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Following a sustainable development pathway designed to keep warming below 2 °C will benefit human health. We quantify premature deaths attributable to fine particulate matter (PM2.5) air pollution and heat exposures for China, South Asia, and the United States using projections from multiple climate models under high- and low-emission scenarios. Projected changes in premature deaths are typically dominated by population aging, primarily reflecting increased longevity leading to greater sensitivity to environmental risks. Changes in PM2.5 exposure typically have small impacts on premature deaths under a high-emission scenario but provide substantial benefits under a low-emission scenario. PM2.5-attributable deaths increase in South Asia throughout the century under both scenarios but shift to decreases by late century in China, and US values decrease throughout the century. In contrast, heat exposure increases under both scenarios and combines with population aging to drive projected increases in deaths in all countries. Despite population aging, combined PM2.5- and heat-related deaths decrease under the low-emission scenario by ~2.4 million per year by midcentury and ~2.9 million by century's end, with ~3% and ~21% of these reductions from heat, respectively. Intermodel variations in exposure projections generally lead to uncertainties of <40% except for US and China heat impacts. Health benefits of low emissions are larger from reduced heat exposure than improved air quality by the late 2090s in the United States. In contrast, in South and East Asia, the PM2.5-related benefits are largest throughout the century, and their valuation exceeds the cost of decarbonization, especially in China, over the next 30 y.
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Contaminación del Aire , Mortalidad Prematura , Humanos , Estados Unidos/epidemiología , Calor , China/epidemiología , Sur de Asia , Material ParticuladoRESUMEN
Induction and suppression of antiviral RNA interference (RNAi) has been observed in mammals during infection with at least seven distinct RNA viruses, including some that are pathogenic in humans. However, while the cell-autonomous immune response mediated by antiviral RNAi is gradually being recognized, little is known about systemic antiviral RNAi in mammals. Furthermore, extracellular vesicles (EVs) also function in viral signal spreading and host immunity. Here, we show that upon antiviral RNAi activation, virus-derived small-interfering RNAs (vsiRNAs) from Nodamura virus (NoV), Sindbis virus (SINV), and Zika virus (ZIKV) enter the murine bloodstream via EVs for systemic circulation. vsiRNAs in the EVs are biologically active, since they confer RNA-RNA homology-dependent antiviral activity in both cultured cells and infant mice. Moreover, we demonstrate that vaccination with a live-attenuated virus, rendered deficient in RNAi suppression, induces production of stably maintained vsiRNAs and confers protective immunity against virus infection in mice. This suggests that vaccination with live-attenuated VSR (viral suppressor of RNAi)-deficient mutant viruses could be a new strategy to induce immunity.
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Vesículas Extracelulares , Infección por el Virus Zika , Virus Zika , Animales , Antivirales , Vesículas Extracelulares/genética , Humanos , Mamíferos/genética , Ratones , Interferencia de ARN , ARN Bicatenario , ARN Interferente Pequeño/genética , Virus Zika/genética , Infección por el Virus Zika/genética , Infección por el Virus Zika/prevención & controlRESUMEN
Sutetinib is an irreversible inhibitor of epidermal growth factor receptor (EGFR) and showed favorable efficacy and safety in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring nondrug-resistant rare EGFR mutations. To evaluate the potential food effect, eighteen healthy Chinese subjects were enrolled in a single-centre, randomized, open-label, two-sequence, two-period crossover study. Sutetinib was administered as a single oral 100 mg under fasting or fed conditions, and pharmacokinetic sampling was performed following each dose and analysed by a validated liquid chromatography/mass spectrometry method. Safety and tolerability were also evaluated. Food intake slightly decreased maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 to infinity (AUC0 - inf) of sutetinib (geometric least-squares mean [GLSM] ratio, 80.94% and 86.11%; 90% confidence interval [CI], 68.43-95.72 and 75.88-97.73) and its active metabolite sutetinib N-Oxide (GLSM ratio, 75.58% and 84.00%; 90% CI, 65.69-86.95 and 75.42-93.56), respectively. In addition, the time to maximum plasma concentration (Tmax) of both sutetinib and its metabolite has been prolonged by 2 h under fed conditions. A total of 31 adverse events (AEs) occurred during the study, with no serious adverse events (SAE) reported, and no obvious difference was observed between the fasting and fed groups. Our results demonstrated that a high-fat and high-calorie diet caused a significant delay in drug absorption and a marginal reduction in drug exposure. Sutetinib was generally well tolerated in healthy Chinese subjects. (This trial was registered at http://www.chinadrugtrials.org.cn . The registration No. is CTR20201933, and the date of registration is 2020-10-16).
