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Energy has always been the engine of human beings; however, because of the environmental pollution caused by traditional fossil fuels, the development of more sustainable energy resources is urgently needed. The hydrogen storage medium is essential for its realization. Here, we introduce a hydrogen storage material, a two-dimensional (2D) square-octagon BCN (SO-BCN) monolayer, composed of lightweight elements (B, C, and N) and strategically functionalized with alkali and alkali earth metal atoms (Li, Na, Mg, and K). Notably, Li@SO-BCN and Mg@SO-BCN exhibit exceptional reversible hydrogen storage capabilities, surpassing the DOE standard of 5.5 wt %, with gravimetric capacities of 7.129 wt % and an impressive value of 11.656 wt %, alongside low adsorption energies of −0.21 eV/H2and −0.268 eV/H2at room temperature, respectively. Our investigation, which combines analysis of the atomic structure, electronic structure, and hydrogen process, reveals distinct mechanisms at play: Li activates the substrate, creating additional adsorption sites on the SO-BCN monolayer. Compared with Li, the functionalization of Mg atoms not only activates SO-BCN via charge transfer but also allows Mg2+to act as a potent attractor for H2molecule adsorption. This work provides both promising candidates for future hydrogen storage media based on 2D monolayers and a design paradigm for next-generation hydrogen storage materials, emphasizing the synergy of electron-donating species, substrate activation, and hierarchical porous structures.

ObjectiveMetastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered.DesignWe performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). We also conducted immunofluorescence staining and functional experiments to examine the mechanism.ResultsIntegrative analyses of epithelial cells reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O(PTPRO) and achaete scute-like 2(ASCL2) expression as the metastatic culprit. This cell cluster comprising distinct subpopulations shows distinct liver or ovary metastatic preference. Population 1 (P1) cells with high delta-like ligand 4 (DLL4)and MAF bZIP transcription factor A (MAFA)expression are enriched in primary CRC and oCRC, thus may be associated with ovarian metastasis. P3 cells having a similar expression pattern as cholangiocytes are found mainly in primary CRC and lCRC, presuming to be likely the culprits that specifically metastasise to the liver. Stem-like cells interacted with cancer-associated fibroblasts and endothelial cells via the DLL4-NOTCH signalling pathway to metastasise from primary CRC to the ovary. In the oCRC microenvironment, myofibroblasts provide cancer cells with glutamine and perform a metabolic reprogramming, which may be essential for cancer cells to localise and develop in the ovary.ConclusionWe uncover a mechanism for organ-specific CRC metastasis.

The wheel-legged biped robot is a typical ground-based mobile robot that can combine the high velocity and high efficiency pertaining to wheeled motion and the strong, obstacle-crossing performance associated with legged motion. These robots have gradually exhibited satisfactory application potential in various harsh scenarios such as rubble rescue, military operations, and wilderness exploration. Wheel-legged biped robots are divided into four categories according to the open–close chain structure forms and operation task modes, and the latest technology research status is summarized in this paper. The hardware control system, control method, and application are analyzed, and the dynamic balance control for the two-wheel, biomimetic jumping control for the legs and whole-body control for integrating the wheels and legs are analyzed. In summary, it is observed that the current research exhibits problems, such as the insufficient application of novel materials and a rigid–flexible coupling design; the limited application of the advanced, intelligent control methods; the inadequate understanding of the bionic jumping mechanisms in robot legs; and the insufficient coordination ability of the multi-modal motion, which do not exhibit practical application for the wheel-legged biped robots. Finally, this study discusses the key research directions and development trends for the wheel-legged biped robots.

With the rapid development of unmanned aerial and underwater vehicles, various tasks, such as biodiversity monitoring, surveying, and mapping, as well as, search and rescue can now be completed in a single medium, either underwater or in the air. By systematically examining the water–air cross-medium locomotion of organisms, there has been growing interest in the development of aerial-aquatic vehicles. The goal of this review is to provide a detailed outline of the design and cross-medium theoretical research of the existing aerial-aquatic vehicles based on the research on the organisms capable of transiting between water and air. Although these designs and theoretical frameworks have been validated in many aerial-aquatic vehicles, there are still many problems that need to be addressed, such as inflexible underwater motion and unstable medium conversion. As a result, supplementation of the existing cross-medium biomimetic research, vehicle design, power selection, and cross-medium theory is urgently required to optimize the key technologies in detail. Therefore, by summarizing the existing designs and theoretical approaches on aerial-aquatic vehicles, including biomimetic research on water–air cross-medium locomotion in nature, different power selections, and cross-medium theoretical research, the relative problems and development trends on aerial-aquatic vehicles were thoroughly explored, providing significant help for the subsequent research process.

