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The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease characterized by an immunosuppressive microenvironment. Here the authors show that a subset of P2RX1-negative neutrophils with immunosuppressive properties accumulate in PDAC metastatic liver tissues and promote tumor growth.

Metastasis is a major cause of cancer-related deaths. Tumor-intrinsic properties can determine whether tumor metastasis occurs or not. Here, by comparing the gene expression patterns in primary colorectal cancer (CRC) patients with or without metastasis, we found that Collagen Triple Helix Repeat Containing 1 (CTHRC1) in primary CRC served as a metastasis-associated gene. Animal experiments verified that CTHRC1 secreted by CRC cells promoted hepatic metastasis, which was closely correlated with macrophage infiltration. Depletion of macrophages by liposomal clodronate largely abolished the promoting effect of CTHRC1 on CRC liver metastasis. Furthermore, we demonstrated that CTHRC1 modulated macrophage polarization to M2 phenotypes through TGF-β signaling. A mechanistic study revealed that CTHRC1 bound directly to TGF-β receptor II and TGF-β receptor III, stabilized the TGF-β receptor complex, and activated TGF-β signaling. The combination treatment of CTHRC1 monoclonal antibody and anti-PD-1 blocking antibody effectively suppressed CRC hepatic metastasis. Taken together, our data demonstrated that CTHRC1 is an intrinsic marker of CRC metastasis and further revealed that CTHRC1 promoted CRC liver metastasis by reshaping infiltrated macrophages through TGF-β signaling, suggesting that CTHRC1 could be a potential biomarker for the early prediction of and a therapeutic target of CRC hepatic metastasis.

High-temperature titanium alloys are significant materials in the aerospace field, and their service life largely depends on creep aging. However, the creep behavior of the TC25 titanium alloy at high temperatures has not been reported. Here, the creep behavior of TC25 before and after heat treatment at 550 °C under different stresses was investigated. It was found that heat treatment significantly enhanced the creep resistance of the TC25 alloy. An increase in creep stress increased the steady-state creep rate and reduced creep life. The smooth αp/βtrans grain boundaries and refined αs improved creep resistance, and the creep mechanism changed from grain boundary sliding to dislocation climbing after heat treatment. This research provides theoretical data support for the application of the TC25 alloy at high temperatures.

Porcine circovirus type 3 (PCV3), initially identified in the United States in 2016, is associated with multisystemic inflammation, myocarditis, reproductive failure in sows, and growth retardation in piglets, posing a significant economic threat to the swine industry. In this study, prokaryotic-expressed recombinant PCV3 Cap protein was used to immunize mice and rabbits. A monoclonal antibody (mAb 4G1) was generated through hybridoma technology, targeting a novel linear epitope (37DYYDKK42) within the first β-sheet of the Cap structure. This epitope exhibits high conservation (99.35%, 1239/1247) based on sequence alignment analysis, and residues 39 and 42 are critical residues affecting mAb binding. Subsequently, using rabbit polyclonal antibody (pAb) as the capture antibody and mAb 4G1 as the detection antibody, a double antibody sandwich ELISA (DAS-ELISA) method was developed. The assay demonstrates a cut-off value of 0.271, a detection limit for positive pig serum is 1:800, and shows no cross-reactivity with other swine pathogens. Intra- and inter-assay coefficients of variation were <10%, with a linear detection range for Cap protein down to 3.4 ng/mL. The coincidence rate between the DAS-ELISA and qPCR was 93.33% (70/75) for PCV3 detection in serum, with a kappa value of 0.837. This study establishes a simple, sensitive, and operationally efficient DAS-ELISA and provides a reference for monitoring PCV3 infection in swine herds.

Porous SnO2 with high sensitivity and fast response has attracted much attention. Herein, we prepared 3D porous SnO2 using carbon balls as a template and studied the effects of sintering time (1 h, 2 h, 3 h, 4 h) at a certain calcination temperature of 500℃ and Ho doping on the gas-sensing performance of 3D porous SnO2. The gas-sensing test results show that, compared with the samples obtained under other sintering time, the gas-sensing property of 3D porous SnO2 calcined for 2 h has the highest gas sensitivity of 31 in the 50-ppm formaldehyde environment. Among the samples doped with Ho, 3D porous SnO2 with a doping amount of 3.5% has the highest sensitivity of 65 at operating temperature of 230℃, which is twice as long as pure 3D porous SnO2 with a calcination time of 2 h. Moreover, the sample has good selectivity, low detection limit, and good linearity. These excellent gas-sensing characteristics are mainly due to the unique morphology of 3D porous SnO2, more oxygen vacancies, and the influence of Ho doping. Therefore, the gas-sensing performance of the metal oxide semiconductor material can be further improved by forming the porous nanocomposite material.(a) Response recovery time of SnO2 obtained under different calcination times;(b) Response recovery time of SnO2 doped with different Ho content.

