Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.

Community-acquired multidrug-resistant pneumonia,bacteraemia,and infective endocarditis:A case report

BACKGROUND The prevalence of multidrug-resistant(MDR)bacteria has increased globally,with extensive drug-resistant(XDR)bacteria posing a threat to patients.CASE SUMMARY This case report describes a young man admitted for suspected tropical fever infections who experienced rapid deterioration in health.Despite negative results for tropical fever infections,he had neutrophilic leucocytosis,acute kidney injury,and chest imaging findings suggestive of bilateral consolidations.On day two,he was diagnosed with infective endocarditis with possible rheumatic heart disease and MDR methicillin-resistant Staphylococcus aureus bacteraemia,and communityacquired pneumonia.Despite treatment with broad-spectrum antibiotics,he did not respond and succumbed to death on day five.CONCLUSION This case highlights that clinicians/public should be aware of MDR communityacquired pneumonia,bacteraemia,and endocarditis which ultimately culminate in high rates of morbidity and mortality.Early identification of pathogenic strain and prompt antibiotic treatment are a mainstay for the management and prevention of early fatalities.Simultaneously,route cause analysis of communityacquired MDR/XDR pathogens is a global need.

Comparative review of corrosion-resistant coatings on metal bipolar plates of proton exchange membrane fuel cells

In the realm of proton exchange membrane fuel cells(PEMFCs),the bipolar plates(BPs)are indispensable and serve pivotal roles in distributing reactant gases,collecting current,facilitating product water removal,and cooling the stack.Metal BPs,characterized by outstanding manufacturability,cost-effectiveness,higher power density,and mechanical strength,are emerging as viable alternatives to traditional graphite BPs.The foremost challenge for metal BPs lies in enhancing their corrosion resistance and conductivity under acidic conditions,necessitating the application of various coatings on their surfaces to ensure superior performance.This review summarizes and compares recent advancements in the research of eight distinct types of coatings for BPs in PEMFCs,including noble metal,carbide,ni-tride,and amorphous carbon(a-C)/metal compound composite coatings.The various challenges encountered in the manufacturing and fu-ture application of these coatings are also delineated.

Diarrheal Diseases: A Review on Gastroenteritis Bacteria Global Burden and Alternative Control of Multidrug-Resistant Strains

Diarrheal diseases represent a significant and pervasive health challenge for humanity. The aetiology of diarrheal diseases is typically associated with the presence of enteropathogens, including viruses, bacteria and parasites. The implementation of preventive measures, including the maintenance of good food hygiene, effective water sanitation, and the development of rotavirus vaccines, has resulted in a notable reduction in the prevalence of the disease. However, the emergence of bacterial multidrug resistance due to the past or present inappropriate use of antibiotics has rendered bacterial infections a significant challenge. The objective of this review is threefold: firstly, to provide an overview of diarrheal diseases associated with bacteria;secondly, to offer a concise analysis of bacterial multidrug resistance on a global scale;and thirdly, to present the potential of filamentous fungi as an alternative solution to the challenge posed by multidrug-resistant strains. Campylobacter spp. is the most dangerous bacteria, followed by Shigella spp. and Vibrio cholerae in all age groups combined. However, Shigella spp. was the deadliest in children under five years of age and, together with E. coli, are the most antibiotic-resistant bacteria. With their highly developed secondary metabolism, fungi are a reservoir of natural bioactive compounds.

Solid-state NMR reveals that oxygen tri-clusters make glass highly crackresistant

In a recent paper,advanced solid-state nuclear magnetic resonance(SSNMR)technology was employed to reveal the underlying mechanism contributing to the high hardness and exceptional resistance to fragmentation observed in certain special glasses[1].This study utilized SSNMR to analyze the atomic-scale internal structure of glass,enabling the quantification of the fraction of three-coordinated oxygen([^((3))O]).The research findings demonstrate a quantitative relationship between[^((3))O]and the resistance of glass to crack initiation.

