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The volumetric density of the metal atomic site is decisive to the operating efficiency of the photosynthetic nanoreactor, yet its rational design and synthesis remain a grand challenge. Herein, we report a shell-regulating approach to enhance the volumetric density of Co atomic sites onto/into multishell ZnxCd1-xS for greatly improving CO2 photoreduction activity. We first establish a quantitative relation between the number of shell layers, specific surface areas, and volumetric density of atomic sites on multishell ZnxCd1-xS and conclude a positive relation between photosynthetic performance and the number of shell layers. The triple-shell ZnxCd1-xS-Co1 achieves the highest CO yield rate of 7629.7 µmol g-1 h-1, superior to those of the double-shell ZnxCd1-xS-Co1 (5882.2 µmol g-1 h-1) and single-shell ZnxCd1-xS-Co1 (4724.2 µmol g-1 h-1). Density functional theory calculations suggest that high-density Co atomic sites can promote the mobility of photogenerated electrons and enhance the adsorption of Co(bpy)32+ to increase CO2 activation (CO2 â CO2* â COOH* â CO* â CO) via the S-Co-bpy interaction, thereby enhancing the efficiency of photocatalytic CO2 reduction.
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Sunlight exposure of grape clusters is frequently reported to influence grape aromas greatly. Among them, the effects of full shading (FS) of clusters on fruit quality and volatile compounds in grape berries has scarcely been investigated. In the present study, the effects of FS from véraison to ripeness on fruit quality and volatile compounds in Cabernet Sauvignon grapes were studied. The results showed that FS treatment reduced fruit size and berry weight, delayed fruit maturity, and decreased the contents of anthocyanins, phenols, and tannins in grape berries. In addition, volatile compounds in grape berries were analyzed, and 55 and 53 volatile compounds were detected in the control (CK) and FS groups, respectively. The results indicated that the concentrations of straight-chain fatty aldehydes, straight-chain fatty alcohols, straight-chain fatty acids, and branched-chain fatty acids, norisoprenoids, and total concentration of volatile compounds were all higher in FS group than in CK group. Specifically, FS treatment had significant promoting effects on the concentrations of ß-damascenone, terpineol, 2-ethyl-1-hexanol, and 2-hexenal, and remarkably decreased the concentrations of geranial, benzeneacetaldehyde, neral, and ethyl acetate. Partial least squares-discriminant analysis (PLS-DA) revealed a clear separation between the control (CK) and FS groups, and showed that 2-hexenal and hexanal were the main characteristic aroma compounds in the FS group. Moreover, an increase in the intensity of fruity, herbaceous, floral, and mushroom aromas was recorded in FS grapes. This study provides new insights into the effects of the exclusion of sunlight exposure on volatile compound accumulation in grape berries.
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In recent years, the ethylene-mediated ripening and softening of non-climacteric fruits have been widely mentioned. In this paper, recent research into the ethylene-mediated ripening and softening of non-climacteric fruits is summarized, including the involvement of ethylene biosynthesis and signal transduction. In addition, detailed studies on how ethylene interacts with other hormones to regulate the ripening and softening of non-climacteric fruits are also reviewed. These findings reveal that many regulators of ethylene biosynthesis and signal transduction are linked with the ripening and softening of non-climacteric fruits. Meanwhile, the perspectives of future research on the regulation of ethylene in non-climacteric fruit are also proposed. The overview of the progress of ethylene on the ripening and softening of non-climacteric fruit will aid in the identification and characterization of key genes associated with ethylene perception and signal transduction during non-climacteric fruit ripening and softening.
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BACKGROUND CONTEXT: A subgroup of patients with pelvic anteversion can present with an unusually large degree of lumbar lordosis (LL), a highly sloped sacrum, and a relatively small pelvic incidence (PI). Prior to lumbar surgery, it can be important to consider such unique sagittal alignment. However, until now, there has been a lack of a predictive model considering different pelvic alignments. Furthermore, the dynamic characteristics of an anteverted pelvis (AP) subgroup have also been unclear. PURPOSE: To build linear predictive formulas for LL that take pelvic anteversion into consideration and to explore the dynamic characteristics of an AP subgroup. STUDY DESIGN: Monocentric, cross-sectional study. PATIENT SAMPLE: Five hundred sixty-five asymptomatic Chinese men and women between the ages of 18 and 80 years. OUTCOME MEASURES: Sagittal parameters including LL, lumbar lordosis minus thoracic kyphosis (LL-TK), PI, pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI-LL), sacral slope (SS), sacral slope divided by pelvic incidence (SS/PI), sagittal vertical axis (SVA), thoracic kyphosis (TK), and T1 (first thoracic vertebra) pelvic angle (TPA) were measured on whole spine radiographs obtained with participants in standing and sitting positions. METHODS: All participants underwent radiography in the standing position; 235 of them underwent additional radiography in the sitting position to allow measurement of sagittal parameters. The participants with pelvic anteversion were placed in an AP (anteverted pelvis) group. Sagittal parameters were compared between the AP group and the non-AP group, and predictive formulas for LL based on PI were created in both groups. In addition, changes in sagittal parameters from standing to sitting were compared in the AP group and a PI-matched control group. RESULTS: Of the 565 participants, 171 (30.3%) had pelvic anteversion. In comparison with the non-AP group, the AP group presented with larger LL, a larger SS, and a smaller PT, with relatively small PI. The predictive formulas for LL were LL=0.60° × PI+21.60° (R2=0.268; p<.001) in the whole cohort, LL=0. 83×PI+18.75° (R2=0.427; p<.001) in AP group, and LL=0.79°×PI+9.66° (R2=0.451; p<.001) in the non-AP group. In moving from standing to sitting, the AP group presented with a larger decrease in SS and LL compared with the control group, indicating different patterns of spinopelvic motion. CONCLUSIONS: In the cohort examined, 30.3% present with pelvic anteversion. Those with AP present with unique characteristics of spinopelvic alignment. In moving from standing to sitting, they exhibit different patterns of spinopelvic motion. We found that identifying the degree of anteversion in each person improves the accuracy of linear models for predicting the degree of LL, which in turn can make plans for spine surgery more accurate.
