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Chemodynamic therapy (CDT) can induce cancer cell death through hydroxyl radicals (·OH) generated from Fenton or Fenton-like reactions. Compared with traditional therapies, CDT effectively overcomes inevitable drug resistance and exhibits low side effects. However, clinical application still faces challenges, primarily due to insufficient ·OH generation and the short-lifetime of ·OH in vivo. To address these challenges, we developed a peroxynitrite (ONOO–)-based CDT nanodrug (DOX@PMOF) composed of MOF-199, NO donor (PArg), and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) activator (doxorubicin, DOX). In DOX@PMOF, MOF-199 serves as both a carrier for loading DOX and a source of Cu+for triggering CDT. Upon uptake by cancer cells, the high concentration of glutathione (GSH) reduces MOF-199 to Cu+, which then reacts with H2O2to generate ·OH. Moreover, the released DOX upregulates NOX4 expression, leading to the elevated H2O2level and thereby promoting a high-efficiency Fenton-like reaction for sufficient ·OH generation. Subsequently, PArg generates abundant NO in response to the tumor microenvironment, leading to a cascade of NO and ·OH for the in situ synthesis of ONOO–. ONOO–is more toxic and has a longer lifetime and diffusion distance than ·OH, resulting in a more effective CDT treatment. To further enhance the in vivo therapeutic effect, we coated DOX@PMOF with a homologous cell membrane to form an active tumor-targeting nanodrug (DOX@MPMOF), which has demonstrated the ability to effectively inhibit tumor growth and metastasis while exhibiting good biosafety.

A 5-layer laminated metal composite composed of ultrahigh-strength maraging steel and ductile 316L stainless steel was fabricated by hot pressing in vacuum and post-heat treatment. Microstructure characterization on hierarchical structure of the composite before and after heat treatment was made by optical microscopy, scanning electron microscopy and electron back-scattered diffraction technique, respectively. Meanwhile, the difference of mechanical performance on both sides of the interface was characterized by nano-hardness testing. Uniaxial tensile test showed that superior interfacial bonding was achieved due to the micro-‘bite’ structure between the two steels without obvious defects or oxides at the interface and with coordinated deformation of the two components. Thus, a laminated metal composite consisting of two different constituents with extreme difference in strength can be well fabricated.

The phase volume fraction has an important role in the match of the strength and plasticity of dual phase steel. The different bainite contents (18–53 vol.%) in polygonal ferrite and bainite (PF + B) dual phase steel were obtained by controlling the relaxation finish temperature during the rolling process. The effect of bainite volume fraction on the tensile deformability was systematically investigated via experiments and crystal plasticity finite element model (CPFEM) simulation. The experimental results showed that the steel showed optimal strain hardenability and strength–plasticity matching when the bainite reached 35%. The 3D-CPFEM models with the same grain size and texture characters were established to clarify the influence of stress/strain distribution on PF + B dual phase steel with different bainite contents. The simulation results indicated that an appropriate increase in the bainite content (18%–35%) did not affect the interphase strain difference, but increased the stress distribution in both phases, as a result of enhancing the coordinated deformability of two phases and improving the strength–plasticity matching. When the bainite content increased to 53%, the stress/strain difference between the two phases was greatly increased, and plastic damage between the two phases was caused by the reduction of the coordinated deformability.

AbstractCalcareous sand foundations may be damaged by waves or earthquakes. Therefore, such foundations should be reinforced. In this study, a series of bacterial solution tests and cyclic triaxial tests were performed to investigate the reinforcing effect of microbially induced carbonate precipitation (MICP) treatment of calcareous sand in different NaCl concentrations. In bacterial solution tests, the microbial activity and microbial mineralization products were examined. At 32 hr, the OD600and urease of MAT35were lower than MAT0by 21.94% and 43.53%. In 0–48 hr, the OD600and activity of MAT80and MAT100were below 0.15 and 1 mM urea/min. The productivity of calcium carbonate after MICP decreased with an increase in NaCl concentration. The cyclic triaxial tests showed that with an increase in NaCl concentration, the accumulation rate of pore pressure increased, and the number of strain-accumulation cycles decreased. Although the stiffness and cyclic resistance of the samples decreased with an increase in NaCl concentration, both were higher than those of untreated sands. Scanning electron microscopy images showed that as the NaCl concentration increased, the calcium carbonate was precipitated gradually changed from a cluster to individual crystals; this change in form is the main reason for the decrease in liquefaction resistance.

