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In cutting, when an insert is subjected to a large mechanical-thermal shock load, a large bending moment may be produced in the front of the insert, causing tensile stress concentration and insert breakage. In this paper, stepped structures with different gradient parameters are designed in the surface layer of the shim used under the insert to reduce the bending moment and the stress concentration in the insert. The simulation model of the insert-shim system was established, and finite element simulation analysis was carried out for the insert with and without the prefabricated crack. The effects of stepped shims with different gradient parameters on the stress, strain, bending moment of the insert, and crack propagation at the crack front in the inserts were investigated under static loading condition. Interrupted cutting experiments were carried out using the stepped shims. The simulation results show that the stepped shims with gradient parameters of 0.005 mm–0.015 mm can effectively reduce the bending moment, maximum tensile stress, and maximum tensile strain of the inserts; the stepped shims with gradient parameters of 0.005 mm–0.015 mm can significantly reduce the maximum tensile stress and the stress intensity factor at the front of the cracks and reduce the internal propagation of the cracks. The experimental results show that the stepped shims with gradient parameters of 0.005 mm–0.015 mm can effectively prevent insert breakage in the cuttings with the large depth of cut and low cutting speed and reduce the degree of insert breakage in the cuttings with the small depth of cut and high cutting speed.

A novel Ni-based superalloy GH4151, with a γ′ volume fraction of about 55% and a service temperature capability up to 800 °C, was investigated. Due to the different cooling conditions of various regions during the solidification of ingots, significant cooling rate variations may lead to the occurrence of hot cracking. Conventional scanning laser microscope was utilised to investigate the solidification process and phase precipitation behaviour of the GH4151 under wide range cooling rates. The characteristics of L → γ transformation were analysed, and the growth rates of γ at each stage were calculated. The segregation behaviour was predicted using the Scheil equation, and the predicted results match well with the experimental results. The sensitivity coefficient for hot cracking was modified, and cracking sensitivity coefficient values for the alloy under different cooling rates were computed, revealing that the alloy is most susceptible to hot cracking at 10 °C/min cooling rate. Therefore, controlling the cooling rate can reduce the possibility of hot cracking in ingot.

Laser cladding is being employed for repairing high-end components including thin-walled parts. The heterogeneous interface between cladding layer and substrate can exacerbate cutting vibration during subsequent machining, becoming a bottleneck in remanufacturing thin-walled parts. This paper focuses on exploring the effect of interfacial structures on cutting vibration suppression in side milling of laser cladded layer on thin-walled parts. First, the interfacial structure was proven to be effective for suppressing cutting vibration by increasing modal damping, although the stiffness shows a decreasing trend. Among different interfacial structures, triangular structure showed the best role in cutting vibration suppression, followed by rectangular, semi-circular, and trapezoid. Then, the effects of different structural parameters on cutting vibration suppression were further analyzed based on a Taguchi design. The results showed that the cutting vibration decreases with the smaller interfacial shape factor, larger depth and smaller spacing of interfacial structures. The interfacial structure would be optimal when the interfacial shape factor is 0.06, the interfacial depth is 3.0 mm, and the spacing is 0 mm. As a result, the cutting vibration during milling was reduced by 55.28 %. These findings provide a theoretical basis for high-quality remanufacturing of the thin-walled parts.

Epimedii Folium (EF) is a botanical dietary supplement to benefit immunity. Baohuoside I (BI), a prenylated flavonoid derived from EF, has exhibited the cholestatic risk before. Here, the mechanism of BI on the stability and membrane localization of liver MRP2, a bile acid exporter in the canalicular membrane of hepatocytes, was investigated. The fluorescent substrate of MRP2, CMFDA was accumulated in sandwich-cultured primary mouse hepatocytes (SCH) under BI stimulation, followed by reduced membrane MRP2 expression. BI triggered MRP2 endocytosis associated with oxidative stress viainhibition of the NRF2 signaling pathway. Meanwhile, BI promoted the degradation of MRP2 by reducing its SUMOylation and enhancing its ubiquitination level. Co-IP and fluorescence colocalization experiments all proved that MRP2 was a substrate protein for SUMOylation for SUMO proteins. CHX assays showed that SUMO1 prolonged the half-life of MRP2 and further increased its membrane expression, which could be reversed by UBC9knockdown. Correspondingly, MRP2 accumulated in the cytoplasm by GP78knockdown or under MG132 treatment. Additionally, the SUMOylation sites of MRP2 were predicted by the algorithm, and a conversion of lysines to arginines at positions 940 and 953 of human MRP2 caused its decreased stability and membrane location. K940 was further identified as the essential ubiquitination site for MRP2 by an in vitroubiquitination assay. Moreover, the decreased ubiquitination of MRP2 enhanced the SUMOylation MRP2 and vice versa, and the crosstalk of these two modifiers could be disrupted by BI. Collectively, our findings indicated the process of MRP2 turnover from the membrane to cytoplasm at the post-translational level and further elucidated the novel toxicological mechanism of BI.

The ability of drugs to cross the blood–brain barrier (BBB) is crucial for treating central nervous system (CNS) disorders. Inspired by natural viruses, here we report a glucose and polydopamine (GPDA) coating method for the construction of delivery platforms for efficient BBB crossing. Such platforms are composed of nanoparticles (NPs) as the inner core and surface functionalized with glucose-poly(ethylene glycol) (Glu-PEG) and polydopamine (PDA) coating. Glu-PEG provides selective targeting of the NPs to brain capillary endothelial cells (BCECs), while PDA enhances the transcytosis of the NPs. This strategy is applicable to gold NPs (AuNPs), silica, and polymeric NPs, which achieves as high as 1.87% of the injected dose/g of brain in healthy brain tissues. In addition, the GPDA coating manages to deliver NPs into the tumor tissue in the orthotopic glioblastoma model. Our study may provide a universal strategy for the construction of delivery platforms for efficient BBB crossing and brain drug delivery.

Targeted delivery of vaccines to the spleen remains a challenge. Inspired by the erythrophagocytotic process in the spleen, we herein report that intravenous administration of senescent erythrocyte-based vaccines profoundly alters their tropism toward splenic antigen-presenting cells (APCs) for imprinting adaptive immune responses. Compared with subcutaneous inoculation, intravenous vaccination significantly upregulated splenic complement expression in vivoand demonstrated synergistic antibody killing in vitro. Consequently, intravenous senescent erythrocyte vaccination produces potent SARS-CoV-2 antibody-neutralizing effects, with potential protective immune responses. Moreover, the proposed senescent erythrocyte can deliver antigens from resected tumors and adjuvants to splenic APCs, thereby inducing a personalized immune reaction against tumor recurrence after surgery. Hence, our findings suggest that senescent erythrocyte-based vaccines can specifically target splenic APCs and evoke adaptive immunity and complement production, broadening the tools for modulating immunity, helping to understand adaptive response mechanisms to senescent erythrocytes better, and developing improved vaccines against cancer and infectious diseases.

