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To simultaneously improve the mechanical strength and plasticity of the CoCu0.5FeNiTa0.1 high entropy alloy, we adopted the heat treatment and investigated the evolution of different phases containing γ′, δ and γ phases. Two different γ′ phases, the Cu-rich phase and the Ta-rich phase, were detected in the as-cast alloy. During heat treatment, Cu outwards diffused from γ′(Cu-rich) into γ matrix, γ′(Ta-rich) phase and δ phase. The accumulation of Cu and Ta into the δ phase strongly promoted its growth. One significant increase was measured in the compressive yield strength from 1040 MPa to 1370 MPa, ultimate compressive strength from 2020 MPa to 2735 MPa, compressive strain from 34% to 50.2% and hardness from 3.854 GPa to 4.315 GPa. The substantial enhancement in ductility mainly resulted from the distance increase among γ′ particles in γ matrix, the reduction of lattice distortion and the decrease in aspect ratio of δ phases. The yield strengthening mechanisms were mainly from solid strengthening and Orowan strengthening.

As one novel reinforcement used in magnesium composite, nano-layered flaky ternary MAX particle exhibits interesting anisotropic ceramic and metal properties. In order to accurately simulate the mechanical properties and damage behavior of MAX particle reinforced magnesium composite, we developed one finite element (FE) model based on 2D and 3D microstructural observations of 10 vol.% Ti2AlC-AZ91D composite. To improve the accuracy, matrix ductile damage, particle internal delamination deformation behaviors, and particle-matrix interfacial behaviors were respectively introduced into this model. The visual deformation processes of crack generation and propagation were carefully presented and discussed. The effects of interfacial strength and particle orientation on material properties were systematically investigated.

Abstract Aortic dissection (AD) is a life-threatening condition with a high mortality rate and without effective pharmacological therapies. Our previous study illustrated that leukocyte immunoglobulin-like receptor B4 (LILRB4) knockdown promoted the contractile phenotypic switch and apoptosis of AD cells. This study aimed to further investigate the role of LILRB4 in animal models of AD and elucidate its underlying molecular mechanisms. Animal models of AD were established using 0.1% beta-aminopropionitrile and angiotensin II and an in vitro model was developed using platelet-derived growth factor BB (PDGF-BB). The effects of LILRB4 knockdown on histopathological changes, pyroptosis, phenotype transition, extracellular matrix (ECM), and Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathways were assessed using a series of in vivo and in vitro assays. The effects of the JAK2 inhibitor AG490 on AD cell function, phenotypic transition, and ECM were explored. LILRB4 was highly expressed in AD and its knockdown increased survival rate, reduced AD incidence, and alleviated histopathological changes in the AD mouse model. Furthermore, LILRB4 knockdown promoted contractile phenotype switch, stabilized the ECM, and inhibited pyroptosis. Mechanistically, LILRB4 knockdown inhibited the JAK2/STAT3 signaling pathway. JAK2 inhibitor AG490 inhibited cell viability and migration, enhanced apoptosis, induced G0/G1 cell cycle arrest, and suppressed S-phase progression in PDGF-BB-stimulated human aortic smooth muscle cells. LILRB4 knockdown suppresses AD development by inhibiting pyroptosis and the JAK2/STAT3 signaling pathway.

Many existing efforts have taken advantage of large-scale spatial-temporal data to partition cities via constructed human interaction networks. However, few studies focus on communities emerging between adjacent cities in big urban agglomerations, which we call “cross-city” communities. In this study, we introduce a novel framework to detect cross-city communities in urban agglomerations under different scales leveraging a large number of fine-grained mobile signaling data aiming to break the original administrative boundaries. Taking the Pearl River Delta (PRD) urban agglomeration in China as study area, we investigate the existence of potential communities at three scales, i.e. city-group level, city level and sub-city level. The partition results are expected to benefit transportation planning, urban zoning and administrative boundary re-delineation. The results from our study highlight the necessity of considering cross-city communities and their scale effects when examining urban spatial interactions.

To investigate the influences of Cr2AlC mass fraction and supersonic plasma spraying process on the microstructure and mechanical properties of Cr2AlC reinforced 410 stainless steel composite coatings, the coatings containing different mass fractions of Cr2AlC were prepared and investigated. The composite coating exhibited low porosity and high adhesion strength. The addition of Cr2AlC significantly enhanced the hardness of the composite coatings through particle strengthening. However, when the mass fraction of Cr2AlC was 20%, the aggregation of Cr2AlC resulted in a strong decrease in the coating preparation efficiency, as well as a decline in adhesion strength. In the supersonic plasma spraying process, the Ar flow rate mainly influenced the flight velocity of the particles, while the H2 flow rate and the current mainly affected the temperature of the plasma torch. Consequently, all of them influenced the melting degree of particles and the quality of the coating. The lowest porosity and the highest hardness and adhesion strength could be obtained when the Ar flow rate is 125 L/min, the H2 flow rate is 25 L/min, and the current is 385 A.

Abstract Functional traits reveal the adaptive strategies of species to their environment, and are relevant to the formation of communities, the function of ecosystems, and the mechanisms underlying biodiversity. However, trait databases have not been established for most biological taxa, especially for insects, which encompass a vast number of species. This study measured the morphological traits of 307 species of Heteroptera insects collected in 2019 from the “Xishuangbanna Priority Conservation Area” in Southwest China using sweep netting and light trapping methods. This study provides a dataset for 307 Heteroptera species, comprising 34 morphometric measurements and 17 morphological traits. The dataset contains information on species sex, abundance, and the average, maximum, and minimum values of traits. This dataset facilitates an enhanced understanding of the functional traits and ecological associations of Heteroptera insects and offers opportunities for exploring a more diverse range of research topics.