Prussian blue analogs (PBAs) are a potential choice for cathodes in sodium-ion batteries. However, their electrochemical performance is hindered by intrinsic structural vacancies and weak electronic conductivity, resulting in a reduced reversible capacity, multiplicative ability, and cycle stability. Herein, the carbon-blended Na2CoFe(CN)6(COHCF@C) prepared by a controlled crystallization method displays improved electrochemical characteristics. With 70% residual capacity after 200 cycles, the reversible specific capacity of the COHCF@C is 123 mAh g–1at 1 C. Furthermore, the COHCF@C also exhibits higher structural stability in aqueous electrolytes. Based on experimental results, this enhancement can be attributed to the introduction of carbon, slowing down the crystallization process and resulting in higher crystallinity. Additionally, the reduced water content leads to fewer defects, which improves the utilization of active sites. Overall, the finding provides an experimental basis and theoretical guidance for the application of PBA cells.

The genesis of giant gold provinces is an international scientific frontier, in which the source of a huge amount of gold and the drive for mineralization are key challenges. The mineralization intensity of the Jiaodong gold province in eastern China is a rare occasion in the world, because it owns gold reserves of ∼5500 tons within an area of less than 10,000 km2. The Jiaodong gold province formed in the superimposed domain of diverse tectonic regimes in an intracontinental setting. Paleoproterozoic regional peak metamorphism and Triassic continental collision are followed by the tectonic transition and gold mineralization at ca. 120 Ma with time intervals of 1.9 billion years and about 100 million years, respectively. The Jiaodong gold deposits are different from orogenic and intrusion-related gold deposits in terms of the tectonic background, types of host rocks, and ore-forming mechanism. These gold deposits show close spatial-temporal and genetic relationships to mafic igneous rocks, implying the derivation of ore-forming fluids from the metasomatic mantle domains. Mafic dykes in Jiaodong have negative εHf(t) values of −29.9 to −9.1, Os content of 0.002–0.16 ppb, heavy δ18O up to 8.23‰, and high initial 187Os/188Os ratios of 0.1352–0.8858. These indicate that the lithospheric mantle was metasomatized by ancient crust-derived components. The lithospheric mantle in the western Jiaodong shows generally more enriched isotope features than that in the eastern part, which is explained to be an important reason for its huge gold resources. The mafic dykes show lighter Mg isotope characteristics (average δ26Mg of −0.33‰, n=50) and high CaO content (overall greater than 6.5 wt%), indicating that the lithospheric mantle would also record the metasomatism by the carbonate rocks from the subducting oceanic slab. Under the background of the rollback of the subducting paleo-Pacific slab and the destruction of the North China Craton, partial melting of the lower crust would produce granitic magmas that led to the enrichment of gold in the residual crust. The syn-mineralization asthenosphere upwelling would promote the recycling of the lower crust and the partial melting of the metasomatic mantle domains. Basic magmas, produced by the partial melting, and the mantle itself would degas to form ore fluids. The ore fluids would further leach gold in the lower crust to increase its fertility. The auriferous fluids were transported to the middle to upper crust along the detachment and strike-slip faults. Water-rock interaction and fluid immiscibility, which occurred in and above the ductile-brittle transition zone to induce gold precipitation, formed the Jiaodong gold deposits. Given the unique geological features and genetic model of the Jiaodong gold deposits, they can be defined as “Jiaodong-type” gold deposits.

By DFT calculations and machine learning algorithms, the HER performance of single-atom catalysts was predicted for doped GaPS42D material.

Immunotherapyis a promising cancer treatment method; however, only a few patients benefit from it. The development of new immunotherapy strategies and effective biomarkersof response and resistance is urgently needed. Recently, high-throughput bulk and single-cell gene expressionprofiling technologies have generated valuable resources. However, these resources are not well organized and systematic analysis is difficult. Here, we present TIGER, a tumor immunotherapy gene expression resource, which contains bulk transcriptome data of 1508 tumor samples with clinical immunotherapy outcomes and 11,057 tumor/normal samples without clinical immunotherapy outcomes, as well as single-cell transcriptome data of 2,116,945 immune cells from 655 samples. TIGER provides many useful modules for analyzing collected and user-provided data. Using the resource in TIGER, we identified a tumor-enriched subset of CD4+T cells. Patients with melanoma with a higher signature score of this subset have a significantly better response and survival under immunotherapy. We believe that TIGER will be helpful in understanding anti-tumor immunity mechanisms and discovering effective biomarkers. TIGER is freely accessible at http://tiger.canceromics.org/.

