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Matriptase is ectopically expressed in neoplastic B-cells, in which matriptase activity is enhanced by negligible expression of its endogenous inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. HAI-1, however, is also involved in matriptase synthesis and intracellular trafficking. The lack of HAI-1 indicates that other related inhibitor, such as HAI-2, might be expressed. Here, we show that HAI-2 is commonly co-expressed in matriptase-expressing neoplastic B-cells. The level of active matriptase shed after induction of matriptase zymogen activation in 7 different neoplastic B-cells was next determined and characterised. Our data reveal that active matriptase can only be generated and shed by those cells able to activate matriptase and in a rough correlation with the levels of matriptase protein. While HAI-2 can potently inhibit matriptase, the levels of active matriptase are not proportionally suppressed in those cells with high HAI-2. Our survey suggests that matriptase proteolysis might aberrantly remain high in neoplastic B-cells regardless of the levels of HAI-2.

Matriptase plays important roles in epithelial integrity and function, which depend on its sorting to the basolateral surface of cells, where matriptase zymogen is converted to an active enzyme in order to act on its substrates. After activation, matriptase undergoes HAI-1-mediated inhibition, internalization, transcytosis, and secretion from the apical surface into the lumen. Matriptase is a mosaic protein with several distinct protein domains and motifs, which are a reflection of matriptase's complex cellular itinerary, life cycle, and the tight control of its enzymatic activity. While the molecular determinants for various matriptase regulatory events have been identified, the motif(s) required for translocation of human matriptase to the basolateral plasma membrane is unknown. The motif previously identified in rat matriptase is not conserved between the rodent and the primate. We, here, revisit the question for human matriptase through the use of a fusion protein containing a green fluorescent protein linked to the matriptase N-terminal fragment ending at Gly-149. A conserved seven amino acid motif EEGEVFL, which is similar to the monoleucine C-terminal to an acidic cluster motif involved in the basolateral targeting for some growth factors, has been shown to be required for matriptase translocation to the basolateral plasma membrane of polarized MDCK cells. Furthermore, time-lapse video microscopy showed that the motif appears to be required for entry into the correct transport vesicles, by which matriptase can undergo rapid trafficking and translocate to the plasma membrane. Our study reveals that the EEGEVFL motif is necessary, but may not be sufficient, for matriptase basolateral membrane targeting and serves as the basis for further research on its pathophysiological roles.

The type 2 transmembrane serine protease matriptase is involved in many pathophysiological processes probably via its enzymatic activity, which depends on the dynamic relationship between zymogen activation and protease inhibition. Matriptase shedding can prolong the life of enzymatically active matriptase and increase accessibility to substrates. We show here that matriptase shedding occurs via a de novo proteolytic cleavage at sites located between the SEA domain and the CUB domain. Point or combined mutations at the four positively charged amino acid residues in the region following the SEA domain allowed Arg-186 to be identified as the primary cleavage site responsible for matriptase shedding. Kinetic studies further demonstrate that matriptase shedding is temporally coupled with matriptase zymogen activation. The onset of matriptase shedding lags one minute behind matriptase zymogen activation. Studies with active site triad Ser-805 point mutated matriptase, which no longer undergoes zymogen activation or shedding, further suggests that matriptase shedding depends on matriptase zymogen activation, and that matriptase proteolytic activity may be involved in its own shedding. Our studies uncover an autonomous mechanism coupling matriptase zymogen activation, proteolytic activity, and shedding such that a proportion of newly generated active matriptase escapes HAI-1-mediated rapid inhibition by shedding into the extracellular milieu.

Mutations of hepatocyte growth factor activator inhibitor (HAI)-2 in humans cause sodium loss in the gastrointestinal (GI) tract in patients with syndromic congenital sodium diarrhea (SCSD). Aberrant regulation of HAI-2 target protease(s) was proposed as the cause of the disease. Here functional linkage of HAI-2 with two membrane-associated serine proteases, matriptase and prostasin was analyzed in Caco-2 cells and the human GI tract. Immunodepletion-immunoblot analysis showed that significant proportion of HAI-2 is in complex with activated prostasin but not matriptase. Unexpectedly, prostasin is expressed predominantly in activated forms and was also detected in complex with HAI-1, a Kunitz inhibitor highly related to HAI-2. Immunohistochemistry showed a similar tissue distribution of prostasin and HAI-2 immunoreactivity with the most intense labeling near the brush borders of villus epithelial cells. In contrast, matriptase was detected primarily at the lateral plasma membrane, where HAI-1 was also detected. The tissue distribution profiles of immunoreactivity against these proteins, when paired with the species detected suggests that prostasin is under tight control by both HAI-1 and HAI-2 and matriptase by HAI-1 in human enterocytes. Furthermore, HAI-1 is a general inhibitor of prostasin in a variety of epithelial cells. In contrast, HAI-2 was not found to be a significant inhibitor for prostasin in mammary epithelial cells or keratinocytes. The high levels of constitutive prostasin zymogen activation and the selective prostasin inhibition by HAI-2 in enterocytes suggest that dysregulated prostasin proteolysis may be particularly important in the GI tract when HAI-2 function is lost and/or dysregulated.

