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Constructing effective and robust biocatalysts with carbonic anhydrase (CA)-mimetic activities offers an alternative and promising pathway for diverse CO2-related catalytic applications. However, there is very limited success has been achieved in controllably synthesizing CA-mimetic biocatalysts. Here, inspired by the 3D coordination environments of CAs, this study reports on the design of an ultrafast ZnN3-OH2 center via tuning the 3D coordination structures and mesoporous defects in a zinc-dipyrazolate framework to serve as new, efficient, and robust CA-mimetic biocatalysts (CABs) to catalyze the hydration reactions. Owing to the structural advantages and high similarity with the active center of natural CAs, the double-walled CAB with mesoporous defects displays superior CA-like reaction kinetics in p-NPA hydrolysis (V0 = 445.16 nM s-1, Vmax = 3.83 µM s-1, turnover number: 5.97 × 10-3 s-1), which surpasses the by-far-reported metal-organic frameworks-based biocatalysts. This work offers essential guidance in tuning 3D coordination environments in artificial enzymes and proposes a new strategy to create high-performance CA-mimetic biocatalysts for broad applications, such as CO2 hydration/capture, CO2 sensing, and abundant hydrolytic reactions.
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The nitridation of noble metals-based catalysts to further enhance their hydrogen evolution reaction (HER) kinetics in neutral and alkaline conditions would be an effective strategy for developing high-performance wide pH HER catalysts. Herein, a facile molten urea method is employed to construct the nitrided Rh nanoclusters (RhxN) supported on N-doped carbon (RhxN-NC). The uniformly distributed RhxN clusters exhibited optimized water bonding and splitting effects, therefore resulting in excellent pH-universal HER performance. The optimized RhxN-NC catalyst only requires 8, 12, and 109 mV overpotentials to reach the current density of 10 mA cm-2 in 0.5 M H2SO4, 1.0 M KOH, and 1.0 M PBS electrolytes, respectively. The spectroscopic characterizations and theoretical calculation further confirm the vital role of Rh-N moieties in RhxN clusters in improving the transfer of electrons and facilitating the generation of H2. This work not only provides a suitable nitridation method for noble metal species in mild conditions but also makes a breakthrough in synthesizing noble metal nitrides-based electrocatalysts to achieve an exceptional wide-pH HER performance and other catalysis.
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Pathogenic variants in HFE and non-HFE genes have been identified in hemochromatosis in different patient populations, but there are still a certain number of patients with unexplained primary iron overload. We recently identified in Chinese patients a recurrent p.(Arg639Gln) variant in SURP and G-patch domain containing 2 (SUGP2), a potential mRNA splicing-related factor. However, the target gene of SUGP2 and affected iron-regulating pathway remains unknown. We aimed to investigate the pathogenicity and underlying mechanism of this variant in hemochromatosis. RNA-seq analysis revealed that SUGP2 knockdown caused abnormal alternative splicing of CIRBP pre-mRNA, resulting in an increased normal splicing form of CIRBP V1, which in turn increased the expression of BMPER by enhancing its mRNA stability and translation. Furthermore, RNA-protein pull-down and RNA immunoprecipitation assays revealed that SUGP2 inhibited splicing of CIRBP pre-mRNA by a splice site variant at CIRBP c.492 and was more susceptible to CIRBP c.492 C/C genotype. Cells transfected with SUGP2 p.(Arg639Gln) vector showed up-regulation of CIRBP V1 and BMPER expression and down-regulation of pSMAD1/5 and HAMP expression. CRISPR-Cas9 mediated SUGP2 p.(Arg622Gln) knock-in mice showed increased iron accumulation in the liver, higher total serum iron, and decreased serum hepcidin level. A total of 10 of 54 patients with hemochromatosis (18.5%) harbored the SUGP2 p.(Arg639Gln) variant and carried CIRBP c.492 C/C genotype, and had increased BMPER expression in the liver. Altogether, the SUGP2 p.(Arg639Gln) variant down-regulates hepcidin expression through the SUGP2/CIRBP/BMPER axis, which may represent a novel pathogenic factor for hemochromatosis.
