RESUMO
Organic photovoltaics (OPVs) suffer from a trade-off between efficient charge transport and suppressed nonradiative recombination due to the aggregation-induced luminance quenching of organic semiconductors. To resolve this grand challenge, a π-extended nonfullerene acceptor (NFA) B6Cl with large voids among the honeycomb network is designed and introduced into photovoltaic systems. We find that the presence of a small amount of (i.e., 0.5 or 1 wt %) B6Cl can compress the molecular packing of the host acceptor L8-BO, leading to shortened π-π stacking distance from 3.59 to 3.50 Å (that will improve charge transport) together with ordered alkyl chain packing (that will inhibit nonradiative energy loss due to the suppressed C-C and C-H bonds vibrations), as validated by high-energy X-ray scattering measurements. This morphology transformation ultimately results in simultaneously improved JSC, FF, and VOC of OPVs. As a result, the maximum PCEs of PM6:L8-BO and D18:L8-BO are increased from 19.1 and 19.3% to 19.8 and 20.2%, respectively, which are among the highest values for single-junction OPVs. The university of B6Cl to increase the performance of OPVs is further evidenced in a range of polymer:NFA OPVs.
RESUMO
The increasing antibiotic resistance of Helicobacter pylori primarily driven by genetic mutations poses a significant clinical challenge. Although previous research has suggested that antibiotics could induce genetic mutations in H. pylori, the molecular mechanisms regulating the antibiotic induction remain unclear. In this study, we applied various techniques (e.g., fluorescence microscopy, flow cytometry, and multifunctional microplate reader) to discover that three different types of antibiotics could induce the intracellular generation of reactive oxygen species (ROS) in H. pylori. It is well known that ROS, a critical factor contributing to bacterial drug resistance, not only induces damage to bacterial genomic DNA but also inhibits the expression of genes associated with DNA damage repair, thereby increasing the mutation rate of bacterial genes and leading to drug resistance. However, further research is needed to explore the molecular mechanisms underlying the ROS inhibition of the expression of DNA damage repair-related genes in H. pylori. In this work, we validated that ROS could trigger an allosteric change in the iron uptake regulatory protein Fur, causing its transition from apo-Fur to holo-Fur, repressing the expression of the regulatory protein ArsR, ultimately causing the down-regulation of key DNA damage repair genes (e.g., mutS and mutY); this cascade increased the genomic DNA mutation rate in H. pylori. This study unveils a novel mechanism of antibiotic-induced resistance in H. pylori, providing crucial insights for the prevention and control of antibiotic resistance in H. pylori.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , DNA Bacteriano/metabolismoRESUMO
The metabolic state of bacteria significantly contributes to their resistance to antibiotics; however, the specific metabolic mechanisms conferring antimicrobial resistance in Helicobacter pylori remain largely understudied. Employing transcriptomic and non-targeted metabolomics, we characterized the metabolic reprogramming of H. pylori when challenged with antibiotic agents. We observed a notable increase in both genetic and key proteomic components involved in fatty acid biosynthesis. Inhibition of this pathway significantly enhanced the antibiotic susceptibility of the sensitive and multidrug-resistant H. pylori strains while also disrupting their biofilm-forming capacities. Further analysis revealed that antibiotic treatment induced a stringent response, triggering the expression of the hp0560-hp0557 operon regulated by Sigma28 (σ28). This activation in turn stimulated the fatty acid biosynthetic pathway, thereby enhancing the antibiotic tolerance of H. pylori. Our findings reveal a novel adaptive strategy employed by H. pylori to withstand antibiotic stress.
Assuntos
Antibacterianos , Proteínas de Bactérias , Biofilmes , Farmacorresistência Bacteriana Múltipla , Ácidos Graxos , Helicobacter pylori , Testes de Sensibilidade Microbiana , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Antibacterianos/farmacologia , Ácidos Graxos/biossíntese , Ácidos Graxos/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Fator sigma/genética , Fator sigma/metabolismo , ÓperonRESUMO
Polymeric semiconducting materials struggle to achieve fast charge mobility due to low structural order. In this work, five 1H-indene-1,3(2H)dione-benzene structured halogenated solid additives namely INB-5F, INB-3F, INB-1F, INB-1Cl, and INB-1Br with gradually varied electrostatic potential are designed and utilized to regulate the structural order of polymer donor PM6. Molecular dynamics simulations demonstrate that although the dione unit of these additives tends to adsorb on the backbone of PM6, the reduced electrostatic potential of the halogen-substituted benzene can shift the benzene interacting site from alkyl side chains to the conjugated backbone of PM6, not only leading to enhanced π-π stacking in out-of-plane but also arising new π-π stacking in in-plane together with the appearance of multiple backbone stacking in out-of-plane, consequent to the co-existence of face-on and edge-on molecular orientations. This molecular packing transformation further translates to enhanced charge transport and suppressed carrier recombination in their photovoltaics, with a maximum power conversion efficiency of 19.4% received in PM6/L8-BO layer-by-layer deposited organic solar cells.