ABSTRACTAmong all industrial accident-induced diseases, musculoskeletal disorders (MSDs) are most prominently observed among nurses. The physical load of everyday tasks involved in nursing work was assessed in this study using a developed risk index, whereby the physical burden was evaluated using the exposure duration and work intensity levels. This survey targeted nine small, medium and large-sized hospitals in South Korea and categorized representative nursing tasks into six groups. The subtasks within these six categories (evaluated as high risk) included changing a patient’s posture and assisting with walkers or wheelchairs, transporting/handling drug carts, bathing patients, replacing bedding, traction therapy, cardiopulmonary resuscitation and artificial manual breathing unit, and computer work. The risk index ratio was significantly different by task type for each task. We demonstrated that the risk index developed in this study can be used to evaluate MSDs in hospitals.

AbstractPlatinum-based chemotherapy is a common clinical treatment for esophageal squamous cell carcinoma (ESCC), and chemoresistance is a major leading reason for cancer treatment failure. MiR-302a-3p is involved in the development of many diseases. Here, we investigated the role of miR-302a-3p in the cisplatin resistance of ESCC cells and explored its potential mechanism viamolecular techniques. The expression of miR-302a-3p was significantly reduced, while the expressions of EphA2 were increased in ESCC tumor tissues and cells. EphA2 was one target gene of miR-302a-3p, and was negatively regulated by miR-302a-3p. By regulating EphA2, miR-302a-3p reduced the viability and promoted the apoptosis of ECA109 cells treated with cisplatin, suggesting that miR-302a-3p could enhance the sensitivity of ECA109 cells to cisplatin treatment by targeting EphA2. MiR-302a-3p plays an important role in reducing cisplatin resistance by inhibiting EphA2, suggesting that it may be a promising therapeutic strategy for cisplatin resistance in ESCC in the future.

The GH4720Li alloy is one of the most widely used precipitation-strengthened nickel-based superalloy. However, systematic study about effect of strain rate on the plastic deformation behavior of GH4720Li alloy at intermediate temperature is lacking. The evolution of the tensile properties and plastic deformation mechanism of GH4720Li alloy with the strain rate at 650 °C were systematically studied with the help of transmission electron microscopy analysis. The results show that the tensile strength of the alloy increases and the plasticity decreases with the increase in strain rate. When the strain rate is 5 min−1, the tensile strength of the alloy is 1448 MPa and the tensile plasticity is 18%. As the strain rate increases from 0.05 to 0.5 min−1, the size and morphology of the primary γ′ phase of the alloy remain unchanged, with an average size of about 1.8 μm. However, when the strain rate further increases to 5 min−1, the average size of the primary γ′ phase increases to 2.5 μm. In addition, the increase of strain rate has no significant effect on the size and distribution of secondary and tertiary γ′ phases. As the strain rate increases from 0.05 to 5 min−1, the deformation mechanism of alloy gradually evolved from dislocation slip and twin to dislocation slip, indicating that the plastic deformation mechanism of the alloy presents a high strain rate sensitivity at 650 °C.

Hard machining, as one of the sustainable manufacturing technologies, tends to introduce highly coupled thermomechanical loads into the machined surface layer, which causes materials to suffer from severe plastic deformation underneath and, thus, the alteration of the mechanical properties. In this paper, a systemic investigation was performed on the correlation of processing parameters, plastic deformation, and mechanical properties of machined surface layer for hardened H13 steel, where the cutting parameters and tool micro-geometry are varied. The plastic deformation layer was composed of an amorphous structure and plastically deformed grain. Compared to cutting parameters, edge micro-geometry significantly influences the depth of the plastic deformation layer. The automated ball indentation (ABI) technique was utilized to evaluate the mechanical properties of the machined surface layers. Finally, the relationship between processing parameters, depth of plastic deformation, and mechanical properties was revealed. The experimental findings provide a solid foundation for processing parameter selection to improve the functional performance of manufactured components.

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been proved a promising clinical strategy for the treatment of diabetes, and time in range (TIR) has been demonstrated a new metric of glycemic control links to diabetes complications. To further assess the therapeutic effect of UC-MSCs on TIR, a phase II study investigating the efficacy of UC-MSCs in Chinese adults with type 2 diabetes (T2D) assessed by retrospective continuous glucose monitoring (CGM) was conducted. In this randomized and placebo-controlled trial, a total of 73 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n= 37) or placebo (n= 36) 3 times at 4-week intervals and followed up for 48 weeks. The primary endpoint was the changes in TIR and glycosylated hemoglobin (HbA1c). TIR and HbA1c were both significantly improved in UC-MSCs and placebo groups after 48 weeks of therapy compared with baseline. Compared with placebo group, UC-MSCs group exhibited more pronounced changes at 9 and 48 weeks from baseline in TIR (26.54 vs. 15.84 and 21.36 vs. 6.32) and HbA1c (−1.79 vs. −0.96 and −1.36 vs. −0.51). More patients in UC-MSCs group achieved the glycemic control target of TIR ≥ 70% and HbA1c < 7% at 9 and 48 weeks than in placebo group (59.5% vs. 27.8% and 43.2% vs. 11.1%). The C-peptide area under the curve (AUCC-pep) was an independent risk factor associated with efficacy in T2D undergoing UC-MSCs intervention. These results illustrate that UC-MSCs administration via intravenous infusion is an effective approach for ameliorating TIR.Graphical Abstract

In the creep fatigue crack growth of GH4169 alloy, oxidation is a prominent damage source, which is mainly manifested as the oxidation damage zone in front of crack tip. In order to investigate the property of the oxidation damage zone formed in the creep fatigue crack growth, crack growth tests of directly aged GH4169 alloy were conducted at 650 °C in air under various load conditions. Interrupted tests were performed to observe the damage characteristics at crack tip. Block tests were systematically executed to quantify the dependency of oxidation damage zone size on load and holding time. The crack propagation of the GH4169 alloy has a close relationship with grain boundary oxidation at 650 °C. An oxidation damage zone in front of crack tip includes intergranular microcracks and oxidised but uncracked grain boundaries. Its size has been calculated from transient crack growth rate and described as a function of maximum stress intensity factor and holding time. Based on oxidation damage zone size, a novel model has been developed to predict the creep fatigue crack growth rate of the GH4169 alloy at 650 °C.