As a part of the global decarbonization agenda, the electrification of the transport sector involving the large-scale integration of electric vehicles (EV) constitutes one of the key initiatives. However, the upstream generation carbon emissions associated with EV charging demand are still accountable which should not be overlooked. In this context, efficient coordination of EV flows and their charging demand in the coupled transportation and power networks promise significant decarbonization potential. Nevertheless, such potential can only be realized under adequate incentive mechanisms. In this article, a novel low carbon EV charging coordination approach in coupled transportation and power network is proposed and formulated as a bi-level optimization. In the upper level, an AC optimal power flow problem is formulated and solved to determine the optimal operation for power system. Then the carbon emission flow tracing is performed to compute rational locational-differentiated price signals. Given price-based incentives, the lower level employs traffic user equilibrium to describe the distribution of EV path flow and charging demands taking into account the uncertain traffic condition, and the aggregate charging demands are fed back to the upper level. The bi-level problem is solved iteratively through a modified particle swarm algorithm with enhanced convergence properties. Case studies demonstrate the effectiveness of the proposed coordination method in effectively mitigating the global carbon emission of the coupled networks.

Extreme weather has induced damages to distribution grids globally. To estimate disaster influences, a fast risk assessment method of the distribution grid is proposed in this work, which is based on iterative inference on the probabilistic graphical model of the outage events. The correlations of the branch failures and load outages are modeled as a probabilistic graph, where each vertex binary states as energized and outage status of buses and edges are weighted by failure probability of branches between corresponding buses. Then, outage probability equations are formulated for all vertexes, which can be solved efficiently by the iterative method to enable accurate and efficient inferences on the graph. Finally, considering the cumulative failure probabilities of branches during extreme weather, the fast outage risk assessment is carried out to predict system losses and vulnerabilities. Moreover, the sensitivity of the branch failure probability regarding system outage risk is derived analytically, which helps to identify critical components for risk leveraging. Case studies are carried out on various distribution grids with different scales, which validate the efficacy of the proposed method.

Personalized immunotherapy targeting tumor-specific antigens (TSAs) could generate efficient and safe antitumor immune response without damaging normal tissues. Although neoantigen vaccines have shown therapeutic effect in clinic trials, precise prediction of neoantigens from tumor mutations is still challenging. The host antitumor immune response selects and activates T cells recognizing tumor antigens. Hence, T cells engineered with T-cell receptors (TCRs) from these naturally occurring tumor antigen-specific T (Tas) cells in a patient will target personal TSAs in his/her tumor. To establish such a personalized TCR-T cell therapy, we comprehensively characterized T cells in tumor and its adjacent tissues by single-cell mRNA sequencing (scRNA-seq), TCR sequencing (TCR-seq) and in vitro neoantigen stimulation. Compared to bystander T cells circulating among tissues, Tas cells were characterized by tumor enrichment, tumor-specific clonal expansion and neoantigen specificity. We found that CXCL13 is a unique marker for both CD4+and CD8+Tas cells. Importantly, TCR-T cells expressing TCRs from Tas cells showed significant therapeutic effects on autologous patient-derived xenograft (PDX) tumors. Intratumoral Tas cell levels measured by CXCL13 expression precisely predicted the response to immune checkpoint blockade, indicating a critical role of Tas cells in the antitumor immunity. We further identified CD200 and ENTPD1 as surface markers for CD4+and CD8+Tas cells respectively, which enabled the isolation of Tas cells from tumor by Fluorescence Activating Cell Sorter (FACS) sorting. Overall, our results suggest that TCR-T cells engineered with Tas TCRs are a promising agent for personalized immunotherapy, and intratumoral Tas cell levels determine the response to immunotherapy.

It is vital to search for highly efficient bifunctional oxygen evolution/reduction reaction (OER/ORR) electrocatalysts for sustainable and renewable clean energy. Herein, we propose a single transition-metal (TM)-based defective AlP system to validate bifunctional oxygen electrocatalysis by using the density functional theory (DFT) method. We found that the catalytic activity is enhanced by substituting two P atoms with two N atoms in the Al vacancy of the TM-anchored AlP monolayer. Specifically, the overpotential of OER(ORR) in Co- and Ni-based defective AlP systems is found to be 0.38 (0.25 V) and 0.23 V (0.39 V), respectively, showing excellent bifunctional catalytic performance. The results are further presented by establishing the volcano plots and contour maps according to the scaling relation of the Gibbs free-energy change of *OH, *O, and *OOH intermediates. The d-band center and the product of the number of d-orbital electrons and electronegativity of the TM atom are the ideal descriptors for this system. To investigate the activity origin of the OER/ORR process, we performed the machine learning (ML) algorithm. The result indicates that the number of TM-d electrons (Ne), the radius of TM atoms (rd), and the charge transfer of TM atoms (Qe) are the three primary descriptors characterizing the adsorption behavior. Our results can provide a theoretical guidance for designing highly efficient bifunctional electrocatalysts and pave a way for the DFT–ML hybrid method in catalysis research.

