Search

In the current work, the micromechanical behavior and work hardening behavior of Fe-0.1C–10Mn (in wt.%) steel deformed at 100, 63, 25 and −50 °C were investigated via in-situ high-energy X-ray diffraction (HE-XRD) technique. As the deformation temperature decreased, the yield strength (YS) and ultimate tensile strength (UTS) increased, while the total elongation (TE) reached a maximum value at 25 °C. The transformation kinetics of retained austenite (RA) was fitted by the Olson and Cohen (OC) model. The phase stress and flow stress contributed by the constituent phases were obtained based on the lattice strain and the volume fraction of the corresponding phase. The work hardening rate was decomposed into four contributors related to the TRIP effect and load partitioning, ie., the austenite phase stress, load partitioning between austenite and martensite, martensitic formation rate and load partitioning between ferrite and austenite. The influence of each contributor on the work hardening behavior was quantitatively evaluated and stacked, the stacked results agreed reasonably well with the experimental work hardening rate obtained from the true stress-strain curve. Finally, the volume fraction of austenite to martensite transformation promoted by the Lüders band (LB) and the stacking fault energy (SFE) of RA were found to be highly temperature-dependent. A linear relationship was revealed between the volume fraction of austenite to martensite transformation during the LB propagation and the SFE of RA. These findings offer insights into the TRIP effect and the LB propagation in medium-Mn steels.

Summary: Cathelicidins, a major class of antimicrobial peptides (AMPs), hold considerable potential for antimicrobial drug development. In the present study, we identified a novel cathelicidin AMP (TC-33) derived from the Chinese tree shrew. Despite TC-33 demonstrating weak antimicrobial activity, the novel peptide TC-14, developed based on its active region, exhibited a 432-fold increase in antimicrobial activity over the parent peptide. Structural analysis revealed that TC-14 adopted an amphipathic α-helical conformation. The bactericidal mechanism of TC-14 involved targeting and disrupting the bacterial membrane, leading to rapid membrane permeabilization and rupture. Furthermore, TC-14 exhibited a high-safety profile, as evidenced by the absence of cytotoxic and hemolytic activities, as well as high biocompatibility and safety in vivo. Of note, its potent antimicrobial activity provided significant protection in a murine model of skin infection. Overall, this study presents TC-14 as a promising drug candidate for antimicrobial drug development.

Abstract Objective The purpose of this study was to evaluate the inhaler skills of patients with asthma and chronic obstructive pulmonary disease in a hospital in western China after receiving one medication education by pharmacists and the factors related to these skills. Methods We included 96 subjects using Turbuhaler and 74 subjects using Diskus in a hospital in western China. They were educated once by pharmacists before medication, and then their skills of operating these inhalers were visually evaluated the next time they were used. Using the seven-step inhalation administration method designed by AnnaMurphy, a clinical pharmacist at GLENFIELD Hospital in the UK, the inhaler use technique score scale was established and scored in turn. The age, sex, time of first illness, smoking status, education level and type of health insurance purchased by each patient were recorded to assess their relationship with overall inhaler skills. Results 19.8% of the subjects who used Turbuhaler could not use it correctly, and 43.2% of the subjects who used Diskus could not use it correctly. The step with the highest error rate with Turbuhaler and Diskus is to "exhale slowly to residual volume". Chi-square test was carried out for each step of the operation of the two kinds of inhalers, and it was found that there was a significant difference in the operation accuracy of the two kinds of inhalers in the first, third and eighth steps. In univariate analysis, advanced age, female and low educational level were related to the lack of inhaler technology, but in multivariate analysis, only low educational level was a significant independent risk factor. Conclusion Among the patients with asthma and chronic obstructive pulmonary disease in western China, some patients have good inhaler operation skills, but there are still many patients who can not use inhalers correctly, and the lower education level is significantly related to the incorrect use of inhalers.

