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Abstract Objective Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear. Methods Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC). Results HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A. Conclusion Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.

Abstract We use observations from the Southern Ocean (SO) biogeochemical profiling float array to quantify the meridional pattern of particle export efficiency (PEeff) during the austral productive season. Float estimates reveal a pronounced latitudinal gradient of PEeff, which is quantitatively supported by a compilation of existing ship‐based measurements. Relying on complementary float‐based estimates of distinct carbon pools produced through biological activity, we find that PEeff peaks near the region of maximum particulate inorganic carbon sinking flux in the polar antarctic zone, where net primary production (NPP) is the lowest. Regions characterized by intermediate NPP and low PEeff, primarily in the subtropical and seasonal ice zones, are generally associated with a higher fraction of dissolved organic carbon production. Our study reveals the critical role of distinct biogenic carbon pool production in driving the latitudinal pattern of PEeff in the SO.

Developing novel catalysts with high activity and high stability for the methanol oxidation reaction (MOR) is of great importance for the ever-broader applications of methanol fuel cells. Herein, we present a facile technique for synthesizing Au10Pt1@MnO2 catalysts using a wet chemical method and investigate their catalytic performance for the MOR. Notably, the Au10Pt1@MnO2-M composite demonstrated a significantly high peak mass activity of 15.52 A mg(Pt)−1, which is 35.3, 57.5, and 21.9 times greater than those of the Pt/C (0.44 A mg(Pt)−1), Pd/C (0.27 A mg(Pt)−1), and Au10Pt1 (0.71 A mg(Pt)−1) catalysts, respectively. Comparative analysis with commercial Pt/C and Pd/C catalysts, as well as Au10Pt1 HSNRs, revealed that the Au10Pt1@MnO2-M composite exhibited the lowest initial potential, the highest peak current density, and superior CO anti-poisoning capability. The results demonstrate that the introduction of MnO2 nanosheets, with excellent oxidation capability, not only significantly increases the reactive sites, but also promotes the reaction kinetics of the catalyst. Furthermore, the high surface area of the MnO2 nanosheets facilitates charge transfer and induces modifications in the electronic structure of the composite. This research provides a straightforward and effective strategy for the design of efficient electrocatalytic nanostructures for MOR applications.

Abstract The interfacial phenomenon between liqiuid iron and coke is important for determining the melting efficiency in the blast furnace iron-making process. In this study, the interaction observed in the case of the iron-carbon (Fe–C) melt on coke substrate was investigated using a high-temperature vacuum wettability test equipment. The Fe–C melt did not wet and spread on the coke substrate with different graphitization degrees (r 0) at a high temperature of 1450 °C. The contact angles changed from 124.5° to 105.3°, and the r 0 increased from 9.30 to 50.00%, thus indicating a nonwetting state. The deepening of graphitization decreased the contact angle. Thereby, increasing the contact area between liquid iron and the carbonaceous material, which facilitated carbon dissolution. The irregular movements of Fe–C melt were observed in situ during the wetting process. The horizontal force of the droplet caused by interfacial tension and the contact angle; the Marangoni convection owing to the gradient of carbon concentration; and the impulse force caused by the generation, aggregation, and release of SiO bubbles at the interface were attributed to the driving force.

Hydrothermal geothermal energy, as a widely distributed, large reserve and easily exploitable renewable source, can be used for both power generation and building heating. In this study, a numerical simulation of heat extraction performance is conducted based on monitoring well temperature data in a geothermal field in Xiong’an New Area. The effects of the reinjection temperature, injection flow rate, and reinjection rate on the outlet temperature and the reservoir temperature during a long-term operation are analyzed. The results indicate that the lower reinjection temperature can generate a critical disturbance scope for the thermal reservoir during the exploitation process. The impact scope on the thermal reservoir can reach 210.3 m at a reinjection temperature of 25 °C, which is not conducive to maintaining the outlet temperature of production wells in the long-term. The reinjection rate significantly affects both the horizontal and vertical temperature fields of the thermal reservoir. Under reinjection conditions of 30 °C and 40 kg/s, the horizontal and vertical impact scope of the thermal reservoir are 262.3 and 588.5 m, respectively. The reinjection rate is inversely related to the outlet temperature. A decrease from 100% to 70% in the reinjection rate can increase the outlet temperature by 4.21%. However, a decrease in the reinjection rate will lead to a decline in the groundwater level. Therefore, balancing the variation in outlet temperature and groundwater level is crucial in practical engineering.