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Hemocromatose , Transdução de Sinais , Hemocromatose/genética , Humanos , Camundongos , Animais , Masculino , Proteínas de Ligação a RNA/genética , Hepcidinas/genética , Hepcidinas/metabolismo , FemininoRESUMO
BACKGROUND: Mandibular malpositioning may result in an abnormal concentration of stresses within the temporomandibular joint (TMJ) in adult rats, which may further lead to a series of pathological changes, such as articular cartilage wear, subchondral bone sclerosis and osteophyte formation. However, the pathological and adaptive changes in condylar cartilage caused by different stress distributions are still controversial. OBJECTIVE: The aim of this study was to observe the effect of sagittal changes in mandibular position on condylar cartilage by changing the occlusal vertical dimension (OVD) in adult rats. METHODS: Fifteen-week-old female rats were divided into three groups: control (CON), increased OVD (iOVD) and loss of occlusion (LO) groups. An occlusal plate and tooth extraction were used to establish the animal model. TMJ samples of the experimental and CON groups were observed and investigated by bone morphological, histomorphological and immunohistochemical staining analyses at 3 days, 1 week, 2 weeks, 4 weeks and 8 weeks. Weight curves were plotted. RESULTS: Micro-computed tomography showed that, compared with the CON group, cartilage destruction followed by repair occurred in both experimental groups, which was similar to the trend observed in haematoxylin-eosin staining. All experimental results for the iOVD group showed an approximately similar time trend. Compared with the iOVD group, the toluidine blue and immunohistochemical staining results in the LO group showed no obvious change trend over time. CONCLUSION: Compared with occlusal loss, an increase in OVD caused faster and more severe damage to condylar cartilage, and subchondral bone repair occurred later.
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Cartilagem Articular , Modelos Animais de Doenças , Côndilo Mandibular , Transtornos da Articulação Temporomandibular , Articulação Temporomandibular , Dimensão Vertical , Microtomografia por Raio-X , Animais , Ratos , Feminino , Articulação Temporomandibular/patologia , Articulação Temporomandibular/diagnóstico por imagem , Côndilo Mandibular/patologia , Côndilo Mandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Cartilagem Articular/patologia , Cartilagem Articular/diagnóstico por imagem , Imuno-Histoquímica , Mandíbula/patologia , Ratos Sprague-Dawley , Má Oclusão/patologiaRESUMO
STATEMENT OF PROBLEM: The accuracy of intraoral scanning techniques for complete arch implant-supported prostheses remains unclear. PURPOSE: The purpose of this in vitro study was to evaluate the accuracy of complete arch intraoral scanning using newly modified scan bodies. MATERIAL AND METHODS: A definitive cast with 6 parallel dental implants (6-246 subgroup, right first molar, right first premolar, right lateral incisor, left lateral incisor, left first premolar, and left first molar) was fabricated. By masking the implants with artificial gingiva, 2 other distinct definitive casts were obtained for 2 subgroups: the 4-24 subgroup, which included 4 implants (right first premolar, right lateral incisor, left lateral incisor, and left first premolar) and the 4-26 subgroup, which also included 4 implants (right first molar, right lateral incisor, left lateral incisor, and left first molar). Three methods were used to record implant location in these 3 subgroups: conventional impression making using the open-tray splinted technique (group CNV), intraoral scanning with the use of conventional scan bodies (group IOS-C), and intraoral scanning using newly modified scan bodies (group IOS-M). To assess accuracy, the best-fit algorithm was used, and root mean square (RMS) values were calculated. Descriptive statistics, including the median, interquartile range, and minimum and maximum values, were used to summarize the variables. Accuracy among different groups was compared, and the influence of the number of implants and the scan distance on the accuracy of group IOS-M was investigated. Appropriate methods were chosen based on the examination of normal distribution and homogeneity of variance, with 1-way analysis of variance (ANOVA) and the Tukey multiple comparison