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The arthropod exoskeleton provides protection and support and is vital for survival and adaption. The integrity and mechanical properties of the exoskeleton are often impaired after pathogenic infection; however, the detailed mechanism by which infection affects the exoskeleton remains largely unknown. Here, we report that the damage to the shrimp exoskeleton is caused by modulation of host lipid profiles after infection with white spot syndrome virus (WSSV). WSSV infection disrupts the mechanical performance of the exoskeleton by inducing the expression of a chitinase (Chi2) in the sub-cuticle epidermis and decreasing the cuticle chitin content. The induction of Chi2 expression is mediated by a nuclear receptor that can be activated by certain enriched long-chain saturated fatty acids after infection. The damage to the exoskeleton, an aftereffect of the induction of host lipogenesis by WSSV, significantly impairs the motor ability of shrimp. Blocking the WSSV-caused lipogenesis restored the mechanical performance of the cuticle and improved the motor ability of infected shrimp. Therefore, this study reveals a mechanism by which WSSV infection modulates shrimp internal metabolism resulting in phenotypic impairment, and provides new insights into the interactions between the arthropod host and virus.
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Exoesqueleto , Metabolismo dos Lipídeos , Penaeidae , Vírus da Síndrome da Mancha Branca 1 , Animais , Penaeidae/virologia , Penaeidae/metabolismo , Exoesqueleto/metabolismo , Exoesqueleto/virologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Metabolismo dos Lipídeos/fisiologia , Interações Hospedeiro-Patógeno , Lipogênese/fisiologiaRESUMO
Open Cu sites were loaded to the UiO-67 metal-organic framework (MOF) skeleton by introduction of flexible Cu-binding pyridylmethylamine (pyma) side chains to the biphenyldicarboxylate linkers. Distance between Cu centers in the MOF pores was tuned by controlling the density of metal-binding side chains. "Interacted" Cu-pair or "isolated" monomeric Cu sites were achieved with high and low (pyma)Cu side chain loading, respectively. Spectroscopic and theoretical studies indicate that "interacted" Cu pairs can effectively bind and activate molecular dioxygen to form Cu2O2 clusters, which showed high catalytic activity for aerobic oxidative C-N coupling. On the contrary, MOF catalyst bearing isolated monomeric Cu sites only showed modest catalytic activity. Enhancement in catalytic performance for the Cu-pair catalyst is attributed to the remote synergistic effect of the paired Cu site, which binds molecular dioxygen and cleaves the OâO bond in a collaborative manner. This work demonstrates that noncovalently interacted metal-pair sites can effectively activate inert small molecules and promote heterogeneous catalytic processes.
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Copper (Cu), with the advantage of producing a deep reduction product, is a unique catalyst for the electrochemical reduction of CO2 (CO2RR). Designing a Cu-based catalyst to trigger CO2RR to a multicarbon product and understanding the accurate structure-activity relationship for elucidating reaction mechanisms still remain a challenge. Herein, we demonstrate a rational design of a core-shell structured silica-copper catalyst (p-Cu@m-SiO2) through Cu-Si direct bonding for efficient and selective CO2RR. The Cu-Si interface fulfills the inversion in CO2RR product selectivity. The product ratio of C2H4/CH4 changes from 0.6 to 14.4 after silica modification, and the current density reaches a high of up to 450 mA cm-2. The kinetic isotopic effect, in situ attenuated total reflection Fourier-transform infrared spectra, and density functional theory were applied to elucidate the reaction mechanism. The SiO2 shell stabilizes the *H intermediate by forming Si-O-H and inhibits the hydrogen evolution reaction effectively. Moreover, the direct-bonded Cu-Si interface makes bare Cu sites with larger charge density. Such bare Cu sites and Si-O-H sites stabilized the *CHO and activated the *CO, promoting the coupling of *CHO and *CO intermediates to form C2H4. This work provides a promising strategy for designing Cu-based catalysts with high C2H4 catalytic activity.