Objective: Joint stiffness results from the coupling of the nervous system and joint mechanics, and thus stiffness is a comprehensive representation of joint stability. It has been reported that moxibustion can alleviate general weakness and fatigue symptoms and subsequently may influence joint stiffness. This study investigated whether moxibustion could enhance knee joint stiffness in recreational athletes pre- and post-fatigue. Methods: Eighteen participants were randomized into intervention (5 males: 20.6 ± 1.5 yr; 4 females: 20.8 ± 1.5 yr) and control groups (5 males: 19.4 ± 0.9 yr; 4 females: 20.5 ± 0.6 yr). The intervention group received indirect moxibustion applied to acupoints ST36 (bilateral) and CV4 for 30 min every other day for 4 consecutive weeks. The control group maintained regular exercise without moxibustion. Peak torque (PT) of right knee extensor, relaxed and contracted muscle stiffness (MS) of vastus lateralis, and knee extensor musculoarticular stiffness (MAS) was assessed with an isokinetic dynamometer (IsoMed 2000), myometer, and free oscillation technique, respectively. Measurements were taken at three time points: pre-intervention, post-intervention/pre-fatigue, and post-fatigue. Results: MAS (P = 0.006) and PT (P = 0.007) in the intervention group increased more from pre-to post-intervention compared with the control group. Post-fatigue MAS (P = 0.016) and PT (P = 0.031) increased more in the intervention group than in the control group. Conclusion: Moxibustion enhanced PT and knee MAS, suggesting that this intervention could be used in injury prevention and benefit fatigue resistance in young recreational athletes.

Cross-talks (e.g., host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes) regulate immunotolerance and intestinal homeostasis. However, underlying mechanisms that regulate the cross-talks remain poorly understood. Here, we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14 (CD14) to inhibit pattern recognition receptor (PRR) signaling and induce host immunotolerance. Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis, which are characterized by impaired intestinal immunotolerance. Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism, suggesting an association between microbial commensalism, transferrin, and host immunotolerance. Mouse colitis models show that transferrin shortage impairs host’s tolerogenic responses, while its supplementation promotes immunotolerance. Designed peptide blocking transferrin–CD14 interaction inhibits immunosuppressive effects of transferrin. In monkeys with idiopathic chronic diarrhea, transferrin shows comparable or even better therapeutic effects than hydrocortisone. Our findings reveal that by up-regulating host transferrin to silence PRR signaling, commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

Water-soluble ammonium polyphosphate (APP) as a promising high phosphorus fertilizer source in agricultural application can be used with ammonium dihydrogen phosphate (MAP) during fertilizer preparation and irrigation. In this work, the pH, density and solubility properties of the phase equilibrium of ternary APP-MAP-water system were systematically determined at the temperature of 278.2–313.2K. A new series of parameters of Simplified Apelblat model, empirical polynomials and Rational 2D function were used to express the solubility data of MAP, solution density and pH value, respectively. The maximum relative deviations of these three models were successively within 1.21, 0.49, and 0.54% and the corresponding model correlation coefficient R2 was close to or greater than 0.9990, which indicating the accuracy and reliability. The experimental results were further verified by observing the effect of APP on MAP supersaturated solution in OptiMax 1001 reactor and through the online detection techniques of FBRM and PVM. With the addition of water-soluble APP can significantly improve the content of P2O5 when it was combined well with MAP into fertilizer application. Therefore, APP can be better used with MAP to improve the utilization rate of phosphorus during irrigation following the basic thermodynamic data and models established in this research.

This work reports the application of an electromembrane process, Donnan dialysis (DD), for the purification of so-called wet-process phosphoric acid (WPA). Nitric acid is used as the stripping solution to remove metallic cations (mostly Fe3+, Al3+, and Mg2+) that are harmful to the further processing of WPA. The paper first presents a set of experimental data on the measurements of the metallic cation fluxes through a perfluorinated sulfonic acid cation-exchange membrane. Not only WPA, but also synthetic phosphoric acid solutions with mixed metallic cations (MPA) and with a single metallic cation (SPA) were studied. This confrontation confirms (1) that the order of metallic cations fluxes is Mg2+ > Al3+ > Fe3+; (2) that, compared with MPA, the purification effect of WPA causes only negligible change; (3) that, by comparing the DD processes with SPA and MPA solutions, the reason for the low transmembrane fluxes of Fe3+ and Al3+ could be explained by the large ionic charge and large hydrated ion radius. Furthermore, by analyzing the ion composition of membranes equilibrated in SPA solutions, we conclude that the forms of cations in the membrane are most likely Fe3+, Al3+, and Mg2+.