The rational design of vaccines and antibody-based therapeutics against newly emerging viruses relies on B cell epitopes mainly. To predict the B cell epitopes of a novel virus, several algorithms have been developed. While most existing algorithms are trained on a dataset in which B cell epitopes are classified as ‘Positive’ or ‘Negative’. However, we found that training on such data contaminates the target pattern of specific viruses, leading to inaccurate predictions in some cases. In this paper, we introduce a novel framework for predicting linear B cell epitopes of novel viruses by exclusively using highly similar viruses for training data. We employed kernel regression based on seropositive rates, which are the percentages of seropositive samples among the population, to predict the potential epitopes. To assess our method, we conducted simulations and utilized two real-world datasets. Our method significantly outperformed other existing methods on the testing data of four viruses with seropositive rates. Also, our strategy showed a better prediction in a larger dataset from the IEDB. Thus, a novel framework providing better linear B cell prediction of newly emerging viruses is established, which will benefit the rational design of vaccines and antibody-based therapeutics in the future.

The inhomogeneous microstructure of the Ni-based superalloys used for turbine disks was an intolerable defect for the mechanical performance. The effects of the distribution of γ′ precipitate, forging temperature, and strain level on the microstructure evolution of GH4730 alloy were investigated by EBSD during hot deformation. The results showed that the heterogeneous factor peaked at the transition temperature from the single-phase to the double-phase region. The coupling effect of heat and stress led to the heterogeneous precipitation and distribution of γ′ phase during the transition region, which was the main reason for the formation of inhomogeneous microstructures. The coherent γ′ phases of approximately 0.3 μm were diffusely distributed inside the large grains, increasing the grain strength, making recrystallization refinement difficult, and thus forming large unrecrystallized grains. The incoherent γ′ phases with a size of approximately 1.1 μm located at the grain boundaries and pinned the grain boundaries, and thus the accumulated strain at the grain boundaries caused the occurrence of discontinuous dynamic recrystallization and promoted continuous refinement of the grains. The microstructure evolution of new Ni-based superalloys during hot forging was focused, and the formation mechanism of inhomogeneous microstructure and control measures was explained. A theoretical basis for improving the microstructure homogeneity of the new cast and wrought superalloys was provided.

During subsequent machining of laser cladded workpiece, the stress transferred in depth direction is different with conventional cast workpiece due to the geometrical discontinuity, resulting in the stress difference and strain discontinuity at the interface between the cladding layer and substrate. Elastic and plastic deformation will occur in the cladding layer and substrate, respectively, which ultimately reduces the service life of the cladded workpiece. In this study, the stress and strain evolution in subsequent machining of laser cladded workpiece was investigated using an orthogonal cutting model by finite element method. A dimensionless thickness ratio between uncut chip thickness and cladding layer thickness was set and the maximum thickness ratio without equivalent plastic strain (PEEQ) discontinuity at the interface was determined. In addition, the results indicated that the maximum thickness ratio first decreased and then increased with the increase of cutting speed, while increases with the increase of the yield strength of substrate. The synergetic effects of thickness ratio, cutting speed and yield strength of substrate on the strain discontinuity at the interface were also investigated based on Taguchi method. The optimal combination of parameters is determined based on the regression model and divided into areas with considering machining efficiency as well. The map of cutting configurations facilitates the selection of proper machining parameters in order to estimate the strain discontinuity in machining laser cladded workpiece, ensuring a better service life of the workpiece.

Metal–organic frameworks (MOFs) show tremendous promise for drug delivery due to their structural and functional versatility. However, MOFs are usually used as biologically inert carriers in most cases. The creation of intrinsically immunostimulatory MOFs remains challenging. In this study, a facile and green synthesis method is proposed for the preparation of a manganese ion (Mn2+)-based immunostimulatory MOF (ISAMn-MOF) for cancer metalloimmunotherapy. ISAMn-MOF significantly facilitates the activation of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) related genes and signaling pathways in bone-marrow-derived dendritic cells (BMDCs). BMDCs treated with ISAMn-MOF secrete 4-fold higher type I interferon and 2- to 16-fold higher proinflammatory cytokines than those treated with equivalent MnCl2. ISAMn-MOF alone or its combination with immune checkpoint antibodies significantly suppresses tumor growth and metastasis and prolongs mouse survival. Mechanistic studies indicate that ISAMn-MOF treatment facilitates the infiltration of stimulatory immune cells in tumors and lymphoid organs. This study provides insight into the design of bioactive MOFs for improved cancer metalloimmunotherapy.

The construction of type-II or S-scheme heterojunctions can effectively accelerate the directional migration of charge carriers and inhibit the recombination of electron–hole pairs to improve the catalytic performance of the composite catalyst; therefore, the construction and formation mechanism of a heterojunction are worth further investigation. Herein, Cu2O@Cu4(SO4)(OH)6·H2O core–shell polyhedral heterojunctions were fabricated via in situ etching Cu2O with octahedral, cuboctahedral, and cubic shapes by sodium thiosulfate (Na2S2O3). Cu2O@Cu4(SO4)(OH)6·H2O polyhedral heterojunctions demonstrated obviously enhanced sterilization and degradation performance than the corresponding single Cu2O polyhedra and Cu4(SO4)(OH)6·H2O. When Cu2O with a different morphology contacts with Cu4(SO4)(OH)6·H2O, a built-in electric field is established at the interface due to the difference in Fermi level (Ef); meanwhile, the direction of band bending and the band alignment are determined. These lead to the different migration pathways of electrons and holes, and thereby, a type-II or S-scheme heterojunction is constructed. The results showed that octahedral o-Cu2O@Cu4(SO4)(OH)6·H2O is an S-scheme heterojunction; however, cuboctahedral co-Cu2O@Cu4(SO4)(OH)6·H2O and cubic c-Cu2O@Cu4(SO4)(OH)6·H2O are type-II heterojunctions. By means of X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), diffuse reflectance spectra (DRS), and Mott–Schottky analyses, the band alignments, Fermi levels, and band offsets (ΔECB, ΔEVB) of Cu2O@Cu4(SO4)(OH)6·H2O polyhedral heterojunctions were estimated; the results indicated that the catalytic ability of the composite catalyst is determined by the type of heterojunction and the sizes of band offsets. Cubic c-Cu2O@Cu4(SO4)(OH)6·H2O has the strongest driving force (namely, biggest band offsets) to accelerate charge migration and effectively separate charge carriers, so it exhibits the strongest catalytic bactericidal and degrading abilities.