Efficacy and Safety of Combined Bedaquiline and Delamanid Use among Patients with Multidrug-Resistant Tuberculosis in Beijing,China

Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Evaluation of the Potential of Araucaria angustifolia Seeds as Source of Oligosaccharides, Resistant Starch and Growth of Probiotic Bacteria

“Pinhão”, the seed of Araucaria angustifolia, is an important food, being part of the eating habits of Indigenous communities. In this study, we evaluated the oligosaccharide content, resistant starch and the growth of probiotic bacteria. GF4 (1-fructofuranosylnystose) was the main fructo-oligosaccharides found, in higher contents compared to other food sources. Maltooligosaccharides (MOS) represented the main part of the oligosaccharides profile of Brazilian pine seeds. In descending order of importance was maltoheptaose (G7), maltohexose (G6) and maltotriose (G3). The starches from the variety Sanct josephi presented the highest amount of resistant starch that could stimulate probiotic strains, mainly B. breve and L. plantarum, and may have a prebiotic effect, potentially promoting health benefits. This study advances the understanding of the chemical composition of the main portion of the “pinhão” enhancing awareness of its potential as a healthy food source, contributing to different uses and indirectly with the species preservation.

Prevalence of Drug Resistant Uropathogenic Escherichia coli from Immunocompromised Diabetic Patients Attending Selected Health Facilities in Benue State

Escherichia coli is the commonest bacterial uropathogen of UTIs, the commonest infections in immunocompromised diabetic patients. Better understanding of their main resistance mechanisms to commonly used antibacterial agents will help to reduce the burden of this infection. The prevalence of drug resistant uropathogenic Escherichia coli isolates from immunocompromised diabetic patients attending selected health facilities in Benue State was investigated. Two hundred and ninety-six midstream urine samples were collected for both study and control diabetic patients. Bacterial isolation was done using semi-quantitative method. Drug resistant Escherichia coli were identified as multidrug resistant (MDR), extensive drug resistant (XDR) and pan-drug resistant organisms (PDR). Statistical significance was considered at p E. coli isolates from the study and control subjects with overall prevalence of 20.9% and 8.4% respectively. The isolates were highly resistant to penicillin (ampicillin), monobactam (aztreonam), older quinolone (nalidixic acid) whereas the majority of them showed high susceptibility to aminoglycoside (streptomycin), cephalosporin (cefotaxime) and carbapenem (imipenem). None showed complete susceptibility to all the tested antibiotics. Twenty-five E. coli were identified in this MDR, eight, XDR while 5 were PDR. High numbers of drug resistant E. coli isolates were identified in the study group of which 25 were MDR, 8 XDR while 5 were PDR isolates. High prevalence of UTI and drug resistant isolates occur in diabetic patients with hyperglycemic condition.

Corrosion-Resistant Polymer-Derived SiOC Membrane for Effective Organic Removal via Synergistic Adsorption and Peroxymonosulfate Activation

A major challenge is to construct ceramic membranes with tunable structures and functions for water treatment.Herein,a novel corrosion-resistant polymer-derived silicon oxycarbide(SiOC)ceramic membrane with designed architectures was fabricated by a phase separation method and was applied in organic removal via adsorption and oxidation for the first time.The pore structure of the as-prepared SiOC ceramic membranes was well controlled by changing the sintering temperature and polydimethylsiloxane content,leading to a pore size of 0.84–1.62μm and porosity of 25.0–43.8%.Corrosion resistance test results showed that the SiOC membranes sustained minimal damage during 24 h exposure to high-intensity acid–base conditions,which could be attributed to the chemical inertness of SiOC.With rhodamine 6G(R6G)as the model pollutant,the SiOC membrane demonstrated an initial eff ective removal rate of 99%via adsorption;however,the removal rate decreased as the system approached adsorption saturation.When peroxymonosulfate was added into the system,efficient and continuous degradation of R6G was observed throughout the entire period,indicating the potential of the as-prepared SiOC membrane in oxidation-related processes.Thus,this work provides new insights into the construction of novel polymer-derived ceramic membranes with well-defined structures and functions.

