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Abstract Myocardial ischemia-reperfusion (I/R) injury, often arising from interventional therapy for acute myocardial infarction, leads to irreversible myocardial cell death. While previous studies indicate that nucleostemin (NS) is induced by myocardial I/R injury and mitigates myocardial cell apoptosis, the underlying mechanisms are poorly understood. Here, our study reveals that NS upregulation is critical for preventing cardiomyocyte death following myocardial I/R injury. Elevated NS protein levels were observed in myocardial I/R injury mouse and rat models, as well as Hypoxia/reoxygenation (H/R) cardiac cell lines (H9C2 cells). We identified binding sites for c-Jun and HIF-1α in the NS promoter region. Inhibition of JNK and HIF-1α led to a significant decrease in NS transcription and protein expression. Furthermore, inhibition of autophagy and NS expression promoted myocardial cell apoptosis in H/R. Notably, the cell model showed reduced LC3I transformation to LC3II, downregulated Beclin1, upregulated p62, and altered expression of autophagy-related proteins upon NS interference in H/R cells. These findings suggest that NS expression, driven by c-Jun and HIF-1α pathways, facilitates autophagy, providing protection against both myocardial I/R injury and H/R-induced cardiomyocyte apoptosis.

In the present work, the corrosion behaviour of 2A97 Al-Cu-Li alloy with different thermomechanical treatments is investigated using electron microscopy and electrochemical measurements. The various thermomechanical treatments allowed the assessment of the individual and synergistic influence of local plastic deformation and precipitation on the corrosion susceptibility and mechanism of the alloy. It is found that in NaCl solution, corrosion of the alloys in T3 and T4 tempers occurs in the form of intergranular corrosion, which is closely associated with stored energy distribution. By contrast, the alloys in T6 and T8 tempers exhibit mainly intragranular corrosion due to high volume fractions of precipitates formed by artificial ageing.

Abstract Background Pancreatic adenocarcinomas (PAADs) often exhibit a “cold” or immunosuppressive tumor milieu, which is associated with resistance to immune checkpoint blockade therapy; however, the underlying mechanisms are incompletely understood. Here, we aimed to improve our understanding of the molecular mechanisms occurring in the tumor microenvironment and to identify biomarkers, therapeutic targets, and potential drugs to improve PAAD treatment. Methods Patients were categorized according to immunologically hot or cold PAAD subtypes with distinct disease outcomes. Cox regression and weighted correlation network analysis were performed to construct a novel gene signature, referred to as ‘Downregulated in hot tumors, Prognostic, and Immune-Related Genes’ (DPIRGs), which was used to develop prognostic models for PAAD via machine learning (ML). The role of DPIRGs in PAAD was comprehensively analyzed, and biomarker genes able to distinguish PAAD immune subtypes and predict prognosis were identified by ML. The expression of biomarkers was verified using public single-cell transcriptomic and proteomic resources. Drug candidates for turning cold tumors hot and corresponding target proteins were identified via molecular docking studies. Results Using the DPIRG signature as input data, a combination of survival random forest and partial least squares regression Cox was selected from 137 ML combinations to construct an optimized PAAD prognostic model. The effects and molecular mechanisms of DPIRGs were investigated by analysis of genetic/epigenetic alterations, immune infiltration, pathway enrichment, and miRNA regulation. Biomarkers and potential therapeutic targets, including PLEC, TRPV1, and ITGB4, among others, were identified, and the cell type-specific expression of the biomarkers was validated. Drug candidates, including thalidomide, SB-431542, and bleomycin A2, were identified based on their ability to modulate DPIRG expression favorably. Conclusions By combining multiple ML algorithms, we developed a novel prognostic model with excellent performance in PAAD cohorts. ML also proved to be powerful for identifying biomarkers and potential targets for improved PAAD patient stratification and immunotherapy.

Abstract EGFR mutations are critical oncogenic drivers in lung adenocarcinoma (LUAD). However, the mechanisms by which they impact the tumor microenvironment (TME) and tumor immunity are unclear. Furthermore, the reasons underlying the poor response of EGFR-mutant (EGFR-MU) LUADs to immunotherapy with PD-1/PD-L1 inhibitors are unknown. Utilizing single-cell RNA (sc-RNA) and bulk RNA sequencing datasets, we conducted high-dimensional weighted gene coexpression network analysis to identify key genes and immune-related pathways contributing to the immunosuppressive TME. EGFR-MU cancer cells downregulated MHC class I genes to evade CD8+ cytotoxic T cells, expressed substantial levels of MHC class II molecules, and engaged with CD4+ regulatory T cells (Tregs). EGFR-MU tumors may recruit Tregs primarily through the CCL17/CCL22/CCR4 axis, leading to a Treg-enriched TME. High levels of MHC class II-positive cancer-associated fibroblasts and tumor endothelial cells were found within EGFR-MU tumors. Owing to the absence of costimulatory factors, they may inhibit rather than activate the tumor antigen-specific CD4+ T-cell response, contributing further to immune suppression. Multiplex immunohistochemistry analyses in a LUAD cohort confirmed increased expression of MHC class II molecules in cancer cells and fibroblasts in EGFR-MU tumors. Our research elucidates the highly immunosuppressive TME in EGFR-MU LUAD and suggests potential targets for effective immunotherapy.

The aluminum alloys used in aerospace applications are susceptible to corrosion. This has led to the development of methodologies that ensure the durability of the parts and pieces of aircraft. These anticorrosive processes involve the use of coatings containing chromate-based corrosion-inhibitor compounds. Although these coatings provide an excellent solution to this problem, their use in protection protocols is restricted owing to their high toxicity and carcinogenic nature.This study evaluates a different process to protect aluminum alloy surfaces that incorporates the derivatization of organic compounds using potentiostatic techniques. The metallic surface was modified in situ by the potentiostatic reduction of aryl diazonium salts, leaving the surface covered with molecular grafts. The grafting of molecules onto the surface is modulated by the application of a potential that causes the formation of aryl radicals. The organic compound selected in this study was p-toluidine in protic medium. The derivatization process in the AA2060-T8 alloy was carried out at different pHs and potentials, observing from the potential/current responses in 0.1 M NaCl solution that the maximum optimization is obtained at pH 3 and -1 V.Likewise, the E/I and electrochemical impedance (EIS) responses of the electrografted samples modified and functionalized with cerium 4-hydroxycinnamate (Ce(4-OHcinn)3) revealed that the presence of this compound in the arylic structure significantly increased the protective capacity of the organic film electrografted on the aluminum alloy.The morphologies and characteristics of the modified surface were studied by SEM, TEM, and XPS. Furthermore, TEM examinations of ultramicrotomed sections of the electrografted specimens revealed the presence of a film approximately 10 nm thick on the AA2060-T8 surface.

Abstract The electrical outputs of single-layer antiferromagnetic memory devices relying on the anisotropic magnetoresistance effect are typically rather small at room temperature. Here we report a new type of antiferromagnetic memory based on the spin phase change in a Mn-Ir binary intermetallic thin film at a composition within the phase boundary between its collinear and noncollinear phases. Via a small piezoelectric strain, the spin structure of this composition-boundary metal is reversibly interconverted, leading to a large nonvolatile room-temperature resistance modulation that is two orders of magnitude greater than the anisotropic magnetoresistance effect for a metal, mimicking the well-established phase change memory from a quantum spin degree of freedom. In addition, this antiferromagnetic spin phase change memory exhibits remarkable time and temperature stabilities, and is robust in a magnetic field high up to 60 T.

Abstract Microbial necromass carbon (MNC) can reflect soil carbon (C) sequestration capacity. However, changes in the reserves of MNC in response to warming in alpine grasslands across the Tibetan Plateau are currently unclear. Based on large-scale sampling and published observations, we divided eco-clusters based on dominant phylotypes, calculated their relative abundance, and found that their averaged importance to MNC was higher than most other environmental variables. With a deep learning model based on stacked autoencoder, we proved that using eco-cluster relative abundance as the input variable of the model can accurately predict the overall distribution of MNC under current and warming conditions. It implied that warming could lead to an overall increase in the MNC in grassland topsoil across the Tibetan Plateau, with an average increase of 7.49 mg/g, a 68.3% increase. Collectively, this study concludes that alpine grassland has the tendency to increase soil C sequestration capacity on the Tibetan Plateau under future warming.