Fe _3 O _4 @C nanoparticles were successfully synthesized by an in situ solid-phase method using FeSO _4 , FeS _2 , and PVP K30 as the starting materials under the nitrogen atmosphere. In addition, the mechanism of the synthetic of Fe _3 O _4 @C nanoparticles was studied through in situ characterizations. The results showed that the pyrolysis of PVP K30 participated in the solid-phase reaction and resulted in the formation of carbon shells and a reduction in particle size. The structure of the Fe _3 O _4 @C nanoparticles was core–shell with the average particle size of ∼30 nm and the thickness of the carbon shell of ∼2 nm. Besides, the Raman spectrum revealed that the carbon shell mostly existed in the form of amorphous carbon. The surface area and the pore volume of the Fe _3 O _4 @C nanoparticles were estimated to be 37.74 m ^2 g ^−1 and 0.227 cm ^3 g ^−1 . Magnetization hysteresis curve exhibited the values of coercivity and remanence and saturation magnetization are found to be approximately 0.16 kOe, 12.8 emu g ^−1 , and 77 emu g ^−1 , respectively.

Fe3O4@C nanoparticles were prepared by an in situ, solid-phase reaction, without any precursor, using FeSO4, FeS2, and PVP K30 as raw materials. The nanoparticles were utilized to decolorize high concentrations methylene blue (MB). The results indicated that the maximum adsorption capacity of the Fe3O4@C nanoparticles was 18.52 mg/g, and that the adsorption process was exothermic. Additionally, by employing H2O2 as the initiator of a Fenton-like reaction, the removal efficiency of 100 mg/L MB reached ~99% with Fe3O4@C nanoparticles, while that of MB was only ~34% using pure Fe3O4 nanoparticles. The mechanism of H2O2 activated on the Fe3O4@C nanoparticles and the possible degradation pathways of MB are discussed. The Fe3O4@C nanoparticles retained high catalytic activity after five usage cycles. This work describes a facile method for producing Fe3O4@C nanoparticles with excellent catalytic reactivity, and therefore, represents a promising approach for the industrial production of Fe3O4@C nanoparticles for the treatment of high concentrations of dyes in wastewater.

Psoriasis is histologically characterized by keratinocytes (KC) hyperproliferation, inflammation, and increased angiogenesis, but the pathological factor responsible for these symptoms is unknown. Here, a neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and mouse psoriatic skins but no significant change in other autoimmune diseases, suggesting that PK2 is a psoriasis-specific factor. Bacterial products significantly up-regulated PK2, implying that infection induces PK2 over-expression. PK2 promoted KC and macrophage to produce interleukin-1 (IL-1), the central player of inflammation and psoriasis, which acts on adjacent fibroblast to induce inflammatory cascades and KC hyperproliferation. IL-1 feeds back on macrophages to induce PK2 production to perpetuate PK2-IL-1 positive feedback loop. PK2 also promoted angiogenesis, another psoriatic symptom. In mouse models, PK2 over-expression aggravated psoriasis while its knock-down inhibited pathological development. The results indicate that PK2 over-production perpetuates psoriatic symptoms by creating PK-2-IL-1 vicious loop. PK2 is a central player in psoriasis and a promising psoriasis-specific target.

An improved method based on reverse flow injection is proposed for determining sulfate concentration in the wet-process of phosphoric acid (WPA). The effect of reagent composition, flow rate, temperature, acid concentration, length of the reaction coil, and linear response range on the flow system is discussed in detail. Optimal conditions are established for determining sulfate in the WPA samples. Baseline drift is avoided by a periodic washing step with EDTA in an alkaline medium. A linear response is observed within a range of 20 - 360 mg L-1, given by the equation A = 0.0020C (mg L-1) + 0.0300, R² = 0.9991. The detection limit of the proposed method for sulfate analysis is 3 mg L-1, and the relative standard deviation (n = 12) of sulfate absorbance peak is less than 1.60%. This method has a rate of up to 29 samples per hour, and the results compare well with those obtained with gravimetric method.