Marine organisms perform a sea of diel rhythmicity. Planktonic diel dynamics have been shown to be driven by light, energy resources, circadian rhythms, and the coordinated coupling of photoautotrophs and heterotrophic bacterioplankton. Here, we explore the diel fluctuation of viral production and decay and their impact on the total and active bacterial community in the coastal and open seawaters of the South China Sea. The results showed that the night-production diel pattern of lytic viral production was concurrent with the lower viral decay at night, contributing to the accumulation of the viral population size during the night for surface waters. The diel variations in bacterial activity, community composition, and diversity were found highly affected by viral dynamics. This was revealed by the finding that bacterial community diversity was positively correlated to lytic viral production in the euphotic zone of the open ocean but was negatively related to lysogenic viral production in the coastal ocean. Such distinct but contrasting correlations suggest that viral life strategies can not only contribute to diversifying bacterial community but also potentially piggyback their host to dominate bacterial community, suggesting the tightly synchronized depth-dependent and habitat-specific diel patterns of virus–host interactions. It further implies that viruses serve as an ecologically important driver of bacterial diel dynamics across the ocean, highlighting the viral roles in bacterial ecological and biogeochemical processes in the ocean.

The stability of a double-row steel sheet pile cofferdam structure under soft ground conditions was investigated in this study, using the temporary cofferdam of the Shenzhen–Zhongshan cross-river channel as the engineering background. The stability of the cofferdam design solution was calculated with a model that incorporates factors such as the coordination of independent pile top displacement, as well as the m-value for backfilled sand and the thrown rock body. The internal force and displacement results of the cofferdam under different working conditions are obtained. And the entire construction process was analyzed using the finite element method. The results indicate that the overall stability and overturning stability of the cofferdam satisfy relevant safety requirements, with minimum safety factors of 1.744 and 1.400, respectively. The maximum displacement of the inner and outer steel sheet piles is 34 mm, the maximum bending moment is 249.30 kN·m, and the maximum shear force is 266.66 kN. The displacements of sheet piles were within an acceptable range, and the internal forces remained below the load capacity of the selected sheet pile type for the design. Based on these findings, the cofferdam structure can be considered safe and satisfying the specified requirements. This work may have instructive value for cofferdam design and construction.

Summary: Adjacent membrane receptors can show different cellular responses to ligand stimulation. Here, we describe a super-resolution microscopy imaging protocol for tracking the dynamics of two different membrane-bound receptors in single cells. We describe the transfection protocol by electroporation. We detail the imaging procedure for receptors in a single cell. We then outline the data analysis pipeline. We have applied this protocol to imaging of endocytosis of the LOX-1 and AT1 in CHO-K1 cells, but the protocol can be applied to a variety of membrane receptors in other cell lines.For complete details on the use and execution of this protocol, please refer to Takahashi et al. (2021).

The importance of dissolved Fe (dFe) in regulating ocean primary production and the carbon cycle is well established. However, the large-scale distribution and temporal dynamics of dFe remain poorly constrained in part due to incomplete observational coverage. In this study, we use a compilation of published dFe observations (n=32,344) with paired environmental predictors from contemporaneous satellite observations and reanalysis products to build a data-driven surface-to-seafloor dFe climatology with 1°×1° resolution using three machine-learning approaches (random forest, supper vector machine and artificial neural network). Among the three approaches, random forest achieves the highest accuracy with overall R2 and root mean standard error of 0.8 and 0.3 nmol L-1, respectively. Using this data-driven climatology, we explore the possible mechanisms governing the dFe distribution at various depth horizons using statistical metrics such as Pearson correlation coefficients and the rank of predictors importance in the model construction. Our results are consistent with the critical role of aeolian iron supply in enriching surface dFe in the low latitude regions and suggest a far-reaching impact of this source at depth. Away from the surface layer, the strong correlation between dFe and apparent oxygen utilization implies that a combination of regeneration, scavenging and large-scale ocean circulation are controlling the interior distribution of dFe, with hydrothermal inputs important in some regions. Finally, our data-driven dFe climatology can be used as an alternative reference to evaluate the performance of ocean biogeochemical models. Overall, the new global scale climatology of dFe achieved in our study is an important step toward improved representation of dFe in the contemporary ocean and may also be used to guide future sampling strategies.