Supplemental Digital Content is Available in the Text.We report a case of pendular seesaw nystagmus caused by bitemporal hemianopia; the nystagmus disappeared while in darkness as previously described, but it also disappeared with monocular occlusion, which indicates the pivotal role of binocular vision in the pathogenesis.

Seed vigor plays an essential role in soybean production. Soybean seed is sensitive to environment and easy to get seed deterioration. Generally soybean seed vigor can be maintained for less than one year and have to be multiplied every year. Varieties with good seed vigor are essential for maintaining planting population and stable yield. In this research, 419 germplasms from three eco-regions, South China, Huanghuai region and Northeast China, were evaluated for seed vigor by assessing germination ratio, germination potential and germination index. About 34.8% of tested germplasm had germination ratio equal or more than 85%, suggested by the national soybean seed quality standard of China. Only 9 from 82 tested cultivars met the seed standard. Seed germination ratio distribution had obvious regional feature. Landraces performed better seed vigor than cultivars. Germplasms from South China had stronger seed vigor compared to those from Huanghuai and Northeast regions. Seed vigor has no significant relationship with maturity and 100-seed weight. Totally 21 germplasms with strong seed vigor, favor maturation and seed size were identified and can be used in future breeding program.

In this article, we propose an end-to-end post-filter method with deep attention fusion features for monaural speaker-independent speech separation. At first, a time-frequency domain speech separation method is applied as the pre-separation stage. The aim of pre-separation stage is to separate the mixture preliminarily. Although this stage can separate the mixture, it still contains the residual interference. In order to enhance the pre-separated speech and improve the separation performance further, the end-to-end post-filter (E2EPF) with deep attention fusion features is proposed. The E2EPF can make full use of the prior knowledge of the pre-separated speech, which contributes to speech separation. It is a fully convolutional speech separation network and uses the waveform as the input features. Firstly, the 1-D convolutional layer is utilized to extract the deep representation features for the mixture and pre-separated signals in the time domain. Secondly, to pay more attention to the outputs of the pre-separation stage, an attention module is applied to acquire deep attention fusion features, which are extracted by computing the similarity between the mixture and the pre-separated speech. These deep attention fusion features are conducive to reduce the interference and enhance the pre-separated speech. Finally, these features are sent to the post-filter to estimate each target signals. Experimental results on the WSJ0-2mix dataset show that the proposed method outperforms the state-of-the-art speech separation method. Compared with the pre-separation method, our proposed method can acquire 64.1%, 60.2%, 25.6% and 7.5% relative improvements in scale-invariant source-to-noise ratio (SI-SNR), the signal-to-distortion ratio (SDR), the perceptual evaluation of speech quality (PESQ) and the short-time objective intelligibility (STOI) measures, respectively.

Monocrystalline silicon-based microstructure functional surfaces are widely used in the field of photoelectricity. However, the traditional process is prone to damage due to the hardness and brittleness of monocrystalline silicon. In this study, the depth, width, and depth-width ratio of the micro-V-groove on the surface of monocrystalline silicon were studied using laser-assisted waterjet technology. Firstly, the nanosecond laser pulse width was optimized to minimize processing damage. Then, the response surface method (RSM) was employed to optimize the V-groove’s depth-width ratio and show the process parameters’ interactive effects. The results show that the heated affected zone (HAZ) and lattice disorder at 10 ns are significantly smaller than those at other pulse widths, and there is almost no amorphous phase on the surface of V-grooves. Single process parameter usually has different effects on the size of the V-groove, and the process parameters have significant interactive effects, which are discussed in detail in the study. According to the prediction model, the highest depth-width ratio of a V-groove is 1.39. Near-damage-free V-groove with a high depth-width ratio helps to lower the reflectivity and increase the hydrophobicity of monocrystalline silicon.