Detection of ARV-Resistant Mutants in HIV-1-Infected Individuals in a Context of Systematic Switching to an Association Based on Dolutegravir in Abidjan, Côte d’Ivoire

The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. Molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://www.hiv-grade.de/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.

Resistant Pulmonary TB-HIV Co-Infection in an Infant: About a Case

Diagnosis of childhood tuberculosis (TB) is difficult, especially in resource-limited countries where the number of reported cases of TB-HIV co-infection continues to rise. This co-infection poses a diagnostic and therapeutic problem for caregivers. We report a case of rifampicin-resistant HIV-TB pulmonary coinfection in a 19-month-old infant.

Effect of Mn addition on microstructure and mechanical properties of GX40CrNiSi25-12 austenitic heat resistant steel

Three types of steels were designed on the basis of GX40CrNiSi25-12 austenitic heat resistant steel by adding different Mn contents(2wt.%,6wt.%,and 12wt.%).Thermodynamic calculation,microstructure characterization and mechanical property tests were conducted to investigate the effect of Mn addition on the microstructure and mechanical properties of the austenitic heat resistant steel.Results show that the matrix structure in all the three types of steels at room temperature is completely austenite.Carbides NbC and M_(23)C_(6)precipitate at grain boundaries of austenite matrix.With the increase of Mn content,the number of carbides increases and their distribution becomes more uniform.With the Mn content increases from 1.99%to 12.06%,the ultimate tensile strength,yield strength and elongation increase by 14.6%,8.0%and 46.3%,respectively.The improvement of the mechanical properties of austenitic steels can be explained by utilizing classic theories of alloy strengthening,including solid solution strengthening,precipitation strengthening,and grain refinement.The increase in alloy strength can be attributed to solid solution strengthening and precipitation strengthening caused by the addition of Mn.The improvement of the plasticity of austenitic steels can be explained from two aspects:grain refinement and homogenization of precipitated phases.

Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

Treatment Resistant Depression, Ketamine versus ECT

Recent studies have highlighted the increase in treatment resistant depression. Of particular concern is the rising trend of depression and suicide rates among Young Adults. Ketamine was approved for treatment resistant depression in 2019 by the US Food and Drug Administration. It received an additional indication for treatment of suicidality. While intranasal Ketamine is approved for depression, recent data about intravenous infusion of Ketamine in controlled inpatient settings has been promising. ECT has a long-standing trend for being used for resistant depression and recent comparison trials have revealed positive results when head-to-head comparisons are made with Ketamine. Future studies need to focus on patient selection and wherein treatment algorithm should Ketamine be selected as treatment modality.

Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the catastrophic costs DRTB patients incur.

Demonstration of irradiation-resistant 4H-SiC based photoelectrochemical water splitting

4H silicon carbide(4H-SiC)has gained a great success in high-power electronics,owing to its advantages of wide bandgap,high breakdown electric field strength,high carrier mobility,and high thermal conductivity.Considering the high carrier mobility and high stability of 4H-SiC,4H-SiC has great potential in the field of photoelectrochemical(PEC)water splitting.In this work,we demonstrate the irradiation-resistant PEC water splitting based on nanoporous 4H-SiC arrays.A new two-step anodizing approach is adopted to prepare 4H-SiC nanoporous arrays with different porosity,that is,a constant low-voltage etching followed by a pulsed high-voltage etching.The constant-voltage etching and pulsed-voltage etching are adopted to control the diameter of the nanopores and the depth of the nanoporous arrays,respectively.It is found that the nanoporous arrays with medium porosity has the highest PEC current,because of the enhanced light absorption and the optimized transportation of charge carriers along the walls of the nanoporous arrays.The performance of the PEC water splitting of the nanoporous arrays is stable after the electron irradiation with the dose of 800 and 1600 k Gy,which indicates that 4H-SiC nanoporous arrays has great potential in the PEC water splitting under harsh environments.

