed by fimH PCR amplification and sequencing. The A2deltafimH mutant with the deletion of fimH adhesin in the fim gene cluster lost the ability of agglutination reaction with both guinea pig erythrocytes and yeast cells. The A2deltafimH deletion mutant restored the agglutination ability of both binding guinea pig erythrocytes and yeast cells when transfected the compatible recombinant plasmid pBR322-fimH with fimH insert in the fimH complementation assay. Very similar to the wild type A2 isolate, The obtained binding activity from the A2deltafimH mutant in the complementation assay was completely inhibited when pretreated with 0.5% mannose solution. Compared with the wild type isolate, the A2deltafimH mutant grew slowly during all stages of growth. This work provides the basis for us to study the molecular pathogenesis mechanisms of interaction between the APEC Type I Fimbriae and susceptible host cells, extra-intestinal infection, prevention and control of the APEC-caused disease.

The surfaces of flexible printed circuit products are discontinuous, it is imperative to provide a non-contact measurement system to measure not only non-continuous surface, but also surface topography and small dimension. Optical detection system based on differential astigmatic can solve the problem. In the existing literature, the mathematic model of differential astigmatic optical system is established by Geometrical optics, it brings imprecision factors. So it is necessary to establish a precise mathematical model of differential astigmatic. This paper analyzes the shortcomings and inadequate of the mathematic model of differential astigmatic optical system which is based on geometrical optics of traditional optical systems, and then analyzes the model based on laser Gaussian beam model, which is more accurately closer to actual situation. Subsequently, according to the mathematic model, this paper optimizes the optical path parameters and also analyzes the impacts of position errors of optical components upon the measurement, which lays the foundation of the improvement of the online FPC quality control system.