Purse-string suture with nylon cords and metal clips under the endoscope is a novel therapeutic technique which is minimally invasive and it is particularly indicated for the closure and repair of gastrointestinal fistula or perforations such as duodenal fistulae. Duodenal fistulae are often caused by medical manipulation, disease progression or trauma. Once this occurs, it leads to a series of pathophysiologic changes and a variety of complications. In most cases, these complications will exacerbate the damage to the organism, and the complications are difficult to treat and can lead to infections, nutrient loss, multi-organ dysfunction and many other adverse effects. In this case report, the use of endoscopic nylon cords combined with purse-string suture and metal clips in the treatment of duodenal fistula is presented and discussed. The patient was treated with endoscopic purse-string suture and the duodenal fistula was significantly improved. The results indicate that endoscopic purse-string suture is an effective strategy for the treatment of duodenal fistulae.

Abstract Quantum Chromodynamics, the theory of quarks and gluons, whose interactions can be described by a local SU(3) gauge symmetry with charges called “color quantum numbers”, is reviewed; the goal of this review is to provide advanced Ph.D. students a comprehensive handbook, helpful for their research. When QCD was “discovered” 50 years ago, the idea that quarks could exist, but not be observed, left most physicists unconvinced. Then, with the discovery of charmonium in 1974 and the explanation of its excited states using the Cornell potential, consisting of the sum of a Coulomb-like attraction and a long range linear confining potential, the theory was suddenly widely accepted. This paradigm shift is now referred to as the November revolution. It had been anticipated by the observation of scaling in deep inelastic scattering, and was followed by the discovery of gluons in three-jet events. The parameters of QCD include the running coupling constant, $$\alpha _s(Q^2)$$ α s ( Q 2 ) , that varies with the energy scale $$Q^2$$ Q 2 characterising the interaction, and six quark masses. QCD cannot be solved analytically, at least not yet, and the large value of $$\alpha _s$$ α s at low momentum transfers limits perturbative calculations to the high-energy region where $$Q^2\gg \varLambda _{{\textrm{QCD}}} ^2\simeq $$ Q 2 ≫ Λ QCD 2 ≃ (250 MeV) $$^2$$ 2 . Lattice QCD (LQCD), numerical calculations on a discretized space-time lattice, is discussed in detail, the dynamics of the QCD vacuum is visualized, and the expected spectra of mesons and baryons are displayed. Progress in lattice calculations of the structure of nucleons and of quantities related to the phase diagram of dense and hot (or cold) hadronic matter are reviewed. Methods and examples of how to calculate hadronic corrections to weak matrix elements on a lattice are outlined. The wide variety of analytical approximations currently in use, and the accuracy of these approximations, are reviewed. These methods range from the Bethe–Salpeter, Dyson–Schwinger coupled relativistic equations, which are formulated in both Minkowski or Euclidean spaces, to expansions of multi-quark states in a set of basis functions using light-front coordinates, to the AdS/QCD method that imbeds 4-dimensional QCD in a 5-dimensional deSitter space, allowing confinement and spontaneous chiral symmetry breaking to be described in a novel way. Models that assume the number of colors is very large, i.e. make use of the large $$N_c$$ N c -limit, give unique insights. Many other techniques that are tailored to specific problems, such as perturbative expansions for high energy scattering or approximate calculations using the operator product expansion are discussed. The very powerful effective field theory techniques that are successful for low energy nuclear systems (chiral effective theory), or for non-relativistic systems involving heavy quarks, or the treatment of gluon exchanges between energetic, collinear partons encountered in jets, are discussed. The spectroscopy of mesons and baryons has played an important historical role in the development of QCD. The famous X,Y,Z states – and the discovery of pentaquarks – have revolutionized hadron spectroscopy; their status and interpretation are reviewed as well as recent progress in the identification of glueballs and hybrids in light-meson spectroscopy. These exotic states add to the spectrum of expected $$q{{\bar{q}}}$$ q q ¯ mesons and qqq baryons. The progress in understanding excitations of light and heavy baryons is discussed. The nucleon as the lightest baryon is discussed extensively, its form factors, its partonic structure and the status of the attempt to determine a three-dimensional picture of the parton distribution. An experimental program to study the phase diagram of QCD at high temperature and density started with fixed target experiments in various laboratories in the second half of the 1980s, and then, in this century, with colliders. QCD thermodynamics at high temperature became accessible to LQCD, and numerical results on chiral and deconfinement transitions and properties of the deconfined and chirally restored form of strongly interacting matter, called the Quark–Gluon Plasma (QGP), have become very precise by now. These results can now be confronted with experimental data that are sensitive to the nature of the phase transition. There is clear evidence that the QGP phase is created. This phase of QCD matter can already be characterized by some properties that indicate, within a temperature range of a few times the pseudocritical temperature, the medium behaves like a near ideal liquid. Experimental observables are presented that demonstrate deconfinement. High and ultrahigh density QCD matter at moderate and low temperatures shows interesting features and new phases that are of astrophysical relevance. They are reviewed here and some of the astrophysical implications are discussed. Perturbative QCD and methods to describe the different aspects of scattering processes are discussed. The primary parton–parton scattering in a collision is calculated in perturbative QCD with increasing complexity. The radiation of soft gluons can spoil the perturbative convergence, this can be cured by resummation techniques, which are also described here. Realistic descriptions of QCD scattering events need to model the cascade of quark and gluon splittings until hadron formation sets in, which is done by parton showers. The full event simulation can be performed with Monte Carlo event generators, which simulate the full chain from the hard interaction to the hadronic final states, including the modelling of non-perturbative components. The contribution of the LEP experiments (and of earlier collider experiments) to the study of jets is reviewed. Correlations between jets and the shape of jets had allowed the collaborations to determine the “color factors” – invariants of the SU(3) color group governing the strength of quark–gluon and gluon–gluon interactions. The calculated jet production rates (using perturbative QCD) are shown to agree precisely with data, for jet energies spanning more than five orders of magnitude. The production of jets recoiling against a vector boson, $$W^\pm $$ W ± or Z, is shown to be well understood. The discovery of the Higgs boson was certainly an important milestone in the development of high-energy physics. The couplings of the Higgs boson to massive vector bosons and fermions that have been measured so far support its interpretation as mass-generating boson as predicted by the Standard Model. The study of the Higgs boson recoiling against hadronic jets (without or with heavy flavors) or against vector bosons is also highlighted. Apart from the description of hard interactions taking place at high energies, the understanding of “soft QCD” is also very important. In this respect, Pomeron – and Odderon – exchange, soft and hard diffraction are discussed. Weak decays of quarks and leptons, the quark mixing matrix and the anomalous magnetic moment of the muon are processes which are governed by weak interactions. However, corrections by strong interactions are important, and these are reviewed. As the measured values are incompatible with (most of) the predictions, the question arises: are these discrepancies first hints for New Physics beyond the Standard Model? This volume concludes with a description of future facilities or important upgrades of existing facilities which improve their luminosity by orders of magnitude. The best is yet to come!

It is recently suggested that air-formed film plays an important role in controlling corrosion resistance of Mg-Li alloys. However, the structure of the air-formed film and its effect on corrosion resistance of Mg-Li alloys has not been fully understood. Firstly, the air-formed films formed on α and β phases in a dual-phase LZ91 Mg-Li alloy after exposure to laboratory air for up to 48 h have been examined by SEM under the assistance of ultramicrotomy. Then, the effect of the air-formed film on surface potential and, consequently, corrosion/oxidation behavior of the alloy has been investigated. Finally, in order to exclude the influence from α phase, the structure of the air-formed film on β phase and its effect on corrosion/oxidation behavior of Mg-Li alloys have been studied based on a single-phase LA141 Mg-Li alloy. The results show that the air-formed film is thin and negligible on α phase but thick on β phase after prolonged exposure to laboratory air. The thick air-formed film on β phase has a multilayer structure with an inner layer consisting of MgO/Mg(OH)2 and outer layer consisting of Li2CO3, which greatly elevates the surface potential of β phase in air. Both LZ91 and LA141 Mg-Li alloys firstly undergo uniform corrosion and then filiform corrosion when immersed in NaCl solution and the pre-existed air-formed film on β-Li phase can retard the occurrence of filiform corrosion in the alloys.

