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Helicobacter pylori has been recognized not only as a causative agent of a spectrum of gastroduodenal diseases including chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, but also as the culprit in several extra-gastric diseases. However, the association of H. pylori infection with extra-gastric diseases remains elusive, prompting a reevaluation of the role of H. pylori-derived outer membrane vesicles (OMVs). Like other gram-negative bacteria, H. pylori constitutively sheds biologically active OMVs for long-distance delivery of bacterial virulence factors in a concentrated and protected form, averting the need of direct bacterial contact with distant host cells to induce extra-gastric diseases associated with this gastric pathogen. Additionally, H. pylori-derived OMVs contribute to bacterial survival and chronic gastric pathogenesis. Moreover, the immunogenic activity, non-replicable nature, and anti-bacterial adhesion effect of H. pylori OMVs make them a desirable vaccine candidate against infection. The immunogenic potency and safety concerns of the OMV contents are challenges in the development of H. pylori OMV-based vaccines. In this review, we discuss recent advances regarding H. pylori OMVs, focusing on new insights into their biogenesis mechanisms and biological functions.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Animais , Fatores de Virulência/metabolismo , Membrana Externa Bacteriana/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismoRESUMO
miR-504 plays a pivotal role in the progression of oral cancer. However, the underlying mechanism remains elusive in vivo. Here, we find that miR-504 is significantly down-regulated in oral cancer patients. We generate miR-504 knockout mice (miR-504-/-) using CRISPR/Cas9 technology to investigate its impact on the malignant progression of oral cancer under exposure to 4-Nitroquinoline N-oxide (4NQO). We show that the deletion of miR-504 does not affect phenotypic characteristics, body weight, reproductive performance, and survival in mice, but results in changes in the blood physiological and biochemical indexes of the mice. Moreover, with 4NQO treatment, miR-504-/- mice exhibit more pronounced pathological changes characteristic of oral cancer. RNA sequencing shows that the differentially expressed genes observed in samples from miR-504-/- mice with oral cancer are involved in regulating cell metabolism, cytokine activation, and lipid metabolism-related pathways. Additionally, these differentially expressed genes are significantly enriched in lipid metabolism pathways that influence immune cell infiltration within the tumor microenvironment, thereby accelerating tumor development progression. Collectively, our results suggest that knockout of miR-504 accelerates malignant progression in 4NQO-induced oral cancer by regulating tumor cell proliferation and lipid metabolism, affecting immune cell infiltration.
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About 140 million people worldwide live at an altitude above 2500 m. Studies have showed an increase of the incidence of hyperuricemia among plateau populations, but little is known about the possible mechanisms. This study aims to assess the effects of high altitude on hyperuricemia and explore the corresponding mechanisms at the histological, inflammatory and molecular levels. This study finds that intermittent hypobaric hypoxia (IHH) exposure results in an increase of serum uric acid level and a decrease of uric acid clearance rate. Compared with the control group, the IHH group shows significant increases in hemoglobin concentration (HGB) and red blood cell counts (RBC), indicating that high altitude hyperuricemia is associated with polycythemia. This study also shows that IHH exposure induces oxidative stress, which causes the injury of liver and renal structures and functions. Additionally, altered expressions of organic anion transporter 1 (OAT1) and organic cation transporter 1 (OCT1) of kidney have been detected in the IHH exposed rats. The adenosine deaminase (ADA) expression levels and the xanthione oxidase (XOD) and ADA activity of liver of the IHH exposure group have significantly increased compared with those of the control group. Furthermore, the spleen coefficients, IL-2, IL-1ß and IL-8, have seen significant increases among the IHH exposure group. TLR/MyD88/NF-κB pathway is activated in the process of IHH induced inflammatory response in joints. Importantly, these results jointly show that IHH exposure causes hyperuricemia. IHH induced oxidative stress along with liver and kidney injury, unusual expression of the uric acid synthesis/excretion regulator and inflammatory response, thus suggesting a potential mechanism underlying IHH-induced hyperuricemia.