Myostatin (MSTN) is principally expressed in skeletal muscle and negatively regulates muscle growth and development. MSTN mutation can induce muscle overgrowth in cattle by activating cell proliferation, presenting a “double-muscle” phenotype. However, the specific regulatory mechanism is still unclear. Here, we found that Ca2+content in muscle tissue and muscle satellite cells of MSTN mutated (MSTN-/-) cattle were significantly increased compared to wild-type (WT). Furthermore, transcriptome analysis of muscle satellite cells revealed that TRPC4 was significantly increased in MSTN-/-cattle. And the expression of TRPC4 in muscle tissue of MSTN-/-cattle was detected by RT-qPCR and Western blot, which was significantly higher than that of WT. These results suggested that MSTN mutation promoted muscle satellite cells proliferation through activation of TRPC4 channel. To further verify, ML204, a specific inhibitor of TRPC4, was used to treat MSTN-/-muscle satellite cells. We found that cell proliferation was inhibited, Calcineurin expression was downregulated, and the entry of NFATc3 into nuclei was reduced, which was similar to WT group. Thus, MSTN mutation leads to the activation of TRPC4 channel, which increases intracellular Ca2+content, further activates Calcineurin/NFATc3 pathway, and ultimately promotes the proliferation of muscle satellite cells.

The co-combustion of sorghum straw and paper-making sludge (PMS) is beneficial to alleviate the ash-related problem in sorghum straw combustion process. In this paper, the mineral migration and transformation behavior in sorghum straw ashes with the addition of PMS ashes under an oxidizing atmosphere were investigated using an X-ray diffractometer, thermogravimetric-derivative thermogravimetric, scanning electron microscopy-energy dispersive X-ray detector, and FactSage software. The results demonstrated that the increase in the PMS ash mass ratio led to an increase in ash fusion temperature (AFT) of sorghum straw mixtures. The generations of high melting-point (MP) calcium feldspar (e.g., Ca2MgSi2O7, Ca2Al2SiO7, Ca3MgSi2O8, and Ca7Mg (SiO4)4) and phosphates (e.g., Ca3P2O8, Ca5P2SiO12, and Ca7P2Si2O16) caused the increases in the AFT. The maximum weight loss of sorghum straw ashes decreased with the increasing PMS ash mass ratio, and the surface of the ashes underwent the transition from smooth to a whole loose and rough, which alleviated the ash-related problems of sorghum straw. The addition of PMS ashes decreasing the liquid-phase content calculated by FactSage at the same temperature also explained the sorghum straw AFT increase. The changes of AFT and its corresponding mechanisms in the sorghum straw with PMS ash addition under an oxidizing atmosphere provided the support for large-scale combustion of biomass.

Defect formation energy as well as the charge transition level (CTL) plays a vital role in understanding the underlying mechanism of the effect of defects on material properties. However, the accurate calculation of charged defects, especially for two-dimensional materials, is still a challenging topic. In this paper, we proposed a simplified scheme to rescale the CTLs from the semilocal to the hybrid functional level, which is time-saving during the charged defect calculations. Based on this method, we systematically calculated the formation energy of four kinds of intrinsic point defects in two-dimensional hexagonal boron nitride (2D h-BN) by uniformly scaling the supercells by which we found a time-saving method to obtain the “special vacuum size” (Komsa, H.-P.; Berseneva, N.; Krasheninnikov, A. V.; Nieminen, R. M. Phys. Rev. X, 2014, 4, 031044). Native defects including nitrogen vacancy (VN), boron vacancy (VB), nitrogen atom anti-sited on boron position (NB), and boron atom anti-sited on nitrogen position (BN) were calculated. The reliability of our scheme was verified by taking VNas a probe to conduct the hybrid functional calculation, and the rescaled CTL is within the acceptable error range with the pure HSE results. Based on the results of CTLs, all the native point defects in the h-BN monolayer act as hole or electron trap centers under certain conditions and would suppress the p- or n-type electrical conduction of h-BN-based devices. Our rescale method is also suitable for other materials for defect charge transition level calculations.

Artificial bacterial flagella (ABF), also known as a magnetic helical microswimmer, has demonstrated enormous potential in various future biomedical applications (e.g., targeted drug delivery and minimally invasive surgery). Nevertheless, when used for in vivo/in vitrotreatment applications, it is essential to achieve the high motion efficiency of the microswimmers for rapid therapy. In this paper, inspired by microorganisms, the surface microstructure was introduced into ABFs to investigate its effect on the swimming behavior. It was confirmed that compared with smooth counterparts, the ABF with surface microstructure reveals a smaller forward velocity below the step-out frequency (i.e., the frequency corresponding to the maximum velocity) but a larger maximum forward velocity and higher step-out frequency. A hydrodynamic model of microstructured ABF is employed to reveal the underlying movement mechanism, demonstrating that the interfacial slippage and the interaction between the fluid and the microstructure are essential to the swimming behavior. Furthermore, the effect of surface wettability and solid fraction of microstructure on the swimming performance of ABFs was investigated experimentally and analytically, which further reveals the influence of surface microstructure on the movement mechanism. The results present an effective approach for designing fast microrobots for in vivo/in vitrobiomedical applications.