Background: Ulinastatin has been applied in a series of diseases associated with inflammation but its clinical effects remain somewhat elusive.Objective: We aimed to investigate the potential effects of ulinastatin on organ failure patients admitted to the intensive care unit (ICU).Methods: This is a single-center retrospective study on organ failure patients from 2013 to 2019. Patients were divided into two groups according to using ulinastatin or not during hospitalization. Propensity score matching was applied to reduce bias. The outcomes of interest were 28-day all-cause mortality, length of ICU stay, and mechanical ventilation duration.Results: Of the 841 patients who fulfilled the entry criteria, 247 received ulinastatin. A propensity-matched cohort of 608 patients was created. No significant differences in 28-day mortality between the two groups. Sequential organ failure assessment (SOFA) was identified as the independent risk factor associated with mortality. In the subgroup with SOFA ≤ 10, patients received ulinastatin experienced significantly shorter time in ICU (10.0 d [interquartile range, IQR: 7.0∼20.0] vs 15.0 d [IQR: 7.0∼25.0]; p = .004) and on mechanical ventilation (222 h [IQR:114∼349] vs 251 h [IQR: 123∼499]; P = .01), but the 28-day mortality revealed no obvious difference (10.5% vs 9.4%; p = .74).Conclusion: Ulinastatin was beneficial in treating patients in ICU with organ failure, mainly by reducing the length of ICU stay and duration of mechanical ventilation.

A graphene hybridizing polyurethane/polyethyl methacrylate (GR-PU/PEMA) damping composite was synthesized using the sequential interpenetration method. The effects of the graphene content and the microphase separation structure on the damping properties, thermal stability, and mechanical properties have been studied in detail. The dynamic mechanical analysis indicated that graphene could improve the damping peak value of PU/PEMA, and the microphase separation structure could be beneficial for broadening the damping temperature range. The damping peak (tan σmax) of PU/PEMA hybridizing with 0.5 wt% graphene reached 0.82, and the temperature range of the loss factor (tan σ≥ 0.3) was expanded to 88.3°C. Analysis of scanning electron microscopy, transmission electron microscopy, and small-angle X-ray scattering reveals that graphene is uniformly dispersed in the polymer matrix, and the composite with interpenetrating polymer network (IPN) shows more microphase separation structures. Fourier transform infrared analysis indicated that there is strong interaction between graphene and IPN matrix. Furthermore, the addition of graphene improved the mechanical properties and thermal stability of composites.

Microbial-induced calcite precipitation (MICP) is a promising method to improve geotechnical engineering properties. In this context, little research has been conducted on the creep behavior of MICP-treated sand. Therefore, the present work performed direct shear creep tests to investigate the creep-related mechanical properties of silica sand and calcareous sand grouted three, six, and nine times in the MICP treatment. Compared to the untreated sand, the creep deformation of the MICP-treated silica sand grouted three and six times was more significant, and the creep deformation of the MICP-treated silica sand grouted nine times decreased by 88.0%, indicating that the treatment of the silica sand with the MICP could reduce its creep deformation. The creep deformation of the MICP-treated calcareous sand was larger than that of the untreated calcareous sand except for the sample grouted three times which had a creep deformation equivalent to that of the untreated calcareous sand, implying that the treatment of the calcareous sand with the MICP could increase its creep deformation. The scanning electron microscopy (SEM) images demonstrated that the calcium carbonate produced by microorganisms in the voids formed a connection between the sand particles as the critical factor affecting the creep behavior of the MICP-treated silica sand. In the case of the calcareous sand, the cavities were filled up with calcium carbonate, which decreased the effect of the interlocking structure of the sand particles.