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Hiperuricemia , Hipóxia , Rim , Fígado , Estresse Oxidativo , Hiperuricemia/metabolismo , Animais , Masculino , Ratos , Fígado/metabolismo , Fígado/patologia , Hipóxia/metabolismo , Hipóxia/complicações , Rim/metabolismo , Rim/patologia , Altitude , Ácido Úrico/sangue , Ácido Úrico/metabolismo , Ratos Sprague-Dawley , Xantina Oxidase/metabolismo , Doença da Altitude/metabolismo , Doença da Altitude/complicações , Doença da Altitude/fisiopatologiaRESUMO
High-altitude exposure has been linked to cardiac dysfunction. Silent information regulator factor 2-related enzyme 1 (sirtuin 1, SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, plays a crucial role in regulating numerous cardiovascular diseases. However, the relationship between SIRT1 and cardiac dysfunction induced by hypobaric hypoxia (HH) remains unexplored. This study aims to assess the impact of SIRT1 on HH-induced cardiac dysfunction and delve into the underlying mechanisms, both in vivo and in vitro. In this study, we have demonstrated that exposure to HH results in cardiomyocyte injury, along with the downregulation of SIRT1 and mitochondrial dysfunction. Upregulating SIRT1 significantly inhibits mitochondrial fission, improves mitochondrial function, reduces cardiomyocyte injury, and consequently enhances cardiac function in HH-exposed rats. Additionally, HH exposure triggers aberrant expression of mitochondrial fission-regulated proteins, with a decrease in PPARγ coactivator 1 alpha (PGC-1α) and mitochondrial fission factor (MFF) and an increase in mitochondrial fission 1 (FIS1) and dynamin-related protein 1 (DRP1), all of which are mitigated by SIRT1 upregulation. Furthermore, inhibiting PGC-1α diminishes the positive effects of SIRT1 regulation on the expression of DRP1, MFF, and FIS1, as well as mitochondrial fission. These findings demonstrate that SIRT1 alleviates HHinduced cardiac dysfunction by preventing mitochondrial fission through the PGC-1α-DRP1/FIS1/MFF pathway.
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OBJECTIVES: The splicing factor transformer-2 homolog beta (Tra2ß) plays a pivotal role in various cancers. Nonetheless, its role in oral squamous cell carcinoma (OSCC) has not been comprehensively explored. This study sought to discern the influence of Tra2ß on OSCC and its underlying mechanisms. MATERIALS AND METHODS: We assessed Tra2ß expression in OSCC utilizing immunohistochemistry, qRT-PCR, and western blotting techniques. siRNA transfection was used to silence Tra2ß. Whole transcriptome RNA sequencing (RNA-seq) analysis was carried out to reveal the alternative splicing (AS) events. KEGG pathway analysis enriched the related pathways. Colony formation, transwell, wound healing, and Annexin V-FITC/PI were employed to appraise the consequences of Tra2ß silencing on OSCC. RESULTS: Tra2ß was highly expressed in both OSCC tissues and cell lines. Knockdown of Tra2ß-regulated AS events with skipped exon (SE) accounts for the highest proportion. Meanwhile, downregulation of Tra2ß reduced cell proliferation, migration, and invasion, however increasing cell apoptosis. Moreover, Wnt signaling pathway involved in the function of Tra2ß knockdown which was demonstrated directly by a discernible reduction in the expression of GSK3/ß-catenin signaling axis. CONCLUSIONS: These findings suggest that knockdown of Tra2ß may exert anti-tumor effects through the GSK3/ß-catenin signaling pathway in OSCC.
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Unlike the traditional studies on multiagent systems (MASs), this article investigates a class of MASs with spatial properties, whose agents are modeled by partial differential equations (PDE), in addition, to make the model more comprehensive, the Markovian switching topology with partially unknown probability is taken into account. The purpose of this article is to achieve the bipartite consensus for the above PDE-based MASs. In fact, the consideration of spatial factors in MASs will exacerbate the network transmission pressure, to overcome this problem, a novel spatiotemporal event-triggered mechanism is developed. Compared with the existing event-triggered mechanism, the proposed one is not only time-dependent but also covers the influence of spatial variables on the trigger conditions, which helps to further reduce the triggering frequency. Finally, three examples are given to verify the validity of the conclusion we proposed.