Abstract Acute type A aortic dissection is a severe cardiovascular disease characterized by rapid onset and high mortality. Traditionally, urgent open aortic repair is performed after admission to prevent aortic rupture and death. However, when combined with malperfusion syndrome, the low perfusion of the superior mesenteric artery can further lead to intestinal necrosis, significantly impacting the surgery’s prognosis and potentially resulting in adverse consequences, bringing. This presents great significant challenges in treatment. Based on recent domestic and international research literature, this paper reviews the mechanism, current treatment approaches, and selection of surgical methods for poor organ perfusion caused by acute type A aortic dissection. The literature review findings suggest that central aortic repair can be employed for the treatment of acute type A aortic dissection with inadequate perfusion of the superior mesenteric artery. The superior mesenteric artery can be windowed and (/or) stented, followed by delayed aortic repair. Priority should be given to revascularization of the superior mesenteric artery, followed by central aortic repair. During central aortic repair, direct blood perfusion should be performed on the distal true lumen of the superior mesenteric artery, leading to resulting in favorable therapeutic outcomes. The research results indicate that even after surgical aortic repair, intestinal ischemic necrosis may still occur. In such cases, prompt laparotomy and necessary necrotic bowel resection are crucial for saving the patient’s life.

Abstract Acute type A aortic dissection is a life-threatening cardiovascular disease characterized by rapid onset and high mortality. Emergency surgery is the preferred and reliable treatment option. However, postoperative complications significantly impact patient prognosis. Hypoxemia, a common complication, poses challenges in clinical treatment, negatively affecting patient outcomes and increasing the risk of mortality. Therefore, it is crucial to study and comprehend the risk factors and treatment strategies for hypoxemia following acute type A aortic dissection to facilitate early intervention.

Background: Surgery is the preferred treatment for acute Stanford type A aortic dissection (STAAD); however, due to the complexity of the procedure, cardiac ischaemia and cardiopulmonary bypass (CPB) time are longer than general heart surgery, leading to complications. In this present study, we used an integrated tetra-furcate graft for both modified aortic root and distal arch anastomoses (frozen elephant trunk technique, [FET]), and investigated postoperative outcomes associated with this technique in patients with STAAD. Methods: We included a total of 140 patients who underwent total arch replacement and FET between January 2019 and June 2022 in the present study, 41 patients who underwent the modified technique, and 99 who underwent the graft eversion technique. We subsequently analyzed the perioperative outcomes to compare the differences between the two techniques. Results: There were no statistically significant differences between the two groups in regards to the preoperative characteristics; however, the intraoperative CPB, cardiac ischaemia, and operation times of the modified technique group were significantly shorter than those of the eversion technique group (P = 0.02, P = 0.01, and P = 0.04, respectively), as were postoperative hypoxaemia, intensive care unit (ICU) stay, and ventilation times (P = 0.04, P = 0.03, and P = 0.04, respectively). Additionally, the degree of postoperative bilirubin elevation was milder in the modified technique group (P = 0.002 for direct bilirubin and P = 0.01 for indirect bilirubin). Conclusions: The modified anastomosis technique can significantly shorten CPB, cardiac ischemia, and operation times, and reduce the intraoperative FFP transfusion and postoperative hypoxemia times. This modified technique, therefore, is worth utilizing for patients with STAAD.

Optimizing the spatial distribution of urban functional zones (UFZs) effectively improves the thermal environment. This study utilized an enhanced regression tree model and relied on Ecosystem Spaceborne Thermal Radiometer Experiment data to analyze the relative contributions and marginal effects of 2-D/3-D urban morphological factors on the diurnal land surface temperature (LST) in Shenyang, China. The results showed that public and residential areas dominated Shenyang's UFZs. The temperature in industrial areas was the highest during the day, and residential and commercial functional areas are high-temperature concentration areas. Furthermore, the effects of the urban spatial morphology on the LST differed between diverse time points and UFZs. The digital elevation model and the normalized difference vegetation index contributed significantly to daytime and nighttime LSTs. Construction indicators, such as the normalized difference built-up index and the proportion of construction land, significantly impacted commercial services. Residential daytime LST had a large contribution value, and the sum of its contribution rates reached approximately 30%. Population greatly contributed to the nighttime LST of the industrial and residential zones, accounting for 16.77% and 22.06%, respectively. Vegetation contributed to the cooling effect on daytime LST in summer, especially in industrial areas, contributing 29.79%. In addition, 3-D indicators, such as building height and building density, contributed to diurnal LST. Finally, when the proportion of construction land reached approximately 45%, it negatively affected LST. In this study, the main factors affecting day and night LSTs were identified, and this work acts as a relevant strategic reference for alleviating the urban heat island effect.

The ICESat-2 photon-counting lidar can simultaneously observe high-resolution radiometric and geometric characteristics of ocean waves. In this study, combining the wave radiometric and geometric characteristics, ICESat-2 can provide robust and accurate wind speeds over oceans that cannot be achieved by using a single characteristic. Specifically, with an along-track segment of 700 m, the sea surface photons and surface profile are detected and generated from ICESat-2 ATL03 geolocated photons by which the received energy and wave height are obtained. The unknown atmospheric transmittance and swell wave height have significant impacts on deriving the water surface reflectance (radiometric characteristic) and the wind-driven water height (geometric characteristic), respectively. We use all available ICESat-2 data in 2018 and 2019 to determine the unknown parameters and further separately estimate wind speeds. The radiation-based method performs better at low wind speeds, while the geometry-based method performs better at high wind speeds, and we combine each specific advantage to obtain more reliable wind speeds. In the Pacific Ocean, Atlantic Ocean, and Indian Ocean, thousands of ICESat-2 ground tracks from 2020 are used to estimate wind speeds, and the performance is validated against a trustworthy data source of ERA5 with a root-mean-square error (RMSE) of ∼0.3 m for wave heights and an RMSE of ∼1.5 m/s for wind speeds. ICESat-2 has shown great ability to provide independent wind speeds over oceans with high accuracy and resolution, which may fill the gap of wind speeds on a small scale as the large-scale results are well observed by spaceborne microwave devices.