RESUMO
Helicobacter pylori (Hp) is a common Gram-negative bacillus causing gastrointestinal infections.It mainly exists on the surface of gastric epithelial cells and in mucus and is associated with gastric ulcers,gastric cancer,and gastric mucosa-associated lymphomas.Studies have shown that Hp can induce or exacerbate certain extragastric diseases and is associated with the occurrence of coronavirus disease 2019.It is hypothesized that Hp may be indirectly or directly involved in the occurrence and development of diseases by stimulating the production of inflammatory cytokines or inducing cross-immune reactions.In addition,Hp can enter Candida to release toxins continuously and play a role in escaping the recognition of the host immune system and the bactericidal effect of drugs.This article reviews the research progress in Hp-associated extragastric diseases in recent years,aiming to draw the attention of clinical workers to Hp-associated extragastric diseases and enrich the knowledge about Hp infection for formulating countermeasures to avoid the aggravation or triggering of other diseases by Hp.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/complicações , COVID-19RESUMO
Featuring diverse structural motions/changes, dynamic molecular systems hold promise for executing complex tasks. However, their structural complexity presents formidable challenge in elucidating their kinetics, especially when multiple structural motions are intercorrelated. We herein introduce a twin-cavity cage that features interconvertible C3- and C1-configurations, with each configuration exhibiting interchangeable P- and M-conformations. This molecule is therefore composed of four interconnected chiral species (P)-C3, (M)-C3, (P)-C1, (M)-C1. We showcase an effective approach to decouple these sophisticated structural changes into two kinetically distinct pathways. Utilizing time-dependent 1Hâ NMR spectroscopy at various temperatures, which disregards the transition between mirror-image conformations, we first determine the rate constant (kc) for the C3- to C1-configuration interconversion, while time-dependent circular dichroism spectroscopy at different temperatures quantifies the observed rate constant (kobs) of the ensemble of all the structural changes. As kobs â« ${{\rm { \gg }}}$ kc, it allows us to decouple the overall molecular motions into a slow configurational transformation and rapid conformational interconversions, with the latter further dissected into two independent conformational interchanges, namely (P)-C3 â â ${ \mathbin{{\stackrel{\textstyle\rightarrow} { {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}} } }} }$ (M)-C3 and (P)-C1 â â ${ \mathbin{{\stackrel{\textstyle\rightarrow} { {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}} } }} }$ (M)-C1. This work, therefore, sheds light on the comprehensive kinetic study of complex molecular dynamics, offering valuable insights for the rational design of smart dynamic materials for applications of sensing, separation, catalysis, molecular machinery, etc.
RESUMO
Recently, there is increased incidence of drug-resistant Helicobacter pylori infection. Biofilm formation confers multidrug resistance to bacteria. Moreover, it has been found that the formation of biofilm on the surface of gastric mucosa is an important reason for the difficulty of eradication of H. pylori The mechanisms underlying H. pylori biofilm formation in vivo have not been elucidated. Reactive oxygen species (ROS) released by the host immune cells in response to H. pylori infection cannot effectively clear the pathogen. Moreover, the extracellular matrix of the biofilm protects the bacteria against ROS-mediated toxicity. This study hypothesized that ROS can promote H. pylori biofilm formation and treatment with low concentrations of hydrogen peroxide (H2O2) promoted this process in vitro The comparative transcriptome analysis of planktonic and biofilm-forming cells revealed that the expression of SpoT, a (p)ppGpp (guanosine 3'-diphosphate 5'-triphosphate and guanosine 3',5'-bispyrophosphate) synthetase/hydrolase, is upregulated in H2O2-induced biofilms and that knockout of spoT inhibited H. pylori biofilm formation. Additionally, this study examined the key target molecules involved in SpoT regulation using weighted gene co-expression network analysis. The analysis revealed that neutrophil-activating protein (NapA; HP0243) promoted H2O2-induced biofilm formation and conferred multidrug resistance. Furthermore, vitamin C exhibited anti-H. pylori biofilm activity and downregulated the expression of napA in vitro These findings provide novel insight into the clearance of H. pylori biofilms.