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The common adverse effects and the complicated administration of tetracycline and metronidazole greatly affect the clinical application of the classical bismuth quadruple therapy (BQT) for Helicobacter pylori eradication. This pilot study aimed to evaluate the efficacy and safety of minocycline/amoxicillin-based BQT for H. pylori eradication. Firstly, consecutive H. pylori isolates collected at West China Hospital of Sichuan University between 2018 and 2021 were included for susceptibility testing of tetracycline and minocycline using E-test strips. Secondly, both treatment-naïve and experienced patients were included to receive a 14-day minocycline/amoxicillin-based BQT: esomeprazole 40 mg or vonoprazan 20 mg, bismuth colloidal pectin 300 mg, amoxicillin 1000 mg, and minocycline 100 mg, all given twice daily. Among a total of 101 H. pylori isolates, tetracycline resistance was 3.0%, whereas minocycline resistance was nil. A total of 114 patients (treatment-naïve/experienced, 72/42) received the minocycline/amoxicillin-based BQT. The overall intention-to-treat (ITT) and per protocol (PP) eradication rates were 94.7% (108/114) and 97.3% (108/111), respectively. The ITT and PP eradication rates were 91.7% (66/72) and 95.7% (66/69) among the treatment-naïve patients, and both were 100.0% among the treatment-experienced patients. No serious adverse event was recorded. This pilot study suggests that minocycline/amoxicillin-based BQT is an excellent therapy for H. pylori eradication.
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The Hedgehog (Hh) signaling pathway plays a crucial role in diverse biological processes such as cell differentiation, proliferation, senescence, tumorigenesis, malignant transformation, and drug resistance. Aberrant Hh signaling, resulting from mutations and excessive activation, can contribute to the development of various diseases during different stages of biogenesis and development. Moreover, it has been linked to unfavorable outcomes in several human cancers, including basal cell carcinoma (BCC), multiple myeloma (MM), melanoma, and breast cancer. Hence, the presence of mutations and excessive activation of the Hh pathway presents obstacles and constraints in the realm of cancer treatment. Extant research has demonstrated that small molecule inhibitors are regarded as the most effective therapeutic approaches for targeting the Hh pathway in contrast to traditional chemotherapy and radiotherapy. Consequently, this review focuses on the present repertoire of small molecule inhibitors that target various components of the Hh pathway, including Hh ligands, Ptch receptors, Smo transmembrane proteins, and Gli nuclear transcription factors. This study provides a comprehensive analysis of small molecules' structural and functional aspects in the preclinical and clinical management of cancer. Additionally, it elucidates the obstacles encountered in targeting the Hh pathway for human cancer therapy and proposes potential therapeutic approaches.
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Antineoplásicos , Proteínas Hedgehog , Neoplasias , Transdução de Sinais , Humanos , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , AnimaisRESUMO
BACKGROUND: Helicobacter pylori lipopolysaccharide (LPS) structures vary among strains of different geographic origin. The aim of this study was to characterize the LPS O-antigen profiles of H. pylori strains isolated from Southwest China, and to further analyze the association of Lewis antigen expression with clinical outcomes and antibiotic resistance. RESULTS: A total of 71 H. pylori isolates from Southwest China were included for LPS profiling by silver staining and Western blotting after SDS-PAGE electrophoresis. We demonstrated that all the clinical isolates had the conserved lipid A and core-oligosaccharide, whereas the O-antigen domains varied significantly among the isolates. Compared with the common presence of the glucan/heptan moiety in LPS O-antigen structure of European strains, the clinical isolates in this study appeared to lack the glucan/heptan moiety. The expression frequency of