Effective prediction of surface variation is of great helpf for developing and controlling machining process to maintain surface quality during face milling of large-scale component with discontinuous surface. However, the simulation ranges of machined surface error in traditional finite element analyses are far less than those needed in characterization of large-scale face milling with multi-tooth cutter in order to maintain efficiency. To address this issue, this paper attempts to develop a numerical methodology to estimate the field data of machined surface error based on iterative finite element analysis integrated with cutting trajectory reconfiguration. Finite element model updating (FEMU) method is applied to analysis the cutting deformation in each cutting instant while considering both the cutting force variation in face milling and the locally geometrical differences of component. A flexible model is established to predict the residual cutting material in each cutting instant with considering the coupling effect between instantaneous cutting force and cutting deformation. And then a sub-iteration scheme is proposed to calculate the equilibrium deflection and the real residual material of flexible cutting system with a modified Newton-Raphson method. The proposed simulation methodology can be generally applied for predicting surface variation field in face milling of large-scale component with multi-holed surface, especially for flexible component.

The goal for current orthopedic implant research is to design implants that have not only good biocompatibility but also antibacterial properties. TiO2 nanotubes (NTs) were fabricated on the titanium surface through electrochemical anodization, which added new properties, such as enhanced biocompatibility and potential utility as drug nanoreservoirs. The aim of the present study was to investigate the antibacterial properties and biocompatibility of NTs loaded with vancomycin (NT-V), both in vitro and in vivo. Staphylococcus aureus was used to study the antibacterial properties of the NT-V. There were three study groups: the commercially pure titanium (Cp-Ti) group, the NT group (nonloaded vancomycin), and the NT-V group. We compared NT-V biocompatibility and antibacterial efficacy with those of the NT and Cp-Ti groups. Compared with Cp-Ti, NT-V showed good antibacterial effect both in vitro and in vivo. Although the NTs reduced the surface bacterial adhesion in vitro, implant infection still developed in in vivo studies. Furthermore, the results also revealed that both NTs and NT-V showed good biocompatibility. Therefore, the NTs loaded with antibiotic might be potentially used for future orthopedic implants.

A theoretical scheme is proposed to generate significant amount of photon-phonon entanglement and asymmetric steering in a cavity magnomechanical system, which is constituted by trapping a yttrium iron garnet sphere in a microwave cavity. By applying a blue-detuned microwave driving field, we obtain an effective Hamiltonian where the magnon mode acting as an engineered resevoir cools the Bogoliubov modes of microwave cavity mode and mechanical mode via a beam-splitter-like interaction. By this means, the microwave cavity mode and mechanical mode can be driven to a two-mode squeezed state in the stationary limit. Particularly, strong two-way and one-way photon-phonon asymmetric quantum steering can be obtained with even equal dissipation. It is widely divergent with the conventional proposal, where additional unbalanced losses or noises should be imposed on the two subsystems. Our finding may be significant to expand our understanding of the essential physics of asymmetric steering and extend the potential application of the cavity spintronics to device-independent quantum key distribution.

Implant-related infection is a major problem postsurgery. As an alternative to a localized antibiotic release system, we used Ag to fabricate Ti-Ag alloys with nanotubular coatings (TiAg-NTs). Ag has excellent antibacterial properties, but its biological toxicity is a concern. Therefore, we performed biological experiments both in vitro and in vivo to evaluate the biocompatibility of TiAg-NTs with different concentrations of Ag (1%, 2%, and 4%). For in vitro experiments, cytocompatibility, including cell attachment, viability, and proliferation, was tested, and genes and proteins related to osteogenic differentiation were also evaluated. For in vivo assays, the rat femoral condylar insertion model was used, and micro-computed tomography (micro-CT) and histological analysis were conducted to analyze bone formation around implants at 1, 2, and 4 weeks after surgery. Both in vitro and in vivo results indicate that Ti2%Ag-NT showed comparable cytocompatibility with commercially pure Ti (cp-Ti), and it could achieve good osseointegration with the surrounding bone tissue. We thus believe that Ti2%Ag-NT is a potential biomaterial for orthopedics.

In recent years, the rapid development of the rare earth industry has had a serious impact on the environment. Some enterprises have taken measures to improve the production process. In order to explore the sustainability of this industry and these improvements’ environmental benefits, this paper combines emergy analysis and lifecycle assessment to evaluate and compare the production process of rare-earth oxides considering the three aspects of emergy flow, pollutant emissions, and emergy-based indicators. Changes in the emergy of pollutant emissions before and after improvement of the production process are discussed. The results show that the greatest inputs in the mining and beneficiation stage and smelting separation stage are labor force and service and non-renewable resources, respectively. These two production stages are highly dependent on external input and have weak competitiveness. Both stages place great pressure on the environment, so the bastnasite production process would be unsustainable in the long term. After the improvement, the environmental impact of the production process for bastnaesite changed significantly, indicating that the improvement effect of the wastewater treatment facilities and the change of fuel from coal to natural gas is remarkable.