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Pueblo Asiatico , Estudios Cruzados , Receptores ErbB , Interacciones Alimento-Droga , Voluntarios Sanos , Inhibidores de Proteínas Quinasas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Cápsulas , Pueblos del Este de Asia , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/sangreRESUMEN
Alginate oligosaccharides (AOS), products of alginate degradation by endotype alginate lyases, possess favorable biological activities and have broad applications. Although many have been reported, alginate lyases with homogeneous AOS products and secretory production by an engineered host are scarce. Herein, the alginate lyase AlyC7 from Vibrio sp. C42 was characterized as a trisaccharide-producing lyase exhibiting high activity and broad substrate specificity. With PelB as the signal peptide and 500 mM glycine as the additive, the extracellular production of AlyC7 in Escherichia coli reached 1122.8 U/mL after 27 h cultivation in Luria-Bertani medium. The yield of trisaccharides from sodium alginate degradation by the produced AlyC7 reached 758.6 mg/g, with a purity of 85.1%. The prepared AOS at 20 µg/mL increased the root length of lettuce, tomato, wheat, and maize by 27.5%, 25.7%, 9.7%, and 11.1%, respectively. This study establishes a robust foundation for the industrial and agricultural applications of AlyC7.
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Escherichia coli , Polisacárido Liasas , Trisacáridos , Vibrio , Polisacárido Liasas/metabolismo , Trisacáridos/biosíntesis , Vibrio/enzimología , Especificidad por Sustrato , Alginatos , Zea mays , OligosacáridosRESUMEN
Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity and angiotensin-converting enzyme (ACE)-inhibitory activity. Based on the optimization of the hydrolysis parameters of protease A69, a process for PPs preparation was set up in which the peanut protein was hydrolyzed by A69 at 3000 U g-1 and 60 °C, pH 7.0 for 4 h. The prepared PPs exhibited a high content of peptides with molecular weights lower than 1000 Da (>80%) and 3000 Da (>95%) and contained 17 kinds of amino acids. Moreover, the PPs displayed elevated scavenging of hydroxyl radical and 1,1-diphenyl-2-picryl-hydrazyl radical, with IC50 values of 1.50 mg mL-1 and 1.66 mg mL-1, respectively, indicating the good antioxidant activity of the PPs. The PPs also showed remarkable ACE-inhibitory activity, with an IC50 value of 0.71 mg mL-1. By liquid chromatography mass spectrometry analysis, the sequences of 19 ACE inhibitory peptides and 15 antioxidant peptides were identified from the PPs. These results indicate that the prepared PPs have a good nutritional value, as well as good antioxidant and antihypertensive effects, and that the marine bacterial metalloprotease A69 has promising potential in relation to the preparation of bioactive peptides from peanut protein.
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Inhibidores de la Enzima Convertidora de Angiotensina , Antioxidantes , Arachis , Bacillus subtilis , Metaloproteasas , Péptidos , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Antioxidantes/farmacología , Antioxidantes/química , Metaloproteasas/química , Metaloproteasas/farmacología , Arachis/química , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/enzimología , Péptidos/farmacología , Péptidos/química , Hidrólisis , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/químicaRESUMEN
Societal benefits from climate change mitigation accrue via multiple pathways. We examine the US impacts of emission changes on several factors that are affected by both climate and air quality responses. Nationwide benefits through midcentury stem primarily from air quality improvements, which are realized rapidly, and include human health, labor productivity, and crop yield benefits. Benefits from reduced heat exposure become large around 2060, thereafter often dominating over those from improved air quality. Monetized benefits are in the tens of trillions of dollars for avoided deaths and tens of billions for labor productivity and crop yield increases and reduced hospital expenditures. Total monetized benefits this century are dominated by health and are much larger than in previous analyses due to improved understanding of the human health impacts of exposure to both heat and air pollution. Benefit-cost ratios are therefore much larger than in prior studies, especially those that neglected clean air benefits. Specifically, benefits from clean air exceed costs in the first decade, whereas benefits from climate alone exceed costs in the latter half of the century. Furthermore, monetized US benefits largely stem from US emissions reductions. Increased emphasis on the localized, near-term air quality-related impacts would better align policies with societal benefits and, by reducing the mismatch between perception of climate as a risk distant in space and time and the need for rapid action to mitigate long-term climate change, might help increase acceptance of mitigation policies.