Constructing infrastructure on soft soils demands the implementation of ground improvement. This study proposed an eco-friendly method of stabilizing marine soil using a calcium carbide residue (CCR)-activated coal gangue (CG) geopolymer derived from industrial waste. Laboratory experiments were conducted to investigate the mechanical properties, durability performance, and stabilization mechanisms of stabilized marine soils under multiple wetting-dry cycles. The results highlighted the effectiveness of CG-CCR geopolymer by a content of 15% to achieve satisfactory strength gain over the engineering requirements. However, the largest decrease in strength (71.89%) was observed when the initial water content was beyond 1.5 times the liquid limit (LL). The optimum solution was proposed to have a geopolymer content of 15% or an initial water content of 1.25·LL to exhibit the highest resistance to strength decay after 12 cycles. Compared with water intrusion, mass loss had a more significant effect on soil strength deterioration. The formation of noncrystalline or amorphous-phase reaction products effectively filled intergranular pores and reduced the void space between soil particles, improving the mechanical properties. The CG-CCR geopolymer was demonstrated to offer a promising solution for soil improvement in geotechnical engineering and waste reduction in industry as a soil stabilizer.

Multiple myeloma (MM) remains an incurable hematological malignancy demanding innovative therapeutic strategies. Targeting MYC, the notorious yet traditionally undruggable oncogene, presents an appealing avenue. Here, using a genome-scale CRISPR-Cas9 screen, we identify the WNK lysine-deficient protein kinase 1 (WNK1) as a regulator of MYCexpression in MM cells. Genetic and pharmacological inhibition of WNK1 reduces MYCexpression and, further, disrupts the MYC-dependent transcriptional program. Mechanistically, WNK1 inhibition attenuates the activity of the immunoglobulin heavy chain (IgH) enhancer, thus reducing MYCtranscription when this locus is translocated near the MYClocus. WNK1 inhibition profoundly impacts MM cell behaviors, leading to growth inhibition, cell-cycle arrest, senescence, and apoptosis. Importantly, the WNK inhibitor WNK463 inhibits MM growth in primary patient samples as well as xenograft mouse models and exhibits synergistic effects with various anti-MM compounds. Collectively, our study uncovers WNK1 as a potential therapeutic target in MM.

Immunotherapy, in particular immune checkpoint blockade (ICB) therapy targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, has remarkably revolutionized cancer treatment in the clinic. Anti-PD-1/PD-L1 therapy is designed to restore the antitumor response of cytotoxic T cells (CTLs) by blocking the interaction between PD-L1 on tumour cells and PD-1 on CTLs. Nevertheless, current anti-PD-1/PD-L1 therapy suffers from poor therapeutic outcomes in a large variety of solid tumours due to insufficient tumour specificity, severe cytotoxic effects, and the occurrence of immune resistance. In recent years, nanosized drug delivery systems (NDDSs), endowed with highly efficient tumour targeting and versatility for combination therapy, have paved a new avenue for cancer immunotherapy. In this review article, we summarized the recent advances in NDDSs for anti-PD-1/PD-L1 therapy. We then discussed the challenges and further provided perspectives to promote the clinical application of NDDS-based anti-PD-1/PD-L1 therapy.