Achieving the sustainable development goals puts new demands on land use/land cover (LULC) forecasting and thermal environment improvement. Local climate zone (LCZ) characterization reduces LULC uncertainty in climate research. This study designed a future multiscenario LCZ thermal environment assessment framework that integrates remote sensing images, a patch-level land use simulation model, and a contribution algorithm. An urban heat island (UHI) classification was used to represent the degree of heat hazard. We sought to quantitatively evaluate the spatiotemporal distribution of LCZ and its heat hazard and explore the coordination mode of LULC patterns and the thermal environment. We considered four future scenarios: a natural development scenario (NDS), urban development scenario (UDS), food security scenario, and ecological protection scenario. The results show that the Shenyang metropolitan area has experienced large-scale land urbanization, forming the main UHI areas with Shenyang–Fushun, Liaoyang–Anshan, and Fuxin as the core. This is expected to become the first area for heat hazard management in the future. The areas that produce heat hazards are mainly distributed as LCZ D and building-LCZs. By 2060, the average heat hazard in the UDS is expected to increase by 1.035 °C and that in the NDS by 0.286 °C compared to that in 2020. From the perspective of the “historical future,” the study results provide a theoretical reference for the continuous improvement of environmental quality in the new era, promoting the coordinated development of metropolitan areas and actively responding to climate change.

The escalation of greenhouse gas emissions has led to a continuous rise in land surface temperature (LST). Studies have highlighted the substantial influence of urban morphology on LST; however, the impact of different dimensional indicators and their gradient effects remain unexplored. Selecting the urban area of Shenyang as a case, we chose various indicators representing different dimensions. By employing XGBoost for regression analysis, we aimed to explore the effects of urban 2-D and 3-D morphology on seasonal LST and its gradient effect. The following results were obtained: 1) the spatial pattern of LST in spring and winter in Shenyang was higher in the suburbs than in the center; 2) the correlation patterns of the indicators in spring and winter were similar, except for the proportion of woodland and grass, digital elevation model, and sky view factor, which exhibited opposing trends in summer and autumn; 3) vegetation and construction had the highest influence on LST in the 2-D index, followed by building forms and natural landscapes in the 3-D urban morphology; and 4) the influence of each indicator varied significantly across different gradients. Among all the indicators, the landscape index, social development, building forms, and skyscape had the highest impacts on urban areas. Vegetation and built-up areas had a greater influence on suburban areas. The findings of this study can assist in adjusting urban morphology and provide valuable recommendations for targeted improvements in thermal environments, thereby contributing to urban sustainable development.

Background Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions.Methods We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients. In this study, the GD2-CAR-T therapy was evaluated for the first time in metastatic melanoma patients in combination with BRAF/MEK inhibitor therapy, and as a monotherapy in patients with colorectal cancer and a patient with fibromyxoid sarcoma. Feasibility and safety were determined and persistence studies, multiplex cytokine arrays on sera and detailed immune phenotyping of the original CAR-T products, the circulating CAR-T cells, and, in select patients, the tumor-infiltrating CAR-T cells were performed.Results We demonstrate the feasibility of manufacturing CAR-T products at point of care for patients with solid cancer and show that a single intravenous infusion was well tolerated with no dose-limiting toxicities or severe adverse events. In addition, we note significant improvements in CAR-T cell immune phenotype, and expansion when a modified manufacturing procedure was adopted for the latter 6 patients recruited to this 12-patient trial. We also show evidence of CAR-T cell-mediated immune activity and in some patients expanded subsets of circulating myeloid cells after CAR-T cell therapy.Conclusions This is the first report of third-generation GD2-targeting CAR-T cells in patients with metastatic melanoma and other solid cancers such as colorectal cancer, showing feasibility, safety and immune activity, but limited clinical effect.Trial registration number ACTRN12613000198729.

Summary: Global warming has led to a surge in heat health risks (HHRs), the impacts of which are particularly pronounced in metropolitan areas of developing countries. In the current study, six metropolitan areas - Beijing, China; Cairo, Egypt; Jakarta, Indonesia; Mumbai, India; Rio de Janeiro, Brazil; and Tehran, Iran - were selected as the study area to further differentiate the built-up landscapes by utilizing the concept of local climate zones. Moreover, we assessed the similarities and differences in HHR associated with the landscape. Results revealed a 30.67% higher HHR in compact built-up landscapes than in the open built-up type. Urban green spaces played an effective but differentiated role in mitigating HHR. That is, low vegetation in urbanized areas and trees in suburban areas significantly mitigated HHR. Collectively, our findings emphasize the role of effective planning and management in addressing HHR and provide empirical support for implementing HHR mitigation and adaptation strategies.

Abstract In the era of globalization and digitization of livestock markets, sheep are considered an essential source of food production worldwide. However, sheep behavior monitoring, disease prevention, and precise management pose urgent challenges in the development of smart ranches. To address these problems, individual identification of sheep has become an increasingly viable solution. Despite the benefits of traditional sheep individual identification methods, such as accurate tracking and record-keeping, they are labor-intensive and inefficient. Popular convolutional neural networks (CNNs) are unable to extract features for specific problems, further complicating the issue. To overcome these limitations, an Attention Residual Module (ARM) is proposed to aggregate the feature mapping between different layers of the CNN. This approach enables the general model of the CNN to be more adaptable to task-specific feature extraction. Additionally, a targeted sheep face recognition dataset containing 4490 images of 38 individual sheep has been constructed. Furthermore, the experimental data was expanded using image enhancement techniques such as rotation and panning. The results of the experiments indicate that the accuracy of the VGG16, GoogLeNet, and ResNet50 networks with the ARM improved by 10.2%, 6.65%, and 4.38%, respectively, compared to these recognition networks without the ARM. Therefore, the proposed method for specific sheep face recognition tasks has been proven effective.

Exploring highly active electrocatalysts as platinum (Pt) substitutes for the oxygen reduction reaction (ORR) remains a significant challenge. In this work, single Mn embedded nitrogen-doped graphene (MnN4) with and without halogen ligands (F, Cl, Br, and I) modifying were systematically investigated by density functional theory (DFT) calculations. The calculated results indicated that these ligands can transform the dyz and dxz orbitals of Mn atom in MnN4 near the Fermi-level into dz2 orbital, and shift the d-band center away from the Fermi-level to reduce the adsorption capacity for reaction intermediates, thus enhancing the ORR catalytic activity of MnN4. Notably, Br and I modified MnN4 respectively with the lowest overpotentials of 0.41 and 0.39 V, possess superior ORR catalytic activity. This work is helpful for comprehensively understanding the ligand modification mechanism of single-atom catalysts and develops highly active ORR electrocatalysts.