The printability of Al6SiMg0·5Er1·0Zr alloy at various laser power, scan speed, and hatch spacing was investigated. The optimal processing window was determined. The relationship between hatch spacing and lack of fusion (LOF) defects and microstructure is discussed. Hatch spacing significantly affects the cellular size, which is formed by eutectic Si network, and medium hatch spacing can achieve the finest microstructure. Samples with high densities and fine microstructures were investigated more carefully. The grain and cellular boundaries have many Al3(Er,Zr) phases. The grain size was refined to 2.64 μm, and the epitaxial growth of columnar crystals was completely suppressed. The cellular structure has been significantly improved. Get the equiaxed - ultrafine equiaxed - columnar multi-cellular structure with dramatically enhanced mechanical properties. The yield strength, tensile strength, and elongation were 373 Mpa, 480 MPa, and 5.5%, respectively. Grain boundary strengthening and Orowan strengthening was the main strengthening mechanisms.

Albumin is derived from human or animal blood, and its ability to bind to a large number of endogenous or exogenous biomolecules makes it an ideal drug carrier. As a result, albumin-based drug delivery systems are increasingly being studied. With these in mind, detailed studies of the transport mechanism of albumin-based drug carriers are particularly important. As albumin receptors, glycoprotein 60 (GP60) and secreted protein acidic and rich in cysteine (SPARC) play a crucial role in the delivery of albumin-based drug carriers. GP60 is expressed on vascular endothelial cells and enables albumin to cross the vascular endothelial cell layer, and SPARC is overexpressed in many types of tumor cells, while it is minimally expressed in normal tissue cells. Thus, this review supplements existing articles by detailing the research history and specific biological functions of GP60 or SPARC and research advances in the delivery of antitumor drugs using albumin as a carrier. Meanwhile, the deficiencies and future perspectives in the study of the interaction of albumin with GP60 and SPARC are also pointed out.

Introduction: Dairy products are loved by people because of their high nutritional value, but they have also become the most ideal breeding places for microorganisms. Some dairy packaging has the problem of lax sealing, resulting in products susceptible to contamination and deterioration. The harmful microorganisms and bacteria contained in them will pose a serious threat to people’s health. Therefore, a good antibacterial protection is very important for dairy products. The purpose of this paper is to study the preparation and reverse recycling logistics of a new type of nano-filled antibacterial layer packaging film for dairy products.Methods: A new type of nano-filled antibacterial layer packaging film is prepared by extrusion casting method, and its mechanical properties and antibacterial properties are analyzed.Results: The experimental results in this article show that the prepared new nano-filled antibacterial layer packaging film has lower light transmittance and water vapor transmission rate, and has obvious antibacterial properties against Staphylococcus aureus and Escherichia coli, and has good barrier properties.Discussion: The antibacterial rate of the bacteria in the petri dish is as high as 99.97% after being placed for 120 days, and the antibacterial performance can be enhanced by the ratio of glycerol and starch content, and the new nano-filled antibacterial film prepared is degradable Sex, can be better recycled.

Infection by the Schistosoma japonicum can result in acute, chronic and late-stage manifestations. The latter often presents with severe organ failures and premature death. Importantly, infection can also produce autoimmune phenomena reflected by the development of autoantibodies. We wished to explore and profile the presence of autoantibodies in sera of patients with different stages of S. japonicum infection with the added aim of providing a reference assisting diagnosis. Blood samples from 55 patients with chronic and 20 patients with late-stage schistosomiasis japonica together, with a control group of 50 healthy people were randomly investigated against a microarray of 121 different autoantigens. In addition, the frequency of antibodies against Schistosoma egg antigen (SEA) was examined. In the sera from patients with chronic schistosomiasis japonica, 14 different highly expressed autoantibodies were detected, while patients with late-stage schistosomiasis were found to express as many as 43 autoantibody specificities together with a significantly higher frequency of antibodies against SEA compared to the control group. The findings presented suggest that autoantibody-based classification of schistosomiasis japonica represents a promising approach for the elucidation of subtypes of the disease. This approach may reflect differential disease mechanisms, which could ultimately lead to better treatment.

Extrachromosomal DNA (ecDNA) is a special class of circular DNA in eukaryotes, which is independent of conventional chromosomes. These circular molecules play important roles in biology, especially in cancer biology. The emergence of sequencing technologies such as CCDA-seq and Amplicon Architect has led to a progressive unraveling of the mystery of ecDNA. Consequently, insights into its function and potential applications have begun to surface. Among these studies, the most noteworthy research pertains to cancer-related investigations into ecDNA. Numerous studies have underscored the significance of ecDNA in the pathogenesis of cancer and its role in accelerating cancer evolution. This review provides an overview of the source, structure, and function of ecDNA, while compiling recent advancements in ecDNA in the field of cancer. Nonetheless, further research is imperative to determine its effectiveness and specificity as a biomarker for early cancer detection.

The constitutive model plays a decisive role in the accuracy and reliability of the simulation results. Because the material flow characteristics obtained by the traditional experimental method are difficult to describe thermoplastic deformation behavior in the cutting process accurately, and the inverse identification is usually carried out based on a two-dimensional orthogonal cutting model, ignoring the actual cutting state, which leads to significant deviations in the results of parameter identification. Therefore, a three-dimensional (3-D) turning finite element simplified model which conforms to the actual cutting scenario was established. Based on this model, a coupling simulation was used to inverse identify the Johnson-Cook (J-C) parameters for turning 304 stainless steel. Firstly, the automatic finite element modeling and calculation of 3-D turning is implemented by Python. Then, the inverse identification framework was built based on the ISIGHT. The initial yield strength of J-C parameters was obtained from quasi-static compression experiments. With the objective function of minimizing the error between the experimental cutting force and the simulated cutting force, the inverse identification of J-C parameters (strain reinforcement factor, strain rate sensitivity, thermal softening index, and hardening index) was carried out by a multi-island genetic algorithm. Finally, compared with cutting forces, chip morphology, and residual stresses, the feasibility of the inverse identification method and the accuracy of the constitutive model is demonstrated, which also provides a reference for the optimal identification method of constitutive parameters of difficult-to-machine materials.

In order to improve the mechanical properties of Al–Si alloys fabricated by selective laser melting process, the microstructure and mechanical properties of Er/Zr modified A357 (Al–7Si-0.6 Mg) alloy in as-built and stress relief annealing conditions were studied. The results show that adding 0.15 wt.% Er helps to refine the cellular size, which is formed by eutectic Si network. The (Al,Si)3(Er,Zr) phases were precipitated during the solidification of Er–Zr composite modified sample, which could act as inoculants to promote the formation of equiaxed grains and refine the grain size. The average grain size of 0.8Er-0.4Zr sample was only 3.1 ± 1.4 μm. The yield strength, tensile strength and elongation reached 333 ± 2 MPa, 454 ± 1 MPa and 12.5 ± 1%, respectively. After stress relief annealing, eutectic Si was spheroidized and its size was increased, resulting in a decrease of strength and an increase of elongation. At the same time, the nano-sized L12-structure particles were precipitated in the Er–Zr composite modified sample, which would make up for the loss of strength and level it up to a certain extent. Therefore, Er–Zr composite modification could be an effective method to improve the comprehensive mechanical properties of SLM processed Al–Si alloys.