RESUMO
Helicobacter pylori are transmissible from person to person and among family members. Mother-to-child transmission is the main intrafamilial route of H. pylori transmission. However, how it transmits from mother to child is still being determined. Vaginal yeast often transmits to neonates during delivery. Therefore, H. pylori hosted in yeast might follow the same transmission route. This study aimed to detect intracellular H. pylori in vaginal and fecal yeasts isolates and explore the role of yeast in H. pylori transmission. Yeast was isolated from the mothers' vaginal discharge and neonates' feces and identified by internal transcribed spacer (ITS) sequencing. H. pylori 16S rRNA and antigen were detected in yeast isolates by polymerase chain reaction and direct immunofluorescence assay. Genetic relationships of Candida strains isolated from seven mothers and their corresponding neonates were determined by random amplified polymorphic DNA (RAPD) fingerprinting and ITS alignment. The Candida isolates from four mother-neonate pairs had identical RAPD patterns and highly homologous ITS sequences. The current study showed H. pylori could be sheltered within yeast colonizing the vagina, and fecal yeast from neonates is genetically related to the vaginal yeast from their mothers. Thus, vaginal yeast presents a potential reservoir of H. pylori and plays a vital role in the transmission from mother to neonate.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Recém-Nascido , Humanos , Feminino , Mães , Helicobacter pylori/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Transmissão Vertical de Doenças Infecciosas , Saccharomyces cerevisiae/genética , RNA Ribossômico 16S/genética , Infecções por Helicobacter/diagnóstico , Candida/genética , FezesRESUMO
BACKGROUND: The multidrug resistance of Helicobacter pylori is becoming an increasingly serious issue. It is therefore necessary to study the mechanism of multidrug resistance of H pylori. We have previously identified that the HP0939, HP0497, and HP0471 transporters affect the efflux of drugs from H pylori. As efflux pumps participate in bacterial multidrug resistance and biofilm formation, we hypothesized that these transporters could be involved in the multidrug resistance and biofilm formation of H pylori. MATERIALS AND METHODS: We therefore constructed three knockout strains, Δhp0939, Δhp0497, and Δhp0471, and three high-expression strains, Hp0939he , Hp0497he , and Hp0471he , using the wild-type (WT) 26 695 strain of H pylori as the template. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of wild strains, knockout strains, and high-expression strains to amoxicillin, metronidazole, and other antibiotics were measured. The efflux capacity of high-expression strains and wild strains was compared by Hoechst 33 342 accumulation assay. RESULTS: Determination of the MIC and MBC of the antibiotics revealed that the knockout strains were more sensitive to antibiotics, while the high-expression strains were less sensitive to antibiotics, compared to the WT. The ability of the high-expression strains to efflux drugs was significantly higher than that of the WT. We also induced H pylori to form biofilms, and observed that the knockout strains could barely form biofilms and were more sensitive to several antibiotics, compared to the WT. The mRNA expression of hp0939, hp0497, and hp0471 in the clinically sensitive and multidrug-resistant strains was determined, and it was found that these genes were highly expressed in the multidrug-resistant strains that were isolated from the clinics. CONCLUSIONS: In this study, we found three transporters involved in intrinsic multidrug resistance of H pylori.