To determine the mechanical properties of the rock mass in the Nansha Branch, three in-situ tests (on-site pressure plate, borehole TV and acoustic wave, and borehole deformation methods) were carried out. Based on the deformation characteristics of the rock mass, the finite element numerical method is used to study the combined stress of the composite lining in the diversion tunnel. The results demonstrate that the deformation modulus values are similar by comparing them to tests of the pressure plate and borehole deformation method. It shows the accuracy and reliability of the deformation modulus obtained by the borehole deformation method. In addition, the deformation modulus of the borehole deformation method and wave velocity were fitted to obtain a power function relationship. The deformation modulus of the pelitic siltstones was estimated. After the Nansha Branch tunnel is filled with water, the maximum principal stress of the pipe piece is 1.953 Mpa in tensile stress, located at the outside of the waist on both sides of the pipe piece. The maximum principal stress of the reinforced concrete lining is 5.407 Mpa, located at the top and bottom inside. The maximum principal stresses have exceeded the standard tensile strength of both the pipe piece and reinforced concrete and are vulnerable to cracking. Special attention should be paid to the deformation of the above parts with regard to long-term operation.

Abstract Yitong Basin is located in subfrigid zone, and it has a good prospect to use geothermal clean heating. The evaluation of economic efficiency for heating with enhanced geothermal system (EGS) is indispensable. A simplified single‐fracture hydrothermal coupling model with laboratory test is developed in the EGS project to calculate temperature and pressure based on Yitong Basin data. The effects of four factors (K, q, D, and T) on heat production and reservoir characteristics are discussed. The parameters and results of H‐T coupling were applied to economic analysis for heating with EGS from private and social perspectives considering costs and revenues. The results indicate that the combination of laboratory tests (rock physical properties) makes the numerical simulation results more suitable for the study area. The production temperature and heating power will decrease with continuous injection of cold water, and the injection pressure and flow impedance will increase due to the increase in μ/ρ. Four factors (K, q, D, and T) will affect difficulty of fluid injection and reservoir thermal breakthrough, and the high injection rate q may trigger secondary fracturing of reservoir. Heating with EGS in single‐fracture model was uneconomical due to expensive drilling costs. However, heating with EGS can be considered from social perspective based on environment, which can provide advice for decision‐making of the government and business.

In the Enhanced Geothermal System (EGS), the flow state of the fracture of the thermal reservoir (granite) is important for heat transfer. In this paper, the effects of reservoir temperature, flow rate and fracture shape on the thermal convection that occurs in the fracture of rough granite are studied based on the fractal dimension theory. The rough fracture is manufactured regularly by carving technology. The shear flow experiments were carried out at confining pressures of 10, 15 and 20 MPa to analyze the flow state. The convective heat transfer experiments were conducted at 60 and 70 °C to simulate different heat reservoir conditions. The results indicated that the outlet temperature and overall heat transfer coefficient (OHTC) increased with the increase in the rock temperature. A higher flow rate can enhance the thermal performance. The complexity of the fracture surface is also an important factor that affects the convective heat transfer process. The larger fractal dimension of the fracture surface can more easily excite turbulence, affecting the thickness of the boundary layer. The OHTC will increase as the fractal dimension increases.