Isothermal hot compression experiments of homogenized Al–Mg–Si–Er–Zr alloy were conducted at temperatures ranging from 350 to 500 °C and strain rates of 0.01–10 s−1 on a Gleeble-3500 thermal simulation tester. The hot deformation behavior and optimum processing parameters of the alloy were determined by analyzing the flow curves and processing maps. Characterization of the microstructures of the deformed specimens was done using electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM), and the geometrically necessary dislocation (GND) density was used based on the kernel average misorientation (KAM). The results showed that the GND density decreased with a decrease in the strain rate and with an increase in the deformation temperature. Dynamic recovery and continuous dynamic recrystallization were the main softening mechanisms during hot deformation, and dynamic recovery was dominant. It was found that the capacity for dynamic recovery was reduced, while dynamic recrystallization was prevented in the Al–Mg–Si–Er–Zr alloy. This was a result of hindered dislocations and sub-grain boundary movement caused by the pinning of dislocations and sub-grain boundaries from the Mg2Si, Al(MnFe)Si, and Al3(Er, Zr) particles. The addition of Er and Zr resulted in an increase in the activation energy, which can be attributed to the formation of Al3(Er, Zr) particles.

Fe-rich intermetallics affect critically the mechanical properties and recyclability of aluminium alloys. Increasing effort has been spent on the inoculation of these intermetallics, hoping to promote a finer distribution. Recently Al-5Ti-1B (wt.%), originally developed to refine α-Al, has been shown to refine Al13Fe4, an intermetallic phase present in a variety of Al alloys. However, mechanisms of the formation and growth of the intermetallics on the inoculants are unclear. In this paper, Ti is added to Fe-containing Al alloys to produce a large number of potent Al3Ti particles, the active inoculant in Al-5Ti-1B. We use a combination of electron backscattered diffraction, in situ synchrotron X-ray radiography and post-solidification X-ray computed tomography to investigate the formation and growth of primary Al13Fe4 on Al3Ti inoculants, first in a model Al-Fe alloy, with key insights then confirmed in a high Fe-containing, recycled 6xxx alloy. Crystallographic orientation relationships between Al13Fe4 and Al3Ti are analysed comprehensively, and the formation and growth dynamics of Al13Fe4 on Al3Ti is also unveiled. A strong link is revealed between the formation of Al13Fe4 on Al3Ti and a twinning-related pseudo-symmetry of Al13Fe4. Finally, a potential strategy to refine both intermetallics and α-Al in recycled alloys with elevated Fe concentration is proposed.

Establishing a material constitutive model reflecting the mechanical behavior of metal materials in the cutting process is the basis of cutting finite element simulation, and has an important guiding role in accurately describing the cutting thermo-mechanical coupling state variables and further optimizing process parameters. This paper proposes a reverse identification method of material constitutive parameters based on co-simulation. The influence of mass scaling factor, mesh size, and Johnson-Cook (J-C) constitutive parameters on cutting force was analyzed, and orthogonal cutting experiments were carried out for two difficult-to-machine materials, die steel H13 and titanium alloy Ti-6Al-4V. ABAQUS is redeveloped based on Python, and then the J-C constitutive parameters are directly optimized for the first time with the minimum error between the finite element simulation value and the experimental value of the cutting force as the objective function, the least square identification of J-C constitutive parameters based on co-simulation is realized by combining genetic algorithm. The results show that the reasonable setting of mass scaling factor and mesh size can significantly reduce the time of simulation calculation and improve the optimization efficiency of constitutive parameters. The yield stress, hardening coefficient, strain rate coefficient, hardening coefficient and softening coefficient of materials have different effects on cutting force, which is the key to effective inverse identification of constitutive parameters. Compared with different J-C parameters reported in the literature, it is found that the constitutive parameters obtained by inverse identification based on co-simulation are more accurate, and the prediction of residual stress and serrated chip characteristics also has good accuracy. This study provides a reference for the optimization of constitutive parameters, and the research results provide a new scheme for the efficient construction of material mechanical behavior required for cutting finite element simulation.

Abstract Closely related with microbial activities, soil developments along the glacier forelands are generally considered a carbon sink; however, those of continental glacier forelands remain unclear. Continental glaciers are characterized by dry conditions and low temperature that limit microbial growth. We investigated the carbon characteristics along a chronosequence of the Laohugou Glacier No. 12 foreland, a typical continental glacier on the Tibetan Plateau, by analyzing soil bacterial community structure and microbial carbon-related functional potentials. We found an unexpected carbon loss in which soil organic carbon decreased from 22.21 g kg−1 to 10.77 g kg−1 after receding 50 years. Structural equation modeling verified the important positive impacts from bacterial community. Lower carbon fixation efficiency along the chronosequence was supported by less autotrophic bacteria and carbon fixation genes relating to the reductive tricarboxylic acid cycle. Lower carbon availability and higher carbon requirements were identified by an increasing bacterial copy number and a shift of the dominant bacterial community from Proteobacteria and Bacteroidetes (r-strategists) to Actinobacteria and Acidobacteria (K-strategists). Our findings show that the carbon loss of continental glacier foreland was significantly affected by the changes of bacterial community, and can help to avoid overestimating the carbon sink characteristics of glacier forelands in climate models.

The infiltration and cooling effect of lubricant droplets in the cutting zone largely depend on setting minimum quantity lubricant (MQL) system parameters appropriately. The study determines the optimal spray angle and spray distance relying on the geometric position relationship between the nozzle and the overall cutting zone. A numerical model that combines computational fluid dynamics (CFD) and discrete phase model (DPM) is presented to simulate droplet transport process for dynamic milling and one-tooth milling by flow field distribution and droplet characteristics. The influences of different spray distances and spray angles on the infiltration process and cutting tool temperature are analyzed. The experiments aimed at verifying the results of the analysis are conducted by measuring cutting force, cutting temperature, surface roughness, surface microtopography and tool wear. The result indicates that the spray distance has a significant impact on the jet divergence, and insufficient lubrication or excessive lubrication is effectively avoided with the optimal cutting distance. Spraying in the direction of cutting-out promotes the accessibility of the lubricant and greater concentration of droplets in the cutting zone, especially later in the cutting process, which results in increased infiltration, reduced friction, and improved heat dissipation. Moreover, experiments demonstate that the optimal state of jetting in the direction of cutting-out is 46 °C lower than that of dry cutting, the surface roughness is reduced by 19.8%, and the wear amount is reduced by roughly 34%. This study has a better understanding of the setting of spray distance and spray angle in MQL milling and the development of equipment, which provides theoretical guidance for the optimization of MQL system parameters in practical applications.

In the present work, a novel one-step plasma electrolytic oxidation (PEO) method is developed for the formation of PEO/Mg-Al layered double hydroxide (LDH) composite coating on AZ31 Mg alloy. Through the control of electrolyte concentration, a Mg-Al LDH layer was formed on the surface of the resultant PEO coating. The corrosion properties of the composite coating were evaluated by electrochemical analysis, hydrogen evolution measurement and salt spraying testing, which exhibited improved corrosion resistance due to the presence of the Mg-Al LDH layer. This work provides a new strategy to take advantage of alloying elements in Mg alloys in PEO treatment to enhance corrosion resistance.

Skeletal muscle satellite cells (SMSCs), which are multifunctional muscle-derived stem cells, can differentiate into adipocytes. Long-chain non-coding RNA (lncRNA) has diverse biological functions, including the regulation of gene expression, chromosome silencing, and nuclear transport. However, the regulatory roles and mechanism of lncRNA during adipogenic transdifferentiation in muscle cells have not been thoroughly investigated. Here, porcine SMSCs were isolated, cultured, and induced for adipogenic differentiation. The expressions of lncRNA and mRNA at different time points during transdifferentiation were analysed using RNA-seq analysis. In total, 1005 lncRNAs and 7671 mRNAs showed significant changes in expression at differential differentiation stages. Time-series expression analysis showed that the differentially expressed (DE) lncRNAs and mRNAs were clustered into 5 and 11 different profiles with different changes, respectively. GO, KEGG, and REACTOME enrichment analyses revealed that DE mRNAs with increased expressions during the trans-differentiation were mainly enriched in the pathways for lipid metabolism and fat cell differentiation. The genes with decreased expressions were mainly enriched in the regulation of cell cycle and genetic information processing. In addition, 1883 DE mRNAs were regulated by 193 DE lncRNAs, and these genes were related to the controlling in cell cycle mainly. Notably, three genes in the fatty acid binding protein (FABP) family significantly and continuously increased during trans-differentiation, and 15, 13, and 11 lncRNAs may target FABP3, FABP4, and FABP5 genes by cis- or trans-regulation, respectively. In conclusion, these studies identify a set of new potential regulator for adipogenesis and cell fate and help us in better understanding the molecular mechanisms of trans-differentiation.