Electrochemical corrosion and stress corrosion cracking (SCC) behavior of X80 steel in the sulfurated marine environment at open circuit potential and −850 mVSCEare investigated. The results show that SCC is controlled by both anodic dissolution and hydrogen evolution, which is attributed to the HSO3−acceleration of the anodic and cathodic current density. Localized anodic dissolution leads to pits, which induce stress that promotes the initiation of stress corrosion cracks. Under a cathodic potential of −850 mVSCE, the effect of dissolution is limited, and SCC susceptibility increases because of the synergistic effect of the high HSO3−concentration and cathodic potential.

Mitochondrial dysfunction plays a key role in the development of heart failure, but targeted therapeutic interventions remain elusive. Previous studies have shown coenzyme Q10 (CoQ10) insufficiency in patients with heart disease with undefined mechanism and modest effectiveness of CoQ10 supplement therapy. Using 2 transgenic mouse models of cardiomyopathy owing to cardiac overexpression of Mst1 (Mst1-TG) or β2-adrenoceptor (β2AR-TG), we studied changes in cardiac CoQ10 content and alterations in CoQ10 biosynthesis genes. We also studied in Mst1-TG mice effects of CoQ10, delivered by oral or injection regimens, on both cardiac CoQ10 content and cardiomyopathy phenotypes. High performance liquid chromatography and RNA sequencing revealed in both models significant reduction in cardiac content of CoQ10 and downregulation of most genes encoding CoQ10 biosynthesis enzymes. Mst1-TG mice with 70% reduction in cardiac CoQ10 were treated with CoQ10 either by oral gavage or i.p. injection for 4–8 weeks. Oral regimens failed in increasing cardiac CoQ10 content, whereas injection regimen effectively restored the cardiac CoQ10 level in a time-dependent manner. However, CoQ10 restoration in Mst1-TG mice did not correct mitochondrial dysfunction measured by energy metabolism, downregulated expression of marker proteins, and oxidative stress nor to preserve cardiac contractile function. In conclusion, mouse models of cardiomyopathy exhibited myocardial CoQ10 deficiency likely due to suppressed endogenous synthesis of CoQ10. In contrast to ineffectiveness of oral administration, CoQ10 administration by injection regimen in cardiomyopathy mice restored cardiac CoQ10 content, which, however, failed in achieving detectable efficacy at molecular and global functional levels.

We report a simple and novel scheme to achieve the reconfigurable frequency mixing based on a filter-free photonic microwave in-phase/quadrature (I/Q) modulator. With proper photodetection configuration, four microwave frequency mixing functions are expediently reconfigured in our system: single-ended mixing, balanced mixing, I/Q mixing and image-reject mixing. The employed crucial optical modulator is a dual-polarization dual-parallel Mach–Zehnder modulator (DPol-DPMZM) driven by in-phase and quadrature intermediate frequency (IF) and local oscillator (LO) signals. The generation and switching of frequency down- and up-conversion and different mixing functions depend on the main direct current (DC) biases of the two sub-DPMZMs, instead of using additional optical hybrid, wavelength division multiplexer (WDM) or two pairs of cascaded polarization controller (PC) and polarization beam splitter (PBS) in previous reports. Our demonstrated experiment shows that the reconfigurable frequency mixer has high mixing spur suppression, frequency tunability, and image rejection ratio (IRR) of over 35 dB. The proposed simple and multifunctional structure may bring a broad potential application in radar and communication systems.

BackgroundChina is experiencing a postpeak smoking epidemic with accelerating population ageing. Understanding the impacts of these factors on the future cancer burden has widespread implications.MethodsWe developed predictive models to estimate smoking-related cancer deaths among men and women aged ≥35 years in China during 2020–2040. Data sources for model parameters included the United Nations World Population Prospects, China Death Surveillance Database, national adult tobacco surveys and the largest national survey of smoking and all causes of death to date. The main assumptions included stable sex-specific and age-specific cancer mortality rates and carcinogenic risks of smoking over time.ResultsIn a base-case scenario of continuing trends in current smoking prevalence (men: 57.4%–50.5%; women: 2.6%–2.1% during 2002–2018), the smoking-related cancer mortality rate with population ageing during 2020–2040 would rise by 44.0% (from 337.2/100 000 to 485.6/100 000) among men and 52.8% (from 157.3/100 000 to 240.4/100 000) among women; over 20 years, there would be 8.6 million excess deaths (0.5 million more considering former smoking), and a total of 117.3 million smoking-attributable years of life lost (110.3 million (94.0%) in men; 54.1 million (46.1%) in working-age (35–64 years) adults). An inflection point may occur in 2030 if smoking prevalence were reduced to 20% (Healthy China 2030 goal), and 1.4 million deaths would be averted relative to the base-case scenario if the trend were maintained through 2040.ConclusionsCoordinated efforts are urgently needed to curtail a rising tide of cancer deaths in China, with intensified tobacco control being key.

Graphical Abstract:

(Ultra)high‐pressure metamorphic rocks provide valuable insights into the properties of slab‐derived fluids. Here, we report CH4‐rich fluid inclusions in garnet of a metapelite from the Zermatt‐Saas ophiolite, western Alps. Two types of metapelite, a CH4‐bearing pelitic schist and a calcareous pelitic schist, were investigated to unravel favorable P‐T‐fO2conditions for preservation of CH4in high‐pressure metapelite. In the CH4‐bearing pelitic schist, CH4‐rich fluid inclusions exclusively occur in the core of garnet (GrtI) rather than the rim (GrtII). GrtI records P‐Tconditions of ∼2.85 GPa and ∼555°C, whereas GrtII records a prograde P‐Tpath from ∼1.75 GPa at 510°C to ∼2.0 GPa at 530°C. Compositional profile of garnet in the calcareous pelitic schist reflects a prograde metamorphic path from ∼1.9 GPa at 510°C to ∼2.12 GPa at 545°C. CH4‐rich fluid formation may primarily rise from graphite reduction at high‐pressure reduced conditions (ΔFMQ −3.5 to −4, 2.85 GPa, ∼550°C), while graphite and carbonates stabilize in a relatively oxidized environment (ΔFMQ ∼0, 2.12 GPa, 545°C). The initial redox budget of subducted sediments is primarily controlled by the amount of sedimentary carbonate and organic carbon, which plays the most important role in deciding the carbon speciation at different subduction depths. CH4formation in COH fluids could primarily be attributed to the reduction of graphite. Subducted metasediments act as conduits for transporting non‐oxidized fluids to arc magmas, which provides crucial evidence to support the heterogeneity for slab‐derived COH fluids and offers new insights into the deep carbon cycle. Subducting slab releases COH fluids at different depths, which can metasomatize and enrich the overlying mantle wedge and lead to changes in the nature of the arc magma source. However, due to the complex redox state of the subduction zone, the properties of the COH fluids released from the slab are not well understood. Carbon, as a crucially redox‐sensitive element, its speciation serves as a significant indicator of the redox state within the subducting slab. We discovered numerous graphite and CH4fluid inclusions within garnet in high‐pressure metasedimentary rocks. These findings suggest that subducting slabs may possess more reduced properties, potentially releasing non‐oxidized fluids. We also selected another metapelite sample without methane but with graphite and carbonate for comparative analysis. We determined P‐Tconditions of the metamorphic peak stage through detailed thermodynamic modeling and estimated the oxygen fugacity at this stage. Our findings show that graphite and methane are stable in a highly reduced environment, whereas coexistence of graphite and carbonate occurs in a more oxidized environment. The formation of CH4likely results from the reduction of graphite with fluid. These observations highlight the heterogeneity of slab‐derived fluids and the complex redox properties of the subducting slab. CH4‐rich fluid inclusions can be preserved in high‐pressure metapelite from oceanic subduction zoneCH4formation in COH fluids could primarily be attributed to the reduction of graphiteLow‐redox budget carbon‐bearing sediments are favorable for forming a reduced condition as the slab descends, facilitating CH4generation CH4‐rich fluid inclusions can be preserved in high‐pressure metapelite from oceanic subduction zone CH4formation in COH fluids could primarily be attributed to the reduction of graphite Low‐redox budget carbon‐bearing sediments are favorable for forming a reduced condition as the slab descends, facilitating CH4generation

In this work, the authors monitored the formation and dissociation process of methane hydrate in four different rock core samples through nuclear magnetic resonance (NMR) relaxation time (T2) and 2D imaging measurement. The result shows that the intensity of T2spectra and magnetic resonance imaging (MRI) signals gradually decreases in the hydrate formation process, and at the same time, the T2spectra move toward the left domain as the growth of hydrate in the pores of the sample accelerates the decay rate. The hydrate grows and dissociates preferentially in the purer sandstone samples with larger pore size and higher porosity. Significantly, for the sample with lower porosity and higher argillaceous content, the intensity of the T2spectra also shows a trend of a great decrease in the hydrate formation process, which means that high-saturation gas hydrate can also be formed in the sample with higher argillaceous content. The changes in MRI of the sample in the process show that the formation and dissociation of methane hydrate can reshape the distribution of water in the pores.

Tool edge preparation is preferred in metal machining processes, which is strongly related to process reliability, tool cutting performance and surface integrity. Therefore, proper edge micro-geometry optimization and selection could be taken as a feasible approach to improve tool cutting performance, slow tool wear and ameliorate surface integrity. This review paper addresses the recent development in tool cutting performance (including cutting forces, temperature and tool wear), surface integrity (including surface geometrical characteristics, metallurgical behaviour and mechanical property) in the metal cutting processes considering the cutting insert with various designed micro-geometry. In addition, the prospective research issue and tool technology development in this field is also presented.

The shaping of the waveform of a two- or three-color driving laser pulse is essential for generating an ultrashort isolated attosecond pulse (IAP) from high-order harmonic generation, which can be implemented in two different ways, i.e., direct coherent synthesizing of electric fields with appropriate parameters (wavelength, intensity, carrier envelope phase, time delay), and superposition of fields undergoing a spectral phase shaping in frequency space view, which additionally results in a chirp and pulse-width broadening. In this work, we perform a comparative study on the IAP generation with these two schemes by virtue of a genetic algorithm, and two very meaningful conclusions are clarified. First, weighing the advantages and disadvantages of the two methods, the width and strength of IAPs optimized from two schemes are basically the same. More optimization parameters in the second method of laser shaping do not show an advantage in shortening width or enhancing the intensity of the IAP compared with the first one. Second, in each case, one can get the shortest IAP when the carrier envelope phases for each spectral component are not required to be precisely controlled. This study provides useful theoretical guidance for generating a shorter IAP with multicolor gating in the experiment.

Purpose: To investigate the clinical characteristics, endocrinological function, and etiology of bilateral adrenal lesions in hospitalized patients. Methods: A retrospective study of 777 patients with bilateral adrenal lesions was conducted at the Chinese People’s Liberation Army General Hospital between January 2013 and January 2018. Patients’ demographic features, hormonal profiles, imaging findings, and histopathological findings were reviewed from database records. Results: Of the 777 patients with bilateral adrenal lesions, 495 were men. The mean age at diagnosis was 52.0 ± 13.0 years. Overall, 511 (65.8%) cases were benign, followed by adrenal metastases (n= 224, 28.8%), pheochromocytoma (n= 26, 3.3%), adrenal lymphoma (n= 9, 1.2%), and adrenal corticocarcinoma (ACC; n= 7, 0.9%). Hormonal evaluation revealed that 34.3% of bilateral adrenal lesions were functional. The primary etiologies of functional lesions were primary aldosteronism (16.6%, 129/777), and primary bilateral macronodular adrenocortical hyperplasia (PBMAH; 8.8%, 68/777). Patients with lymphoma and metastases were significantly older than those with benign nonfunctional lesions (60.4 ± 11.0 years vs. 54.5 ± 10.4 years and 57.9 ± 10.8 years vs. 54.5 ± 10.4 years, respectively; both P&lt; 0.001). Lesions in patients with adrenal lymphoma, ACC, pheochromocytoma, metastases, congenital adrenal hyperplasia, tuberculosis, and Cushing’s syndrome were significantly larger than benign nonfunctional lesions (all P&lt; 0.001). Conclusion: Benign adrenal lesions and metastases from the lungs are the most common causes of bilateral adrenal lesions. Primary aldosteronism and PBMAH are the most prevalent functional lesions. Moreover, patients with lymphoma or metastases are older and their masses are larger.