Assuntos
Antibacterianos/metabolismo , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Helicobacter pylori/fisiologia , Proteínas de Membrana Transportadoras/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Expressão Gênica , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Patients with esophageal cancer often experience clinically relevant deterioration of quality of life (QOL) after esophagectomy owing to malnutrition, lack of physical exercise, and psychological symptoms. OBJECTIVE: This study aimed to evaluate the feasibility, safety, and efficacy of a comprehensive intervention model using a mobile health system (CIMmH) in patients with esophageal cancer after esophagectomy. METHODS: Twenty patients with esophageal cancer undergoing the modified McKeown surgical procedure were invited to join the CIMmH program with both online and offline components for 12 weeks. The participants were assessed before surgery and again at 1 and 3 months after esophagectomy. QOL, depressive symptoms, anxiety, stress, nutrition, and physical fitness were measured. RESULTS: Of the 20 patients, 16 (80%) completed the program. One month after esophagectomy, patients showed significant deterioration in overall QOL (P=.02), eating (P=.005), reflux (P=.04), and trouble with talking (P<.001). At the 3-month follow-up, except for pain (P=.02), difficulty with eating (P=.03), dry mouth (P=.04), and trouble with talking (P=.003), all other QOL dimensions returned to the preoperative level. There were significant reductions in weight (P<.001) and BMI (P=.02) throughout the study, and no significant changes were observed for physical fitness measured by change in the 6-minute walk distance between baseline and the 1-month follow-up (P=.22) or between baseline and the 3-month follow-up (P=.52). Depressive symptoms significantly increased 1 month after surgery (P<.001), while other psychological measures did not show relevant changes. Although there were declines in many measures 1 month after surgery, these were much improved at the 3-month follow-up, and the recovery was more profound and faster than with traditional rehabilitation programs. CONCLUSIONS: The CIMmH was feasible and safe and demonstrated encouraging efficacy testing with a control group for enhancing recovery after surgery among patients with esophageal cancer in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-1800019900); http://www.chictr.org.cn/showprojen.aspx?proj=32811.
Assuntos
Neoplasias Esofágicas/terapia , Esofagectomia/métodos , Qualidade de Vida/psicologia , Neoplasias Esofágicas/psicologia , Esofagectomia/psicologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
The present study was conducted to investigate the effects of the strong van der Waals interaction and sterol skeleton of surfactants on their interfacial rheological behaviors by comparing the interfacial properties of sodium cholesteryl glycylglycine (Chol-GG-Na) and sodium lauryl glycylglycine (C12-GG-Na) at the oil-aqueous interface. The interfacial dilational rheological experiment results indicate a significant increase in the interfacial activity and intermolecular interaction with the introduction of the cholesteryl group. Therefore, a compact interfacial layer with a remarkably high dilational modulus was obtained with the adsorption of Chol-GG-Na. The cholesteryl group also has a significant impact on the dynamic processes such as it slows down the motion of the molecules due to which the diffusion exchange between the bulk and the interface decreases. Besides, the rigid skeleton makes rearrangement and conformation adjustment difficult. These impacts become more pronounced when the adsorption layer approaches a close and ordered arrangement, which has been confirmed by the relaxation measurements. The reported results provide a theoretical foundation for the potential applications of cholesteryl-based surfactants in the food, pharmaceutical, cosmetic and petroleum industries.
Assuntos
Colesterol/química , Glicilglicina/química , Interações Hidrofóbicas e Hidrofílicas , Reologia , Colesterol/análogos & derivados , Difusão , Tensão Superficial , Tensoativos/químicaRESUMO
BACKGROUND: China bears the biggest stroke burden in the world. However, little is known about the current prevalence, incidence, and mortality of stroke at the national level, and the trend in the past 30 years. METHODS: In 2013, a nationally representative door-to-door survey was conducted in 155 urban and rural centers in 31 provinces in China, totaling 480 687 adults aged ≥20 years. All stroke survivors were considered as prevalent stroke cases at the prevalent time (August 31, 2013). First-ever strokes that occurred during 1 year preceding the survey point-prevalent time were considered as incident cases. According to computed tomography/MRI/autopsy findings, strokes were categorized into ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and stroke of undetermined type. RESULTS: Of 480 687 participants, 7672 were diagnosed with a prevalent stroke (1596.0/100 000 people) and 1643 with incident strokes (345.1/100 000 person-years). The age-standardized prevalence, incidence, and mortality rates were 1114.8/100 000 people, 246.8 and 114.8/100 000 person-years, respectively. Pathological type of stroke was documented by computed tomography/MRI brain scanning in 90% of prevalent and 83% of incident stroke cases. Among incident and prevalent strokes, ischemic stroke constituted 69.6% and 77.8%, intracerebral hemorrhage 23.8% and 15.8%, subarachnoid hemorrhage 4.4% and 4.4%, and undetermined type 2.1% and 2.0%, respectively. Age-specific stroke prevalence in men aged ≥40 years was significantly greater than the prevalence in women (P<0.001). The most prevalent risk factors among stroke survivors were hypertension (88%), smoking (48%), and alcohol use (44%). Stroke prevalence estimates in 2013 were statistically greater than those reported in China 3 decades ago, especially among rural residents (P=0.017). The highest annual incidence and mortality of stroke was in Northeast (365 and 159/100 000 person-years), then Central areas (326 and 154/100 000 person-years), and the lowest incidence was in Southwest China (154/100 000 person-years), and the lowest mortality was in South China (65/100 000 person-years) (P<0.002). CONCLUSIONS: Stroke burden in China has increased over the past 30 years, and remains particularly high in rural areas. There is a north-to-south gradient in stroke in China, with the greatest stroke burden observed in the northern and central regions.