ABSTRACTNew TiC-TiB2ceramic cutting tool materials TiC-TiB2-Ni-Mo (TBNM8) and TiC-TiB2-Ni (TBN5) with high comprehensive mechanical properties were fabricated by hot pressed sintering with the optimised sintering processes. The cutting performance of TBNM8 in continuously turning austenitic stainless steel (1Cr18Ni9Ti) was experimentally investigated. With the optimal cutting parameters, the cutting performance of TBN5 and commercial tool LT55 were compared in wet and dry turning 1Cr18Ni9Ti. The failure mechanisms of the cutting tools were analysed combined with their high-temperature mechanical properties. The results showed that the tool life of TBN5 and TBNM8 was much longer in continuous dry turning 1Cr18Ni9Ti than that in wet turning, the possible reason was analysed as that the tool materials keeping high mechanical properties at elevated temperature, which led to the great improvement in machining efficiency and good characteristics of environmental friendliness because no cutting fluid was used during the cutting process.

Glucagon-like peptide-1 (GLP-1), an incretin hormone, has diuretic and natriuretic effects. The present study was designed to explore the possible underlying mechanisms for the diuretic and natriuretic effects of GLP-1 via renal nerves in rats. Immunohistochemistry revealed that GLP-1 receptors were avidly expressed in the pelvic wall, the wall being adjacent to afferent renal nerves immunoreactive to calcitonin gene-related peptide, which is the dominant neurotransmitter for renal afferents. GLP-1 (3 μM) infused into the left renal pelvis increased ipsilateral afferent renal nerve activity (110.0 ± 15.6% of basal value). Intravenous infusion of GLP-1 (1 µg·kg−1·min−1) for 30 min increased renal sympathetic nerve activity (RSNA). After the distal end of the renal nerve was cut to eliminate the afferent signal, the increase in efferent renal nerve activity during intravenous infusion of GLP-1 was diminished compared with the increase in total RSNA (17.0 ± 9.0% vs. 68.1 ± 20.0% of the basal value). Diuretic and natriuretic responses to intravenous infusion of GLP-1 were enhanced by total renal denervation (T-RDN) with acute surgical cutting of the renal nerves. Selective afferent renal nerve denervation (A-RDN) was performed by bilateral perivascular application of capsaicin on the renal nerves. Similar to T-RDN, A-RDN enhanced diuretic and natriuretic responses to GLP-1. Urine flow and Na+excretion responses to GLP-1 were not significantly different between T-RDN and A-RDN groups. These results indicate that the diuretic and natriuretic effects of GLP-1 are partly governed via activation of afferent renal nerves by GLP-1 acting on sensory nerve fibers within the pelvis of the kidney.

Less container load (LCL) has become an increasingly important element in containerised cargo export, due to the involvement of numerous small and medium size enterprises. Traditional cargo collection and consolidation processes are extremely complex and inefficient, which provides an excellent opportunity for improvement through integration. In this paper, we design a two-stage model comprising vehicle route optimisation for cargo collection and vehicle and unloading dock scheduling. In the first stage, namely, the route optimisation model, the Clarke-Wright saving algorithm is used, with the objective of minimising the total transport cost for a given shipment size, weight, and capacity constraint of cargo collection vehicles. In the second stage, the scheduling of both collection vehicles and unloading dock are modelled, using two sub-models for given constraints on the time window of the unloading docks and cargo collection routes. An application of this integrated model is illustrated based on the cargo collection problems in the hinterland of Shanghai port.

There is considerable interest in harnessing innate immunity to treat Alzheimer’s disease (AD). Here, we explore whether a decoy receptor strategy using the ectodomain of select TLRs has therapeutic potential in AD. AAV-mediated expression of human TLR5 ectodomain (sTLR5) alone or fused to human IgG4 Fc (sTLR5Fc) results in robust attenuation of amyloid β (Aβ) accumulation in a mouse model of Alzheimer-type Aβ pathology. sTLR5Fc binds to oligomeric and fibrillar Aβ with high affinity, forms complexes with Aβ, and blocks Aβ toxicity. Oligomeric and fibrillar Aβ modulates flagellin-mediated activation of human TLR5 but does not, by itself, activate TLR5 signaling. Genetic analysis shows that rare protein coding variants in human TLR5 may be associated with a reduced risk of AD. Further, transcriptome analysis shows altered TLR gene expression in human AD. Collectively, our data suggest that TLR5 decoy receptor–based biologics represent a novel and safe Aβ-selective class of biotherapy in AD.

Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle with an excessively activated immune response. Numerous interventions have been investigated for the treatment of myocarditis while success is limited. Interleukin-37 (IL-37), a novel member of the IL-1 cytokine family, is a natural inhibitor of innate immunity associated with autoimmune diseases. However, the modulatory effect of IL-37 in myocarditis is unknown. In this study, we investigated the immunological regulation of IL-37 in the coxsackievirus B3-induced model of murine viral myocarditis. The results show that IL-37 significantly ameliorates the signs of myocarditis with increased survival rate and bodyweight, improved histological changes, reduced activities of MB isoenzyme of creatine kinase and cardiac troponin I, and a suppressed response of Th17 cells and enhanced response of regulatory T cells (Tregs) in the spleen. Moreover, IL-37 down-regulates the expression of Th17-related cytokines IL-6 and IL-17A, while promoting Treg-related cytokine IL-10 levels in the heart. Therefore, IL-37 may exhibit anti-inflammatory activity in the murine model of myocarditis by regulating the balance between Th17 and Treg cells, thereby providing a possible novel therapeutic target in myocarditis.

Adoptive cell immunotherapy (ACT) is an innovative promising treatment for tumors. ACT is characterized by the infusion of active anti-tumor immune cells (specific and non-specific) into patients to kill tumor cells either directly or indirectly by stimulating the body's immune system. The patient's (autologous) or a donor's (allogeneic) immune cells are used to improve immune function. Chimeric antigen receptor (CAR) T cells (CAR-T) is a type of ACT that has gained attention. T cells from the peripheral blood are genetically engineered to express CARs that rapidly proliferate and specifically recognize target antigens to exert its anti-tumor effects. Clinical application of CAR-T therapy for hematological tumors has shown good results, but adverse reactions and recurrence limit its applicability. Tumor infiltrating lymphocyte (TIL) therapy is effective for solid tumors. TIL therapy exhibits T cell receptor (TCR) clonality, superior tumor homing ability, and low targeted toxicity, but its successful application is limited to a number of tumors. Regardless, TIL and CAR-T therapies are effective for treating cancer. Additionally, CAR-natural killer (NK), CAR-macrophages (M), and TCR-T therapies are currently being researched. In this review, we highlight the current developments and limitations of several types of ACT.

In recent decades, many additives with different characteristics have been applied to strengthen and toughen Al2O3-based ceramic cutting tool materials. Among them, SiC whiskers and SiC nanoparticles showed excellent performance in improving the material properties. While no attempts have been made to add SiC whiskers and SiC nanoparticles together into the ceramic matrix and the synergistically toughening effects of them have not been studied. An Al2O3-SiCw-SiCnpadvanced ceramic cutting tool material is fabricated by adding both one-dimensional SiC whiskers and zero-dimensional SiC nanoparticles into the Al2O3matrix with an effective dispersing and mixing process. The composites with 25 vol% SiC whiskers and 25 vol% SiC nanoparticles alone are also investegated for comparison purposes. Results show that the Al2O3-SiCw-SiCnpcomposite with both 20 vol% SiC whiskers and 5 vol% SiC nanoparticles additives have much improved mechanical properties. The flexural strength of Al2O3-SiCw-SiCnpis 730±95 MPa and fracture toughness is 5.6±0.6 MPa·m1/2. The toughening and strengthening mechanisms of SiC whiskers and nanoparticles are studied when they are added either individually or in combination. It is indicated that when SiC whiskers and nanoparticles are added together, the grains are further refined and homogenized, so that the microstructure and fracture mode ratio is modified. The SiC nanoparticles are found helpful to enhance the toughening effects of the SiC whiskers. The proposed research helps to enrich the types of ceramic cutting tool and is benefit to expand the application range of ceramic cutting tool.

Novel magnetically recyclable Pd/γ-AlOOH@Fe3O4catalysts were prepared using γ-AlOOH@Fe3O4as a magnetic supporter and nano-Pd particles as the active catalytic component. The structure of the catalysts was characterized by XRD (X-ray diffraction), TEM (transmission electron microscopy), N2adsorption-desorption, and a VSM (vibration sample magnetometer). The catalytic activity and recyclability for the Heck coupling reaction were investigated. Results showed that the magnetic γ-AlOOH@Fe3O4possessed a core-shell structure, as well as that the nano-Pd particles were 6–8 nm and had been well dispersed in the γ-AlOOH shell. In the Heck coupling reactions, the magnetic Pd/γ-AlOOH@Fe3O4catalysts exhibited good catalytic activity and recyclability. For the (0.021 mol%)Pd/γ-AlOOH@Fe3O4catalyst, the bromobenzene conversion and product yield reached about 100% and 96.3%, respectively, under a 120°C reaction temperature and 12 h reaction time. After being recycled 8 times, the conversion of bromobenzene and the recovery of the catalyst were about 90% and 93%, respectively. The nano-Pd particles were kept well dispersed in the used Pd/γ-AlOOH@Fe3O4catalyst.