The thermal degradation process of epoxy resin/intumescent flame retardant/flake graphite/hexagonal boron nitride (EP/IFR/FGP/h-BN) was analyzed by thermogravimetry. The effects of binary nano flake graphite/hexagonal boron nitride as synergistic flame retardant on the thermal stability. Flynn wall Ozawa method was used to calculate the activation energy of thermal degradation kinetics of EP/IFR/FGP/h-BN. The mechanism functions of the EP/IFR/FGP/h-BN in different reaction stages were determined according to Malek method, and the thermal degradation mechanism of EP/IFR/FGP/h-BN was obtained. The binary nanoFGP/h-BN is helpful to improve the thermal stability of EP.

Since the 21st century, the development of automotive and home appliance industries has greatly contributed to the prosperity of the plastics industry, which has led to an increasing demand for molding molds. In the production process, the molds will be impacted, worn and corroded, especially in the production of plastic products made of PVC, fluoroplastics and flame retardant ABS, etc. The molds will be corroded by the corrosive gases generated such as hydrogen chloride, hydrogen fluoride and sulfur dioxide, which requires plastic molds to have a certain degree of corrosion resistance while ensuring strong toughness.S136 SUP is a modified martensitic stainless steel based on S136 from ASSAB, Sweden, which has fine-tuned the content ratio of some elements to ensure a certain strength and high toughness at the same time. The chemical composition, heat treatment and microstructure of the steel have a certain influence on its corrosion resistance, and the tempering temperature of the heat treatment has a greater influence on the corrosion resistance of martensitic stainless steel. Therefore, in this paper, the microstructure and corrosion resistance of S136 SUP at different tempering temperatures are explored and studied.

High-temperature fatigue property of Ni-based GH4720Li superalloy at 550 °C has been investigated at maximum strain from 0.8% to 1.1%. Microstructural characterization and oxidation behavior of superalloy during high-temperature fatigue have been analyzed by transmission electron microscopy and scanning transmission electron microscopy. The results show that a stable response following a slight cyclic hardening during initial cycles was revealed at the maximum strain from 0.8% to 1.0%. The stable response decreased with an increase in maximum strain. Continuous cyclic hardening was observed at the maximum strain of 1.1%. There is difference in dislocation substructures between primary γ′ precipitates and γ grains. Dislocation cell and mechanical twin were formed in the interior of primary γ′ precipitates and γ grains. The primary γ′ precipitate interface would migrate toward the interior of primary γ′ precipitates along twin boundaries, leading to instability of primary γ′ precipitates. The secondary γ′ depleted zone was distinctly generated near the surface due to the decomposition of secondary γ′ precipitates. The crack initiation and propagation during high-temperature fatigue were found inside the secondary γ′ depleted zone. The primary γ′ precipitates could effectively hinder the crack propagation. Al-rich oxide films (Al2O3) were initially produced at crack tips, because the rate of diffusion of Al was relatively higher than that of other elements at crack tips.

During subsequent machining of laser cladded workpiece, the stress transferred in depth direction is different from the conventional cast workpiece due to the geometrical discontinuity, resulting in the stress difference and strain discontinuity at the interface between the cladding layer and substrate. Distinguishing from the traditional finite element method model, this paper establishes a model with an inclined interface to investigate the thickness ratio, i.e., the ratio of the removal thickness in subsequent machining to cladding thickness on the machining-induced stress and strain. The results show that the maximum thickness ratio is 0.352 when the removal thickness is 0.1 mm. The change in interfacial shear stress energy dissipation due to interfacial inclination makes this result 22.8% lower than a traditional model with a horizontal interface. With the help of the presented model, the effect of removal thickness on machining-induced stress and strain evolution was investigated. The results show that an increase in the removal thickness will lead to an increase in machining-induced stress and strain. The stress difference and strain increment at the interface increase proportionally with the removal thickness, implying that variations in removal thickness will have a consequential impact on the maximum thickness ratio. Thus, the interaction of material removal thickness and thickness ratio on PEEQ increment at the interface was further analyzed. The response surface results indicate that an increase in the removal thickness leads to a corresponding increase in the maximum thickness ratio, albeit with a minor degree of influence. Therefore, the challenge of fixing the maximum thickness ratio in actual machining due to multi-step processes can be resolved through micro-adjustments. Simultaneously, in engineering applications, workpiece surface defects exhibit varying depths and require different removal amounts after cladding. This study provides further theoretical guidance for repairing and remanufacturing surface defects with diverse depths.

The study of complex networks is to discover the characteristics of these connections and to discover the nature of the system between them. Link prediction method is a classic in the study of complex networks. It ca not only reflect the relationship between the node similarity. More can be estimated through the edge, which reveals the intrinsic factors of network evolution, namely the network evolution mechanism. Threat information network is the evolution and development of the network. The introduction of such a complex network of interdisciplinary approach is an innovative research perspective to observe that the threat intelligence occurs. The characteristics of the network show, at the same time, also can predict what will happen. The evolution of the network for network security situational awareness of the research provides a new approach.

Inclusions in wrought superalloys significantly affect the stability of the alloy properties and limit their use and development in aeroengines and other applications. The types and sources of inclusions in wrought superalloys were reviewed with analysis of the conditions of inclusion formation from the viewpoints of thermodynamics and kinetics. The thermodynamic data for inclusion formation in nickel-based and cobalt-based alloys were summarized and improved. The damage of inclusions to the fatigue and tensile properties and workability of these alloys and the mechanisms of crack initiation and propagation caused by inclusions were also discussed, and the effects of inclusions with different characteristics on crack propagation were reviewed. In addition, the control methods and mechanisms of inclusions in the triple smelting process (vacuum induction melting + protective electroslag remelting + vacuum arc remelting) were covered, providing a reference for improving the control technology of inclusions in wrought superalloys. Finally, the difficulties and development trends for inclusion control in wrought superalloys were discussed.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Sorafenib (sfb) is widely used in clinics for advanced HCC therapy. However, the therapeutic efficacy of sfb is suboptimal due to its poor water solubility, low bioavailability, and side effects. Here, we employed a clinically safe polymer poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) to prepare a nanoparticle (NP)-based sfb formulation (NP-sfb) and tested its antitumor effect in multiple HCC models. NP-sfb could achieve effective drug loading and remain stable under physiological conditions. NP-sfb could be taken up by HepG2, Hepa1-6, and H22 cells and could efficiently inhibit cell proliferation and/or promote cell apoptosis. In vivostudies indicated that NP-sfb showed significantly improved therapeutic efficacy compared with free-sfb at the same dose or even higher doses. Mechanistic studies demonstrated that NP-sfb not only inhibited tumor proliferation and angiogenesis but also stimulated the tumor microenvironment by reducing the infiltration of immunosuppressive myeloid cells and increasing the ratio of cytotoxic T cells. This study demonstrates that the NP-based formulation is a promising strategy to improve the clinical application of sfb.