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Observational studies provide evidence that metabolites may be involved in the development of autoimmune diseases (ADs), but whether it is causal is still unknown. Based on the large-scale genome-wide association studies (GWAS) summary statistics, we performed two-sample Mendelian randomization (MR) to evaluate the causal associations between human blood metabolites and multiple ADs, which were inflammatory bowel disease (IBD), ulcerative colitis (UC), crohns disease (CD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). After Bonferroni adjustment, we identified 6 causal features of metabolites, i.e., glycerol 2-phosphate for T1D, hexadecanedioate, phenylacetylglutamine and laurylcarnitine for RA, glycine and arachidonate (20:4n6) for CD. Comprehensive sensitive analysis was further performed to validate the robustness of associations. We also observed some overlaps of metabolites among different ADs, implying similar or shared underlying mechanisms in such pathogenic processes. Multivariable MR analysis was then conducted to avoid potential pleiotropic effect of other complex traits. After controlling for several common traits, multivariable MR analysis ruled out most of potential pleiotropic effects and validated independence of identified metabolites. Finally, metabolic pathway analysis was performed based on suggestive metabolites for each AD respectively and a total of seven metabolic pathways were identified. In conclusion, this study provided novel insights into investigating causal role of blood metabolites in development of multiple ADs through a comprehensive genetic pathway.
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Artrite Reumatoide , Doenças Autoimunes , Doença de Crohn , Diabetes Mellitus Tipo 1 , Artrite Reumatoide/genética , Doenças Autoimunes/genética , Doença de Crohn/genética , Diabetes Mellitus Tipo 1/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Bifidobacterium animalis ssp. lactis DN-173 010/CNCM I-2494 (B. animalis) is a probiotic strain commonly added to yogurt. Yogurt and honey are a popular culinary pairing. Honey improves bifidobacteria survival in vitro. However, probiotic survival in yogurt with honey during in vitro digestion has not been investigated. OBJECTIVES: The study aimed to evaluate the effects of different honey varietals and concentrations on B. animalis survivability in yogurt through in vitro digestion. METHODS: Yogurt with honey or control-treated samples underwent in vitro simulated oral, gastric, and intestinal digestion. B. animalis cells were enumerated on de Man Rogosa and Sharpe (MRS) medium followed by an overlay with a modified selective MRS medium; all underwent anaerobic incubation. B. animalis were enumerated predigestion and after oral, gastric, and intestinal digestion. There were 2 study phases: Phase 1 tested 4 honey varietals at 20% wt/wt per 170 g yogurt, and Phase 2 tested 7 dosages of clover honey (20, 14, 10, 9, 8, 6, and 4% wt/wt) per 170 g yogurt. RESULTS: Similar B. animalis counts were observed between all treatments after oral and gastric digestion (<1 Log colony forming units (CFU)/g probiotic reduction). Higher B. animalis survivability was observed in yogurt with clover honey after exposure to simulated intestinal fluids (â¼3.5 Log CFU/g reduction; P < 0.05) compared to all control treatments (â¼5.5 Log CFU/g reduction; P < 0.05). Yogurt with 10-20% wt/wt clover honey increased B. animalis survivability after simulated in vitro digestion (≤ â¼4.7 Log CFU/g survival; P < 0.05). CONCLUSIONS: Yogurt with added honey improves probiotic survivability during in vitro digestion. The effective dose of clover honey in yogurt was 10-20% wt/wt per serving (1-2 tablespoons per 170 g yogurt) for increased probiotic survivability during in vitro digestion.
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Bifidobacterium animalis , Mel , Probióticos , Humanos , Iogurte/microbiologia , Bifidobacterium , Probióticos/uso terapêutico , DigestãoRESUMO
Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT-PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress-inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.