Renal tubular dysfunction could be involved in the increased sodium and water reabsorption in chronic heart failure (CHF). The goal of the present study was to examine the molecular basis for the increased renal sodium and water retention in CHF. We hypothesized that dysregulation of renal epithelial sodium channels (ENaC) could be involved in the pathogenesis of CHF. The left coronary ligation-induced model of heart failure in the rat was used. Real-time PCR and Western blot analysis indicated that the mRNA and protein abundance of α-, β-, and γ-subunits of ENaC were significantly increased by in the cortex (mRNA: α-ENaC Δ104 ± 24%, β-ENaC Δ47 ± 16%, γ-ENaC Δ55 ± 18%; protein: α-ENaC Δ114 ± 28%, β-ENaC Δ150 ± 31%, γ-ENaC Δ39 ± 5% compared with sham rats) and outer medulla (mRNA: α-ENaC Δ52 ± 18%, β-ENaC Δ38 ± 8%, γ-ENaC Δ39 ± 13%; protein: α-ENaC Δ88 ± 16%, β-ENaC Δ94 ± 28%, γ-ENaC Δ45 ± 9% compared with sham rats) of CHF compared with sham-operated rats. Immunohistochemistry microscopy confirmed the increased labeling of α-, β-, and γ-ENaC subunits in the collecting duct segments in rats with CHF. Furthermore, there was a significant increase in diuretic (7-fold compared with sham) and natriuretic responses (3-fold compared with sham) to ENaC inhibitor benzamil in the rats with CHF. Absence of renal nerves produced a greater contribution of ENaC in sodium retention in rats with CHF. These results suggest that the increased expression of renal ENaC subunits may contribute to the renal sodium and water retention observed during CHF.

Abstract: This paper presents several novel approaches to control and synchronize a set of chaotic and hyperchaotic systems. It shows that the feedback gain coefficient of the proposed enhancing control approach is smaller compared with that of the general feedback control method, thus the complexity and cost is reduced. This paper also shows that the novel adaptive control and synchronization approaches is easy to achieve. The classical Lorenz chaotic system and hyperchaotic Chen system are used as the examples to illustrate the approaches. [Copyright &y& Elsevier]

Background:Cytomegalovirus (CMV) infection is a major and potentially life-threatening complication after allogenic hematopoietic stem cell transplantation (allo-SCT). Adoptive transfer of CMV-specific T cells (CTL) from original transplant donor or third-party donor has both emerged as an effective method for CMV infection after allo-SCT. The potential advantages of third party CTL versus transplant donor CTL includes that it is not limited by donor viral immune and can be banked in advance for clinical use. However, as the expansion and persistent of transfused third-party CTL in vivo was considered to be shorter when compared with donor CTL, can third-party CTL provide comparable long-term antiviral efficacy as transplant donor CTL? In fact, the safety and efficacy of these two kinds of CTL have not been compared directly. In addition, the mechanisms driving sustained antiviral immunity induced by these two kinds of CTL remains to be established and compared.

No relevant conflicts of interest to declare.

Backgroud:Refractory cytomegalovirus (CMV) infection remains important causes of morbidity and mortality after allogeneic hematopoietic stem cells transplantation (allo-HSCT). Previous researches reported that adaptive immunity, such as CD8+CMV-CTL, plays an important role in the in the control of refractory CMV infection. In mouse, Lanier et al. found there existed subsets of adaptive NK cells with the features of expanding, contracting after control of mouse CMV, and generating long-lived “memory” NK cells. In human, these adaptive NK cells were initially identified based on the high expression of the NKG2C which against HCMV through their cytotoxic potential and the production of TNF-α and IFN-γ upon Ab-mediated stimuli in vitro. Meanwhile, the expression levels of the NKG2C+adaptive NK cells has been positively correlated with the NKG2Ccopy number. Several researchers had found that NKG2C+adaptive NK cells persistent expanded and were potent producers of IFN-γ during CMV reactivation after solid-organ transplant or allo-HSCT. However, the role of NKG2C+adaptive NK cells on refractory CMV reactivation were still unknown. Whether the rapid reconstitution of NKG2C+adaptive NK cells can reduce the refractory CMV reactivation merit to be investigated.

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