Abstract We report a sensitive study of $$D_s^+ \rightarrow \tau ^+ \nu _{\tau }$$ D s + → τ + ν τ decay via $$\tau ^+ \rightarrow e^+ \nu _e \bar{\nu }_{\tau }$$ τ + → e + ν e ν ¯ τ with an integrated luminosity of 1 ab $$^{-1}$$ - 1 at the center-of-mass energy of 4.009 GeV at a future Super Tau Charm Facility (STCF). Under the help of the fast simulation software package, the statistical sensitivity for the absolute branching fraction of $$D_s^+ \rightarrow \tau ^+ \nu _{\tau }$$ D s + → τ + ν τ is determined to be $$2\times 10^{-4}$$ 2 × 10 - 4 . Combining with our previous prospect of $$D_s^+ \rightarrow \mu ^+ \nu _{\mu }$$ D s + → μ + ν μ , the ratio of the branching fractions for $$D_s^+ \rightarrow \tau ^+ \nu _{\tau }$$ D s + → τ + ν τ over $$D_s^+ \rightarrow \mu ^+ \nu _{\mu }$$ D s + → μ + ν μ can achieve a relative statistical precision of 0.5%, which will provide the most stringent test of the $$\tau $$ τ - $$\mu $$ μ lepton flavor universality in heavy quark decays. Taking the decay constant $$f_{D_s^+}$$ f D s + from lattice QCD calculations or the CKM matrix element $$|V_{cs}|$$ | V cs | from the CKMfitter group as an input, the relative statistical uncertainties for $$|V_{cs}|$$ | V cs | and $$f_{D_s^+}$$ f D s + are estimated to be 0.3% and 0.2%, respectively.

Rheumatoid arthritis (RA) is an inflammatory condition that causes severe cartilage degradation and synovial damage in the joints with multiple systemic implications. Previous studies have revealed that fibroblast-like synoviocytes (FLSs) play a pivotal role in the pathogenesis of RA. The appropriate regulation of FLS function is an efficient approach for the treatment of this disease. In the present study, we explored the effects of methyl canthin-6-one-2-carboxylate (Cant), a novel canthin-6-one alkaloid, on the function of FLSs. Our data showed that exposure to Cant significantly suppressed RA-FLS migration and invasion properties in a dose-dependent manner. Meanwhile, pre-treatment with Cant also had an inhibitory effect on the release of several pro-inflammatory cytokines, including IL-6 and IL-1β, as well as the production of MMP1 and MMP3, which are important mediators of FLS invasion. In further mechanistic studies, we found that Cant had an inhibitory effect on the Hippo/YAP signaling pathway. Treatment with Cant suppressed YAP expression and phosphorylation on serine 127 and serine 397 while enhancing LATS1 and MST1 levels, both being important upstream regulators of YAP. Moreover, YAP-specific siRNA or YAP inhibition significantly inhibited wound healing as well as the migration and invasion rate of FLS cells, an impact similar to Cant treatment. Meanwhile, the over-expression of YAP significantly reversed the Cant-induced decline in RA-FLS cell migration and invasion, indicating that YAP was required in the inhibitory effect of Cant on the migration and invasion of RA-FLS cells. Additionally, supplementation of MMP1, but not MMP3, in culture supernatants significantly reversed the inhibitory effect of Cant on RA-FLS cell invasion. Our data collectively demonstrated that Cant may suppress RA-FLS migration and invasion by inhibiting the production of MMP1 via inhibiting the YAP signaling pathway, suggesting a potential of Cant for the further development of anti-RA drugs.

Finite element simulation is able to predict cutting force, temperature, stress distribution and chip formation. Constructing a constitutive model suitable for cutting simulation can accurately describe the state of the cutting process, which plays an important role in improving surface quality as well as optimizing cutting parameters and tool geometric design. Nickel-based superalloys are widely used in aerospace due to their excellent physical and mechanical properties at high temperatures. In this study, J-C parameters reverse identification of Inconel 718 alloy was carried out in both the solution annealed state and precipitation hardened state. The average cutting force and chip thickness were obtained by conducting orthogonal cutting experiments, after which the shear angle was calculated. Through quasi-static compression experiments, the yield strength, strain hardening modulus and hardening index of the material were then obtained. Considering the influence of the cutting-edge radius on cutting force during the cutting process, the Waldorf model was introduced into the analytical model in order to describe the deformation characteristics (strain, temperature, strain rate and stress) of the primary shear zone, after which the shear force was modified. The J-C constitutive parameters of the solution annealed state and precipitation hardened state were inversely identified by the intelligent optimization algorithm. According to the given range of cutting conditions, the accuracy of the method was verified through comparison with the cutting force and chip morphology of the finite element simulation. The differences in quasi-static and cutting dynamic mechanical responses of the two states were subsequently expounded. The effects of tool wear types and cutting parameters on the material flow characteristics at the tool tip as well as the thermal-mechanical load on the machined surface of precipitation hardened state Inconel 718 alloy were analyzed via numerical simulation. Accordingly, this study may provide insight into the identification of constitutive parameters of superalloys as well as the control of machined surface quality.

Doseo depression of Central African Rift System is an important onshore frontier area for oil and gas exploration in Africa, with rift development characterized by the dual control of fault-depression development and strike slip faulting. According to the latest drilling and seismic data in recent years, through the fine seismic interpretation, the calculation of paleo-fault throw and fault growth index and the method of balanced profile cross-section restorations, the fault characteristics and tectonic setting of Doseo depression are analyzed in detail, especially the fault activity, tectonic evolution and genetic mechanism of two large-scale strike slip movements in Doseo depression. The results show that the Doseo depression experienced five main tectonic phases, including two stages of strike slip tectonic movements with different mechanisms. The first stage is characterized by strike slip tectonic movements under tilting extension, which controls the overall structure of the depression. The second stage is characterized by strike slip tectonic movements under transform compression, which play an important role in the formation of some inversion structures and SW-NE trending anticlines and faulted anticlines. The superposition of an early faulted-depression and two later stages of strike slip tectonics led to current pattern of Doseo depression.

IntroductionThe functions of terrestrial ecosystems are mainly maintained by bacteria, as a key component of microorganisms, which actively participate in the nutrient cycling of ecosystems. Currently, there are few studies have been carried out on the bacteria contributing to the soil multi-nutrient cycling in responding to climate warming, which hampers our obtainment of a comprehensive understanding of the ecological function of ecosystems as a whole.MethodsIn this study, the main bacteria taxa contributing to the soil multi-nutrient cycling under the long-term warming in an alpine meadow was determined based onphysichemical properties measurement and high-throughput sequencing, and the potential reasons that warming altered the main bacteria contributing to the soil multi-nutrient cycling were further analyzed.ResultsThe results confirmed that the bacterial β-diversity was crucial to the soil multi-nutrient cycling. Furthermore, Gemmatimonadetes, Actinobacteria, and Proteobacteria were the main contributors to the soil multi-nutrient cycling, and played pivotal roles as keystone nodes and biomarkers throughout the entire soil profile. This suggested that warming altered and shifted the main bacteria contributing to the soil multi-nutrient cycling toward keystone taxa.DiscussionMeanwhile, their relative abundance was higher, which could make them have the advantage of seizing resources in the face of environmental pressures. In summary, the results demonstrated the crucial role of keystone bacteria in the multi-nutrient cycling under the climate warming in the alpine meadow. This has important implications for understanding and exploring the multi-nutrient cycling of alpine ecosystems under the global climate warming.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) accounts for 70% of the total number of patients with cleft lip with or without cleft palate (CL/P) and is the most common type of congenital deformity of the craniomaxillofacial region. In this study, whole exome sequencing (WES) and Sanger sequencing were performed on affected members of a Han Chinese family, and a missense variant in the platelet-derived growth factor C (PDGFC) gene (NM_016205: c.G93T: p.Q31H) was identified to be associated with NSCL/P. Bioinformatic studies demonstrated that the amino acid corresponding to this variation is highly conserved in many mammals and leads to a glutamine-to-histidine substitution in an evolutionarily conserved DNA-binding domain. It was found that the expression of PDGFC was significantly decreased in the dental pulp stem cells (DPSCs) of NSCL/P cases, compared to the controls, and that the variant (NM_016205: c.G93T) reduced the expression of PDGFC. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Pdgfc deficiency disrupted NSCL/P-related signaling pathways such as the MAPK signaling pathway and cell adhesion molecules. In conclusion, our study identified a missense variant (NM_016205: c.G93T) in exon 1 of PDGFC potentially associated with susceptibility to NSCL/P.