test for data normally (or log-normally) distributed and having equal variances and the Brown-Forsythe ANOVA test and Dunnett T3 multiple comparisons test for data normally (or log-normally) distributed but having unequal variances (α=.05). For data that did not follow a normal or log-normal distribution, the nonparametric Kruskal-Wallis test and Dunn multiple comparisons test was used. RESULTS: The trueness of group IOS-M ranged from 15.5 to 37.5 µm, with a median (Q1, Q3) of 22.8 (20.3, 25.5) µm, better than that of group IOS-C (P<.001), ranging from 10.1 to 110.0 µm, with a median (Q1, Q3) of 32.1 (26.3, 47.6) µm. Although the trueness of group IOS-M was worse than group CNV (P<.001), ranging from 6.7 to 22.5 µm, with a median (Q1, Q3) of 14.9 (10.5, 17.8) µm, it was within the threshold deemed acceptable to produce clinically suitable complete arch restorations (<59 to 72 µm). The precision of group IOS-M, ranging from 7.2 to 40.8 µm, with a median (Q1, Q3) of 19.5 (16.4, 23.0) µm, was better than that of group IOS-C (P<.001), ranging from 9.8 to 86.8 µm, with a median (Q1, Q3) of 33.7 (25.2, 44.5) µm, but not as good as group CNV (P<.001), ranging from 7.0 to 34.3 µm, with a median (Q1, Q3) of 18.8 (14.3, 21.4) µm. No significant difference in accuracy was found in group IOS-M among subgroups 6-246, 4-26, and 4-24 (P>.05). CONCLUSIONS: For complete arch implant scans, the modified scan body significantly improved the accuracy of intraoral scanning, with trueness <59 to 72 µm (threshold deemed acceptable to produce clinically suitable complete arch restorations). The accuracy of intraoral scanning using the modified scan bodies was not affected by the number of implants or the scan distance.
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Macroporous resin column chromatography, MCI medium pressure column chromatography, and semi-preparative high performance liquid chromatography were employed to isolate the chemical components from the aqueous extract of the whole herb of Scindapsus officinalis. The structures of the compounds were identified based on the physical and chemical properties and the spectroscopic data. Ten compounds were isolated from the aqueous extract and identified as 3,4-dihydroxyphenylethyl-8-O-[ß-D-apiofuranosyl-(1â4)]-ß-D-glucopyranoside(1), alternamide B(2), 3,4-dihydroxyphenylethyl-O-ß-D-glucopyranoside(3), 1-(4-hydroxy)-phenylethyl-ß-D-galactopyranoside(4), 3,4-dihydroxyphenylethyl-8-O-[ß-D-apiofuranosyl-(1â2)]-ß-D-glucopyranoside(5), hydroxytyrosol-4-O-ß-D-glucopyranoside(6), 3,5-dihydroxyphenylethyl-3-O-ß-D-glucopyranoside(7), salidroside(8), dihydroisoquinolone(9), and 4-methoxybenzenepropanol-3-O-ß-D-glucopyranoside(10). Among them, compound 1 was a new one, and compounds 2-10 were obtained from S. officinalis for the first time. The RAW264.7 cells were exposed to lipopolysaccharide for the mode-ling of inflammation, and the cells were then used to examine anti-inflammatory activities of the compounds. The results showed that compounds 6 and 7 had strong anti-inflammatory activities, while compounds 1, 2, and 5 had moderate anti-inflammatory activities.
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Anti-Inflamatórios , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta PressãoRESUMO
With the sharp rise of antibiotic-resistant pathogens worldwide, it is of enormous importance to create new strategies for combating pathogenic bacteria. Here, we create an iron oxide-based spiky artificial peroxidase (POD) with V-O-Fe pair sites (V-Fe2 O3 ) for combating methicillin-resistant Staphylococcus aureus (MRSA). The experimental studies and theoretical calculations demonstrate that the V-Fe2 O3 can achieve the localized "capture and killing" bifunction from the spiky morphology and massive reactive oxygen species (ROS) production. The V-Fe2 O3 can reach nearly 100 % bacterial inhibition over a long period by efficiently oxidizing the lipid membrane. Our wound disinfection results identify that the V-Fe2 O3 can not only efficiently eliminate MRSA and their biofilm but also accelerate wound recovery without causing noticeable inflammation and toxicity. This work offers essential insights into the critical roles of V-O-Fe pair sites and localized "capture and killing" in biocatalytic disinfection and provides a promising pathway for the de novo design of efficient artificial peroxidases.