Purpose: To describe the trends of socioeconomic disparity in global vision loss burden associated with diabetic retinopathy (DR) based on prevalence and years lived with disability (YLDs). Methods: In the Global Burden of Disease (GBD) 2017 study, we extracted global, regional, national, and World Bank categorical epidemiological data in vision impairment by time and age. We searched the Human development index (HDI) from the Human Development Report. Pearson correlation, linear regression, and Kruskal–Wallis test were conducted to analyze the correlation between YLD rates and HDI. We used the Gini coefficient and concentration index to evaluate the socioeconomic inequality trendency. Results: The global and World Bank categorical prevalence and YLDs increased from 1990 to 2017, and rose with ageing. The age-standardized prevalence and YLD rates varied geographically and highest in the Eastern Mediterranean countries. Higher vision loss burden of DR was concentrated in countries with medium level of socioeconomic development, including lower/upper middle-income and medium/high-HDI countries. The Gini coefficient decreased from 0.572 in 1990 to 0.542 in 2017, showing the decreasing between-country inequality. The concentration index decreased from 0.153 in 2000 to 0.061 in 2017, showing the reducing socioeconomic-associated disparity. Conclusion: The vision loss burden of DR increased in the past few decades, with a notable declining socioeconomic disparity since 2000. Our results highlight the necessity to provide more services to reduce the vision loss burden.

Catalytic fast pyrolysis of sewage sludge was conducted considering the effects of pyrolysis temperature, atmospheres and catalysts on carbon and nitrogen distributions using a fixed-bed reactor. H2atmosphere gave the lowest carbon selectivity of solid products and highest gaseous products yield over HZSM-5 (HZ) at the same temperature compared to Ar and steam. Higher temperature led to an increase in the carbon selectivity of gaseous products and a decrease in the carbon selectivity of solids. H2increased the carbon yield of light aromatics (LAs), whereas steam reduced the generation of LAs. Over 0.5Ni-HZ, H2gave the highest LAs carbon yield of 11.4%, compared to 1.6% obtained from noncatalytic fast pyrolysis of SS. Higher temperature, H2and steam atmospheres, and metal-loaded HZ promoted the transfer of nitrogen into gaseous products. The highest nitrogen yield of NH3of 55.6% was obtained from sludge pyrolysis over HZ at 700 °C under H2atmosphere.

•A longitudinal mechanical model for flexible joints that incorporates the longitudinal limit device was proposed.•The rationality of the longitudinal mechanical model for flexible joints was verified through experiments.•The longitudinal mechanical model for flexible joints is applied in the seismic numerical simulation of the immersed tunnel.•The influence of the longitudinal limit device on the internal force and opening amount of the immersed tunnel under seismic actions were analyzed.

Hot processing behavior of an ultra-high-strength Fe–Ni–Co-based maraging steel was studied in temperature range of 900–1200 °C and strain rate range of 0.001–10 s−1. Deformation processing parameters and optimum hot working window were characterized via flow stress analysis, constitutive equation construction, hot processing map calculation and microstructure evolution, respectively. Critical strain value for dynamic recrystallization was determined through theoretical mathematical differential method: the inflection point of θ–σand − ∂θ/∂σ− σcurves. It was found that the flow stress increased with the decrease in deformation temperature and increase in the strain rate. The power dissipation maps in the strain range of 0.1–0.6 were entirely similar with the tendency of contour lines which implied that strain had no strong effect on the dissipation maps. Nevertheless, the instability maps showed obvious strain sensitivity with increasing strain, which was ascribed to the flow localization and instability. The optimized hot processing window of the experimental steel was obtained as 1100–1200 °C/0.001–1 s−1and 1000–1100 °C/0.001–0.1 s−1, with the efficiency range of 20–40%. Owing to high Mo content in the experimental steel, high dynamic activation energy, Q = 439.311 kJ mol−1, was achieved, indicating that dynamic recrystallization was difficult to occur in the hot deformation process, which was proved via microstructure analysis under different hot deformation conditions.

The hot deformation behavior and workability of a new reduced activation ferritic/martensitic steel named SIMP steel for accelerator-driven system were studied. The flow curve and its microstructure were studied at 900–1200 °C and strain rate range of 0.001–10 s−1. The results showed that the deformation behavior of the SIMP steel during hot compression could be manifested by the Zener–Hollomon parameter in an exponent-type equation. Based on the obtained constitutive equation, the calculated flow stresses were in agreement with the experimentally measured ones, and the average activity energies QDRVand QHWfor the initiation of dynamic recrystallization and the peak strain were calculated to be 476.1 kJ/mol and 462.7 kJ/mol, respectively. Furthermore, based on the processing maps and microstructure evolution, the optimum processing condition for the SIMP steel was determined to be 1050–1200 °C/0.001–0.1 s−1.

Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy.

Despite the ubiquity and carcinogenicity of polycyclic aromatic hydrocarbons (PAHs), their dermal absorption for the general population has not been adequately addressed. Aiming to verify the importance of dermal absorption of PAHs, barbecue (BBQ) in Guangzhou, China was chosen as a case study. Urine samples were collected and analyzed for nine hydroxyl (OH)-PAHs. Air, food, and cotton clothing samples were analyzed for 16 PAHs. Dietary exposure was the dominant exposure route with the greatest amounts of OH-PAH excretion and PAH intake. Dermal intake of low molecular-weight PAHs was greater than inhalation intake from the occurrence of atmospheric PAHs. In addition, the net excreted amounts of OH-naphthalene, OH-fluorene, OH-phenanthrene, and OH-pyrene via dermal absorption were 367, 63, 98, and 28 ng, respectively, upon 2.5-h exposure, comparable to those via combined dermal and inhalation exposure, which were 453, 98, 126, and 38 ng. The ratios of excretion to intake via dermal absorption were 0.11, 0.036, and 0.043 for fluorene, phenanthrene, and pyrene, respectively, lower than the ratios from dietary exposure (0.38, 0.14, and 0.060) but higher than the ratios from inhalation (0.097, 0.016, and 0.025). In the case of BBQ fumes, dermal absorption was a more important pathway for intake of low molecular-weight PAHs than inhalation.

Corrosion resistance behavior of Co-containing maraging stainless steels was investigated. Neutral salt spray and polarization test showed that maraging stainless steel with high Co content showed poor corrosion behavior. Microstructure observation proved that segregation of Cr in the matrix deteriorated its corrosion resistance. The surface morphology of the aged maraging stainless steel with high Co content indicated that during passivation process, the newly formed passive film with sinusoidal distribution readily destroyed by the corrosive medium, hence, causing poor corrosion resistance. Moreover, through first-principles calculation it was proved that Co increased Fe–Fe ferromagnetic interaction which facilitated the formation Cr-rich clusters.