Lex, Ley, Lea, and Leb was 66.2% (47/71), 84.5% (60/71), 56.3% (40/71), and 31.0% (22/71), respectively. In total, the expression of type II Lex and/or Ley was observed in 69 (97.2%) isolates, while type I Lea and/or Leb were expressed in 49 (69.0%) isolates. No association of Lewis antigen expression with clinical outcomes or with antibiotic resistance was observed. CONCLUSIONS: H. pylori strains from Southwest China tend to produce heptan-deficient LPS and are more likely to express type I Lewis antigens as compared with Western strains. This may suggest that H. pylori evolves to change its LPS structure for adaptation to different hosts.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Lipopolissacarídeos/metabolismo , Antígenos O , Antígenos do Grupo Sanguíneo de Lewis/metabolismo , GlucanosRESUMO
This article focuses on the neural adaptive output feedback control study related to nonaffine stochastic multiple-input, multiple-output nonlinear plants. First, a K-filter state observer based on a radial basis function neural network is designed to estimate the remaining unavailable states. Then, a novel adaptive command-filtered backstepping output feedback control framework is established, where an improved command filter with a fractional-order parameter is applied to conquer the calculation size problem. Specifically, the highlight of this work is that it designs a modified error compensation signal and incorporates the concept of deferred constraint to eradicate the negative effect caused by the filter errors. In addition, the network bandwidth resources, control impulse, and control accuracy are synthesized using an amended switching event-triggered mechanism. The theoretical analysis proved that the proposed control approach guarantees that the tracking error can converge to a preassigned region within a user-defined time while the violation of the deferred output constraint can be excluded. Two illustrative studies are provided to demonstrate the validity and superiority of the developed control method.
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Algoritmos , Dinâmica não Linear , Simulação por Computador , Retroalimentação , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: Frizzled 6 (Fzd6) is involved in the development of various disorders; however, its role in the etiology of depression remains unclear. We aimed to determine the potential regulatory mechanisms of Fzd6 as a Wnt receptor in depression. METHODS: Mice were divided into four groups: wild-type control (Fzd6WT-control), Fzd6 mutant control (Fzd6Q152E-control), wild-type reserpine (Fzd6WT-reserpine), and Fzd6 mutant reserpine (Fzd6Q152E-reserpine). Reserpine (0.5 mg/kg) was injected intraperitoneally for 10 days. Four behavioral experiments were performed to assess the effects of Fzd6Q152E on depression-like behaviors in the reserpine-treated mice. Blood samples were collected for an enzyme-linked immunosorbent assay (ELISA). Gene expression in the hippocampus was quantified using quantitative real-time polymerase chain reaction (qRT-PCR), and protein expression levels in the hippocampus were identified using western blotting. RESULTS: The Fzd6 mutation affected reserpine-induced depression-like behavioral changes in mice. ELISA revealed significantly reduced serum levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), and norepinephrine in both Fzd6Q152E-reserpine and Fzd6WT-reserpine mice, with a more pronounced decrease in Fzd6Q152E-reserpine mice, especially in norepinephrine expression. The qRT-PCR results showed significantly decreased Fzd6 expression in Fzd6Q152E-reserpine mice and altered expression of Dkk2, Gsk-3ß, Lrp6, Wnt2, Wnt3, and Wnt3a in the Wnt pathway. Western blotting revealed decreased Fzd6 protein expression in Fzd6Q152E-control mice compared to Fzd6WT-control mice, whereas Fzd6 protein expression was restored in Fzd6Q152E-reserpine mice, and Gsk-3ß expression was significantly changed. CONCLUSION: Fzd6 potentially influences reserpine-induced depressive behavioral changes and serum depressive factor alterations and modulates the expression of the Wnt signaling pathway in the hippocampus of depressed mice.