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Contaminación del Aire/efectos adversos , Cambio Climático/estadística & datos numéricos , Productos Agrícolas/crecimiento & desarrollo , Contaminantes Atmosféricos/efectos adversos , Análisis Costo-Beneficio , Política Ambiental , Humanos , Material Particulado/efectos adversos , Estados UnidosRESUMEN
The interferon-regulated antiviral responses are essential for the induction of both innate and adaptive immunity in mammals. Production of virus-derived small-interfering RNAs (vsiRNAs) to restrict virus infection by RNA interference (RNAi) is a recently identified mammalian immune response to several RNA viruses, which cause important human diseases such as influenza and Zika virus. However, little is known about Dicer processing of viral double-stranded RNA replicative intermediates (dsRNA-vRIs) in mammalian somatic cells. Here we show that infected somatic cells produced more influenza vsiRNAs than cellular microRNAs when both were produced by human Dicer expressed de novo, indicating that dsRNA-vRIs are not poor Dicer substrates as previously proposed according to in vitro Dicer processing of synthetic long dsRNA. We report the first evidence both for canonical vsiRNA production during wild-type Nodamura virus infection and direct vsiRNA sequestration by its RNAi suppressor protein B2 in two strains of suckling mice. Moreover, Sindbis virus (SINV) accumulation in vivo was decreased by prior production of SINV-targeting vsiRNAs triggered by infection and increased by heterologous expression of B2 in cis from SINV genome, indicating an antiviral function for the induced RNAi response. These findings reveal that unlike artificial long dsRNA, dsRNA-vRIs made during authentic infection of mature somatic cells are efficiently processed by Dicer into vsiRNAs to direct antiviral RNAi. Interestingly, Dicer processing of dsRNA-vRIs into vsiRNAs was inhibited by LGP2 (laboratory of genetics and physiology 2), which was encoded by an interferon-stimulated gene (ISG) shown recently to inhibit Dicer processing of artificial long dsRNA in cell culture. Our work thus further suggests negative modulation of antiviral RNAi by a known ISG from the interferon response.
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ARN Helicasas DEAD-box/metabolismo , ARN Helicasas/metabolismo , Virus ARN/fisiología , ARN Bicatenario/genética , ARN Interferente Pequeño/genética , Ribonucleasa III/metabolismo , Virosis/prevención & control , Replicación Viral , Animales , Antivirales/metabolismo , ARN Helicasas DEAD-box/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , ARN Helicasas/genética , Ribonucleasa III/genética , Virosis/genéticaRESUMEN
BACKGROUND: Alginate oligosaccharides (AOs) are the degradation products of alginate, a natural polysaccharide abundant in brown algae. AOs generated by enzymatic hydrolysis have diverse bioactivities and show broad application potentials. AOs production via enzymolysis is now generally with sodium alginate as the raw material, which is chemically extracted from brown algae. In contrast, AOs production by direct degradation of brown algae is more advantageous on account of its cost reduction and is more eco-friendly. However, there have been only a few attempts reported in AOs production from direct degradation of brown algae. RESULTS: In this study, an efficient Laminaria japonica-decomposing strain Pseudoalteromonas agarivorans A3 was screened. Based on the secretome and mass spectrum analyses, strain A3 showed the potential as a cell factory for AOs production by secreting alginate lyases to directly degrade L. japonica. By using the L. japonica roots, which are normally discarded in the food industry, as the raw material for both fermentation and enzymatic hydrolysis, AOs were produced by the fermentation broth supernatant of strain A3 after optimization of the alginate lyase production and hydrolysis parameters. The generated AOs mainly ranged from dimers to tetramers, among which trimers and tetramers were predominant. The degradation efficiency of the roots reached 54.58%, the AOs production was 33.11%, and the AOs purity was 85.03%. CONCLUSION: An efficient, cost-effective and green process for AOs production directly from the underutilized L. japonica roots by using strain A3 was set up, which differed from the reported processes in terms of the substrate and strain used for fermentation and the AOs composition. This study provides a promising platform for scalable production of AOs, which may have application potentials in industry and agriculture.