Assuntos
Acidente Vascular Cerebral/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , Fatores Sexuais , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/patologia , Inquéritos e Questionários , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , População Urbana , Adulto JovemRESUMO
The drug resistance of Helicobacter pylori is gradually becoming a serious problem. Biofilm formation is an important factor that leads to multidrug resistance (MDR) in bacteria. The ability of H. pylori to form biofilms on the gastric mucosa is known. However, there are few studies on the regulatory mechanisms of H. pylori biofilm formation and multidrug resistance. Guanosine 3'-diphosphate 5'-triphosphate and guanosine 3',5'-bispyrophosphate [(p)ppGpp] are global regulatory factors and are synthesized in H. pylori by the bifunctional enzyme SpoT. It has been reported that (p)ppGpp is involved in the biofilm formation and multidrug resistance of various bacteria. In this study, we found that SpoT also plays an important role in H. pylori biofilm formation and multidrug resistance. Therefore, it was necessary to carry out some further studies regarding its regulatory mechanism. Considering that efflux pumps are of great importance in the biofilm formation and multidrug resistance of bacteria, we tried to determine whether efflux pumps controlled by SpoT participate in these activities. We found that Hp1174 (glucose/galactose transporter [gluP]), an efflux pump of the major facilitator superfamily (MFS), is highly expressed in biofilm-forming and multidrug-resistant (MDR) H. pylori strains and is upregulated by SpoT. Through further research, we determined that gluP is involved in H. pylori biofilm formation and multidrug resistance. Furthermore, the average expression level of gluP in the clinical MDR strains (C-MDR) was considerably higher than that in the clinical drug-sensitive strains (C-DSS). Taken together, our results revealed a novel molecular mechanism of H. pylori resistance to multidrug exposure.
Assuntos
Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla/fisiologia , Helicobacter pylori/metabolismo , Regulação para Cima/fisiologia , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Guanosina Pentafosfato/metabolismo , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos , Ovinos , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/fisiologia , Regulação para Cima/efeitos dos fármacosRESUMO
Clostridioides (Clostridium) difficile and Bacillus cereus infections are frequently reported in human individually. However, co-infection of both pathogens in human is extremely rare. In the present study, we reported a case of human enteric disease caused by co-infection of C. difficile and B. cereus in Guizhou, China. The 16S rDNA sequencing result showed that C. difficile GMU1 and B. cereus GMU2 were most related to C. difficile ATCC 9689 and B. cereus ATCC 14579. The toxin genotype of C. difficile GMU1 and B. cereus GMU2 were tcdA+tcdB+tcdC+ and bceT+nheA+nheB+nheC+, respectively. Cytotoxicity assay demonstrated that C. difficile GMU1 produced significantly higher toxin B compare to C. difficile 630 stain. In contrast, B. cereus GMU2 has comparable NheA toxin productivity compare to previous report. The antimicrobial susceptibility test showed that the combination of ampicillin and vancomycin was most efficient to inhibit both C. difficile GMU1 and B. cereus GMU2.