This paper investigates the corrosion behavior of Fe-SG series metals with different graphite nodule counts to molten Al by using the ultrasonic vibration hot-dip aluminum experimental method. Fe-SG series metals to aluminum melt exhibited a much better corrosion resistance compared to H13 tool steel. As the graphite nodule count increases, the hot melting loss rate of Fe-SG series metals gradually decreases, indicating an improvement in corrosion resistance to aluminum melt. Scanning and EDS analysis of the samples after hot-dip aluminum testing revealed that the thickness of the product layer increased progressively with the extension of hot-dip aluminum time. Through the analysis of the structure and composition of the product layer, it was found that the corrosion products in H13 steel were composed of Fe2Al5 and FeAl3. In addition to the two phases, the product layer of the Fe-SG series metals also contained granularly distributed Fe–Al–Si intermetallic compounds within the Fe2Al5 phase. This resulted in a better corrosion resistance to aluminum melt.

Soil acidification is a global environmental problem with significant impacts on agricultural production, environmental protection, and ecosystem health. Soil acidification is widespread in China, affecting crop yields, agricultural product quality, and biodiversity. Since the 1980s, much work has been done on acidic soils in China, but it is controversial whether excessive nitrogen fertilizer application can lead to soil acidification mechanisms. To address the above issues, we conducted a meta-analysis of 115 published papers to integrate and analyze the effects of N fertilizer application on soil acidification and biological properties from 1980 to 2024. We also quantified the effect of nitrogen fertilization on soil acidification and biological changes under different climatic conditions. The results showed that under long-term application of nitrogen fertilizers in China from 1980 to 2024, soil pH decreased by an average of 15.27%, and the activities of soil urease, nitrate reductase, nitrite reductase, catalase, glutamate dehydrogenase, and glutamate synthetase decreased by an average of 9.82–22.37%. The soil microbial community richness (Chao1 index) increased by 6.53%, but the community diversity (Shannon index) decreased by 15.42%. Among the dominant soil microorganisms, the relative abundance of bacteria decreased by an average of 9.67–29.38% and the abundance of gene expression of nifH, amoA-AOA, amoA-AOB, and qnorB decreased by 9.92–19.83%. In addition, we found that the mean annual temperature and rainfall impacted soil acidification via their effect on soil microbial diversity and community composition. This study provides a scientific basis for an in-depth understanding of the spatial and temporal variation of soil acidification and biological properties in China.

Ferrite-martensite (F/M) dual-phase ductile iron with different relative amounts of martensite was fabricated via intercritical quenching in the present study. The mechanical properties and tribological behavior were investigated. The strength of ductile iron increased linearly with the increase of martensite level, while the ductility decreased rapidly. Fracture surface morphology analysis indicated that ductile fracture was predominant when the proportion of martensite in ductile iron was less than 20%. However, the samples with more than 40% martensite exhibited brittle fractures. Wear tests indicated that F/M dual-phase ductile iron exhibited a significantly lower friction coefficient compared with directly quenched ductile iron. Additionally, the martensite amounts affected the tribological behavior of ductile iron significantly. Abrasive wear was predominant in ductile iron with small amounts of martensite, while delamination wear was the main wear mechanism in case of ductile iron with high amounts of martensite.

A nanobainitic matrix composing of nanoscale α phase and carbon-riched γ phase was obtained for the ductile iron by austempering treatment. The microstructure and properties of ductile iron were compared with GCr15. The microstructural characteristic gave rise to a good strength with an ultimate tensile strength higher than 1200 MPa, which was comparable and even superior to conventionally forged steels. The friction coefficient of the ductile iron was approximate 1/3 compared with that of commercial GCr15 under dry sliding wear condition, which was related to the existence of homogeneously distributed spheroidal graphite in ductile iron. The low friction coefficient and moderate strength resulted in a superior wear resistance of ductile iron with nanobainitic matrix by contrast to GCr15.