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Depressão , Via de Sinalização Wnt , Animais , Camundongos , Depressão/induzido quimicamente , Depressão/genética , Glicogênio Sintase Quinase 3 beta , Reserpina , Mutação , Norepinefrina , SerotoninaRESUMO
Helicobacter pylori has a unique lipopolysaccharide structure that is essential in maintaining its cell envelope integrity and imbues the bacterium with natural resistance to cationic antimicrobial peptides (CAMPs). Our group has recently elucidated the complete set of LPS glycosyltransferase genes in H. pylori reference strain G27. Here, with a series of eight systematically constructed LPS glycosyltransferase gene mutants (G27ΔHP1578, G27ΔHP1283, G27ΔHP0159, G27ΔHP0479, G27ΔHP0102, G27ΔwecA, G27ΔHP1284 and G27ΔHP1191), we investigated the roles of H. pylori LPS glycosyltransferases in maintaining cell morphology, cell wall permeability, and antimicrobial susceptibilities. We demonstrated that deletion of these LPS glycosyltransferase genes did not interfere with bacterial cell wall permeability, but resulted in significant morphological changes (coccoid, coiled "c"-shape, and irregular shapes) after 48 h growth as compared to the rod-like cell shape of the wild-type strain. Moreover, as compared with the wild-type, none of the LPS mutants had altered susceptibility against clarithromycin, levofloxacin, amoxicillin, tetracycline, and metronidazole. However, the deletion of the conserved LPS glycosyltransferases, especially the O-antigen-initiating enzyme WecA, displayed a dramatic increase in susceptibility to the CAMP polymyxin B and rifampicin. Taken together, our findings suggest that the LPS glycosyltransferases play critical roles in the maintenance of the typical spiral morphology of H. pylori, as well as resistance to CAMPs and rifampicin. The LPS glycosyltransferases could be promising targets for developing novel anti-H. pylori drugs.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Lipopolissacarídeos , Helicobacter pylori/genética , Glicosiltransferases/genética , Rifampina , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Metronidazol , Amoxicilina , Claritromicina , Parede Celular , Peptídeos Catiônicos Antimicrobianos , Permeabilidade , Infecções por Helicobacter/microbiologiaRESUMO
Hydraulic servo actuators (HSAs) are often used in the industry in tasks that request great power, high accuracy and dynamic motion. It is well known that an HSA is a highly complex nonlinear system, and that the system parameters cannot be accurately determined due to various uncertainties, an inability to measure some parameters and disturbances. This paper considers an event-triggered learning control problem of the HSA with unknown dynamics based on adaptive dynamic programming (ADP) via output feedback. Due to increasing practical application of the control algorithm, a linear discrete model of HSA is considered and an online learning data driven controller is used, which is based on measured input and output data instead of unmeasurable states and unknown system parameters. Hence, the ADP-based data driven controller in this paper requires neither the knowledge of the HSA dynamics nor exosystem dynamics. Then, an event-based feedback strategy is introduced to the closed-loop system to save the communication resources and reduce the number of control updates. The convergence of the ADP-based control algorithm is also theoretically shown. Simulation results verify the feasibility and effectiveness of the proposed approach in solving the optimal control problem of HSAs.
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BACKGROUND: Helicobacter pylori eradication regimens should be guided by antimicrobial susceptibility testing. The objective of this study was to evaluate the molecular-based Mosprie assay for detecting H. pylori resistance to clarithromycin and levofloxacin using gastric biopsies. METHODS: A total of 185 culture-positive frozen gastric biopsies were included for Mosprie assay and also for 23S rRNA and gyrA gene sequencing. The susceptibility results by the Mosprie assay were compared with the E-test results retrospectively retrieved. The discordant results were analyzed by sequencing of the 23S rRNA and gyrA genes. RESULTS: Susceptibility concordance between the Mosprie assay and E-test for clarithromycin and levofloxacin was 97.30% (180/185) and 88.11% (163/185), respectively. The full agreement between clarithromycin genotypes by Mosprie assay and the 23S rRNA sequencing results was observed in the 5 samples with discordant Mosprie assay and E-test results. However, for levofloxacin, of the 16 discordant samples with resistant phenotype but a susceptible genotype by Mosprie assay, 6 were found to have levofloxacin resistance-related gyrA gene mutations. CONCLUSIONS: The rapid and reliable Mosprie assay can be recommended for H. pylori susceptibility testing of clarithromycin and levofloxacin on gastric biopsies. Future technical improvements are needed in detecting levofloxacin resistance-associated gene mutations.