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Several major roadblocks, including the "shuttle effect" caused by the dissolved higher-order sodium polysulfides (NaPSs), extremely poor conductivity of sulfur cathodes, and sluggish conversion kinetics of charging-discharging reactions, have hindered the commercialization of sodium-sulfur batteries (NaSBs). In our study, representative C2N-based single-atom catalysts (SACs), TM@C2N (TM = Fe, Ni and V), are proposed to improve the comprehensive performance of NaSBs. Based on first-principles calculations, we first discuss in detail the anchoring behavior of all adsorption systems, TM@C2N/(S8 and NaPSs). The results indicate that compared to pristine C2N, TM@C2N substrates exhibit a stronger capability to capture S8/NaPSs clusters through physical/chemical binding, with V@C2N showing the most outstanding capability ranging from -2.37 to -5.03 eV. The density of states analysis reveals that metallic properties can be well maintained before and after adsorption of polysulfides. More importantly, TM@C2N configurations can greatly reduce the energy barriers of charging and discharging reactions, thereby accelerating the conversion efficiency of NaSBs. It is worth mentioning that V@C2N has lower charge-discharge energy barriers and Na ion migration rates, since the embedded TM atom weakens the strong binding of Na+ in the N6 cavity of C2N. The intrinsic mechanism analysis reveals that the interaction between the d orbitals of V and the p orbitals of S leads to the weakening of Na-S bonds, which can not only effectively inhibit the shuttle effect, but also promote the dissociation of Na2S. Overall, this work not only offers excellent catalytic materials, but also provides vital guidance for designing SACs in NaSBs.
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Perovskites exhibit considerable potential as catalysts for various applications, yet their performance modulation in the carbon dioxide reduction reaction (CO2RR) remains underexplored. In this study, we report a strategy to enhance the electrocatalytic carbon dioxide (CO2) reduction activity via Ce-doped La2CuO4 (LCCO) and Sr-doped La2CuO4 (LSCO) perovskite oxides. Specifically, compared to pure phase La2CuO4 (LCO), the Faraday efficiency (FE) for CH4 of LCCO at -1.4 V vs. RHE (reversible hydrogen electrode) is improved from 38.9% to 59.4%, and the FECO2RR of LSCO increased from 68.8% to 85.4%. In situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy spectra results indicate that the doping of A-site ions promotes the formation of *CHO and *HCOO, which are key intermediates in the production of CH4, compared to the pristine La2CuO4. X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and double-layer capacitance (Cdl) outcomes reveal that heteroatom-doped perovskites exhibit more oxygen vacancies and higher electrochemical active surface areas, leading to a significant improvement in the CO2RR performance of the catalysts. This study systematically investigates the effect of A-site ion doping on the catalytic activity center Cu and proposes a strategy to improve the catalytic performance of perovskite oxides.
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Halociline, a derivative of alkaloids, was isolated from the marine fungus Penicillium griseofulvum by our group. This remarkable compound exhibits promising antineoplastic activity, yet the precise molecular mechanisms underlying its anticancer properties remain enigmatic. To unravel these mechanisms, we employed an integrated approach of network pharmacology analysis, molecular docking simulations, and molecular dynamics simulations to explore halociline therapeutic targets for gastric cancer. The data from network pharmacology indicate that halociline targets MAPK1, MMP-9, and PIK3CA in gastric cancer cells, potentially mediated by diverse pathways including cancer, lipid metabolism, atherosclerosis, and EGFR tyrosine kinase inhibitor resistance. Notably, molecular docking and dynamics simulations revealed a high affinity between halociline and these targets, with free binding energies (ΔEtotal) of - 20.28, - 27.94, and - 25.97 kcal/mol for MAPK1, MMP-9, and PIK3CA, respectively. This study offers valuable insights into the potential molecular mechanism of halociline's inhibition of gastric cancer cells and serves as a valuable reference for future basic research efforts.