Anlotinib is an anti‐angiogenic drug that targets vascular endothelial growth factor receptor, platelet‐derived growth factor receptor, fibroblast growth factor receptor, c‐Kit, and other kinases and has been approved for the treatment of advanced non‐small cell lung cancer (NSCLC). As in other small‐molecule tyrosine kinase inhibitors, adverse effects such as hypertension and cardiotoxicity may be seen. However, the relationship between anlotinib and aortic dissection has not been previously reported. Here, we present a case of aortic dissection in a 58‐year‐old male patient with advanced NSCLC without history of hypertension who received anlotinib as third‐line treatment. After four courses of anlotinib treatment, he suffered a sudden onset of back pain, sweating, anxiety, and high blood pressure (180/120 mmHg) and heart rate (137 bpm). Emergency computed tomographic angiography revealed aortic dissection and thrombosis of the distal false lumen. Thereafter, the patient was administered nitroglycerin as antihypertensive treatment and he underwent stent‐graft intervention for aortic dissection. Anticoagulants and antihypertensive drugs were administered after the operation, and a moderate control of blood pressure was achieved. Thus, the adverse reactions of antolinib must be monitored and clinicians must be vigilant.

The mechanical properties and tribological behavior of ductile iron tempered at different temperatures were investigated. The tempered sample was composed of spheroidal graphite, α phase, and carbides. The strength and hardness decreased near-linearly but the plasticity increased with the increase of tempering temperature, which was mainly because carbon atoms precipitated from martensite and thus reduced the distortion of martensite. Wear tests indicated that the friction coefficient of the sample tempered at 420 °C decreased first and then increased with the increasing loads and exhibited the lowest friction coefficient of 0.37. No obvious change was detected for the friction coefficient of the sample tempered at 500 °C at different loads. The friction coefficient of the sample tempered at 580 °C increased to a stable value with the increase of loads. The wear rate of tempered ductile iron was increased with the increase of tempering temperature, which indicated that hardness was the critical factor for wear properties of ductile iron. The main wear mechanisms of tempered ductile iron were adhesive and abrasive wear. Adhesive wear was predominant for the sample tempered at low temperature but was gradually replaced by abrasive wear with the increase of tempering temperature and normal loads.

Magnetron sputtering was used to deposit (Ti, Al)N films with different Al/Ti atomic ratios by changing the current of the Al target and to study their tribological properties. The phase composition, microstructure and elemental distribution of films were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and energy dispersive spectroscopy (EDS). The influence of the ratio between Al and Ti atoms on the tribological properties and the mechanical properties of the films was analyzed. The conclusions showed that there was a tendency for films to shift from the crystalline to the amorphous state as the Al/Ti atomic ratio increases. Herein, changes in film microhardness were related to the substitution relationship between Ti atoms and Al atoms. Especially, when the Al/Ti atomic ratio was 0.54, coefficient of friction (COF) and specific wear rate were the lowest. Compared with TiN film, (Ti, Al)N films have higher microhardness due to the solid solution hardening caused by the substitution between Al and Ti atoms to produce lattice distortion. These factors make films have excellent tribology performance.

Micro-arc oxidation (MAO) coatings were prepared on the AZ31 Mg alloy under the constant/gradient current control modes. The effects of current output modes on the growth rate, energy consumption, microstructure, and corrosion resistance of MAO coatings were studied. The results shows that the current step-down mode (G852) exhibited a lower unit energy consumption than the constant current mode (C5) and the current step-up mode (G258), even though the same average current density current was used during MAO process. Meanwhile, the G852 is conducive to a thick and dense coating, resulting in a better corrosion resistance. The method of energy saving preparation of corrosion resistant MAO coating by adjusting the current mode is of great significance for practical production.

This study aimed to prepare self-lubricating micro-arc oxidation (MAO)/graphite composite coatings on 6061 aluminium alloy by adding graphite nanoparticles into an alkaline electrolyte during the MAO process. The microstructure, phase composition and element distribution of MAO coatings were studied using Scanning Electron Microscope (SEM), x-ray diffraction (XRD) and Energy Dispersive Spectrometer (EDS). The results showed that graphite nanoparticles can be coated uniformly in the MAO coatings, and the porosity and surface roughness of the MAO coatings were reduced by the addition of graphite nanoparticles. However, when the content of graphite nanoparticles was more than 6 g l ^−1 , graphite aggregation occurred. The wear resistance of the coatings was investigated using the ball-on-disk friction tester. After incorporating the graphite nanoparticles, the MAO coatings showed excellent self-lubricating properties and a reduction in the friction coefficient during the wear process. In addition, the MAO coatings showed the best result with the addition of 4 g l ^−1 graphite nanoparticles compared with all the other composite coatings under investigation. In conclusion, the incorporation of graphite nanoparticles improved the wear properties of the MAO coatings.