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Claritromicina , Helicobacter pylori , Claritromicina/farmacologia , Levofloxacino/farmacologia , Helicobacter pylori/genética , Estudos RetrospectivosRESUMO
BACKGROUND: The aim of this study was to evaluate the rifamycin cross-resistance in Helicobacter pylori, and whether the use of rifampicin E-test strips to screen H. pylori rifabutin resistance is appropriate. METHODS: A total of 89 H. pylori isolates were included. Rifampicin minimum inhibitory concentrations (MICs) were obtained by E-test, while the MICs for rifapentine, rifaximin, and rifabutin were determined by agar dilution method. The rifamycin resistance rates based on different breakpoints were compared. Isolates with high-level rifampicin resistance were subjected to whole-genome sequencing. RESULTS: A wide distribution of MICs (mostly in the range 0.125-8â mg/L) was observed for rifampicin, rifapentine, and rifaximin. Using MIC >1, ≥ 4, and > 4â mg/L as the breakpoints, resistance rates to rifampicin/rifapentine/rifaximin were 60.4%/48.3%/38.2%, 28.1%/25.8%/23.6%, and 15.7%/16.9%/7.9%, respectively. However, the rifabutin MICs of all the tested H. pylori isolates were extremely low (≤0.016â mg/L). Applying MIC ≥ 0.125â mg/L as the breakpoint, rifabutin resistance was nil. No mutation was found in the rpoB gene sequences of the 2 isolates with high-level rifampicin resistance. CONCLUSIONS: There is a lack of cross-resistance between rifabutin and other rifamycins in H. pylori. The use of rifampicin E-test to predict H. pylori rifabutin resistance is inappropriate.
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Helicobacter pylori , Rifabutina , Rifabutina/farmacologia , Helicobacter pylori/genéticaRESUMO
BACKGROUND: Helicobacter pylori infection is an infectious disease and thus the eradication treatment should be guided by susceptibility testing. This study aimed to assess the applicability of broth microdilution as a routine susceptibility testing method for H. pylori. METHODS: Susceptibility profiles of clarithromycin (CLR) and levofloxacin (LEV) resistance in 76 clinical H. pylori isolates were simultaneously assessed using agar dilution and broth microdilution methods. The correlation between the minimum inhibitory concentrations (MICs) obtained by the 2 methods was assessed by means of linear regression analysis. RESULTS: The correlation between the MICs determined by broth microdilution method and agar dilution method was good for both CLR (r = 0.966) and LEV (r = 0.959). The susceptibility agreement between the 2 methods was 100% for CLR and 96.1% for LEV. Using the broth microdilution method, the false resistance was found in 3.9% (3 of 76) strains for LEV susceptibility testing. No false susceptibility was found for either CLR or LEV, and no false resistance was found for susceptibility testing of CLR. CONCLUSIONS: The broth microdilution method is suitable for routine susceptibility testing of clinical H. pylori isolates.
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Infecções por Helicobacter , Helicobacter pylori , HumanosRESUMO
The pathogenesis of type 2 diabetes (T2D) is highly related to the abnormal self-assembly of the human islet amyloid polypeptide (hIAPP) into amyloid aggregates. To inhibit hIAPP aggregation is considered a promising therapeutic strategy for T2D treatment. Melatonin (Mel) was reported to effectively impede the accumulation of hIAPP aggregates and dissolve preformed fibrils. However, the underlying mechanism at the atomic level remains elusive. Here, we performed replica-exchange molecular dynamics (REMD) simulations to investigate the inhibitory effect of Mel on hIAPP oligomerization by using hIAPP20-29 octamer as templates. The conformational ensemble shows that Mel molecules can significantly prevent the ß-sheet and backbone hydrogen bond formation of hIAPP20-29 octamer and remodel hIAPP oligomers and transform them into less compact conformations with more disordered contents. The interaction analysis shows that the binding behavior of Mel is dominated by hydrogen bonding with a peptide backbone and strengthened by aromatic stacking and CH-π interactions with peptide sidechains. The strong hIAPP-Mel interaction disrupts the hIAPP20-29 association, which is supposed to inhibit amyloid aggregation and cytotoxicity. We also performed conventional MD simulations to investigate the influence and binding affinity of Mel on the preformed hIAPP1-37 fibrillar octamer. Mel was found to preferentially bind to the amyloidogenic region hIAPP20-29, whereas it has a slight influence on the structural stability of the preformed fibrils. Our findings illustrate a possible pathway by which Mel alleviates diabetes symptoms from the perspective of Mel inhibiting amyloid deposits. This work reveals the inhibitory mechanism of Mel against hIAPP20-29 oligomerization, which provides useful clues for the development of efficient anti-amyloid agents.