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BACKGROUND: Traditional sun-drying aquatic products are popular and recognized by customers, owing to their unique flavor and long-term preservation. However, the product quality and production efficiency cannot be guaranteed. Cololabis saira is rich in unsaturated fatty acids, which are susceptible to hyperoxidation during the drying process. This study aimed to make clear the role of ultraviolet (UV) radiation in flavor formation during drying processes of Cololabis saira to develop a modern drying technology. RESULTS: Lipid oxidation analysis revealed that moderate hydrolytic oxidation occurred in the UV-assisted cold-air drying group due to the combined influence of UV and cold-air circulation, resulting in the thiobarbituric acid reactive substances value being higher than that of cold-air drying group but lower than the natural drying group. Hexanal, heptanal, cis-4-heptenal, octanal, nonanal, (trans,trans)-2,4-heptadienal, (trans,trans)-2,6-nonanedial, 1-octen-3-ol, heptanol, 2,3-pentanedione, 3,5-octadien-2-one and trimethylamine were identified as the characteristic flavor odor-active compounds present in all Cololabis saira samples. Yet, during the natural drying process, sunlight promoted the lipid oxidation, resulting in the highest degree of lipid oxidation among three drying methods. Light and heat promoted lipid oxidation in Cololabis saira prepared through natural drying process, leading to a large accumulation of volatile compounds, such as 3-methylbutyraldehyde, 2,3-pentanedione, 1-propanol, and 3-pentanone. Cold air circulation inhibited lipid oxidation to some extent, resulting in a blander flavor profile. More cis-4-heptenal, cis-2-heptenal, octanal and 2-ethylfuran accumulated during the UV-assisted cold-air drying process, enriching its greasy flavor and burnt flavor. CONCLUSION: UV-assisted cold-air drying could promote moderate lipid oxidation, which is beneficial for improving product flavor. To sum up, UV radiation played a crucial role in the flavor formation during the drying process of Cololabis saira. © 2024 Society of Chemical Industry.
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The increasing ground-level ozone (O3) is threatening food security, especially in Asian areas, where rice is one of the most important staple crops. O3 impacts on rice could be exacerbated by its spatiotemporal heterogeneity. To improve evaluation accuracy and develop effective adaptations, direct data is urgently needed. Studies on the short-term effects of O3 on rice grain, however, are lacking. Which may lead to an underestimation of the O3 impacts. Through a field experiment, we studied the responses of grain nitrogen, grain carbon, and grain protein in rice cultivars to elevated concentrations of O3 (40 ppb plus that in background air, eO3), especially examining the effects of short-term eO3 during different plant growth stages. We found that long-term eO3 increased grain nitrogen by 29.29% in a sensitive rice cultivar, and short-term eO3 at the tillering and jointing stages increased grain nitrogen by 19.31%, and the grain carbon to nitrogen ratio was decreased by 14.70%, and 21.14% by short-term and long-term eO3. Here we demonstrate that short-term eO3 may significantly affect the chemical composition of rice grains. Previous evaluations of the effects of eO3 may be underestimated. Moreover, changes in the grain nitrogen and grain protein were greater when the short-term eO3 was added to rice plants during the tillering and jointing stage, compared to heading and ripening stage. These results suggest that to improve the tolerance of rice to eO3 to achieve food security, studies on cultivar screening, as well as developing growth-stage-specific adaptations are needed in future.
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Poluentes Atmosféricos , Nitrogênio , Oryza , Ozônio , Oryza/crescimento & desenvolvimento , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Nitrogênio/análise , Grão Comestível/química , Carbono/análise , Monitoramento AmbientalRESUMO
Large-scale metal contamination across the food web is an intractable problem due to increasing pollutant emissions, atmospheric transport, and dry and wet deposition of elements. The present study focus on several trace metals that are rarely studied but have special toxicity, including tin (Sn), antimony (Sb), gold (Au), hafnium (Hf), palladium (Pd), platinum (Pt), ruthenium (Ru), tellurium (Te) and iridium (Ir). We investigated trace metals residues and distribution characteristics, and further evaluated the potential health risks from major daily food intakes in 33 cities in China. Sn, Sb, Ir, Hf, and Au were frequently detected in food samples with the concentrations ranged from ND (not detected) to 24.78 µg/kg ww (wet weight). Eggs exhibited the highest residual level of all detected metals (13.70 ± 14.70 µg/kg ww in sum), while the lowest concentrations were observed in vegetables (0.53 ± 0.17 µg/kg ww in sum). Sn accounting for more than 50% of the total trace metals concentration in both terrestrial and aquatic animal origin foods. In terrestrial plant origin foods, Sn and Ir were the most abundant elements. Hf and Au were the most abundant elements in egg samples. In addition, Sb and Ir showed a clear trophic dilution effect in terrestrial environments, while in aquatic ecosystems, Sn, Hf, and Au exhibited obvious trophic amplification effects. The calculated average estimated daily intake (EDI) via food consumption in five regions of China was 0.09 µg/(kg·day), implying the health risk of aforementioned elements was acceptable.