Sorghum northern anthracnose is a leaf disease affecting sorghum, which results in plant death and substantial yield loss. This study aimed to effectively understand the disease, clarify its biological characteristics, and evaluate the resistance of germplasm resources. A field sample was collected to isolate and purify the pathogen. The pathogen, identified as Kabatiella zeae Narita et Hiratsuka using both morphological and molecular techniques, was further confirmed as the causative agent of northern anthracnose of sorghum following Robert Koch’s principles. The results revealed the optimal culture temperature to be 25 °C, preferred dark culture conditions, and the best growth on potato glucose agar medium with sucrose and L-leucine as the optimal carbon and nitrogen sources, respectively. A total of 138 sorghum germplasm resources were inoculated and evaluated using the isolated pathogen, with 20 lines (14.49%) exhibiting high resistance, 18 lines (13.04%) showing disease resistance, 27 lines (19.57%) demonstrating medium resistance, 37 lines (26.81%) being susceptible, and 36 lines (26.09%) classified as highly susceptible. The indoor fungicide screening was conducted through pathogen medium application, and enilconazole, pyraclostrobin, methylthiophanate, and flusilazole were screened for the best fungicide inhibition with a 100% inhibition rate compared with the control. This study provides reference for field pharmaceutical control in sorghum production.

In order to enhance the ablation-resistant performance of stainless-steel conductive rails, Mo coating, 410 stainless steel coating and 15 wt% Cr2AlC particles reinforced 410 stainless steel composite coating were prepared and evaluated. Different from the weak interfacial strength caused by the dissimilar metals between Mo and steel rails, 410 stainless steel coating has better interfacial contact with steel rails. The introduction of Cr2AlC into 410 stainless steels further strengthened the mechanical properties of coating by alloy strengthening effect and particle strengthening effect, as the decomposition of Cr2AlC into nano CrC particles is accompanied with the diffusion of Al atoms into 410 stainless steels. It was found that the composite coating can still resist arc erosion at 150 A current, as a dense oxide film formed during the ablation process and the decomposition of Cr2AlC contributed to the heat absorption.

Abstract Objectives CAR‐T cells are being investigated as a novel immunotherapy for glioblastoma, but clinical success has been limited. We recently described fibroblast activation protein (FAP) as an ideal target antigen for glioblastoma immunotherapy, with expression on both tumor cells and tumor blood vessels. However, CAR‐T cells targeting FAP have never been investigated as a therapy for glioblastoma. Methods We generated a novel FAP targeting CAR with CD3ζ and CD28 signalling domains and tested the resulting CAR‐T cells for their lytic activity and cytokine secretion function in vitro (using real‐time impedance, flow cytometry, imaging and bead‐based cytokine assays), and in vivo (using a xenograft mimicking the natural heterogeneity of human glioblastoma). Results FAP‐CAR‐T cells exhibited target specificity against model cell lines and potent cytotoxicity against patient‐derived glioma neural stem cells, even when only a subpopulation expressed FAP, indicating a bystander killing mechanism. Using co‐culture assays, we confirmed FAP‐CAR‐T cells mediate bystander killing of antigen‐negative tumor cells, but only after activation by FAP‐positive target cells. This bystander killing was at least partially mediated by soluble factors and amplified by IL‐2 which activated the non‐transduced fraction of the CAR‐T product. Finally, a low dose of intravenously administered FAP‐CAR‐T cells controlled, without overt toxicity, the growth of subcutaneous tumors created using a mixture of antigen‐negative and antigen‐positive glioblastoma cells. Conclusions Our findings advance FAP as a leading candidate for clinical CAR‐T therapy of glioblastoma and highlight under‐recognised antigen nonspecific mechanisms that may contribute meaningfully to the antitumor activity of CAR‐T cells.

BackgroundAcute Stanford type A aortic dissection (STAAD) is a fatal condition requiring urgent surgical intervention. Owing to the complexity of the surgical process, various complications, such as neurological disorders, are common. In this study, we prioritized the reconstruction of aortic arch branches during surgery and investigated the association between prioritizing the branches and the postoperative outcomes of patients with STAAD.MethodsNinety-seven patients were included in the observational study and underwent total arch replacement and frozen elephant trunk technique between January 2018 and June 2021. Of these, 35 patients underwent the branch-priority technique, and 62 patients underwent the classic technique. By analyzing the perioperative outcomes, we compared the differences between the two techniques.ResultsThe branch priority group had significantly shorter cardiopulmonary bypass and ventilator times and earlier postoperative wake-up times than the classic group. Additionally, the ICU stay time was shorter, with a significant decrease in neurological complications and 24 h drainage in the branch priority group compared to the classic group.ConclusionThe branch priority technique can effectively provide better brain protection, resulting in earlier awakening of patients after surgery, reduced neurological complications, shorter ventilation time and decreased ICU hospitalization time. Therefore, it is recommended for use in aortic dissection surgeries.

The effects of electro-pulse on microstructure and mechanical properties of Al-Cu-Mn-Zr-V alloy were investigated, and the ageing mechanism was analyzed. As the current density increases, the size and quantity of precipitates gradually transit from continuous aggregation to dispersion at grain boundaries, and the mechanical properties are improved. When the current density is 15 A·mm−2, the precipitates are smallest and the mechanical properties are best. The tensile strength is 443.5 MPa and the elongation is 8.1%, which are 51.7% and 42.1% higher than those of conventional ageing treatment, respectively. Once the current density exceeds 15 A·mm−2, the precipitates will increase again and gather at grain boundaries, and the mechanical properties also decrease. An additional electrical free energy arising from an electro-pulse provides thermodynamic and kinetic conditions for the ageing precipitation of second phases. The electro-pulse can enhance the ageing diffusion coefficient, being improved by 34 times for 15 A·mm−2. The electro-pulse improves the nucleation rate and decreases the critical nucleation radii of second phases. However, it also accelerates the grain growth, making the second phases become coarse. An electro-pulse with a current density of 15 A·mm−2 can rapidly nucleate the second phase at 463 K while the precipitates are relatively small after growth.