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Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Peroxidases , BiofilmesRESUMO
Tuning the interfacial structure of metal oxide substrates is an essential strategy to induce electronic structure reconstruction of supported catalysts, which is of great importance in optimizing their catalytic activities. Herein, vanadium oxides-supported Ir catalysts (Ir-V2O3, Ir-VO2, and Ir-V2O5) with different interfacial bonding environments (Ir-V, Ir-Obri, and Ir-O, respectively) were investigated for hydrogen evolution reaction (HER). The regulating mechanism of the influence of different interfacial bonding environments on HER activity was investigated by both experimental results and computational evidence. Benefiting from the unique advantages of interfacial Ir-V direct metal bonds in Ir-V2O3, including enhanced electron transfer and electron donation ability, an optimized HER performance can be obtained with lowest overpotentials of 16 and 26â mV at 10â mA cm-2, high mass activities of 11.24 and 6.66â A mg-1, and turnover frequency values of 11.20 and 6.63â s-1, in acidic and alkaline conditions respectively. Furthermore, the assembled Ir-V2O3||RuO2 anion exchange membrane (AEM) electrolyzer requires only 1.92â V to achieve a high current density of 500â mA cm-2 and realizes long-term stability. This study provides essential insights into the regulating mechanism of interfacial chemical bonding in electrocatalysts and offers a new pathway to design noble metal catalysts for different applications.
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Previous investigations have reported on the ability of copper (Cu)-bearing biomaterials to accelerate vascular formation and bone regeneration. However, few studies have explored the effects of Cu-bearing materials on the interactions between angiogenesis and osteogenesis. Therefore, in this study, we prepared Cu-containing alloys using selective laser melting (SLM) technology and investigated the impact of preosteoblasts seeded on Ti6Al4V-4.5Cu alloy on angiogenesis. Our results indicated that Ti6Al4V-4.5Cu alloys increased the expression of proangiogenic genes and proteins in preosteoblasts, which further stimulated vascular formation in endothelial cells. Besides, we discovered that the biological effects of the Ti6Al4V-4.5Cu alloy were partly attributed to the release of Cu ions. In short, our research demonstrated the ability of Ti6Al4V-4.5Cu alloys to promote the coupling of angiogenesis and osteogenesis by releasing Cu ions.
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Osteogênese , Titânio , Titânio/farmacologia , Cobre/farmacologia , Células Endoteliais , Ligas/farmacologia , ÍonsRESUMO
Tuning the microenvironment and electronic structure of support materials is essential strategy to induce electron transfer between supports and active centers, which is of great importance in optimizing catalytic kinetics. In this study, the molybdenum oxycarbide supported Rh-clusters are synthesized with modulated interstitial C-O microenvironments (Rh/MoOC) for promoting efficient hydrogen evolution in water splitting. Both electronic structure characterizations and theoretical calculations uncover the apparent charge transfer from Rh to MoOC, which optimizes the d-band center, H2 O adsorption energy, and hydrogen binding energy, thus enhancing its intrinsic hydrogen-evolving activities. In addition, the co-occurrence of interstitial C and O atoms in MoOC supports plays a vital role in the dissociation reaction of water during the hydrogen-evolving process. Impressively, the Rh/MoOC exhibits excellent hydrogen-evolving activities in terms of exceptional turnover frequency values (11.4 and 39.41 H2 s-1 in alkaline and acidic media) and mass activities (21.3 and 73.87 A mg-1 in alkaline and acidic media) at an overpotential of 100 mV, which is more than 40 times higher than that of the benchmark commercial Rh/C catalysts. This work sheds new light on designing water dissociation materials that surpasses most of the reported catalysts.
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Synchronized lasers working at different wavelengths are of great significance for numerous applications, such as high-energy femtosecond pulse emission, Raman microscopy, and precise timing distribution. Here, we report synchronized triple-wavelength fiber lasers working at 1, 1.55, and 1.9 µm, respectively, by combining the coupling and injection configurations. The laser system consists of three fiber resonators gained by ytterbium-doped fiber, erbium-doped fiber, and thulium-doped fiber, respectively. Ultrafast optical pulses formed in these resonators are obtained by passive mode-locking with the use of a carbon-nanotube saturable absorber. A maximum cavity mismatch of â¼1.4 mm is reached by the synchronized triple-wavelength fiber lasers in the synchronization regime by finely tuning the variable optical delay lines incorporated in the fiber cavities. In addition, we investigate the synchronization characteristics of a non-polarization-maintaining fiber laser in an injection configuration. Our results provide a new, to the best of our knowledge, perspective on multi-color synchronized ultrafast lasers with broad spectral coverage, high compactness, and a tunable repetition rate.