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Dieta , Ecossistema , Oligoelementos , Animais , Humanos , Dieta/efeitos adversos , População do Leste Asiático , Metais/análise , Medição de Risco , Oligoelementos/análiseRESUMO
Herein, we propose an oxygen-containing species coordination strategy to boost CO2 electroreduction in the presence of O2. A two-dimensional (2D) conjugated metal-covalent organic framework (MCOF), denoted as NiPc-Salen(Co)2-COF that is composed of the Ni-phthalocyanine (NiPc) unit with well-defined Ni-N4-O sites and the salen(Co)2 moiety with binuclear Co-N2O2 sites, is developed and synthesized for enhancing the CO2RR under aerobic condition. In the presence of O2, one of the Co sites in the NiPc-Salen(Co)2-COF that coordinated with the intermediate of *OOH from ORR could decrease the energy barrier of the activation of CO2 molecules and stabilize the key intermediate *COOH of the CO2RR over the adjacent Co center. Besides, the oxygen species axially coordinated Ni-N4-O sites can favor in reducing the energy barrier of the intermediate *COOH formation for the CO2RR. Thus, NiPc-Salen(Co)2-COF exhibits high oxygen-tolerant CO2RR performance and achieves outstanding CO Faradaic efficiency (FECO) of 97.2 % at -1.0â V vs. the reversible hydrogen electrode (RHE) and a high CO partial current density of 40.3â mA cm-2 at -1.1â V in the presence of 0.5 % O2, which is superior to that in pure CO2 feed gas (FECO=94.8 %, jCO=19.9â mA cm-2). Notably, the NiPc-Salen(Co)2-COF achieves an industrial-level current density of 128.3â mA cm-2 in the flow-cell reactor with 0.5 % O2 at -0.8â V, which is higher than that in pure CO2 atmosphere (jCO=104.8â mA cm-2). It is worth noting that an excellent FECO of 86.8 % is still achieved in the presence of 5 % O2 at -1.0â V. This work provides an effective strategy to enable the CO2RR under O2 atmosphere by utilizing the *OOH intermediates of ORR to boost CO2 electroreduction.
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A copper porphyrin-derived metal-organic framework electrocatalyst, FICN-8, was synthesized and its catalytic activity for CO2 reduction reaction (CO2RR) was investigated. FICN-8 selectively catalyzed electrochemical reduction of CO2 to CO in anhydrous acetonitrile electrolyte. However, formic acid became the dominant CO2RR product with the addition of a proton source to the system. Mechanistic studies revealed the change of major reduction pathway upon proton source addition, while catalyst-bound hydride (*H) species was proposed as the key intermediate for formic acid production. This work highlights the importance of electrolyte composition on CO2RR product selectivity.
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Achieving active site engineering at the atomic level poses a significant challenge in the design and optimization of catalysts for energy-efficient catalytic processes, especially for a reaction with two reactants competitively absorbed on catalytic active sites. Herein, we show an example that tailoring the local environment of cobalt sites in a robust metal-organic framework through substituting the bridging atom from -Cl to -OH group leads to a highly active catalyst for oxygen activation in an oxidation reaction. Comprehensive characterizations reveal that this variation imparts drastic changes on the electronic structure of metal centers, the competitive reactant adsorption behavior, and the intermediate formation. As a result, exceptional low-temperature CO oxidation performance was achieved with T25(Temperature for 25 % conversion)=35 °C and T100 (Temperature for 100 % conversion)=150 °C, which stands out from existing MOF-based catalysts and even rivals many noble metal catalysts. This work provides a guidance for the rational design of catalysts for efficient oxygen activation for an oxidation reaction.