A carbon Fabric/epoxy composite material can be prepared with carbon Fabric as the reinforcement phase and epoxy resin as the binder phase. Use it as the substrate, add six potassium titanate whisker (SPTW) therein, a nano-modified composite will be prepared to investigate how its friction and wear are subjected to change with different loads and what effect the fillers of different doses play on the tribological properties of the composites. Beyond that, its wear mechanism is also discussed herein. The results reveal that the SPTW can exert a good wear resistance effect; there is an optimal dosage of 2.0% for SPTW. In this process, the wear mode of the composite material turns from brittle peeling to adhesive wear.

Micro-arc oxidation (MAO) coating was initially prepared on 6061 Al alloy, and subsequently coated with Ag using magnetron sputtering. Laser beam scan (LBS) treatments were then applied to infiltrate the sputtered Ag into the MAO coating in order to simulate the corrosion behaviour of the MAO coating during the neutral salt spray test (NSST). Cross-sectional morphologies and Ag element distribution maps were studied by using the field emission scanning electron microscopy (FESEM) on the MAO-Ag coated samples after LBS infiltration. The results showed that there existed the micro-cracks with tree-root or lightning shape within the MAO coating. Interconnected aggregates, including micro-pores, large cavities far beneath the surface and tree-root like micro-cracks, served as complex corrosion channels during salt spray corrosion. Through these corrosion channels, the salt spray penetrated gradually into the interface between the MAO coating and the original Al substrate, thus causing corrosion of the Al substrate during the NSST. The LBS treatment is presented as a method to explore the subtle micro-crack and pore channels associated to the MAO coating and to provide information that paves the way towards understanding of corrosion phenomena in these porous systems.

Aluminum nitride (AlN) films were deposited by DC reactive magnetron sputtering using two high purity aluminum targets, at selected target current densities (0.055, 0.083, 0.110 and 0.138 A cm ^−2 ). The effects of the target current density on the ionization rate of Al atoms, morphology, chemical composition, crystal structure and breakdown strength of AlN films were studied by self-made device, SEM, XPS, XRD and withstanding voltage tester. It was found that the ionization rate of Al atoms gradually increased from 6% to 19% as target current density increased to 0.138 A cm ^−2 . The results of XPS showed that the Al/N atomic ratio of AlN films gradually approached 1:1. Compared with low target current densities, the AlN films deposited at 0.110 and 0.138 A cm ^−2 exhibited a fine-crystal structure with average grain size

The magnesium alloys attract the light-weight manufacture due to its high strength to weight ratio, however the poor corrosion resistance limits the application in automobile industry. The Micro-arc Composite Ceramic (MCC) coatings on AZ91D magnesium alloys were prepared by Micro-arc Oxidation (MAO) and electrophoresis technologies. The microstructure, corrosion resistance, abrasion resistance, stone impact resistance and adhesion of MCC coatings were studied respectively. The cross section morphologies showed that the outer organic coating was filled into the hole on surface of MAO coating, and it acted as a shelter against corrosive products. The copper-accelerated acetic acid salt spray Test, abrasion resistance test, stone impact resistance test, thermal shock resistance test and adhesion test were used to evaluate the protective characterization by the third testing organization which approved by GM. The test results showed the composite coatings meet all the requirements. The MCC coating on Mg presents excellent properties, and it is a promising surface treatment technology on magnesium alloys for production vehicles.

Micro-arc oxidation (MAO) was performed on AZ31 and AZ91 Mg alloys to explore the relationship between Mg substrates and corrosion behaviors of resultant coatings. The microstructure and long-term corrosion performance of the two coatings were investigated. Results showed that MAO coating on AZ91 alloy provided a longer-term corrosion protection to substrate than that on AZ31 alloy, despite having similar microstructure and phase composition. However, once corrosion occurred, the corrosion area of MAO coating on AZ91 alloy enlarged at a faster rate compared to that on AZ31 alloy during immersion tests, and their corrosion morphologies were different. Based on the corrosion features of Mg substrates and MAO coatings, roles of substrates on the corrosion processes of coatings were analyzed.