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Alginatos , Laminaria , Análisis Costo-Beneficio , OligosacáridosRESUMEN
BACKGROUND: Mycobacterium haemophilum is a slow-growing non-chromogenic nontuberculous Mycobacterium species that can cause skin infection or arthritis in an immunocompromised population or in children. Primary infection of the healthy adult cornea is rare. The special requirements for culture make this pathogen difficult to diagnose. The study aims to report the clinical manifestation and treatment process of corneal infection and notify the awareness of M. Haemophilus keratitis among clinicians. This is the first case report of primary M. haemophilum infection in the cornea of healthy adults reported in the literature. CASE PRESENTATION: A 53-year-old healthy goldminer presented with left eye redness and a history of vision loss for four months. The patient was misdiagnosed with herpes simplex keratitis until M. haemophilum was detected using high-throughput sequencing. Penetrating keratoplasty was performed, and a large number of mycobacteria were detected by Ziehl-Neelsen staining of the infected tissue. Three months later, the patient developed conjunctival and eyelid skin infections that manifested as caseous necrosis of the conjunctiva and skin nodules. After excision and debridement of the conjunctival lesions and systemic antituberculosis drug treatment for 10 months, the patient was cured. CONCLUSION: M. haemophilum could cause primary corneal infection in healthy adults, which is an infrequent or rare infection. Owing to the need for special bacterial culture conditions, conventional culture methods do not provide positive results. High-throughput sequencing can rapidly identify the presence of bacteria, which aids in early diagnosis and timely treatment. Prompt surgical intervention is an effective treatment option for severe keratitis. Long-term systemic antimicrobial therapy is crucial.
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Infecciones del Ojo , Mycobacterium haemophilum , Adulto , Niño , Humanos , Persona de Mediana Edad , Córnea , Micobacterias no Tuberculosas , PielRESUMEN
We mistakenly diagnosed a patient with pulmonary embolism as ST-elevation acute myocardial infarction. The case complained of chest pain with ST-elevation in leads AVR, III, AVF, V1, V3R, V4R and V5R. In addition, we also found ST- elevation AVR, III>ST- elevation AVF, QIII>QAVF and QV1. Multi-site pulmonary embolism can lead to type 2 myocardial infarction or special type of myocardial infarction with non-obstructive coronary arteries through multiple pathological mechanisms.
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Embolia Pulmonar , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico por imagenRESUMEN
China is challenged with the simultaneous goals of improving air quality and mitigating climate change. The "Beautiful China" strategy, launched by the Chinese government in 2020, requires that all cities in China attain 35 µg/m3 or below for annual mean concentration of PM2.5 (particulate matter with aerodynamic diameter less than 2.5 µm) by 2035. Meanwhile, China adopts a portfolio of low-carbon policies to meet its Nationally Determined Contribution (NDC) pledged in the Paris Agreement. Previous studies demonstrated the cobenefits to air pollution reduction from implementing low-carbon energy policies. Pathways for China to achieve dual targets of both air quality and CO2 mitigation, however, have not been comprehensively explored. Here, we couple an integrated assessment model and an air quality model to evaluate air quality in China through 2035 under the NDC scenario and an alternative scenario (Co-Benefit Energy [CBE]) with enhanced low-carbon policies. Results indicate that some Chinese cities cannot meet the PM2.5 target under the NDC scenario by 2035, even with the strictest end-of-pipe controls. Achieving the air quality target would require further reduction in emissions of multiple air pollutants by 6 to 32%, driving additional 22% reduction in CO2 emissions relative to the NDC scenario. Results show that the incremental health benefit from improved air quality of CBE exceeds 8 times the additional costs of CO2 mitigation, attributed particularly to the cost-effective reduction in household PM2.5 exposure. The additional low-carbon energy polices required for China's air quality targets would lay an important foundation for its deep decarbonization aligned with the 2 °C global temperature target.
