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Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid tumors. Repolarizing TAMs from M2 to the antitumor M1 phenotype is crucial for reshaping the tumor immunosuppressive microenvironment (TIME). Herein, we developed self-assembled nanoparticles from the polymeric prodrug of resiquimod (R848) to reprogram the TIME for robust cancer immunotherapy. The polymeric prodrug was constructed by conjugating the R848 derivative to terminal amino groups of the linear dendritic polymer composed of linear poly(ethylene glycol) and lysine dendrimer. The amphiphilic prodrug self-assembled into nanoparticles (PLRS) of around 35 nm with a spherical morphology. PLRS nanoparticles could be internalized by antigen-presenting cells (APCs) in vitroand thus efficiently repolarized macrophages from M2 to M1 and facilitated the maturation of APCs. In addition, PLRS significantly inhibited tumor growth in the 4T1 orthotopic breast cancer model with much lower systemic side effects. Mechanistic studies suggested that PLRS significantly stimulated the TIME by repolarizing TAMs into the M1 phenotype and increased the infiltration of cytotoxic T cells into the tumor. This study provides an effective polymeric prodrug-based strategy to improve the therapeutic efficacy of R848 in cancer immunotherapy.

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.

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.

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.

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.

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 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.

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.

Enabling macrophages to phagocytose tumor cells holds great potential for cancer therapy but suffers from tremendous challenges because the tumor cells upregulate antiphagocytosis molecules (such as CD47) on their surface. The blockade of CD47 alone is insufficient to stimulate tumor cell phagocytosis in solid tumors due to the lack of “eat me” signals. Herein, a degradable mesoporous silica nanoparticle (MSN) is reported to simultaneously deliver anti-CD47 antibodies (aCD47) and doxorubicin (DOX) for cancer chemo-immunotherapy. The codelivery nanocarrier aCD47-DMSN was constructed by accommodating DOX within the mesoporous cavity, while adsorbing aCD47 on the surface of MSN. aCD47 blocks the CD47-SIRPα axis to disable the “don’t eat me” signal, while DOX induces immunogenic tumor cell death (ICD) for calreticulin exposure as an “eat me” signal. This design facilitated the phagocytosis of tumor cells by macrophages, which enhanced antigen cross-presentation and elicited efficient T cell-mediated immune response. In 4T1 and B16F10 murine tumor models, aCD47-DMSN generated a strong antitumor effect after intravenous injection by increasing tumor-infiltration of CD8+T cells. Taken together, this study offers a nanoplatform to modulate the phagocytosis of macrophages for efficacious cancer chemo-immunotherapy.

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.

Cancer vaccines have received tremendous attention in cancer immunotherapy due to their capability to induce a tumor-specific immune response. However, their effectiveness is compromised by the insufficient spatiotemporal delivery of antigens and adjuvants in the subcellular level to induce a robust CD8+T cell response. Herein, a cancer nanovaccine G5-pBA/OVA@Mn is prepared through multiple interactions of manganese ions (Mn2+), benzoic acid (BA)-modified fifth generation polyamidoamine (G5-PAMAM) dendrimer, and the model protein antigen ovalbumin (OVA). In the nanovaccine, Mn2+not only exerts a structural function to assist OVA loading as well as its endosomal escape, but works as an adjuvant of stimulator of interferon genes (STING) pathway. These collaboratively facilitate the orchestrated codelivery of OVA antigen and Mn2+into cell cytoplasm. Vaccination with G5-pBA/OVA@Mn not only shows a prophylactic effect, but also significantly inhibits growth against B16-OVA tumors, indicating its great potential for cancer immunotherapy.

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.

Graphical Abstract:

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.

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.

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.

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.

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.

This study aims to develop a new folate receptor (FR)-targeting agent for SPECT imaging with improved contrast and evaluate the modification strategies of multimerization and/or PEGylation in the development of new radio-folates. A series of novel folate derivatives have been synthesized and radiolabeled with 99mTc using tricine and TPPTS as coligands. To better investigate their pharmacokinetics, cell uptake, biodistribution, and microSPECT/CT imaging were evaluated. Four radioligands displayed high KB cell uptake after incubation for 2 and 4 h. Presaturated with excess folic acid (FA) resulted in a significant blocking effect in KB cells, indicating specificity of these radioligands toward FR. Biodistribution and microSPECT imaging studies in KB tumor-bearing mice showed that the folate conjugate 99mTc-HYNFA with poly(ethylene glycol) (PEG) and triazole linkage displayed the highest tumor uptake (16.30 ± 2.01 %ID/g at 2 h p.i. and 14.9 ± 0.62 %ID/g at 4 h p.i. in mice biodistribution) and best imaging contrast, indicating promising application prospect. More interestingly, the in vivo performance of this monomeric 99mTc-HYNFA was much better than that of FA multimers and non-PEGylated monomers, suggesting that multimerization may not be a feasible method for the design of radio-folates. PEG linkage rather than FA multimerization should be taken into consideration in the development of folate-based radiopharmaceuticals in the future.

Preventing thermal runaway (TR) propagation in lithium-ion battery (LIB) modules is essential for the safe application of LIBs. The current study proposes a novel dual-purpose system using a liquid cooling pipe with aperture sealed by films (LCPASF). The system can maintain the module within the desired temperature by the rapid heat dissipation of the liquid cooling during the normal operation. Once TR occurs, the film on the aperture of the pipe melts and the coolant in the pipe correspondingly releases to cool the cells to prevent the TR propagation. Induced by heater, all of the cells in the module get involved in TR without preventing measures. Systems using polyethylene (PE), biaxially oriented polypropylene (BOPP), polyimide (PI) and polytetrafluoroethylene (PTFE) films limit the TR within 0, 1, 1 and 3 cells, respectively. The melting temperature of PE is much lower than the TR onset temperature, thus the PE film melts before the TR occurrence and no cells get TR. For the film with melting temperature much higher than the TR onset temperature, increasing the aperture diameter can improve the cooling effect. This study provides critical insights for the design of thermal management and TR propagation mitigation system for LIB modules.

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.

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.