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Lordose , Postura Sentada , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Lordose/diagnóstico por imagem , Adolescente , Pelve/diagnóstico por imagem , Posição Ortostática , Idoso de 80 Anos ou mais , Estudos Transversais , Adulto Jovem , Vértebras Lombares/diagnóstico por imagem , Ossos Pélvicos/diagnóstico por imagemRESUMO
The primary objective of this paper is to serve as a valuable resource for policymakers who are confronted with the evolving landscape of the coronavirus disease 2019 (COVID-19), considering both free and cost-based vaccination approaches. The potential consequences of shifting from free to cost-based vaccination are explored, encompassing its impact on global vaccine equity and prioritization, economic well-being, healthcare systems and delivery, public health policies, and vaccine distribution strategies. Examining past studies on willingness to pay for the initial COVID-19 vaccine dose and booster shots provides insights into how individuals value COVID-19 vaccinations and underscores the significance of addressing issues related to affordability. If COVID-19 vaccinations incur expenses, using effective communication strategies that emphasize the importance of vaccination and personal health benefits can increase willingness to pay. Making COVID-19 vaccines accessible through public health programs or health insurance can help alleviate financial barriers and increase vaccination rates.
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Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Pandemias , Vacinação , Imunização SecundáriaRESUMO
Dodecahydro-N-ethylcarbazole (12H-NEC) is regarded as the most promising liquid organic hydrogen carrier for hydrogen storage and transportation. Understanding the mechanism of 12H-NEC dehydrogenation and developing cost-effective catalysts are significant. Pd is a high-performance catalyst for 12H-NEC but is not cost-effective, and Ni is just the opposite. How to understand the whole process of full dehydrogenation and improve the performance of Ni become two key questions. Herein, we systematically investigated the mechanism of the full dehydrogenation of 12H-NEC on Pd(111) and Ni(111) for the first time. By calculating all the barriers in the whole dehydrogenation process, we identified that 3H-NEC to 2H-NEC is the rate-determining step and Ni is catalytically less effective than Pd, which is attributed to its narrower d-band distribution and a 0.32 eV higher d-band center than that of Pd. To improve the performance of Ni, we further introduced dopants of Au, Ag, Cu, Pd, Pt, Ru, Rh, Zn, and Al. We found that Ag doping brings a downshift of the d-band center from -1.29 to -1.67 eV and reduces the barrier of 4H-NEC to NEC from 0.94 to 0.76 eV. This study provides new insights into the catalytic mechanism and performance-tuning strategy to help future experimental synthesis.
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OBJECTIVE: This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis. METHODS: Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies. RESULTS: Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in vitro and in vivo. CONCLUSIONS: The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.
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Neutrófilos , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Meios de Cultivo Condicionados/metabolismo , RNA/metabolismo , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo , Microambiente TumoralRESUMO
The antigenic evolution of the influenza A virus hemagglutinin (HA) gene poses a major challenge for the development of vaccines capable of eliciting long-term protection. Prior efforts to understand the mechanisms that govern viral antigenic evolution mainly focus on HA in isolation, ignoring the fact that HA must act in concert with the viral neuraminidase (NA) during replication and spread. Numerous studies have demonstrated that the degree to which the receptor binding avidity of HA and receptor cleaving activity of NA are balanced with each other influences overall viral fitness. We recently showed that changes in NA activity can significantly alter the mutational fitness landscape of HA in the context of a lab-adapted virus strain. Here, we test whether natural variation in relative NA activity can influence the evolutionary potential of HA in the context of the seasonal H1N1 lineage (pdmH1N1) that has circulated in humans since the 2009 pandemic. We observed substantial variation in the relative activities of NA proteins encoded by a panel of H1N1 vaccine strains isolated between 2009 and 2019. We comprehensively assessed the effect of NA background on the HA mutational fitness landscape in the circulating pdmH1N1 lineage using deep mutational scanning and observed pronounced epistasis between NA and residues in or near the receptor binding site of HA. To determine whether NA variation could influence the antigenic evolution of HA, we performed neutralizing antibody selection experiments using a panel of monoclonal antibodies targeting different HA epitopes. We found that the specific antibody escape profiles of HA were highly contingent upon NA background. Overall, our results indicate that natural variation in NA activity plays a significant role in governing the evolutionary potential of HA in the currently circulating pdmH1N1 lineage.