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Contaminación del Aire/análisis , Dióxido de Carbono/química , Contaminantes Atmosféricos/efectos adversos , Carbono/química , China , Ciudades , Cambio Climático , Monitoreo del Ambiente/métodos , Humanos , Paris , Material Particulado/químicaRESUMEN
OBJECTIVES: To investigate the fracture strength of angulated hybrid abutments supporting anterior single crowns on narrow-diameter implants (NDIs). MATERIAL AND METHODS: Zirconia abutment with angulations of labial inclination 0° (TZ0Z), 15° (TZ15Z), 30° (TZ30Z) and palatal inclination 15° (TZ - 15Z) was designed on 3.3-mm titanium-zirconium (Ti-Zr) NDIs. Titanium abutment connected with Ti-Zr implant (TZ0T) and 0° zirconia abutment connected with pure titanium (Ti) implant (T0Z) were control groups. Thirty-six un-restored abutments and 36 abutments restored with highly translucent zirconia (HTZ) crowns were tested. Failure loads were compared among 6 groups, and bending moments were calculated for comparison between un-restored and restored abutments. RESULTS: Failure loads of un-restored abutments were affected by the abutment angle. Sixty-seven percent samples in TZ30Z and 83% samples in TZ - 15Z group fractured at the thinnest part of the zirconia abutment and exhibited lower failure load (p < .05). Failure loads of restored abutments were close to or exceeded the maximum bite force of anterior teeth, and no differences were found among six groups (p > .05). Except TZ15Z and TZ0T group, the bending moment increased with the crown construction, especially for TZ30Z and TZ - 15Z groups (p < .001). CONCLUSIONS: The fracture strength of hybrid abutments restored with HTZ crown on Ti-Zr NDIs exceeded the bite forces of anterior teeth for all the groups and were not affected by the abutment angle. CLINICAL RELEVANCE: In terms of fracture strength, Ti-Zr NDIs combined with angulated hybrid abutments and HTZ crowns can be used in the anterior region.
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Implantes Dentales , Circonio , Titanio , Ensayo de Materiales , Diseño de Implante Dental-Pilar , Pilares Dentales , Fracaso de la Restauración Dental , Análisis del Estrés Dental , CoronasRESUMEN
BACKGROUND: Evidence concerning the effects of different chemical components of particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) on asthma is limited, and the methodology to compare the relative importance of different PM2.5 components is lacking. OBJECTIVE: Our aim was to examine the associations between PM2.5 components and asthma and investigate which constituent of PM2.5 possessed the most harmful effect on asthma. METHODS: A total of 45,690 subjects in 6 countries were surveyed from 2007 to 2010. We geocoded the residential community addresses of the participants and used satellite remote sensing and chemical transport modeling to estimate their annual average concentrations of PM2.5 constituents. Mixed-effects generalized additive models were utilized to examine the associations between PM2.5 constituents and prevalence of asthma. We further used counterfactual analyses to determine the potential number of asthma cases. RESULTS: We identified 6178 patients with asthma among the participants, producing an asthma prevalence of 13.5%. The odds ratio for asthma associated with per-SD increment was 1.12 for PM2.5 mass, 1.12 for organic carbon, 1.18 for black carbon, 1.19 for sulfate, 1.28 for ammonium, and 1.21 for nitrate after controlling for potential confounders. Our counterfactual analyses suggested that ammonium was responsible for a substantial decline in asthma cases (by 1382 cases, corresponding to 22.37% of overall cases) if the concentration was reduced to the 5th percentile of the current level. CONCLUSIONS: Our study suggests that some chemical components of PM2.5 (including black carbon, organic carbon, sulfate, ammonium, and nitrate) might be hazardous constituents contributing to the prevalence of asthma; among them, ammonium might be responsible for a substantial proportion of asthma cases if reduced to a certain level.
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Contaminantes Atmosféricos , Contaminación del Aire , Compuestos de Amonio , Asma , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Compuestos de Amonio/análisis , Asma/epidemiología , Carbono/análisis , Países en Desarrollo , Exposición a Riesgos Ambientales/análisis , Humanos , Nitratos/análisis , Óxidos de Nitrógeno , Material Particulado/efectos adversosRESUMEN
Enhanced recovery after surgery protocol is a multidisciplinary and multimodal approach designed to improve perioperative outcomes for patients. This meta-analysis aimed to identify and elaborate on the efficacy of this protocol in women undergoing gynecologic surgery. Four databases were searched for randomized controlled trials from inception to December 2021. A total of 14 studies met the inclusion criteria and were analyzed. There was a significant reduction in the length of stay, the time to first flatus and first defecation, complications, and readmission rates in patients undergoing enhanced recovery after surgery when compared to routine care. The rate of discharge on the first postoperative day significantly increased in patients from the enhanced recovery group. There was no significant difference in the surgery time and blood loss. In conclusion, the enhanced recovery after surgery protocol might have a positive effect on patients undergoing gynecologic surgery. However, there is still heterogeneity between the included studies, and we need more research to draw reliable conclusions that enhanced recovery after surgery is favorable.