Summary: Arrestin-dependent activation of a G-protein-coupled receptor (GPCR) triggers endocytotic internalization of the receptor complex. We analyzed the interaction between the pattern recognition receptor (PRR) lectin-like oxidized low-density lipoprotein (oxLDL) receptor (LOX-1) and the GPCR angiotensin II type 1 receptor (AT1) to report a hitherto unidentified mechanism whereby internalization of the GPCR mediates cellular endocytosis of the PRR ligand. Using genetically modified Chinese hamster ovary cells, we found that oxLDL activates Gαi but not the Gαq pathway of AT1 in the presence of LOX-1. Endocytosis of the oxLDL-LOX-1 complex through the AT1-β-arrestin pathway was demonstrated by real-time imaging of the membrane dynamics of LOX-1 and visualization of endocytosis of oxLDL. Finally, this endocytotic pathway involving GPCR kinases (GRKs), β-arrestin, and clathrin is relevant in accumulating oxLDL in human vascular endothelial cells. Together, our findings indicate that oxLDL activates selective G proteins and β-arrestin-dependent internalization of AT1, whereby the oxLDL-LOX-1 complex undergoes endocytosis.

As fluid passes through the fracture of an enhanced geothermal system, the flow direction exhibits distinct angular relationships with the geometric profile of the rough fracture. This will inevitably affect the heat transfer characteristics in the fracture. Therefore, we established a hydro-thermal coupling model to study the influence of the fluid flow direction on the heat transfer characteristics of granite single fractures and the accuracy of the numerical model was verified by experiments. Results demonstrate a strong correlation between the distribution of the local heat transfer coefficient and the fracture morphology. A change in the flow direction is likely to alter the transfer coefficient value and does not affect the distribution characteristics along the flow path. Increasing injection flow rate has an enhanced effect. Although the heat transfer capacity in the fractured increases with the flow rate, a sharp decline in the heat extraction rate and the total heat transfer coefficient is also observed. Furthermore, the model with the smooth fracture surface in the flow direction exhibits a higher heat transfer capacity compared to that of the fracture model with varying roughness. This is attributed to the presence of fluid deflection and dominant channels.

The advent of convolutional neural networks (CNNs) has accelerated the progress of computer vision from many aspects. However, the majority of the existing CNNs heavily rely on expensive GPUs (graphics processing units). to support large computations. Therefore, CNNs have not been widely used to inspect surface defects in the manufacturing field yet. In this paper, we develop a compact CNN-based model that not only achieves high performance on tiny defect inspection but can be run on low-frequency CPUs (central processing units). Our model consists of a light-weight (LW) bottleneck and a decoder. By a pyramid of lightweight kernels, the LW bottleneck provides rich features with less computational cost. The decoder is also built in a lightweight way, which consists of an atrous spatial pyramid pooling (ASPP) and depthwise separable convolution layers. These lightweight designs reduce the redundant weights and computation greatly. We train our models on groups of surface datasets. The model can successfully classify/segment surface defects with an Intel i3-4010U CPU within 30 ms. Our model obtains similar accuracy with MobileNetV2 while only has less than its 1/3 FLOPs (floating-point operations per second) and 1/8 weights. Our experiments indicate CNNs can be compact and hardware-friendly for future applications in the automated surface inspection (ASI).

Through biological activity, marine dissolved inorganic carbon (DIC) is transformed into different types of biogenic carbon available for export to the ocean interior, including particulate organic carbon (POC), dissolved organic carbon (DOC), and particulate inorganic carbon (PIC). Each biogenic carbon pool has a different export efficiency that impacts the vertical ocean carbon gradient and drives natural air-sea carbon dioxide gas (CO2) exchange. In the Southern Ocean (SO), which presently accounts for ~40% of the anthropogenic ocean carbon sink, it is unclear how the production of each biogenic carbon pool contributes to the contemporary air-sea CO2 exchange. Based on 107 independent observations of the seasonal cycle from 63 biogeochemical profiling floats, we provide the basin-scale estimate of distinct biogenic carbon pool production. We find significant meridional variability with enhanced POC production in the subantarctic and polar Antarctic sectors and enhanced DOC production in the subtropical and sea-ice-dominated sectors. PIC production peaks between 47°S and 57°S near the "great calcite belt." Relative to an abiotic SO, organic carbon production enhances CO2 uptake by 2.80 ± 0.28 Pg C y-1, while PIC production diminishes CO2 uptake by 0.27 ± 0.21 Pg C y-1. Without organic carbon production, the SO would be a CO2 source to the atmosphere. Our findings emphasize the importance of DOC and PIC production, in addition to the well-recognized role of POC production, in shaping the influence of carbon export on air-sea CO2 exchange. [ABSTRACT FROM AUTHOR]