Abstract Administration of neutralizing antibodies (nAbs) has proved to be effective by providing immediate protection against SARS‐CoV‐2. However, dual strategies combining virus neutralization and immune response stimulation to enhance specific cytotoxic T cell responses, such as dendritic cell (DC) cross‐priming, represent a promising field but have not yet been explored. Here, a broadly nAb, TNT, are first generated by grafting an anti‐RBD biparatopic tandem nanobody onto a trimerbody scaffold. Cryo‐EM data show that the TNT structure allows simultaneous binding to all six RBD epitopes, demonstrating a high‐avidity neutralizing interaction. Then, by C‐terminal fusion of an anti‐DNGR‐1 scFv to TNT, the bispecific trimerbody TNTDNGR‐1 is generated to target neutralized virions to type 1 conventional DCs (cDC1s) and promote T cell cross‐priming. Therapeutic administration of TNTDNGR‐1, but not TNT, protects K18‐hACE2 mice from a lethal SARS‐CoV‐2 infection, boosting virus‐specific humoral responses and CD8+ T cell responses. These results further strengthen the central role of interactions with immune cells in the virus‐neutralizing antibody activity and demonstrate the therapeutic potential of the Fc‐free strategy that can be used advantageously to provide both immediate and long‐term protection against SARS‐CoV‐2 and other viral infections.

3D reconstruction and 2D observation were conducted to characterize the microstructure of the castings produced through high pressure die casting with different parameters. Our results indicate that shrinkage pores generally co-existed with externally solidified crystals (ESCs). In specimen produced without fast slow shot speed, big net-shrinkage pores accompanied with ESCs were found in the center of the specimen. When the casting pressurization was introduced, the shrinkage pores gathered to the specimen center and became much less due to the optimization of melt feeding. Much more porosity was found near the gate rather than in the middle of the rod bar, especially gas pores. The filling process simulation reveals that the middle position of the bars was firstly filled and followed by the near gate position accompanied with one intense turbulent flow.

Abstract Pseudo-human settlements (PHS) reflect the subjective wishes and needs of residents. An in-depth characterization of PHS aids in clarifying the actual development needs and future development directions of the city from the residents’ perspective. China is currently undergoing high-speed urbanization and advocates improving the quality of cities. It is particularly important to test the achievements of urbanization through PHS. This study quantitatively analyses spatiotemporal characteristics and the realistic driving mechanism of PHS in 286 Chinese cities through spatial autocorrelation analysis and geographic detectors. The results indicate that (1) the PHS level exhibited notable hierarchical characteristics and spatial differences (high in the eastern coastal regions and low in the western inland regions), with weak positive autocorrelation characteristics; (2) nighttime light index, per capital GRP, and population size are major drivers of heterogeneity of development level and functional structure of PHS; and (3) the functional structure followed an emergence-development-maturity-decline-extinction life cycle. Overall, the development of PHS must play a leading role in high-level areas, and urban decision-makers should clarify and adapt to local preferences of PHS and predict future changes. The findings of this study can help China and other countries promote realistic development by unveiling the characteristics of PHS.

Global climate change is causing various negative impacts on urban ecosystems and energy systems. To effectively mitigate and adapt to these changes, it is important to understand the contributions of background climate and local effects to urban thermal environment variation. This study utilized the empirical orthogonal function (EOF) approach to deconstruct long-term MODIS land surface temperature (LST) datasets to obtain the main features of change in daytime and nighttime thermal environments. Local bivariate spatial autocorrelation analysis was used to explore the underlying causes of these changes. The main EOF modes explained 73.14% and 81.33% of daytime and nighttime thermal environment variation, respectively. The correlation coefficient between the time coefficient of the main modes and the average LST was > 0.99, reflecting the role of global effect caused by background climate change. The secondary EOF modes explained 12.51% and 4.12% of daytime and nighttime thermal environment variation, respectively, and were spatially correlated with changes in landscape thermal intensity, reflecting local effect caused by landscape change and anthropogenic heat emissions. In expansion and renewal areas, industrial zones and compact high-rise buildings had the most obvious warming effect on the daytime thermal environment, while mid-to-high-rise buildings had the most obvious warming effect on the nighttime thermal environment. The results of this study provide valuable insights into the mechanisms of background climate and local effects on the urban thermal environment, and provide a reference for formulating effective strategies for mitigating and adapting to change in urban areas, and for promoting sustainable development.

BackgroundAortic dissection (AD) is a severe cardiovascular disease characterized by aortic rupture, aortic valve insufficiency, aortic branch lumen stenosis, and occlusion. Acute ST-segment elevation myocardial infarction may be the primary manifestation when aortic dissection affects the coronary artery, leading to delayed or missed diagnosis of aortic dissection, and preventing patients from receiving timely and comprehensive treatment. Simultaneous aortic repair and coronary artery bypass grafting surgery are controversial because of their high mortality rates. Personalized and optimal treatment plans for patients should be taken seriously based on their different conditions and treatment options.Case presentationA 42-year-old man who experienced 1 h of persistent precordialgia was admitted to a local second-level hospital for emergency treatment. Electrocardiogram (ECG) showed evidence of ST-segment elevation, and myocardial enzyme levels were CK-MB 18.35 ng/ml and troponin 0.42 ng/ml. The patient was treated for acute myocardial infarction (AMI) and urgently sent to the interventional catheter room. Coronary angiography showed stenosis of the starting part of the right coronary artery trunk. Thus, stent implantation was performed, and the stenosis section recovered patency; however, postoperative precordialgia was not alleviated. Computed tomography angiography (CTA) revealed a type A AD. The patient was immediately transferred to a higher-level hospital, underwent emergency surgery with cardiopulmonary bypass (CPB) ascending aorta replacement, SUN's procedure (total arch replacement and stented elephant trunk implantation), and simultaneous implantation of extracorporeal membrane oxygenation (ECMO), and regained consciousness within intensive care unit care. ECMO was discontinued when hemodynamics stabilized. The patient ultimately recovered well and was discharged.ConclusionThis case demonstrated that precordialgia is not limited to myocardial infarction but may also be accompanied by aortic dissection. Percutaneous coronary intervention (PCI) can timely and effectively restore coronary artery perfusion, strive for the opportunity of aortic repair surgery, and can overcome pump failure caused by myocardial infarction, cardiopulmonary bypass, heart block time, and myocardial ischemia-reperfusion injury. Personalized treatment is crucial for patients with complex type A aortic dissection.