Antimalarial drug resistance is an enormous global threat. Recently, antimicrobial peptides (AMPs) are emerging as a new source of antimalarials. In this study, an AMP LZ1 derived from snake cathelicidin was identified with antimalarial activity. In the in vitro antiplasmodial assay, LZ1 showed strong suppression of blood stage Plasmodium falciparum (P. falciparum) with an IC50 value of 3.045 μM. In the in vivo antiplasmodial assay, LZ1 exerted a significant antimalarial activity against Plasmodium berghei (P. berghei) in a dose- and a time- dependent manner. In addition, LZ1 exhibited anti-inflammatory effects and attenuated liver-function impairment during P. berghei infection. Furthermore, by employing inhibitors against glycolysis and oxidative phosphorylation in erythrocytes, LZ1 specifically inhibited adenosine triphosphate (ATP) production in parasite-infected erythrocyte by selectively inhibiting the pyruvate kinase activity. In conclusion, the present study demonstrates that LZ1 is a potential candidate for novel antimalarials development.

We investigated the changes in the conformation and crystalline structure of polypropylene (PP) using a combination of Fourier transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WAXD), and differential scanning calorimetry (DSC) based on PP/chlorinated PP (CPP)/polyaniline (PANI) composites. The DSC heating thermograms and WAXD patterns of the PP/CPP/PANI composites showed that the β-crystal was affected greatly by the CPP content. Characterization of the specific regularity in the infrared band variation showed that the conformational orders of the helical sequences in PP exhibited major changes that depended on the CPP content. Initially, the intensity ratio of A840/A810 increased with the CPP concentration and reached its maximum level when the CPP content was

Wound-healing represents a major health burden, such as diabetes-induced skin ulcers and burning. Many works are being tried to find ideal clinical wound-healing biomaterials. Especially, small molecules with low cost and function to promote production of endogenous wound healing agents (i.e. transforming growth factor beta, TGF-β) are excellent candidates. In this study, a small peptide (tiger17, c[WCKPKPKPRCH-NH2]) containing only 11 amino acid residues was designed and proved to be a potent wound healer. It showed strong wound healing-promoting activity in a murine model of full thickness dermal wound. Tiger17 exerted significant effects on three stages of wound healing progresses including (1) the induction of macrophages recruitment to wound site at inflammatory reaction stage; (2) the promotion of the migration and proliferation both keratinocytes and fibroblasts, leading to reepithelialization and granulation tissue formation; and (3) tissue remodeling phase, by promoting the release of transforming TGF-β1 and interleukin 6 (IL-6) in murine macrophages and activating mitogen-activated protein kinases (MAPK) signaling pathways. Considering its easy production, store and transfer and function to promote production of endogenous wound healing agents (TGF-β), tiger17 might be an exciting biomaterial or template for the development of novel wound-healing agents.

Since 2003, H5N1-subtype avian influenza viruses (AIVs) with both a deletion of 20 amino acids in the stalk of the neuraminidase (NA) glycoprotein (A-) and a deletion of five amino acids at positions 80 to 84 in the non-structural protein NS1 (S-) have become predominant. To understand the influence of these double deletions in the NA and NS1 proteins on the pathogenicity of H5N1-subtype AIVs, we selected A/mallard/Huadong/S/2005 as a parental strain to generate rescued wild-type A-S- and three variants (A-S+ with a five-amino-acid insertion in the NS1 protein, A+S- with a 20-amino-acid insertion in the NA stalk, and A+S+ with insertions in both NA and NS1 proteins) and evaluated their biological characteristics and virulence. The titers of the AIVs with A- and/or S- replicated in DEF cells were higher than that of A+S+, and the A-S- virus exhibited a replication predominance when co-infected with the other variants in DEF cells. In addition, A-S- induced a more significant increase in the expression of immune-related genes in peripheral blood mononuclear cells of mallard ducks in vitro compared with the other variants. Furthermore, an insertion in the NA and/or NS1 proteins of AIVs resulted in a notable decrease in virulence in ducks, as determined by intravenous pathogenicity index, and the two insertions exerted a synergistic effect on the attenuation of pathogenicity in ducks. In addition, compared with A+S+ and A+S-, the A-S+ and A-S- viruses that were introduced via the intranasal inoculation route exhibited a faster replication ability in the lungs of ducks. These data indicate that both the deletions in the NA stalk and the NS1 protein contribute to the high pathogenicity of H5N1 AIVs in ducks.