ABSTRACTWe aimed to explore the role of miR-21-5p in the inhibitory effects of astragaloside IV (As-IV) on hypoxia/reoxygenation injury-induced apoptosis of type II alveolar epithelial cells. Rat type II alveolar epithelial cells RLE-6TN were cultured in vitroand randomly divided into control (C), hypoxia/reoxygenation injury (H/R), As-IV and miR-21-5p-siRNA + As-IV groups (n = 6). H/R model was established by 24 h of hypoxia and 4 h of reoxygenation. As-IV group was given 1 nmol/L As-IV and incubated for 1 h before modeling. MiR-21-5p-siRNA + As-IV group was transfected with 50 nmol/L miR-21-5p-siRNA. After 48 h, they were incubated with 1 nmol/L As-IV for 1 h before modeling. Cell viability was detected by cell counting kit-8 assay, and apoptosis rate was detected by flow cytometry. The expression levels of TLR4 and NF-κB were measured by immunofluorescence assay. The targeting relationship between miR-21-5p and TLR4 was determined by luciferase assay. Compared with H/R group, the cell viability, miR-21-5p, bax and cleaved caspase-3 expressions of As-IV group increased, apoptosis rate and Bcl-2 expression decreased, and TLR4 and NF-κB expressions were down-regulated (P < 0.05). Compared with As-IV group, the cell viability, miR-21-5p, bax and cleaved caspase-3 expressions of miR-21-5p-siRNA + As-IV group decreased, apoptosis rate and Bcl-2 expression increased, and the expressions of TLR4 and NF-κB were up-regulated (P < 0.05). As-IV up-regulates miR-21-5p expression, inhibits the TLR4/NF-κB signaling pathway and suppresses the apoptosis of type II alveolar epithelial cells during hypoxia/reoxygenation injury.

The relaxation properties of GH4169 alloy were studied contrastively at temperatures ranging from 600 oC to 700 °C and initial stress ranging from 550 MPa to 850 MPa. The relationship between the microstructure and relaxation behavior was evaluated using transmission electron microscopy techniques. It was found that the relaxation limit and relaxation stability of the alloy decreased obviously with the increase of temperature. Further investigations show that the relaxation behavior is mainly depend on both precipitate characteristics and its interaction with dislocations. The alloy with higher strength lever has more excellent stress relaxation stability, because of the inhibition of a large number subgrains on dislocations motion.

Six Cd(II) coordination polymers (CPs) {[Cd(mbbt)(1,2-bdc)(H2O)]·H2O}n(1), [Cd(mbbt)(1,3-bdc)]n(2), [Cd(mbbt)2(1,4-bdc)]n(3), [Cd(mbbt)(1,4-ndc)]n(4), [Cd(mbbt)(1,3-adc)]n(5), and {[Cd(mbbt)(1,3-ada)(H2O)]·H2O}n(6) were constructed by selecting dicarboxylate ligands in the system Cd(II)/mbbt (mbbt = 1-(2-methylbenzimidazol-1-ylmethyl)benzotriazole, 1,2-H2bdc = 1,2-benzenedicarboxylic acid, 1,3-H2bdc = 1,3-benzenedicarboxylic acid, 1,4-H2bdc = 1,4-benzenedicarboxylic acid, 1,4-H2ndc = 1,4-naphthalenedicarboxylic acid, 1,3-H2adc = 1,3-adamantanedicarboxylic acid, 1,3-H2ada = 1,3-adamantanediacetic acid). Structural analyses indicate that CP 1manifests a three-dimensional (3D) 66-diaframework. CP 2displays a 3D 412·63network based on dinuclear units Cd2(COO)2. CP 3shows a one-dimensional (1D) zigzag chain structure. CP 4presents a 65·8 framework with paddle-wheel-like Cd2(COO)4secondary building units. CPs 5and 6show a 1D double-chain structure and a 1D linear chain structure, respectively. The structural discrepancy of CPs 1–6demonstrates that dicarboxylate ligands have a major impact on the structures of CPs. Furthermore, CP 4shows remarkable sensing performance for Fe3+ions and pesticides with luminescent quenching, which can function as a luminescent sensor for Fe3+ions and pesticides.

Tumor-infiltrating dendritic cells (TIDCs) are mostly immature and immunosuppressive, usually mediating immune inhibition. The utilization of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate the activation of TIDCs has been demonstrated to be effective for improving antitumor immunity. However, a series of biological barriers has limited the efficacy of previous nanocarriers for delivering CpG to TIDCs. Herein, we developed a dual-sensitive dendrimer cluster-based nanoadjuvant for delivering CpG ODNs into TIDCs. We show that the tumor acidity triggers the rapid release of CpG conjugated polyamidoamine (PAMAM) dendrimers from the nanoadjuvant, thus facilitating its perfusion deep into tumors and phagocytosis by TIDCs. Thereafter, the reductive condition of the endolysosomes led to the subsequent release of CpG, which promotes the DCs activation and enhances antitumor immunotherapies. Programmable delivery of immune adjuvant efficiently overcomes the barriers for targeted delivery to TIDCs and provides a promising strategy for improving cancer immunotherapy.

The machinability of the Al–Si alloys becomes worse with the Si content increasing. This article explored the influence of Si content on the machinability including cutting forces and chip breakability in machining the Al–Si alloys. The change in machinability of the Al–Si alloys with different Si content attributes to the evolution of microstructure. The cutting forces when cutting hypoeutectic Al–Si alloys are higher than the hypereutectic alloys because only Mg2Si (β-phase) precipitations are formed in the former one versus cooperative precipitation of Al2Cu (θ-phase) and Mg2Si in the latter. With regard to hypereutectic Al–Si alloys, cutting force components decrease with the increase in Si content due to the formation of brittle primary Si, which induces the initiation of cracks in material removal process. Moreover, the cutting stability of Al–Si alloys is improved with Si contents in the range of 12–18 wt%, while deteriorates for the Si content of 25 wt%. Besides, the chip breakability is improved due to the increase in eutectic silicon in hypoeutectic and eutectic ranges and because of the formation of block-shaped primary Si for hypereutectic alloys. The optimization of Si content is 12–18 wt% with cutting speed not less than 150 m/min.