Abstract Interrupted sampling repeater jamming (ISRJ) is a novel intra‐pulse coherent jamming based on digital radio frequency memory (DRFM). By repeatedly sampling and retransmitting the radar transmitting signal fragments, a series of false targets can be formed after pulse compression (PC), posing a severe threat to modern radar systems. Inspired by the energy function method and histogram analysis in image processing, an adaptive time‐frequency (TF) filtering method is proposed in this letter. The ISRJ‐contaminated regions can be accurately determined in the TF image after histogram analysis and subsequent energy accumulation. Guided by the energy function, the proposed method can automatically adjust the intensity threshold in TF image histogram analysis and therefore reveals better robustness compared with other competing methods. Simulations have verified the effectiveness and robustness of the proposed method against ISRJ under various circumstances.

Abstract Inspired by the framework of the rolling guidance filter (RGF), a novel improved RGF for synthetic aperture radar (SAR) images is proposed in this letter, named SAR‐IRGF. Based on the model of additive noise, the RGF has the complete control of detailed smoothing under a scale measure for optical images. However, the speckle is well known as a multiplicative noise, which invalidates the RGF for SAR images. In this letter, an appropriate edge guidance is utilized to optimize the RGF for SAR image denoising. Compared with the original version, better convergence is achieved. Experimental results on natural Ku‐band airborne SAR images show that the proposed SAR‐IRGF reduces more speckle while sharpening the edges effectively. Simultaneously, the SAR‐IRGF demonstrates a significant nearly 5.5‐fold improvement than RGF in the equivalent number of looks (ENL).

The human ether-a-go-go-related gene (hERG) potassium channel is a well-known contributor to drug-induced cardiotoxicity and therefore is an extremely important target when performing safety assessments of drug candidates. Ligand-based approaches in connection with quantitative structure active relationships (QSAR) analyses have been developed to predict hERG toxicity. The availability of the recent published cryogenic electron microscopy (cryo-EM) structure for the hERG channel opened the prospect of using structure-based simulation and docking approaches for hERG drug liability predictions. In recent times, the idea of combining structure- and ligand-based approaches for modeling hERG drug liability has gained momentum offering improvements in predictability when compared to ligand-based QSAR practices alone. The present article demonstrates uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade. This combination leads to improved model predictability based on Pearson’s R and percent correct (represents rank-ordering of ligands) metric for different validation sets of hERG blockers involving a diverse chemical scaffold and wide range of pIC50 values. The inclusion of the SILCS structure-based approach allows determination of the hERG region to which compounds bind and the contribution of different chemical moieties in the compounds to the blockade, thereby facilitating the rational ligand design to minimize hERG liability.

Radio frequency interference (RFI) poses major threats to synthetic aperture radar (SAR) systems. Due to the suppression of useful target signals via high-power RFI, the SAR imaging quality is severely degraded. Nevertheless, existing studies on RFI mitigation mainly focus on narrowband filtering, while wideband RFI mitigation methods are relatively lacking and perform non-robustly. In this paper, an RFI mitigation scheme is proposed based on instantaneous spectrum forward consecutive mean excision (FCME), which is suitable for both narrowband and wideband RFI mitigation. The SAR echo signal is first transformed into a time–frequency (TF) domain through a short-time Fourier transform (STFT). On this basis, the instantaneous spectra polluted via RFI are detected via a kurtosis-based statistical test and then filtered via FCME to achieve RFI mitigation. Finally, connected component analysis is applied as a safety measure so as to avoid the unnecessary loss of useful target signal. The combination of FCME and connected component analysis enables the proposed method to thoroughly filter out RFI while retaining more useful target signals compared with other competing methods. The experimental results on real SAR raw data validate the effectiveness of the proposed method.

Large-scale sheep farming has conventionally relied on barcodes and ear tags, devices that can be difficult to implement and maintain, for sheep identification and tracking. Biological data have also been used for tracking in recent years but have not been widely adopted due to the difficulty and high costs of data collection. To address these issues, a noncontact facial recognition technique is proposed in this study, in which training data were acquired in natural conditions using a series of video cameras, as Dupo sheep walked freely through a gate. A key frame extraction algorithm was then applied to automatically generate sheep face data sets representing various poses. An improved MobilenetV2 framework, termed Order-MobilenetV2 (O-MobilenetV2), was developed from an existing advanced convolutional neural network and used to improve the performance of feature extraction. In addition, O-MobilenetV2 includes a unique conv3x3 deep convolution module, which facilitated higher accuracy while reducing the number of required calculations by approximately two-thirds. A series of validation tests were performed in which the algorithm identified individual sheep using facial features, with the proposed model achieving the highest accuracy (95.88%) among comparable algorithms. In addition to high accuracy and low processing times, this approach does not require significant data pre-processing, which is common among other models and prohibitive for large sheep populations. This combination of simple operation, low equipment costs, and high robustness to variable sheep postures and environmental conditions makes our proposed technique a viable new strategy for sheep facial recognition and tracking.

The success of CAR-T cells for treating acute myeloid leukaemia (AML) is hampered by toxicity to normal cells and low CAR-T cell persistence. Here, the authors show that the demethylating compound 5′-Azacitdine increases anti-CD123 CAR-T cell cytotoxicity against AML.