Assuntos
Bacillus cereus/isolamento & purificação , Clostridioides difficile/isolamento & purificação , Coinfecção/microbiologia , Idoso , Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Bacillus cereus/classificação , Bacillus cereus/efeitos dos fármacos , Bacillus cereus/genética , China , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Clostridioides difficile/fisiologia , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Genótipo , Humanos , Masculino , Vancomicina/administração & dosagemRESUMO
Clarithromycin (CLA) is a commonly recommended drug for Helicobacter pylori eradication. However, the prevalence of CLA-resistant H. pylori is increasing. Although point mutations in the 23S rRNA are key factors for CLA resistance, other factors, including efflux pumps and regulation genes, are also involved in the resistance of H. pylori to CLA. Guanosine 3'-diphosphate 5'-triphosphate and guanosine 3',5'-bispyrophosphate [(p)ppGpp)], which are synthesized by the bifunctional enzyme SpoT in H. pylori, play an important role for some bacteria to adapt to antibiotic pressure. Nevertheless, no related research involving H. pylori has been reported. In addition, transporters have been found to be related to bacterial drug resistance. Therefore, this study investigated the function of SpoT in H. pylori resistance to CLA by examining the shifts in the expression of transporters and explored the role of transporters in the CLA resistance of H. pylori A ΔspoT strain was constructed in this study, and it was shown that SpoT is involved in H. pylori tolerance of CLA by upregulating the transporters HP0939, HP1017, HP0497, and HP0471. This was assessed using a series of molecular and biochemical experiments and a cDNA microarray. Additionally, the knockout of genes hp0939, hp0471, and hp0497 in the resistant strains caused a reduction or loss (the latter in the Δhp0497 strain) of resistance to CLA. Furthermore, the average expression levels of these four transporters in clinical CLA-resistant strains were considerably higher than those in clinical CLA-sensitive strains. Taken together, our results revealed a novel molecular mechanism of H. pylori adaption to CLA stress.
Assuntos
Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Proteínas de Membrana Transportadoras/metabolismo , Enzimas Multifuncionais/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Guanosina Pentafosfato/metabolismo , Guanosina Tetrafosfato/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: In China, stroke is the leading cause of death and contributes to a heavy disease burden. However, a nationwide population-based survey of the mortality of stroke and its subtypes is lacking for this country. METHODS: Data derived from the National Epidemiological Survey of Stroke in China, which was a multistage, stratified clustering sampling-designed, cross-sectional survey, were analyzed. Mortality rate analyses were performed for 476,156 participants ≥20 years old from September 1, 2012 to August 31, 2013. RESULTS: Of the 476,156 participants in the investigated population, 364 died of ischemic stroke, 373 of hemorrhagic stroke, and 21 of stroke of undetermined pathological type. The age-standardized mortality rates per 100,000 person-years among those aged ≥20 years were 114.8 for total stroke, 56.5 for ischemic stroke, and 55.8 for hemorrhagic stroke. The age-standardized mortality rates of total stroke, ischemic stroke, and hemorrhagic stroke were all higher in rural areas than those in urban areas. The stroke mortality rate was higher in the northern regions than in the south. An estimated 1.12 million people aged ≥20 years in China died of stroke during the period from September 1, 2012 to August 31, 2013. CONCLUSIONS: The burden of stroke in China is still heavy. Greater attention should be paid to improve strategies for preventing stroke.
Assuntos
Isquemia Encefálica/mortalidade , Acidente Vascular Cerebral/mortalidade , Adulto , Isquemia Encefálica/complicações , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Acidente Vascular Cerebral/complicações , População UrbanaRESUMO
OBJECTIVES: The present study analyzed the hospital charges for stroke patients in China and determined the factors associated with hospital costs. METHODS: Medical records of hospitalized patients with a primary diagnosis of acute stroke were collected from 121 hospitals in Beijing (2012). Distribution characteristics of hospital charges for different stroke types, hospital levels and types were studied. Factors influencing total hospital charges were analyzed. RESULTS: 60.8% of the 94â 906 stroke patients were male and the mean age of these patients was 66.5 ± 13.2 years. The median length of hospital stay (LOHS) for these patients was 14 d (interquartile range, IQR 9-19). The mean hospital charge per patient was 19â 270 Chinese Yuan. Forty-five percent of these charges were for medicine, 18% for laboratory and examination, 16% for material, 15% for therapy, 5% for service and 1% for blood product. The mean hospital charge for patients suffering from hemorrhagic stroke was significantly more than ischemic stroke (34â 937 vs. 17â 049, p < 0.001), and was significantly more for Level 3 than Level 2 hospitals (23â 762 vs. 14â 554, p < 0.001). LOHS, hospital level and stroke severity were key determinants of the hospital charge. CONCLUSIONS: Though hospital charges for stroke patients in China were low, it brought a heavy economic burden for the larger stroke population. Medicine accounted for the largest percentage of hospital charges in China. LOHS emerged to be the main predictor of the cost. Decreasing medicine charge and LOHS might be strategies to decrease hospital charges and reduce economic burden of stroke in China.