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Diabetes Mellitus Tipo 2 , Melatonina , Amiloide/metabolismo , Proteínas Amiloidogênicas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Ligação de Hidrogênio , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Melatonina/farmacologia , Simulação de Dinâmica Molecular , Conformação Proteica em Folha betaRESUMO
The finite-time synchronization issue of reaction-diffusion memristive neural networks (RDMNNs) is studied in this paper. To better synchronize the parameter-varying drive and response systems, an innovative gain-scheduled integral sliding mode control scheme is proposed, where the 2n controller gains can be scheduled and an integral switching surface function that contains a discontinuous term is involved. Moreover, by constructing a novel Lyapunov-Krasovskii functional and combining reciprocally convex combination (RCC) method, a less conservative finite-time synchronization criterion for RDMNNs is derived in the form of linear matrix inequalities (LMIs). Finally, three numerical simulations are exploited to illustrate the effectiveness, superiority and practicability of this paper.
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Redes Neurais de Computação , Difusão , Fatores de TempoRESUMO
BACKGROUND: The prevalence of Helicobacter pylori antibiotic susceptibility in the Tibet Autonomous Region, China is not determined. This study aimed to evaluate the antibiotic resistance patterns of H. pylori isolates there. RESULTS: A total of 153 (38.5%) H. pylori strains were successfully isolated from 397 patients in People's Hospital of Tibet Autonomous Region, China. The overall resistance rates were as follows: clarithromycin (27.4%), levofloxacin (31.3%), metronidazole (86.2%), amoxicillin (15.6%), tetracycline (0%), furazolidone (0.6%), and rifampicin (73.2%). Only 2.0% of H. pylori isolates were susceptible to all tested antimicrobials, with mono resistance, dual resistance, triple resistance, quadruple resistance, and quintuple resistance being 18.3%, 44.4%, 18.3%, 12.4%, and 4.6%, respectively. The resistance rates to levofloxacin (40.5%) and amoxicillin (21.5%) in strains isolated from female patients were significantly higher than those from male patients (21.6% and 9.5%, respectively). CONCLUSIONS: This study demonstrates high H. pylori resistance rates to clarithromycin, levofloxacin, metronidazole, and rifampicin, whereas moderate resistance to amoxicillin, and negligible resistant to tetracycline, and furazolidone in Tibet Autonomous Region, China. The high resistance to rifampicin warns further investigation of its derivative, rifabutin.
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Infecções por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , Claritromicina , Farmacorresistência Bacteriana , Feminino , Furazolidona , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Levofloxacino , Masculino , Metronidazol , Testes de Sensibilidade Microbiana , Rifampina , Tetraciclina/farmacologia , Tibet/epidemiologiaRESUMO
Herein, a novel type of red-emitting carbon dots called TN-CDs was created via a one-step hydrothermal approach using neutral red and tartaric acid as raw materials. The fluorescence of TN-CDs was gradually quenched as the amount of water increased, and the color of the solution changed from yellow to pink mauve (or purple to pink). The reaction could be completed within only 5 s in various organic solvents such as N,N-Dimethylformamide (DMF), methanol (MeOH), acetonitrile (ACN), and ethanol (EtOH) with linear detection ranges of 1.2%-35.0%, 0.5%-20.0%, 0.25%-5.0% and 0%-16.0%, respectively. In addition, we prepared a reusable test strip and then combined it with TN-CDs to detect water content in DMF, as well as integrated it with smartphone software, a UV lamp, and a dark chamber for real-time, on-site, visual quantitative detection of the water content.