Resistance to the BCR-ABLtyrosine kinase inhibitor (TKI) remains a challenge for curing the disease in chronic myeloid leukemia (CML) patients as leukemia cells may survive through BCR-ABLkinase activity-independent signal pathways. To gain insight into BCR-ABL kinase activity-independent mechanisms, we performed an initial bioinformatics screen and followed by a quantitative PCR screen of genes that were elevated in CML samples. A total of 33 candidate genes were identified to be highly expressed in TKIs resistant patients. Among those genes, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), controlling the limiting step of glycolysis, was found to be strongly associated with TKIs resistance. PFKFB3knockdown or pharmacological inhibition of its kinase activity markedly enhanced the sensitivity of CML cells to TKIs. Furthermore, pharmacological inhibition of PFKFB3inhibited CML cells growth and significantly prolonged the survival of both allograft and xenograft CML mice. ChIP-seq data analysis combined with subsequent knockdown experiment showed that the Ets transcription factor PU.1regulated the elevated expression of PFKFB3in TKIs-resistant CML cells. Therefore, our results showed that targeting PFKFB3sensitizes CML cells to TKIs and PFKFB3may be a potential BCR-ABLkinase activity-independent mechanism in CML.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC)-driven neoplasia characterized by expression of the constitutively active tyrosine kinase BCR/Abl. CML therapy based on tyrosine kinase inhibitors (TKIs) is highly effective in inducing remission but not in targeting leukemia stem cells (LSCs), which sustain minimal residual disease and are responsible for CML relapse following discontinuation of treatment. The identification of molecules capable of targeting LSCs appears therefore of primary importance to aim at CML eradication. LSCs home in bone marrow areas at low oxygen tension, where HSCs are physiologically hosted. This study addresses the effects of pharmacological inhibition of hypoxia-inducible factor-1 (HIF-1), a critical regulator of LSC survival, on the maintenance of CML stem cell potential. We found that the HIF-1 inhibitor acriflavine (ACF) decreased survival and growth of CML cells. These effects were paralleled by decreased expression of c-Myc and stemness-related genes. Using different in vitro stem cell assays, we showed that ACF, but not TKIs, targets the stem cell potential of CML cells, including primary cells explanted from 12 CML patients. Moreover, in a murine CML model, ACF decreased leukemia development and reduced LSC maintenance. Importantly, ACF exhibited significantly less-severe effects on non-CML hematopoietic cells in vitro and in vivo. Thus, we propose ACF, a US Food and Drug Administration (FDA)-approved drug for nononcological use in humans, as a novel therapeutic approach to prevent CML relapse and, in combination with TKIs, enhance induction of remission.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC)-driven neoplasia characterized by expression of the constitutively active tyrosine kinase BCR/Abl. CML therapy based on tyrosine kinase inhibitors (TKIs) is highly effective in inducing remission but not in targeting leukemia stem cells (LSCs), which sustain minimal residual disease and are responsible for CML relapse following discontinuation of treatment. The identification of molecules capable of targeting LSCs appears therefore of primary importance to aim at CML eradication. LSCs home in bone marrow areas at low oxygen tension, where HSCs are physiologically hosted. This study addresses the effects of pharmacological inhibition of hypoxia-inducible factor-1 (HIF-1), a critical regulator of LSC survival, on the maintenance of CML stem cell potential. We found that the HIF-1 inhibitor acriflavine (ACF) decreased survival and growth of CML cells. These effects were paralleled by decreased expression of c-Myc and stemness-related genes. Using different in vitro stem cell assays, we showed that ACF, but not TKIs, targets the stem cell potential of CML cells, including primary cells explanted from 12 CML patients. Moreover, in a murine CML model, ACF decreased leukemia development and reduced LSC maintenance. Importantly, ACF exhibited significantly less-severe effects on non-CML hematopoietic cells in vitro and in vivo. Thus, we propose ACF, a US Food and Drug Administration (FDA)-approved drug for nononcological use in humans, as a novel therapeutic approach to prevent CML relapse and, in combination with TKIs, enhance induction of remission.

The rapid coarsening of the M23C6carbides has been held responsible for the creep fracture in 9–12Cr martensitic heat resistant steels. A commercial P92 steel was subjected to thermal aging at a high temperature of 800 °C to investigate the ripening behavior of the M23C6carbides. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to characterize the microstructure evolution, especially the ripening process of the M23C6carbides. The new concept of the effective mean size, dependent on the critical radius, was introduced to correct the measured mean size and then the Ostwald theory was applied to describe the ripening behavior of the M23C6carbides. The ripening of the M23C6carbides was revealed to be grain boundary diffusion controlled.

The rapid coarsening of the M23C6carbides has been held responsible for the creep fracture in 9–12Cr martensitic heat resistant steels. A commercial P92 steel was subjected to thermal aging at a high temperature of 800 °C to investigate the ripening behavior of the M23C6carbides. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to characterize the microstructure evolution, especially the ripening process of the M23C6carbides. The new concept of the effective mean size, dependent on the critical radius, was introduced to correct the measured mean size and then the Ostwald theory was applied to describe the ripening behavior of the M23C6carbides. The ripening of the M23C6carbides was revealed to be grain boundary diffusion controlled.

The segregation of Cu and Ni in a 17-4PH stainless steel piston rod has been confirmed to be responsible for the cracking after heat treatment. Further investigation showed that the segregation zone was composed of three layers, namely the fine grain martensitic layer, the coarse grain martensitic layer and the coarse grain austenitic layer from the matrix to the crack surface. Three button ingots with the same chemical compositions as those three layers have been prepared to evaluate the grain size distribution, microstructure and mechanical properties. The effects of Cu and Ni segregation on the microstructures of those three layers have been explored by thermodynamic calculation. Based on the microstructure and mechanical properties results, an intensive understanding of the cracking in the segregation zone was therefore reached.