Assuntos
Preços Hospitalares/estatística & dados numéricos , Pacientes Internados , Tempo de Internação/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Hospitais/classificação , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/economiaRESUMO
The following are our views regarding the "letter to the editor" (Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?) by Alipour and Gaeini, and the response "letter to the editor" (Candida accommodates non-culturable Helicobacter pylori in its vacuole-Koch's postulates aren't applicable) by Siavoshi and Saniee. Alipour and Gaeini rejected the methods, results, discussion, and conclusions summarized in a review article by Siavoshi and Saniee. The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori (H. pylori) to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse, transporting potentially infectious H. pylori into the stomach of humans.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Helicobacter pylori/patogenicidade , Humanos , Infecções por Helicobacter/microbiologia , Candida/fisiologia , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Vacúolos/microbiologia , Vacúolos/metabolismo , Estômago/microbiologia , Mucosa Gástrica/microbiologiaRESUMO
Dense packing of particles has provided powerful models to elaborate the important structural features of matter in various systems such as liquid, glassy, and crystalline phases. The simplest sphere packing models can represent and capture salient properties of the building blocks for covalent, metallic, and ionic crystals; it, however, becomes insufficient to reflect the broken symmetry of the commonly anisotropic molecules in molecular crystals. Here, we develop spheroid models with a minimal degree of anisotropy, which serve as a simple geometrical representation for a rich spectrum of molecules-including both isotropic and anisotropic, convex and concave ones-in crystalline phases. Our models are determined via an inverse packing approach: Given a molecular crystal, an optimal spheroid model is constructed using a contact diagram, which depicts the packing relationship between neighboring molecules within the crystal. The spheroid models are capable of accurately capturing the broken symmetry and characterizing the equivalent volume of molecules in the crystalline phases. Moreover, our model retrieves such molecular information from low-quality x-ray diffraction data with poorly resolved structures, and by using soft spheroids, it can also describe the packing behavior in cocrystals.
RESUMO
The southwest region of China has abundant groundwater and high-temperature geothermal energy. Carbonaceous shale, as one of the typical surrounding rocks in this region, often suffers from deterioration effects due to the coupled action of groundwater chemical erosion and high temperature, which affects the long-term stability of tunnel engineering. In order to investigate the deterioration effects of carbonaceous shale under the coupled action of chemical erosion and high temperature, carbonaceous shale from a tunnel of Lixiang Railway in Yunnan Province was taken as the research object. The microstructure and mineral composition of the samples before and after chemical erosion were obtained with a scanning electron microscope-energy dispersive spectrometer and an X-ray diffraction test. Then, triaxial compression tests were conducted on the samples under different time points and different temperature effects of chemical erosion, and the stress-strain curves and the deterioration laws under a single factor were obtained. An improved numerical simulation method based on the parallel bond model was developed, which can account for the coupled effects of chemical erosion and high temperature on the rock. By simulating the triaxial compression test of carbonaceous shale, the deterioration law of carbonaceous shale under the coupled action was discussed. The results show that chemical erosion has a significant deterioration effect on the triaxial compressive strength of carbonaceous shale, and the degree of deterioration is related to the erosion time. In the first 30 days of erosion, the triaxial compressive strength of carbonaceous shale decreased by 11.38%, which was the largest deterioration range. With the increase in erosion time, the deterioration rate gradually decreased; temperature had a significant threshold effect on the strength of carbonaceous shale, and a clear turning point appeared at about 200 °C. By simulating the deterioration effects of carbonaceous shale under the coupled action of chemical erosion and high temperature, it was found that the longer the duration of chemical erosion, the stronger the temperature sensitivity of carbonaceous shale, and the more serious the loss of compressive strength during the heating process. When the temperature was low, the strength of carbonaceous shale changed little, and some samples even showed an increase in strength; when the temperature was high, the strength of carbonaceous shale decreased significantly, showing deterioration characteristics. The numerical simulation method was compared and verified with the indoor test results, and it was found that the numerical calculation had a good agreement with the test results.