Understanding the thermal characteristics and contribution ranking of local climate zones (LCZs) is essential since they can help in maintaining environmental harmony. However, previous studies only considered independent effects and could not analyze the combined effects of LCZ on land surface temperature (LST). In this study, we propose a new method to establish an interaction model between LCZs. Five first-level grids with different scales from 270 to 990 m were established to calculate the area proportion of LCZ. The area proportion of LCZ was then applied in the stepwise regression model to quantitatively analyze its magnitude and direction of impact on the LST. The results suggest that the LCZ types of the study area with the highest and lowest average LST were LCZ2 (compact middle-rise building, 39.82°C) and LCZG (water body, 34.24°C), respectively. However, on most scales, the warming effect of LCZ2 was lower than that of LCZE (bare rock or paver), and the cooling effect of LCZG was lower than that of LCZD (low plants). The optimum results were obtained at a scale of 810 m. At this scale, the warming effect was in the order: LCZE (0.314) > LCZ2 (0.236) > LCZ3 (compact low-rise building, 0.135) > LCZ5 (open middle-rise, 0.084) > LCZ6 (open low-rise, 0.056); the cooling effect was in the order: LCZD (−0.272) > LCZA (dense trees, −0.104) > LCZG (−0.103). These findings can help to elucidate the unique warming and cooling effects of LCZ on the interaction condition and the construction of an urban human settlement.

(1) Background: Solanum nigrum L. is a plant of the genus Solanum in the family Solanaceae and is commonly used to treat tumors. Solasonin (SS) is a steroidal alkaloid extracted from Solanum nigrum L. that has anti-colorectal cancer (CRC) activity. (2) Methods: Column chromatography, semi-preparative HPLC and cellular activity screening were used to isolate potential anti-CRC active compounds in Solanum nigrum L., and structure identification using 1H-NMR and 13C-NMR techniques. Expression levels of HDAC in CRC were mined in the UALCAN database. The in vitro effects of SS on SW620 cell line and its mechanism were examined via Western blot, EdU staining, flow cytometry and immunofluorescence. CRC xenograft model and IHC staining were mainly used to evaluate the role of SS in vivo. (3) Results: The results showed that SS was the most potent anti-CRC component in Solanum nigrum L., which induced apoptosis and cell cycle arrest in the SW620 cell line. HDAC was highly expressed in CRC. The treatment of SW620 cell line with SS resulted in a significant downregulation of HDAC, an increase in the level of P53 acetylation and a subsequent increase in the level of P21. The in vivo validation results showed that SS could effectively inhibit CRC growth, which was associated with the downregulation of HDAC. (4) Conclusions: SS treatment for CRC mainly works through the induction of apoptosis and cycle arrest, and its mechanism of action is mainly related to HDAC-induced P53 acetylation, and the HDAC/P53 signaling pathway may be a potential pathway for the treatment of CRC.

Deep learning has achieved significant success in various synthetic aperture radar (SAR) imagery interpretation tasks. However, automatic aircraft detection is still challenging due to the high labeling cost and limited data quantity. To address this issue, we propose a multi-stage domain adaptation training framework to efficiently transfer the knowledge from optical imagery and boost SAR aircraft detection performance. To overcome the significant domain discrepancy between optical and SAR images, the training process can be divided into three stages: image translation, domain adaptive pretraining, and domain adaptive finetuning. First, CycleGAN is used to translate optical images into SAR-style images and reduce global-level image divergence. Next, we propose multilayer feature alignment to further reduce the local-level feature distribution distance. By applying domain adversarial learning in both the pretrain and finetune stages, the detector can learn to extract domain-invariant features that are beneficial to the learning of generic aircraft characteristics. To evaluate the proposed method, extensive experiments were conducted on a self-built SAR aircraft detection dataset. The results indicate that by using the proposed training framework, the average precision of Faster RCNN gained an increase of 2.4, and that of YOLOv3 was improved by 2.6, which outperformed other domain adaptation methods. By reducing the domain discrepancy between optical and SAR in three progressive stages, the proposed method can effectively mitigate the domain shift, thereby enhancing the efficiency of knowledge transfer. It greatly improves the detection performance of aircraft and offers an effective approach to address the limited training data problem of SAR aircraft detection.

A multi-exposure imaging approach proposed in earlier studies is used to increase star sensors’ attitude update rate by N times. Unfortunately, serious noises are also introduced in the star image due to multiple exposures. Therefore, a star centroid extraction method based on Kalman Filter is proposed in this paper. Firstly, star point prediction windows are generated based on centroids’ kinematic model. Secondly, the classic centroid method is used to calculate the coarse centroids of the star points within the prediction windows. Lastly, the coarse centroids are, respectively, processed by each Kalman Filter to filter image noises, and thus fine centroids are obtained. Simulations are conducted to verify the Kalman-Filter-based estimation model. Under noises with zero mean and ±0.4, ±1.0, and ±2.5 pixel maximum deviations, the coordinate errors after filtering are reduced to about 37.5%, 26.3%, and 20.7% of the original ones, respectively. In addition, experiments are conducted to verify the star point prediction windows. Among 100 star images, the average proportion of the number of effective star point objects obtained by the star point prediction windows in the total object number of each star image is calculated as only 0.95%. Both the simulated and experimental results demonstrate the feasibility and effectiveness of the proposed method.

The mutton sheep breeding industry has transformed significantly in recent years, from traditional grassland free-range farming to a more intelligent approach. As a result, automated sheep face recognition systems have become vital to modern breeding practices and have gradually replaced ear tagging and other manual tracking techniques. Although sheep face datasets have been introduced in previous studies, they have often involved pose or background restrictions (e.g., fixing of the subject’s head, cleaning of the face), which restrict data collection and have limited the size of available sample sets. As a result, a comprehensive benchmark designed exclusively for the evaluation of individual sheep recognition algorithms is lacking. To address this issue, this study developed a large-scale benchmark dataset, Sheepface-107, comprising 5350 images acquired from 107 different subjects. Images were collected from each sheep at multiple angles, including front and back views, in a diverse collection that provides a more comprehensive representation of facial features. In addition to the dataset, an assessment protocol was developed by applying multiple evaluation metrics to the results produced by three different deep learning models: VGG16, GoogLeNet, and ResNet50, which achieved F1-scores of 83.79%, 89.11%, and 93.44%, respectively. A statistical analysis of each algorithm suggested that accuracy and the number of parameters were the most informative metrics for use in evaluating recognition performance.