The segregation of Cu and Ni in a 17-4PH stainless steel piston rod has been confirmed to be responsible for the cracking after heat treatment. Further investigation showed that the segregation zone was composed of three layers, namely the fine grain martensitic layer, the coarse grain martensitic layer and the coarse grain austenitic layer from the matrix to the crack surface. Three button ingots with the same chemical compositions as those three layers have been prepared to evaluate the grain size distribution, microstructure and mechanical properties. The effects of Cu and Ni segregation on the microstructures of those three layers have been explored by thermodynamic calculation. Based on the microstructure and mechanical properties results, an intensive understanding of the cracking in the segregation zone was therefore reached.

In the present study, Cu-modified pipeline steels were fabricated to mitigate MIC by the antimicrobial ability of Cu element. The microstructure, mechanical properties and the antimircobial performance of the Cu-modified steel were systematically investigated. The Cu-modified steels showed good antimicrobial performance with remarkable strength enhancement by nanoscale Cu-rich precipitates and good impact toughness without changing the original base microstructures after the optimal aging treatment of 500 °C/1 h.

In a multicenter study, a deep learning algorithm for evaluation of head and neck CT angiography had equivalent diagnostic performance for arterial stenosis and plaque classification compared with experienced radiologists.

Membrane protein (MP)-based biomaterials have a wide range of applications in drug screening, antigen detection, and ligand–receptor interaction analysis. Traditional MP immobilization methods have the disadvantage of disordered protein immobilization orientation, leading to the shielded binding domain and unreliable binding pattern. Herein, we describe a site-specific covalent immobilization of MPs, which utilizes the styrene maleic acid (SMA) detergent-free extraction method of MPs as well as the covalent reaction between His-tag and divinyl sulfone (DVS). As an example, we covalently immobilized angiotensin-converting enzyme 2 (ACE2) on a cell membrane chromatography system (ACE2-His-SMALPs/CMC) in a site-specific manner and verified the specificity and stability of this system. This technique significantly improves the service life compared to the physisorption CMC column. The improved protein immobilization strategies of the ACE2-His-SMALPs/CMC system enable it to effectively recognize SARS-CoV-2 pseudoviral particles as well as detect viral particles in ambient air once combined with an aerosol collector; as a powerful ligand biosensor, the ACE2-His-SMALPs/CMC system was used to screen for compounds with anti-SARS-CoV-2 pseudovirus activity. In conclusion, the optimized MP immobilization strategy has been successfully applied to CMC technology, showing enhanced stability and sensitivity, which can provide an efficient and convenient membrane protein immobilization method for biomaterials.

Hyphal fusion (anastomosis) is a common process serving many important functions at various developmental stages in the life cycle of ascomycetous fungi. However, the biological roles and molecular mechanisms in plant pathogenic fungi was widely unknown. In this study, a hyphal fusion protein FpHam-2 was screened from a T-DNA insertion mutant library of Fusarium pseudograminearum, and FpHam-2 interacts with another two hyphal fusion protein homologues FpHam-3 and FpHam-4. Each of these three genes deletion mutant revealed in similar defective phenotypes compared with the WT and complemented strains, including reduction in growth rate, defects in hyphal fusion and conidiation, more sensitive for cell membrane, cell wall and oxidative stress responses, and decreased in virulence. The Yeast two-hybrid assay was used to identify that FpHam-2 interacts with three autophagy related proteins, including FpAtg3, FpAtg28 and FpAtg33. Furthermore, FpHam-2-deleted mutant showed decreased accumulation of autophagic bodies in hypha. In conclusion, FpHam-2, FpHam-3 and FpHam-4 are essential role for hyphal fusion and regulating the growth, conidiation and virulence in F. pseudograminearum.