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Introducing an external visible-light field would be a promising strategy to improve the activity of the electrocatalytic CO2 reduction reaction (CO2RR), but it still remains a challenge due to the short excited-state lifetime of active sites. Herein, Ru(bpy)3Cl2 struts as powerful photosensitive donors were immobilized into the backbones of Co-porphyrin-based covalent organic frameworks (named Co-Bpy-COF-Rux, x is the molar ratio of Ru and Co species, x = 1/2 and 2/3) via coordination bonds, for the photo-coupled CO2RR to produce CO. The optimal Co-Bpy-COF-Ru1/2 displays a high CO Faradaic efficiency of 96.7% at -0.7 V vs reversible hydrogen electrode (RHE) and a CO partial current density of 16.27 mA cm-2 at -1.1 V vs RHE under the assistance of light, both of which were far surpassing the values observed in the dark. The significantly enhanced activity is mainly attributed to the incorporation of a Ru(bpy)3Cl2 donor with long excited-state lifetime and concomitantly giant built-in electric field in Co-Bpy-COF-Ru1/2, which efficiently accelerate the photo-induced electron transfer from Ru(bpy)3Cl2 to the cobalt-porphyrin under the external light. Thus, the cobalt-porphyrin active sites have a longer excited-state lifetime to lower the rate-determining steps' energy occurring during the actual photo-coupled electrocatalytic CO2RR process. This is the first work of porphyrin-based COFs for photo-coupled CO2RR, opening a new frontier for the construction of efficient photo-coupled electrocatalysts.
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The photocatalytic conversion of CO2 into C2+ products such as ethylene is a promising path toward the carbon neutral goal but remains a big challenge due to the high activation barrier for CO2 and similar reduction potentials of many possible multi-electron-transfer products. Herein, an effective tandem photocatalysis strategy has been developed to support conversion of CO2 to ethylene by construction of the synergistic dual sites in rhenium-(I) bipyridine fac-[ReI(bpy)(CO)3Cl] (Re-bpy) and copper-porphyrinic triazine framework [PTF(Cu)]. With these two catalysts, a large amount of ethylene can be produced at a rate of 73.2 µmol g-1 h-1 under visible light irradiation. However, ethylene cannot be obtained from CO2 by use of either component of the Re-bpy or PTF(Cu) catalysts alone; with a single catalyst, only monocarbon product CO is produced under similar conditions. In the tandem photocatalytic system, the CO generated at the Re-bpy sites is adsorbed by the nearby Cu single sites in PTF(Cu), and this is followed by a synergistic C-C coupling process which ultimately produces ethylene. Density functional theory calculations demonstrate that the coupling process between PTF(Cu)-*CO and Re-bpy-*CO to form the key intermediate Re-bpy-*CO-*CO-PTF(Cu) is vital to the C2H4 production. This work provides a new pathway for the design of efficient photocatalysts for photoconversion of CO2 to C2 products via a tandem process driven by visible light under mild conditions.
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Rheumatoid arthritis (RA) is associated with increased localized and generalized bone loss, but the complex genetic mechanism between them is still unknown. By leveraging large-scale genome-wide association studies summary statistics and individual-level datasets (i.e. UK Biobank), a series of genetic approaches were conducted. Linkage disequilibrium score regression reveals a shared genetic correlation between RA and estimated bone mineral density (eBMD) (rg = -0.059, P = 0.005). The PLACO analysis has identified 74 lead (8 novel) pleiotropic loci that could be mapped to 99 genes, the genetic functions of which reveal the possible mechanism underlying RA and osteoporosis. In European, genetic risk score (GRS) and comprehensive Mendelian randomization (MR) were utilized to evaluate the causal association between RA and osteoporosis in European and Asian. The increase in GRS of RA could lead to a decrease of eBMD (beta = -0.008, P = 3.77E-6) and a higher risk of facture [odds ratio (OR) = 1.012, P = 0.044]. MR analysis identified that genetically determined RA was causally associated with eBMD (beta = -0.021, P = 4.14E-05) and fracture risk (OR = 1.036, P = 0.004). Similar results were also observed in Asian that osteoporosis risk could be causally increased by RA (OR = 1.130, P = 1.04E-03) as well as antibodies against citrullinated proteins-positive RA (OR = 1.083, P = 0.015). Overall, our study reveals complex genetic mechanism between RA and osteoporosis and provides strong evidence for crucial role of RA in pathogenesis of osteoporosis.