A designed peptide named LZ1 with 15 amino acid residues containing strong antimicrobial activity against bacteria pathogens of acne vulgaris including Propionibacterium acnes, Staphylococcus epidermidis and S. aureus. Especially, it exerted strong anti-P. acnes ability. The minimal inhibitory concentration against three strains of P. acnes was only 0.6 µg/ml, which is 4 times lower than that of clindamycin. In experimental mice skin colonization model, LZ1 significantly reduced the number of P. acnes colonized on the ear, P. acnes-induced ear swelling, and inflammatory cell infiltration. It ameliorated inflammation induced by P. acnes by inhibiting the secretion of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. LZ1 showed little cytotoxicity on human keratinocyte and hemolytic activity on human blood red cells. Furthermore, LZ1 was very stable in human plasma. Combined with its potential bactericidal and anti-inflammatory properties, simple structure and high stability, LZ1 might be an ideal candidate for the treatment of acne.

Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules in innate immunity. Cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and it is the first identified cathelicidin antimicrobial peptide in reptiles. In this study, cathelicidin-BF was found exerting strong antibacterial activities against Propionibacterium acnes. Its minimal inhibitory concentration against two strains of P. acnes was 4.7 µg/ml. Cathelicidin-BF also effectively killed other microorganisms including Staphylococcus epidermidis, which was possible pathogen for acne vulgaris. Cathelicidin-BF significantly inhibited pro-inflammatory factors secretion in human monocytic cells and P. acnes-induced O2.- production of human HaCaT keratinocyte cells. Observed by scanning electron microscopy, the surfaces of the treated pathogens underwent obvious morphological changes compared with the untreated controls, suggesting that this antimicrobial peptide exerts its action by disrupting membranes of microorganisms. The efficacy of cathelicidin-BF gel topical administering was evaluated in experimental mice skin colonization model. In vivo anti-inflammatory effects of cathelicidin-BF were confirmed by relieving P. acnes-induced mice ear swelling and granulomatous inflammation. The anti-inflammatory effects combined with potent antimicrobial activities and O2.- production inhibition activities of cathelicidin-BF indicate its potential as a novel therapeutic option for acne vulgaris.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between several lipid-lowering and hypoglycemic drugs and the risk of gastric cancer (GC) in elderly population. Methods: A total of 160 elderly patients with GC who attended The First Affiliated Hospital of Henan University of Science and Technology from January 1, 2014 to December 31, 2020 were enrolled in the study group. Furthermore, 320 healthy volunteers within the same period were assigned to the control group. Clinical data (such as history of statin, sulfonylurea and biguanide administration) were collected from the patient's medical records. Multifactorial logistic regression was used to determine the association between these lipid-lowering and glucose-lowering drugs, and the risk of developing GC. Results: After adjusting for numerous confounding factors, multifactorial logistic regression showed that long-term use (>12 months of treatment) of statins and biguanides significantly reduced the risk of GC in elderly population (p = 0.006, p = 0.004, respectively), while long-term use of sulphonylureas increased the risk of GC in elderly population (p = 0.004). Conclusion: Statins, sulfonylureas and biguanides may be closely associated with the development of GC in elderly population. Therefore, a detailed understanding of the efficacy and mechanisms of action of these drugs may benefit the elderly in the prevention and control of GC. [ABSTRACT FROM AUTHOR]