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The antigenic evolution of the influenza A virus hemagglutinin (HA) gene poses a major challenge for the development of vaccines capable of eliciting long-term protection. Prior efforts to understand the mechanisms that govern viral antigenic evolution mainly focus on HA in isolation, ignoring the fact that HA must act in concert with the viral neuraminidase (NA) during replication and spread. Numerous studies have demonstrated that the degree to which the receptor-binding avidity of HA and receptor-cleaving activity of NA are balanced with each other influences overall viral fitness. We recently showed that changes in NA activity can significantly alter the mutational fitness landscape of HA in the context of a lab-adapted virus strain. Here, we test whether natural variation in relative NA activity can influence the evolutionary potential of HA in the context of the seasonal H1N1 lineage (pdmH1N1) that has circulated in humans since the 2009 pandemic. We observed substantial variation in the relative activities of NA proteins encoded by a panel of H1N1 vaccine strains isolated between 2009 and 2019. We comprehensively assessed the effect of NA background on the HA mutational fitness landscape in the circulating pdmH1N1 lineage using deep mutational scanning and observed pronounced epistasis between NA and residues in or near the receptor-binding site of HA. To determine whether NA variation could influence the antigenic evolution of HA, we performed neutralizing antibody selection experiments using a panel of monoclonal antibodies targeting different HA epitopes. We found that the specific antibody escape profiles of HA were highly contingent upon NA background. Overall, our results indicate that natural variation in NA activity plays a significant role in governing the evolutionary potential of HA in the currently circulating pdmH1N1 lineage.
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BACKGROUND: Human genetic studies have identified several mitochondrial amidoxime-reducing component 1 (MTARC1) variants as protective against metabolic dysfunction-associated steatotic liver disease. The MTARC1 variants are associated with decreased plasma lipids and liver enzymes and reduced liver-related mortality. However, the role of mARC1 in fatty liver disease is still unclear. METHODS: Given that mARC1 is mainly expressed in hepatocytes, we developed an N-acetylgalactosamine-conjugated mouse Mtarc1 siRNA, applying it in multiple in vivo models to investigate the role of mARC1 using multiomic techniques. RESULTS: In ob/ob mice, knockdown of Mtarc1 in mouse hepatocytes resulted in decreased serum liver enzymes, LDL-cholesterol, and liver triglycerides. Reduction of mARC1 also reduced liver weight, improved lipid profiles, and attenuated liver pathological changes in 2 diet-induced metabolic dysfunction-associated steatohepatitis mouse models. A comprehensive analysis of mARC1-deficient liver from a metabolic dysfunction-associated steatohepatitis mouse model by metabolomics, proteomics, and lipidomics showed that Mtarc1 knockdown partially restored metabolites and lipids altered by diet. CONCLUSIONS: Taken together, reducing mARC1 expression in hepatocytes protects against metabolic dysfunction-associated steatohepatitis in multiple murine models, suggesting a potential therapeutic approach for this chronic liver disease.
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Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Hepatócitos , Animais , Camundongos , Hepatócitos/metabolismo , Fígado/metabolismo , Masculino , RNA Interferente Pequeno/genética , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Camundongos Endogâmicos C57BLRESUMO
Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is an advanced stage of metabolic fatty liver disease. The pathogenic mechanisms of MASH center on hepatocyte injury and the ensuing immune response within the liver microenvironment. Recent work has implicated TREM2+ macrophages in various disease conditions, and substantial induction of TREM2+ NASH-associated macrophages (NAMs) serves as a hallmark of metabolic liver disease. Despite this, the mechanisms through which NAMs contribute to MASH pathogenesis remain poorly understood. Here, we identify membrane-spanning 4-domains a7 (MS4A7) as a NAM-specific pathogenic factor that exacerbates MASH progression in mice. Hepatic MS4A7 expression was strongly induced in mouse and human MASH and associated with the severity of liver injury. Whole-body and myeloid-specific ablation of Ms4a7 alleviated diet-induced MASH pathologies in male mice. We demonstrate that exposure to lipid droplets (LDs), released upon injury of steatotic hepatocytes, triggered NAM induction and exacerbated MASH-associated liver injury in an MS4A7-dependent manner. Mechanistically, MS4A7 drove NLRP3 inflammasome activation via direct physical interaction and shaped disease-associated cell states within the liver microenvironment. This work reveals the LD-MS4A7-NLRP3 inflammasome axis as a pathogenic driver of MASH progression and provides insights into the role of TREM2+ macrophages in disease pathogenesis.
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Inflamassomos , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Masculino , Camundongos , Inflamassomos/metabolismo , Fígado/metabolismo , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores Imunológicos/metabolismoRESUMO
Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.