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Artrite Reumatoide/etiologia , Suscetibilidade a Doenças , Osteoporose/etiologia , Algoritmos , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Biomarcadores , Densidade Óssea/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Análise da Randomização Mendeliana , Modelos Genéticos , Osteoporose/metabolismo , Osteoporose/patologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Grupos Raciais/genéticaRESUMO
BACKGROUND: The study aimed to validate the prognostic value of the Prostatype® risk score (P-score), which includes a three-gene signature and conventional risk factors, in a retrospective cohort. METHODS: All 716 patients diagnosed with prostate cancer from 2008 to 2010 at Skåne University Hospital, Sweden, were included. After excluding patients based on pathological and clinical eligibility criteria, RNA quality, and presence of metastases at diagnosis, a final cohort comprising 316 patients was further analyzed. Expression levels of three genes (IGFBP3, F3, and VGLL3) were measured in archived formalin-fixed paraffin-embedded core needle biopsies. The gene expression data were combined with clinical parameters (Gleason score, prostate-specific antigen, and clinical tumor stage) to calculate the P-score for each patient. Predictive performance of the P-score in terms of prostate cancer-specific mortality (PCSM), distant metastasis and adverse pathological outcomes were investigated. RESULTS: The P-score predicted both PCSM (hazard ratio [HR] = 1.6) and metastasis (HR = 1.46). The P-score had an area under curve (AUC) of 0.93 when predicting the PCSM risk at 10 years (95% confidence interval [CI]: 0.89-0.98), which was significantly better than both D'Amico (AUC: 0.81, 95% CI: 0.72-0.90, p < 0.001) and UCSF-CAPRA (AUC: 0.88, 95% CI: 0.80-0.96, p < 0.05). Decision curve analysis showed a higher net benefit of the P-score compared to both D'Amico and CAPRA. All three risk scores performed similarly in the prediction of distant metastases. For patients who underwent radical prostatectomy (RP), a higher P-score correlated with adverse pathological features such as pathologic tumor stage T3-4 (p < 0.0001) and ≥International Society of Urological Pathology grade group 3 (p < 0.0001). CONCLUSIONS: Our findings provide evidence for the prognostic value of the P-score. The P-score predicted the risk for PCSM more accurately than the D'Amico and CAPRA scores. Performance was similar when predicting the risk for development of distant metastases within 10 years. Moreover, the P-score correlated with adverse pathological outcomes in RP specimens. Thus, the P-score could provide useful information for patients and their doctors to make informed decisions at the time of diagnosis.
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Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Fatores de Risco , Gradação de Tumores , Prostatectomia , Medição de Risco , Fatores de TranscriçãoRESUMO
Fabrication of a patterned hydrogen-bonded organic framework (HOF) films on a large scale is an extreme challenge. In this work, a large area HOF film (30 × 30 cm2 ) is prepared via an efficient and low-cost electrostatic spray deposition (ESD) approach on the un-modified conductive substrates directly. Combining the ESD with a template method, variously patterned HOF films can be easily produced, including deer- and horse-shaped films. The obtained films exhibit excellent electrochromic performance with multicolor change from yellow to green and violet, and two-band regulation at 550 and 830 nm. Benefiting from the inherently present channels of HOF materials and the additional film porosity created by ESD, the PFC-1 film could quickly change color (within 10 s). Furthermore, the large-area patterned EC device is constructed based on the above film to prove practical potential application. The presented ESD method can be extended to other HOF materials; thus, this work paves a feasible path for constructing large-area patterned HOF films for practical optoelectronic applications.