Abstract Background Liquid–liquid phase separation (LLPS) within the nucleus is directly linked to driving gene expression through transcriptional complexes. Histone lysine methyltransferase 2D (KMT2D) is widely present in many cancers. It is known to epigenetically stimulate the expression of genes associated with tumorigenesis and metastasis. Our analyses show that KMT2D possesses two distinct low-complexity domains (LCDs) capable of driving the assembly of membrane-less condensates. The dependence of the mechanisms underlying monomethylation of H3K4 on the LLPS microenvironment derived from KMT2D LCDs is unclear in tumor. Methods KMT2D LCD-depletion cells were used to investigate tumor cell proliferation, apoptosis, and migration. We identified some core proteins, including WDR5, RBBP5, and ASH2L, which are involved in the KMT2D-associated catalytic complex in KMT2D LCD-deficient cells to further elucidate the mechanism that decreases monomethylation of H3K4. We also evaluated the viability of KMT2D LCD-deficient cells in vivo. Finally, using 1,6-hexanediol (HD), an inhibitor of LLPS, we determined cell activities associated with KMT2D function in wild-type PANC-1 cells. Results Without the LLPS microenvironment in KMT2D LCD-deficient cells or wild-type PANC-1 cells treated with HD, the WDR5 protein was significantly less stable and the protein–protein interactions between the components of the KMT2D–enzyme complex were attenuated, impairing the formation of the complex. Moreover, with the decrease in H3K4me1 level at enhancers, transcription factors such as LIFR and KLF4 were markedly downregulated, effectively inhibiting tumor progression. In xenograft tumor models, PANC-1 cells lacking the KMT2D LCDs showed effectively suppressed tumor growth compared to normal cells. Conclusions Our data indicate that the two low-complexity domains of the KMT2D protein could form a stable LLPS microenvironment, promoting the KMT2D catalysis of H3K4 monomethylation through stabilization of the WDR5 protein and KMT2D–enzyme complex. Therefore, finding ways to regulate the LLPS microenvironment will be benefitial for new cancer treatment strategies.

In this work, organic coating films loaded with leachable anticorrosive pigments, cerium 4-hydroxycinnamate (Ce(4OHCin)3) and strontium zinc phosphosilicate (SZP 391) were immersed in 3.5% NaCl solution at pH 3, pH 5.6, and pH 10. Extracts from each bulk solutions were taken after 24 h, 72 h, 168 h, 240 h, and 336 h to quantitatively measure the leaching of the inhibitive species as a function of time using inductively coupled plasma optical emission spectroscopy (ICP-OES). Other part of the extracts was also employed as test solution to monitor the inhibitive properties of the leached species on AA2198-T851 substrates using electrochemical impedance spectroscopy (EIS). After the immersion process, the unexposed and exposed film surfaces were characterized using optical microscopy, transmission, and scanning electron microscopy (TEM & SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). The leaching test results confirmed the release of inhibitive species from the coating films into the test solutions, whose rate increased with immersion time but decrease with increasing pH of the bulk solution. Greater leaching rate was observed at the lowest pH, whose release follows non-Fickian diffusion. Furthermore, the EIS results indicated significant protection of the alloy and the efficiency increased with increasing immersion time and decreasing pH. The extract with Ce(4OHCin)3 pigment shows comparatively higher release rate and better inhibitive properties, with the best at the lowest pH 3. This is attributed to its smaller cluster size and high solubility. The optical and electron Microscopy, XRD and FT-IR of coating films have further complemented the leaching process by revealing pores left behind due to dissolution of large clusters. The pores networks provided excellent transport path for both inward migration of aggressive solution and the release of dissolved inhibitive species.

Mammalian transducin-like enhancer of split family proteins (TLEs) are homologous to Drosophila Groucho (Gro) and are essential transcriptional repressors. Seven TLE family members, TLE1-7, have been identified to date. These proteins do not bind DNA directly; instead, they bind a set of transcription factors and thereby inhibit target gene expression. Loss of TLEs in mice usually leads to defective early development; however, TLE functions in developmentally mature cells are unclear. Recent studies have revealed that TLEs are dysregulated in certain human cancer types and may function as oncogenes or tumor suppressors in different contexts. TLE levels also affect the efficacy of cancer treatments and the development of drug resistance. In addition, TLEs play critical roles in the development and function of immune cells, including macrophages and lymphocytes. In this review, we provide updates on the expression, function, and mechanism of TLEs; discuss the roles played by TLEs in tumorigenesis and the inflammatory response; and elaborate on several TLE-associated signaling pathways, including the Notch, Wnt, and MAPK pathways. Finally, we discuss potential strategies for targeting TLEs in cancer therapy.

This paper centers on high-strength Al-Mg-Mn-Er-Zr alloy, which was developed through the addition of Er, a cheap rare earth element, and suitable for additive manufacturing (3D printing). The microstructure and mechanical properties of Al-Mg-Mn-Er-Zr alloy of as-built and heat treated samples have been characterized, which shows: the precipitation of Al3Zr primary phase at the boundary of molten pool promotes heterogeneous nucleation and refines the grains, which suppresses the formation of solidification cracking in Al-Mg alloy. To bring the Er-Zr synergistic effect into play during the aging heat treatment, the nano-scale precipitation phase of Al3Er that diffuses nucleation at an earlier stage promotes the precipitation of Zr, leading to the formation of Al3(Er,Zr) core-shell structure and enhancing precipitation strengthening effect. Under the combined effects of multiple strengthening mechanisms, the yield strength could reach 440 ± 3 MPa; tensile strength, 520 ± 2 MPa and elongation 15.5 ± 1.0 %.

To explore and profile the level of cytokines in the sera of patients infected with Schistosoma japonicum to explore the helper T-cell response of patients either at the chronic or advanced stage of the disease. We randomly selected 58 subjects from several areas endemic for schistosomiasis japonica in China and collected serum samples to be tested for 18 different cytokines secreted by (1) Th1/Th2 cells (GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-12p70, IL-10, IL-13, IL-18 and TNF-α) and (2) Th9/Th17/Th22/Treg cells (IL-9, IL-17A, IL-21, IL-22, IL-23 and IL-27). The Th1/Th2 cytokines in chronic patients were not significantly different from those in healthy people, while patients with advanced schistosomiasis had higher levels of IL-2, IL-23 and IL-27 and lower levels of IL-18 and IFN-γ. With respect to the Th9/Th17/Th22/Treg cell cytokines, there were higher levels of IL-23. Thus, a limited variation of the cytokine response between the three patient groups was evident, but only in those with advanced infection, while there was no difference between chronic schistosomiasis infection and healthy subjects in this respect. The cytokine expression should be followed in patients with advanced schistosomiasis who show a cytokine pattern of a weakened Th1 cell response and an increased Th17 response.

Inflammatory bowel disease (IBD), mainly including Crohn’s disease and ulcerative colitis, seriously affects human health and causes substantial social and economic burden. The pathogenesis of IBD is still not fully elucidated, whereas recent studies have demonstrated that its development is associated with the dysfunction of intestinal immune system. Accumulating evidence have proven that inflammasomes such as NLRP3 and NLRP6 play a prominent role in the pathogenesis of IBD. Thus, regulating the activation of inflammasomes have been considered to be a promising strategy in IBD treatment. A number of recent studies have provided evidence that blocking inflammasome related cytokine IL-1β can benefit a group of IBD patients with overactivation of NLRP3 inflammasome. However, therapies for targeting inflammasomes with high efficacy and safety are rare. Traditional medical practice provides numerous medical compounds that may have a role in treatment of various human diseases including IBD. Recent studies demonstrated that numerous medicinal herb derived compounds can efficiently prevent colon inflammation in animal models by targeting inflammasomes. Herein, we summarize the main findings of these studies focusing on the effects of traditional medicine derived compounds on colitis treatment and the underlying mechanisms in regulating the inflammasomes. On this basis, we provide a perspective for future studies regarding strategies to improve the efficacy, specificity and safety of available herbal compounds, and to discover new compounds using the emerging new technologies, which will improve our understanding about the roles and mechanisms of herbal compounds in the regulation of inflammasomes and treatment of IBD.