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Procedimientos Quirúrgicos Ginecológicos , Alta del Paciente , Humanos , Femenino , Tiempo de Internación , Ensayos Clínicos Controlados Aleatorios como Asunto , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Procedimientos Quirúrgicos Ginecológicos/métodos , Complicaciones Posoperatorias/etiologíaRESUMEN
This article presents a technique for fabricating two-piece labial guides using resin and cobalt-chromium for guided alveoloplasty, implant placement, and immediate full-arch implant-supported fixed complete denture placement. This technique reduces tissue damage and overcomes the negative effect of the anatomical position of the palatal neuropore and mobility of the tissue flap on the positioning and stability of the guide. The use of labial retention metal guides with improved mechanical properties of cobalt-chromium and fixation plugs allows the unilateral placement of the guide. Thus, minimally invasive implant surgery can be performed owing to the absence of large palatal flap elevation and obstruction. Such a design provides better stability of the guides and clear visual access during surgery.
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Exploiting dual-functional photoelectrodes to harvest and store solar energy is a challenging but efficient way for achieving renewable energy utilization. Herein, multi-heterostructures consisting of N-doped carbon coated MoS2 nanosheets supported by tubular TiO2 with photoelectric conversion and electronic transfer interfaces are designed. When a photo sodium ion battery (photo-SIB) is assembled based on the heterostructures, its capacity increases to 399.3â mAh g-1 with a high photo-conversion efficiency of 0.71 % switching from dark to visible light at 2.0â A g-1 . Remarkably, the photo-SIB can be recharged by light only, with a striking capacity of 231.4â mAh g-1 . Experimental and theoretical results suggest that the proposed multi-heterostructures can enhance charge transfer kinetics, maintain structural stability, and facilitate the separation of photo-excited carriers. This work presents a new strategy to design dual-functional photoelectrodes for efficient use of solar energy.
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Alginate lyases play a vital role in the degradation of alginate, an important marine carbon source. Alginate is a complex macromolecular substrate, and the synergy of alginate lyases is important for the alginate utilization by microbes and the application of alginate lyases in biotechnology. Although many studies have focused on the synergy between different alginate lyases, the synergy between two alginate lyase domains of one alginate lyase has not been reported. Here, we report the synergism between the two catalytic domains of a novel alginate lyase, AlyC6', from the marine alginate-degrading bacterium Vibrio sp. NC2. AlyC6' contains two PL7 catalytic domains (CD1 and CD2) that have no sequence similarity. While both CD1 and CD2 are endo-lyases with the highest activity at 30°C, pH 8.0, and 1.0 M NaCl, they also displayed some different properties. CD1 was PM-specific, but CD2 was PG-specific. Compared with CD2, CD1 had higher catalytic efficiency, but lower substrate affinity. In addition, CD1 had a smaller minimal substrate than CD2, and the products from CD2 could be further degraded by CD1. These distinctions between the two domains enable them to synergize intramolecularly in alginate degradation, resulting in efficient and complete degradation of various alginate substrates. The bioinformatics analysis revealed that diverse alginate lyases have multiple catalytic domains, which are widespread, especially abundant in Flavobacteriaceae and Alteromonadales, which may secret multimodular alginate lyases for alginate degradation. This study provides new insight into bacterial alginate lyases and alginate degradation and is helpful for designing multimodular enzymes for efficient alginate depolymerization. IMPORTANCE Alginate is a major component in the cell walls of brown algae. Alginate degradation is carried out by alginate lyases. Until now, while most characterized alginate lyases contain one single catalytic domain, only a few have been shown to contain two catalytic domains. Furthermore, the synergy of alginate lyases has attracted increasing attention since it plays important roles in microbial alginate utilization and biotechnological applications. Although many studies have focused on the synergy between different alginate lyases, the synergy between two catalytic domains of one alginate lyase has not been reported. Here, a novel alginate lyase, AlyC6', with two functional alginate lyase domains was biochemically characterized. Moreover, the synergism between the two domains of AlyC6' was revealed. Additionally, the distribution of the alginate lyases with multiple alginate lyase domains was investigated based on the bioinformatics analysis. This study provides new insight into bacterial alginate lyases and alginate degradation.