As a new object in judicial practice, electronic evidence is of great practical significance. To locate the probative force of electronic evidence, which can be used to prove the facts of the crime, judging the electronic evidence validity, and how to establish scientific rules of electronic evidence, which not only effectively contains crime, but also protects civil rights from illegal infringement of state power becomes very important. This article outlines the definition of electronic evidence and rules and establishes a suitable electronic evidence system of China's criminal procedure system based on the analysis of problems in each link of judicial proof in judicial practice and the four aspects of judicial proof.

The Al3Ti compound has potential application in the high temperature structure materials due to its low density, high strength and stiffness. The mechanical behaviors of the material under different loading rates were studied using compression tests. The results indicate that Al3Ti is a typical brittle material and its compressive strength is dependent on the strain rate. Therefore, a series of rate-dependent constitutive equations are needed to describe its mechanical behaviors accurately. However, it is still short of professional research on the material model for Al3Ti. In this study, the material model was developed on the basis of JH-2 constitutive equations using the experimental data. The model was then applied in simulating the impact process of Ti/Al3Ti metal-intermetallic laminate composites so as to validate the established model. Good agreement between simulation and experiment results shows the constitutive model predict the material responses under high rate and large deformation accurately. This work provides more support for the theoretical and numerical research on the intermetallic.

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor. Its therapeutic efficacy is much lower than that of traditional lymphoma, largely due to the presence of the blood–brain barrier (BBB), which hinders the effective drug delivery and deposition on the disease site. Angiopep-2 (ANG) can target low-density lipoprotein receptor-related protein (LRP) on the surface of brain capillary endothelial cells (BCECs) and exhibits high BBB transport capability. In this study, we designed an ANG conjugated poly(ethylene glycol)-b-poly(-caprolactone) (PEG-b-PCL) (APP) nanoparticle to deliver doxorubicin (DOX) for the treatment of PCNSL. Our data indicated that the targeted APP nanoparticles showed significantly increased cellular uptake by BCECs compared with the control nanoparticles. In the intracranial SU-DHL-2-LUC lymphoma xenograft mice model, APP enhanced drug deposition in tumor tissues, and DOX-loaded APP (APP@DOX) exhibited a better therapeutic effect than free DOX and nontargeted PP@DOX, which significantly prolonged the survival time of mice.

The reliability of data centers can be severely affected when battery failure occurs in the Uninterruptible Power Supply (UPS). Thus it has become a central issue for the industry to discover failure-impending batteries in UPS. In this paper, we consider this important problem and present a data-driven method for predictive battery maintenance. The major contributions are as follows.First, we develop a changepoint detection technique for efficient data labeling. Second, new features are designed to fully utilize the dataset. Third, we build a predictive classification model which can discriminate between healthy and failure-impending batteries. Our method has been built and evaluated on 209,912,615 records from Tencent data center involving nearly 300 batteries monitored over 2 years. The experiment on test set shows that our method is able to predict battery replacement with 98% accuracy and averagely 15 days in advance, which outperforms the previous maintenance policy by more than 8%.

In recent years, small nanoparticles (NPs) with a diameter of less than 10 nm have aroused considerable interest in biomedical applications. However, their intratumor performance, as well as the antitumor efficacy, has not been well understood due to their size-dependent pharmacokinetics, which presents a formidable challenge for delivering a comparable amount of different small NPs to tumor tissues. Utilizing the multistage delivery strategy, we construct G3-, G5-, and G7-iCluster delivery systems by using poly(amidoamine) (PAMAM) dendrimers of different generations (G3-, G5-, and G7-PAMAM) as building blocks. The iCluster nanoparticles showed comparable pharmacokinetics and similar initial tumor deposition due to their similarity in size and surface chemistry. After accumulating at a tumor site, individual small dendrimers were released, and thus, their intratumor performance was comparatively investigated. Our results indicated that a subtle change in generation markedly affects their intratumor activities. G5-iCluster outperformed G3-iCluster and G7-iCluster in the treatment efficacy in an orthotopic pancreatic tumor model. The mechanistic study revealed that G3-PAMAM showed reduced particle retention in tumor tissue due to its small size and weak cell internalization, while G7-PAMAM was much less penetrative because of its relatively large size and strong particle–cell interaction. In contrast, G5-PAMAM exhibited balanced tumor penetration, cell internalization, and tumor retention. Our finding highlights the huge influence of the subtle difference of small NPs in their intratumor performance.

Compacted graphite iron is one of the existing structural materials for automobile engines that is difficult to machine using the conventional machining method. This article focuses on the effects of cutting fluid with different pressures and jetting paths on machined surface integrity in the machining of compacted graphite iron. The machined surface integrity is compared between dry cutting and 6 MPa wet cutting at cutting speeds of 100–500 m/min and the influences of the cutting fluid jetting paths (pouring, 2–6 MPa) along the tool flank face and rake face on the machined surface integrity are evaluated. Microstructure, roughness, work hardening, and residual stresses of the machined surface are also analyzed. The results suggest that cutting fluid can reduce surface defects and improve the machined surface finish. Of note, the roughness reduction effect decreases with an increase in fluid pressure; the roughness Ra of 6 MPa wet cutting with the cutting fluid jetting along the flank face is 0.2–1.56 µm lower than that seen with dry cutting in the cutting speed range of 100–500 m/min. The degree of hardening in 6 MPa wet cutting is 11%–19% lower than in dry cutting, and cutting fluid enhances the formation of residual compressive stress in the machined surface which reaches its maximum at 3 MPa.

V-domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in regulating innate and adaptive immune responses within the tumor immune microenvironment. Quantifying VISTA expression is necessary to determine whether patients respond to a related combination immunotherapy. This study developed two 68Ga-labeled small-molecule probes ([68Ga]Ga-DCA and [68Ga]Ga-DNCA) for visualizing and differentiating VISTA expression. These probes exhibited excellent targeting capabilities for multiple tumor types (including B16-F10, 4T1, MC38, and CT26 tumors), consistent with the levels of VISTA expression determined by immunoblotting. Co-injection of inhibitor CA-170 led to decreased tumor uptake of both [68Ga]Ga-DCA and [68Ga]Ga-DNCA. [68Ga]Ga-DCA was used to verify the feasibility of monitoring VISTA expression in lung metastasis models. In summary, this study describes the use of 68Ga-labeled CA-170 analogues as small-molecule probes for imaging VISTA. This could provide a visual method and enable personalized immunotherapy in patients.