Abstract Tyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers including non-small-cell lung cancer (NSCLC). This study aims to evaluate the utility of plasma cell-free DNA (cfDNA) as a prognostic biomarker and efficacy predictor of chemotherapy (CT) with or without these precision therapies in NSCLC patients. Peripheral cfDNA levels in 154 NSCLC patients were quantified before and after the first target cycle of chemotherapy. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS)/disease-free survival (DFS), objective response ratio (ORR), and therapy regimens were analyzed respectively. Baseline cfDNA, but not post-chemotherapeutic cfDNA, positively correlates with tumor burden. Notably, cfDNA kinetics (cfDNA Ratio, the ratio of post-chemotherapeutic cfDNA to baseline cfDNA) well distinguished responsive individuals (CR/PR) from the non-responsive (PD/SD). Additionally, cfDNA Ratio was found negatively correlated with PFS in lung adenocarcinoma (LUAD), but not lung squamous-cell carcinoma (LUSC) which may be due to a limited number of LUSC patients in this cohort. LUAD patients with low cfDNA Ratio have prolonged PFS and improved ORR, compared to those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs, while more patients need be included to validate the value of cfDNA Ratio in other regimens. Thus, the kinetics of plasma cfDNA during chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.

Chronic inflammatory disease (CID) is a category of medical conditions that causes recurrent inflammatory attacks in multiple tissues. The occurrence of CID is related to inappropriate immune responses to normal tissue substances and invading microbes due to many factors, such as defects in the immune system and imbalanced regulation of commensal microbes. Thus, effectively keeping the immune-associated cells and their products in check and inhibiting aberrant activation of the immune system is a key strategy for the management of CID. Canthin-6-ones are a subclass of β-carboline alkaloids isolated from a wide range of species. Several emerging studies based on in vitro and in vivo experiments reveal that canthin-6-ones may have potential therapeutic effects on many inflammatory diseases. However, no study has yet summarized the anti-inflammatory functions and the underlying mechanisms of this class of compounds. This review provides an overview of these studies, focusing on the disease entities and the inflammatory mediators that have been shown to be affected by canthin-6-ones. In particular, the major signaling pathways affected by canthin-6-ones, such as the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the NF-κB signaling pathway, and their roles in several CIDs are discussed. Moreover, we discuss the limitations in studies of canthin-6-ones and provide possible solutions. In addition, a perspective that may suggest possible future research directions is provided. This work may be helpful for further mechanistic studies and possible therapeutic applications of canthin-6-ones in the treatment of CID.

In the present study, to understand the mechanism of Mn on inhibiting Fe-caused Mg corrosion, the corrosion behaviour of commercial pure Mg and Mg-6Mn alloy in 0.6 M NaCl solution is investigated. It is found that in Mg-6Mn alloy, Fe impurity is incorporated into Mn to form Mn (Fe) phase with Fe as solid solute. The initial galvanic corrosion cannot be reduced through converting Fe-rich phase to Mn (Fe) phase, since Mn (Fe) phase also has relatively strong cathodic activity and has much larger volume fraction than Fe-rich phase. However, the cathodic activation behaviour of pure Mg is inhibited. The cathodic activity even decreases for Mg-Mn alloy with increased exposure time, due to the reduced cathodic HER at the Mn (Fe) particles. Mn can be oxidized at the OCP of Mg-6Mn alloy, resulting in relatively dense Mn-rich corrosion film on particle surface, which separates the particle from the electrolyte and, consequently, inhibits HER.

Abstract Objective This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. Methods A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. Results Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p = 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. Conclusion Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

Alpine ecosystem stability and biodiversity of the Tibetan plateau are facing threat from dry valley vegetation uplift expansion, a process which is highly connected to variations in the soil microbial community and soil nutrients. However, the variation of microbial community properties and their relationship to soil nutrients have scarcely been explored in Tibetan dry valleys, which is a gap that hampers understanding the dry valley ecosystem’s response to vegetation change. In this study, we sampled grasslands (G), a grass-shrub transition area (T), and shrublands (S) along an uplift expansion gradient and investigated the link between microbial community properties and soil nutrients. The results showed that shrub degradation by grass expansion in Tibetan dry valley was accompanied by increasing relative phosphorus (P) limitation, which was the main driver for bacterial and fungal composition variation as it offered highest total effect on PC1 (0.38 and 0.63, respectively). Total phosphorus (TP) was in the center module of bacterial and fungal network under shrub soil and even acted as key nodes in fungal networks. During the replacement by grass, TP was gradually marginalized from both bacterial and fungal center network module and finally disappeared in networks, with ammonia and nitrate gradually appearing in the bacterial network. However, TC and total nitrogen (TN) were always present in the center modules of both fungal and bacterial network. These support that a TP variation-induced compositional and network functional shift in the microbial community was a potential reason for vegetation uplift expansion in Tibetan dry valley. This study highlighted the effect of TP on microbial community properties during dry valley vegetation uplift expansion and offered basic information on Tibetan alpine dry valley ecosystem’s response to climate change.

Macrophages play critical roles in tumor progression. In the tumor microenvironment, macrophages display highly diverse phenotypes and may perform antitumorigenic or protumorigenic functions in a context-dependent manner. Recent studies have shown that macrophages can be engineered to transport drug nanoparticles (NPs) to tumor sites in a targeted manner, thereby exerting significant anticancer effects. In addition, macrophages engineered to express chimeric antigen receptors (CARs) were shown to actively migrate to tumor sites and eliminate tumor cells through phagocytosis. Importantly, after reaching tumor sites, these engineered macrophages can significantly change the otherwise immune-suppressive tumor microenvironment and thereby enhance T cell-mediated anticancer immune responses. In this review, we first introduce the multifaceted activities of macrophages and the principles of nanotechnology in cancer therapy and then elaborate on macrophage engineering via nanotechnology or genetic approaches and discuss the effects, mechanisms, and limitations of such engineered macrophages, with a focus on using live macrophages as carriers to actively deliver NP drugs to tumor sites. Several new directions in macrophage engineering are reviewed, such as transporting NP drugs through macrophage cell membranes or extracellular vesicles, reprogramming tumor-associated macrophages (TAMs) by nanotechnology, and engineering macrophages with CARs. Finally, we discuss the possibility of combining engineered macrophages and other treatments to improve outcomes in cancer therapy.

The influence of pH on the electrochemical behavior of hydrogen peroxide in the presence of Pseudomonas aeruginosa was investigated using electrochemical techniques. Cyclic and square wave voltammetry were used to monitor the enzymatic activity. A modified cobalt phthalocyanine (CoPc) carbon electrode (OPG), a known catalyst for reducing O2 to H2O2, was used to detect species resulting from the enzyme activity. The electrolyte was a sterilized aqueous medium containing Mueller-Hinton (MH) broth. The open-circuit potential (OCP) of the Pseudomonas aeruginosa culture in MH decreased rapidly with time, reaching a stable state after 4 h. Peculiarities in the E / I response were observed in voltammograms conducted in less than 4 h of exposure to the culture medium. Such particular E/I responses are due to the catalase’s enzymatic action related to the conversion of hydrogen peroxide to oxygen, confirming the authors’ previous findings related to the behavior of other catalase-positive microorganisms. The enzymatic activity exhibits maximum activity at pH 7.5, assessed by the potential at which oxygen is reduced to hydrogen peroxide. At higher or lower pHs, the oxygen reduction reaction (ORR) occurs at higher overpotentials, i.e., at more negative potentials. In addition, and to assess the influence of bacterial adhesion on the electrochemical behavior, measurements of the bacterial-substrate metal interaction were performed at different pH using atomic force microscopy.