The oxide coatings were prepared on 6061 Al alloy at different negative current densities in oxalic acid using the hybrid pulse anodization (HPA) method at room temperature. The variation curves of positive and negative voltages with anodization time were recorded. The nanopore diameters and distribution regularities in HPA coatings were analyzed with the Image-Pro Plus software based on field-emission scanning electron microscope (FE-SEM) images. The results showed that the negative current could reduce the growth rate of HPA coatings, and thus led to a small thickness of the coatings within the same anodization time. Besides, appropriate negative current densities resulted in the better distribution uniformity of nanopores, but the excessive negative current densities tended to cause inferior nanopore arrangement. These were attributed to the existence of the negative current, causing H+ and O2− to move in opposite directions, so that a large number of H+ concentrated on the surface of the HPA coatings, resulting in the accelerated dissolution of the coatings.

Two kinds of metal oxide coatings were fabricated on 7050 Al alloy by hard anodization (HA) and micro-arc oxidation (MAO) techniques. The microstructure, phase composition, and corrosion behavior of the two coatings were studied by scanning electron microscopy, X-ray diffraction, and corrosion tests, respectively. When compared with the HA coating, the MAO one was more effective to isolate the substrate from the corrosive environment. In addition, as confirmed by electrochemical tests, the MAO coating was of better corrosion resistance than the HA coating. Furthermore, it was revealed by neutral salt spray test that the MAO coating could protect substrate alloy over 1140 h, while the HA coating can only protect substrate alloy for 46 h due to the amorphous composition and through thickness defects (micro-pores and micro-cracks).

Background Helicobacter pylori (H.pylori) infection is strongly associated with peptic ulcer, gastric cancer, gastric lymphoma, and other diseases. A new dual therapy has proven effective in the eradication of H.pylori, but it has not been verified in some areas with a high prevalence of H.pylori infection in central China. Objective To explore the clinical efficacy of rabeprazole combined with amoxicillin or furazolidone dual therapy in the eradication of H.pylori infection. Methods 161 patients with a first diagnosis of H.pylori infection were recruited from Department of Gastroenterology, Henan Provincial People's Hospital during April 2020 to October 2021, and randomized into three groups with different 14-day therapies: group A (n=55) received a twice-daily quadruple therapy consisting of rabeprazole (20 mg) + bismuth potassium citrate (220 mg) + amoxicillin (1 000 mg) + furazolidone (100 mg) , group B (n=54) received a three-time daily dual therapy consisting of rabeprazole (20 mg) + high-dose amoxicillin (1 000 mg) , and group C (n=52) received a three-time daily dual therapy consisting of rabeprazole (20 mg) + high-dose furazolidone (100 mg) . The eradication rate, side effects and cost-effectiveness ratio were compared among the groups. Results Intention-to-treat analysis (ITT) revealed that, the eradication rates of H.pylori in groups A, B and C were 83.6% (46/55) , 81.5% (44/54) and 48.1% (25/52) , respectively. Per-protocol (PP) analysis found that, the eradication rates of H.pylori in groups A, B and C were 88.5% (46/52) , 83.0% (44/53) and 51.0% (25/49) , respectively. Both analyses demonstrated that groups A, B had higher eradication rates of H.pylori than group C (P

Background Helicobacter pylori (H. pylori) infection induced precancerous lesions of gastric mucosa mostly in adulthood. However, it is debatable whether these pathological changes could also occur in children. Objective To investigate the relationship between H. pylori infection and precancerous lesions of gastric mucosa in children hospitalized due to upper gastrointestinal symptoms in central plain area of China. Methods A total of 1 015 children under the age of 18 years old were enrolled. These children attended the People's Hospital of Zhengzhou University for upper gastrointestinal symptoms such as abdominal pain, bloating, nausea, vomiting, hiccups, and acid reflux from August 2018 to July 2021. All children underwent gastroscopy, from which gastric mucosal biopsy tissues were taken for rapid urease test and histopathological examination. The clinical and pathological data of the patients were collected retrospectively. The children were divided into infected and uninfected groups according to H. pylori infection status. The age, sex, endoscopic diagnosis, and H. pylori infection rate were compared between children in infected and uninfected groups. The incidence of precancerous lesions of gastric mucosa, inflammatory activity and the degree of inflammatory cell infiltration were compared between infected and uninfected groups, meanwhile these tests were also compared in children of different age groups. Results Among the 1 015 children, 854 (84.14%) were infected with H. pylori and 161 (15.86%) were not infected. H. pylori-infected children were significantly older than those of non-infected subjects (P