Background Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers to therapy, and the potential for severe toxicity. Effective treatments for primary brain tumors are limited, and 5-year survival rates remain poor. Immune checkpoint inhibitor therapy has transformed treatment of some other cancers but has yet to significantly benefit patients with glioblastoma. Early phase trials of chimeric antigen receptor (CAR) T-cell therapy in patients with glioblastoma have demonstrated that this approach is safe and feasible, but with limited evidence of its effectiveness. The choices of appropriate target antigens for CAR-T-cell therapy also remain limited.Methods We profiled an extensive biobank of patients’ biopsy tissues and patient-derived early passage glioma neural stem cell lines for GD2 expression using immunomicroscopy and flow cytometry. We then employed an approved clinical manufacturing process to make CAR- T cells from patients with peripheral blood of glioblastoma and diffuse midline glioma and characterized their phenotype and function in vitro. Finally, we tested intravenously administered CAR-T cells in an aggressive intracranial xenograft model of glioblastoma and used multicolor flow cytometry, multicolor whole-tissue immunofluorescence and next-generation RNA sequencing to uncover markers associated with effective tumor control.Results Here we show that the tumor-associated antigen GD2 is highly and consistently expressed in primary glioblastoma tissue removed at surgery. Moreover, despite patients with glioblastoma having perturbations in their immune system, highly functional GD2-specific CAR-T cells can be produced from their peripheral T cells using an approved clinical manufacturing process. Finally, after intravenous administration, GD2-CAR-T cells effectively infiltrated the brain and controlled tumor growth in an aggressive orthotopic xenograft model of glioblastoma. Tumor control was further improved using CAR-T cells manufactured with a clinical retroviral vector encoding an interleukin-15 transgene alongside the GD2-specific CAR. These CAR-T cells achieved a striking 50% complete response rate by bioluminescence imaging in established intracranial tumors.Conclusions Targeting GD2 using a clinically deployed CAR-T-cell therapy has a sound scientific and clinical rationale as a treatment for glioblastoma and other aggressive primary brain tumors.

TMAO is a new risk biomarker for cardiovascular disease. With trimethylammonium as its main chemical skeleton, TMAO is structurally similar to many endogenous metabolites, such as acetylcholine, carnitine, phosphorylcholine, etc. The mechanism of TMAO on the pathological process of CVD is still unclear. In this study, the quantitative analysis of plasma TMAO is conducted, and the contribution of Cathepsin B and NLRP3 inflammasome during the process of TMAO-induced endothelial injury was proposed and investigated at animal and cellular levels. Immunofluorescence assay was applied to represent the protein expression of Cathepsin B and NLRP3 inflammasome located at endothelial cells. The results showed that TMAO could disrupt endothelial cells permeability to induce endothelial injury, meanwhile, TMAO could increase NLRP3 inflammasome activation and promote the activity and expression of Cathepsin B in vitro and in vivo, whereas inhibition of NLRP3 inflammasome activation by MCC950 could protect the endothelial cells from TMAO associated endothelial injury via Cathepsin B. The study reveals that TMAO can cause endothelial injury via Cathepsin B-dependent NLRP3 inflammasome, and inhibition of Cathepsin B and NLRP3 inflammasome can reduce the TMAO-induced damage. The results provide new insight into the role of TMAO in CVD, which can be a potential therapeutic target for disease treatment and drug design.

Resource-based urban agglomerations often encounter greater challenges in the sustainable development of human settlements. The aim of this study is to propose an approach to the coordinated development of competitiveness by analyzing the interaction of human settlements competitiveness (HSC) in resource-based urban agglomerations. Through the compound evaluation model of HSC and urban network analysis, this study finds: 1) the HSC measure increased from 35.12 in 1990 to 52.15 in 2015 and showed a downward trend from 2015 to 2019, with an average value of 47.82 in 2019; 2) The change trend of the relevance network density is the same as that of the HSC, while the difference network density reaches the lowest value of 0.441 when the HSC is the highest, indicating that the HSC of the urban agglomerations has improved to a certain extent but is more unsustainable, and 3) Communities in the relevance network are obviously bounded by the borders of provinces or urban agglomerations, while the communities in the difference network are differentiated into two types: high-competitiveness and low-competitiveness. Using the theory of “co-opetition” to analyze the sustainable development path of resource-based urban agglomerations, the study believes that a coordination mechanism and a guarantee mechanism for benefit distribution should be established between urban agglomerations to curb local protectionism, and promote regional dislocation development. The development gradient level also should be established within the urban agglomeration to narrow the gap between HSC of cities, and innovative development should be the core of promoting industrial transformation and upgrading.

To investigate the effect of Al8Mn4Gd phase on microstructural and mechanical properties of Mg–Al–Ca magnesium alloy, two Mg–2.5Al2Ca and Mg–2.5Al2Ca-0.1Al8Mn4Gd alloys were designed and compared in this work. The results show that a small amount of Gd can significantly refine α-Mg grains and change the morphology of Al2Ca particles. Indeed, the formed Al8Mn4Gd phase could serve as a heterogeneous nucleation site for the α-Mg grains and Al2Ca particles. Furthermore, the introduction of Gd not only optimized the mechanical properties of Mg–Al–Ca alloy, but also facilitated the thermal deformation (such as hot rolling).

Two kinds of high Cr white iron (HCWI) composites reinforced with directly added TiC (TiC/HCWI) and in situ formed TiCx (TiCx/HCWI) have been successfully synthesized by powder metallurgy method. The directly added TiC grains are irregular in shape with a mean size of about 2−4 μm, but the in situ formed TiCx grains from the decomposition of Ti3AlC2 are spherical and about 1–2 μm in size. The microstructure, mechanical properties and wear resistance of the two composites were compared. The in situ TiCx/HXCWI composite possesses finer microstructures and superior mechanical and wear resistant properties than TiC/HCWI composite. The phase composition and microstructure were characterized with X-ray diffraction analysis, scanning electron microscopy and transmission electron microscopy.