Studying Λc+ decays provides important and complementary information to help understand the effects of non-perturbative quantum chromodynamics. Recently, many interesting results about Λc+ decays have been reported thanks to the high luminosity in Belle and dedicated operation at the Λc+ pair production threshold in BESIII. This paper reviews the recent progress in experimental measurements, containing sections about the hadronic weak decay, semileptonic decay, and decay asymmetry parameters and CP violation.

Control of Fe in Al alloys is a severe challenge for the full metal circulation to produce the recycled alloys with mechanical and physical performance as high as the primary alloys. The high restriction of Fe content is mainly due to the deterioration caused by the large-scale Fe-containing intermetallic compounds (FIMCs) in Al alloys. In this paper, recent knowledge gained regarding nucleation, formation, and technical developments on microstructural control and refinement of FIMCs are overviewed. Specific characteristics of the multiple types of FIMCs in Al alloys are presented in two- and three- dimensional (2D and 3D) form. Phase relationships between the FIMCs in different structures, such as primary phase, binary eutectic, and ternary eutectic, formed at different solidification stages are studied. Phase transformations between the FIMCs with or without intermediate phases during the solidification process are examined in different Al alloys, with the mechanisms being clarified. Various approaches to microstructural control of FIMCs are proposed and validated. Significant refinement of FIMCs has been achieved through inoculation of TiB2 particles that had been previously modified with deliberately interfacial segregation of desirable alloying elements, leading to the development of the novel “compositional templating” concept.

The aim of this study is to construct a SYL3C aptamer-anchored microemulsion based on β-elemene and PTX (SYL3C/EP-MEs) for enhancement on colorectal cancer therapy. Such microemulsion is consist of encapsulated drugs (β-elemene and PTX), tumor targeting ligand (3’-end thiolated SYL3C aptamer), thiol conjugated site (maleimide-modified PEGylated 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, mal-DOPE-PEG), pH-sensitive component (DOPE) and other necessary excipients. SYL3C/EP-MEs showed a spherical particle with an average particle size around 30 nm and a high encapsulation efficiency (>80%) for both drugs. β-elemene and PTX could be released controllably from SYL3C/EP-MEs as pH values changed. SYL3C/EP-MEs displayed a selective affinity to HT-29 cells, leading to an obvious increase in cellular uptake, cell apoptosis and cytotoxicity. In the HT-29 tumor xenograft-bearing nude mice model studies, SYL3C/EP-MEs showed an overwhelming tumor growth inhibition, the longest survival time and the lowest systemic toxicity among all the treatments. The potential mechanism of enhanced anti-cancer ability was probably associated with the induction of M1 macrophage polarization, the downregulation of mutant p53 protein and the reduction of bcl-2 protein expression. Collectively, the microemulsion codelivery of β-elemene and PTX using functionalization with SYL3C aptamer provides a novel approach for combinational colorectal cancer-targeted treatment.

This article provides an overview of high-pressure die casting (HPDC)-related research undertaken at the EPSRC Future LiME Hub between 2015–2022. The project aimed to identify the cause of variability in the tensile ductility of die-cast structures, and to develop novel processing techniques to address this issue. Variability in tensile ductility was related to the size of large pores and non-metallic inclusions. It was proposed that these non-metallic inclusions formed during the pyrolysis of commercial plunger lubricants in the shot sleeve, and that these large pores derived from dilatational strains introduced during semi-solid deformation. Processing parameters and die design were found to significantly influence the microstructure of die-cast products, and the subsequent variability in tensile ductility. To close, recent progress on the application of intensive melt shearing to HPDC is reviewed. Intensive melt shearing was found to induce significant grain refinement in both Al and Mg alloys due to the effective dispersion of native oxide particles, and the use of these particles as heterogeneous nucleation substrates. The presence of native oxide particles also enabled the use of novel heat treatment procedures that avoided conventional issues such as surface blistering and geometrical distortion.

During solidification of metallic materials, heterogeneous nucleation occurs on substrates, either endogenous or exogenous. The potency of the substrates for nucleation is mainly dependent upon the atomic arrangements on the substrate surface, which are affected by the lattice misfit between the substrate and the nucleated solid, the surface roughness at atomic scale, and the chemical interaction between the substrates and the melt. Extensive examinations on metal/substrate (M/S) interfaces at atomic scale by the state-of-the-art aberration (Cs) corrected STEM and associated EDS and EELS have shown that alloying elements in liquid melts tend to segregate at the interfaces, leading to the formation of various 2-dimensional compounds (2DCs) or 2-dimensional solutions (2DSs), depending upon segregation behavior of the elements. For instance, Al3Ti 2DC and Ti2Zr 2DC at the Al/TiB2 interface, Y2O3 2DC at the Mg/MgO interface, and a Si-rich 2DS layer at Al-Si/TiB2 interface have been identified. Such interfacial segregations significantly affect nucleation potency of the substrates, resulting in either promoting or impeding the heterogeneous nucleation process during solidification. In this paper, we present an overview of the current studies of interfacial segregation behavior, the structure and chemistry of interfaces, and their impacts on the subsequent heterogeneous nucleation and grain initiation processes. Our focus is on the advances made in the understanding of the mechanisms for nucleation and grain refinement. It is demonstrated that it is feasible to manipulate heterogeneous nucleation by modifying nucleation potency of a substrate through deliberate interfacial segregation of desirable elements, achieving effective control of the grain structure of cast metallic materials.

NLRP3 inflammasome has emerged as a crucial regulator of inflammatory bowel disease (IBD) characterized by a chronic inflammatory disease of the gastrointestinal tract. The expression of MCT4 is significantly increased in intestinal mucosal tissue of IBD, which has been identified to regulate intestinal barrier function. However, the function of MCT4 in cell pyroptosis remained unknown. In this study, we have established a stable cell line with MCT4 overexpression in HT-29 and CaCO2 cells, respectively. Functional analysis revealed that ectopic expression of MCT4 in CaCO2 cells contributed to cell pyroptosis as evidenced by LDH assay, which is largely attributed to Caspase-1-mediated canonical pyroptosis, but not Caspase-4 and Caspase-5, leading to cleave pro-IL-1β and IL-18 into mature form and release mediated by cleaved GSDMD. Mechanically, MCT4 overexpression in HT-29 and CaCO2 cell triggered the phosphorylation of ERK1/2 and NF-κB p65, while inhibition of MCT4 by MCT inhibitor α-Cyano-4-hydroxycinnamic acid (α-CHCA) in HT-29 and CaCO2 cells led to a significant downregulation of ERK1/2 and NF-κB activity. What’s more, blockade of ERK1/2-NF-κB pathway could reverse the promotion effect of MCT4 on IL-1β expression. Importantly, both MCT4 and Caspase-1, GSDMD were significantly increased in patients with IBD, and a positive clinical correlation between MCT4 and Caspase-1 expression was observed (p < 0.001). Taken together, these findings suggested that MCT4 promoted Caspase-1-mediated canonical cell pyroptosis to aggravate intestinal inflammation in intestinal epithelial cells (IECs) through the ERK1/2-NF-κB pathway.

The investigation of the fundamental properties of the nucleon is one of the most important topics in the modern hadron physics. Its internal structure and dynamics can be studied through the measurement of electromagnetic form factors which represent the simplest structure observables and serve as a test ground for our understanding of the strong interaction. Since the first attempt to measure the time-like form factors of the neutron, only four experiments published results on its structure from annihilation reactions. Due to the lack of statistics and experimental challenges, no individual determination of the form factors of the neutron has been possible so far. Modern developments of electron-positron colliders and the associated detectors allow to measure the effective FF of the neutron with the process e+e−→nn¯ with unprecedented precision at the BESIII experiment, which is based at the BEPCII collider in Beijing, China. In this report, we review the published results of the form factors on the neutron in the time-like regime, describe the experimental setup, and discuss their impact on our understanding of the strong interaction. Future works at BESIII will help to improve the precision of the neutron FFs and, combined with theoretical progress in this field, help to illuminate the properties of the neutron structure.