Development and performance evaluation of high temperature resistant strong adsorption rigid blocking agent

As drilling wells continue to move into deep ultra-deep layers,the requirements for temperature resistance of drilling fluid treatments are getting higher and higher.Among them,blocking agent,as one of the key treatment agents,has also become a hot spot of research.In this study,a high temperature resistant strong adsorption rigid blocking agent(QW-1)was prepared using KH570 modified silica,acrylamide(AM)and allyltrimethylammonium chloride(TMAAC).QW-1 has good thermal stability,average particle size of 1.46μm,water contact angle of 10.5.,has a strong hydrophilicity,can be well dispersed in water.The experimental results showed that when 2 wt%QW-1 was added to recipe A(4 wt%bentonite slurry+0.5 wt%DSP-1(filtration loss depressant)),the API filtration loss decreased from 7.8to 6.4 m L.After aging at 240.C,the API loss of filtration was reduced from 21 to 14 m L,which has certain performance of high temperature loss of filtration.At the same time,it is effective in sealing 80-100mesh and 100-120 mesh sand beds as well as 3 and 5μm ceramic sand discs.Under the same conditions,the blocking performance was superior to silica(5μm)and calcium carbonate(2.6μm).In addition,the mechanism of action of QW-1 was further investigated.The results show that QW-1 with amide and quaternary ammonium groups on the molecular chain can be adsorbed onto the surface of clay particles through hydrogen bonding and electrostatic interaction to form a dense blocking layer,thus preventing further intrusion of drilling fluid into the formation.

Current progress of research on heat -resistant Mg alloys: A review

With the increasing attention received by lightweight metals,numerous essential fields have increased requirements for mag-nesium(Mg)alloys with good room-temperature and high-temperature mechanical properties.However,the high-temperature mechanic-al properties of commonly used commercial Mg alloys,such as AZ91D,deteriorate considerably with increasing temperatures.Over the past several decades,extensive efforts have been devoted to developing heat-resistant Mg alloys.These approaches either inhibit the gen-eration of thermally unstable phases or promote the formation of thermally stable precipitates/phases in matrices through solid solution or precipitation strengthening.In this review,numerous studies are systematically introduced and discussed.Different alloy systems,includ-ing those based on Mg–Al,Mg–Zn,and Mg–rare earth,are carefully classified and compared to reveal their mechanical properties and strengthening mechanisms.The emphasis,limitations,and future prospects of these heat-resistant Mg alloys are also pointed out and dis-cussed to develop heat-resistant Mg alloys and broaden their potential application areas in the future.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.

Ultra wear resistant TiC-Fe coating prepared by high efficient and economic plasma cladding method

The key components of engineering machinery frequently failed due to working in the high load and high wear operating envir-onment.And the performance of the Fe-based alloy coatings typically employed need to be improved for fulfilling the service requirements.Herein,a TiC strengthened Fe-based alloy cladding layer,named TiC-Fe coating,was designed and prepared by plasma cladding technology.The frictional wear performance of coating under various loads was tested.The wear morphology of the coating was observed,and its wear mechanism was examined.The results indicated that the TiC-Fe coating was well formed and metallurgically bonded to the Q345C substrate.Its microstructure mainly consisted of Fe-Cr solid solution,α-Fe phase,(Fe,Cr)_(7)C_(3) phase and TiC phase.The coating exhibited an average microhardness of 980 HV0.2,which was about 5.4 times that of the Q345C substrate.The wear mass loss of the TiC-Fe coatings was much smaller than that of the Q345C substrate,which indicated that the wear resistance of the Q345C coating was superior to the substrate,and the wear mechanism of the coating was mainly attributed to the abrasive wear.