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Polisacárido Liasas , Vibrio , Secuencia de Aminoácidos , Polisacárido Liasas/metabolismo , Vibrio/metabolismo , Alginatos/metabolismo , Especificidad por SustratoRESUMEN
A Gram-stain-negative, aerobic and rod-shaped bacterium, designated strain SM 2104T, was isolated from a deep-sea sediment sample collected from the Southwest Indian Ocean. Strain SM 2104T grew at 10-37 °C (optimum at 25 °C), and with 1.0-9.0% (w/v, optimum with 2-4%) NaCl. It hydrolyzed starch, tween 80 and gelatin but did not reduced nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SM 2104T was affiliated with the genus Alteromonas, sharing the highest 16S rRNA gene sequence similarities with type strains of Alteromonas flava (97.5%) and Alteromonas facilis (97.4%) and forming a distinct clade together with the two Alteromonas species. The digital DNA-DNA hybridization and average nucleotide identity values between strain SM 2104 T and type strains of Alteromonas flava and Alteromonas facilis were below 14.5%, and 71.0%, respectively. The major fatty acids of strain SM 2104T were summed feature 3 (C16:1ω6c/C16:1ω7c), C16:0 and summed feature 8 (C18:1ω7c/C18:1ω6c). The major polar lipids of strain SM 2104T were phosphatidylethanolamine and phosphatidylglycerol and the only respiratory quinone of strain SM 2104T was ubiquinone-8. The genomic DNA G + C content of strain SM 2104T was 48.0%. On the basis of the phylogenetic, phenotypic, chemotaxonomic and genomic analyses presented in this study, strain SM 2104T is considered to represent a novel species within the genus Alteromonas, for which the name Alteromonas oceansediminis sp. nov. is proposed. The type strain is SM 2104T (= CCTCC AB 2021121T = KCTC 82867T).
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Alteromonas , Alteromonas/genética , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Ácidos Grasos , Fosfolípidos , Filogenia , ARN Ribosómico 16S/genética , Agua de Mar/microbiología , Análisis de Secuencia de ADN , UbiquinonaRESUMEN
Drug resistance is a major problem in cancer therapy with cisplatin. It has not been reported that pleiotrophin, which is anti-apoptotic in some cancer cells, is associated with cisplatin resistance. Pleiotrophin was exogenously expressed in 293 cells. Viability and apoptosis of PC3 cells treated with different concentrations of cisplatin in the presence or absence of purified pleiotrophin were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. PC3 cells transfected with shRNAs were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting 24 h after transfection. MTT assay data indicated that the EC50 value of cisplatin for PC3 cells was significantly increased in the presence of pleiotrophin. Flow cytometry data demonstrated the pleiotrophin dose-dependent anti-apoptosis in PC3 cells treated with cisplatin. Knockdown of pleiotrophin with sh-RNA, as justified by RT-PCR and western blotting analysis, led to increased cisplatin induced-apoptosis in PC3 cells with an increased level of the cleaved poly ADP-ribose polymerase protein. Pleiotrophin may be a potential antiapoptotic protein associated with cisplatin susceptibility, which warrants further study on the role of pleiotrophin in cisplatin resistance.
Asunto(s)
Antineoplásicos/farmacología , Proteínas Portadoras/farmacología , Cisplatino/farmacología , Citocinas/farmacología , Neoplasias de la Próstata/patología , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Células PC-3 , ARN Interferente Pequeño/metabolismoRESUMEN
A Gram-negative, aerobic, non-flagellated and rod-shaped bacterium, strain ASW11-22T, was isolated from an intertidal sediment collected from a coastal area of Qingdao, PR China. The strain grew at 15-40 °C (optimum, 37 °C), at pH 6.0-9.0 (optimum, pH 7.0) and with 0.5-10â% (w/v) NaCl (optimum, 1.0â%). It hydrolysed gelatin and aesculin but did not reduce nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ASW11-22T belonged to the genus Celeribacter, showing the highest sequence similarity to the type strains of Celeribacter halophilus MCCC 1A06432T (98.20â%) and Celeribacter ethanolicus NH195T (97.84â%). The genomic DNA G+C content was 59.1 mol%. The major cellular fatty acid (>10â%) of the strain was summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c) and its main polar lipids were phosphatidylglycerol and one unidentified aminolipid. The sole respiratory quinone of strain ASW11-22T was ubiquinone-10. On the basis of the polyphasic evidence presented in this paper, strain ASW11-22T represents a novel Celeribacter species, for which the name Celeribacter litoreus sp. nov. is proposed. The type strain is ASW11-22T (=KCTC 82495T=MCCC 1K05584T).