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CdS nanoparticles were introduced on E. coli cells to construct a hydrogen generating biohybrid system via the biointerface of tannic acid-Fe complex. This hybrid system promotes good biological activity in a high salinity environment. Under light illumination, the as-synthesized biohybrid system achieves a 32.44 % enhancement of hydrogen production in seawater through a synergistic effect.
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Escherichia coli , Nanopartículas , Semicondutores , HidrogênioRESUMO
BACKGROUND: High serum CA19-9 is usually caused by pancreaticobiliary malignancies, but it has also been found in a tiny minority of calculous cholecystitis patients. AIMS: To clarify the relationship between calculous cholecystitis and serum CA19-9. METHODS: Clinical data of calculous cholecystitis patients with high serum CA19-9 (high group, n = 20) and normal serum CA19-9 (normal group, n = 40) who underwent cholecystectomy were analyzed. Serum CA19-9 of high group were followed-up and gallbladder specimens were analyzed by immunohistochemistry. RESULTS: Serum CA19-9 in the high group ranged from 105 to 1635 U/ml, of which 30% exceeded 1000 U/ml. Follow-up results showed that 20 patient's serum CA19-9 returned to normal after cholecystectomy, including 4 closely followed-up patients whose serum CA19-9 recovered within one month. Immunohistochemical results revealed that CA19-9 was mildly positive only in mucosal epithelial cells in the normal group, but positive in mucosal epithelial cells, vascular endothelial cells, and intercellular substances in the high group, accounting for high serum CA19-9. CONCLUSION: Serum CA19-9 is proved to be associated with calculous cholecystitis for the first time, so that clinicians should consider calculous cholecystitis associated CA19-9 elevation in the clinic practice besides other CA19-9 related diseases.
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Antígeno CA-19-9 , Colecistectomia , Colecistite , Humanos , Colecistite/cirurgia , Antígeno CA-19-9/sangue , Biomarcadores Tumorais , Resultado do Tratamento , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Vesícula Biliar/patologiaRESUMO
Colorectal cancer (CRC) ranks third in cancer incidence and second in cancer mortality globally. MicroRNAs (miRNAs) are promising biomarkers and therapeutic targets for CRC diagnosis and treatment. The miR-155 is reported to induce radiation resistance in CRC. In this study, we aimed to further clarify the role and underlying mechanism of the miR-155 in CRC cell malignancy. We found that miR-155 was significantly up-regulated in CRC tissues. The results of loss-of-function experiments revealed that miR-155 deficiency suppressed the proliferative capacity, invasion, and migration of CRC cells. Moreover, the downstream target genes of miR-155 were screened, and miR-155 was demonstrated to directly bind to FOXO3a in CRC cells to negatively regulate FOXO3a expression. FOXO3a was downregulated in CRC tissues and the expression of FOXO3a and miR-155 was in negative correlation in CRC tissues. FOXO3a overexpression alone was revealed to inhibit CRC cell growth, migration and invasion. Additionally, rescue assays showed that FOXO3a silencing significantly reversed the inhibitory effect of miR-155 deficiency on CRC cell malignant behaviors. In conclusion, miR-155 induces malignant phenotypes of CRC cells including cell proliferation, migration and invasion by targeting FOXO3a, which might provide clues for the targeted therapy of CRC.
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Neoplasias Colorretais , Proteína Forkhead Box O3 , MicroRNAs , Humanos , Carcinogênese/genética , Carcinógenos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/patologia , Proteína Forkhead Box O3/genéticaRESUMO
STATEMENT OF PROBLEM: The conventional workflow for the fabrication of implant-supported fixed complete dentures (IFCDs) is complex and makes it impossible to maintain jaw relationships. A fully digital workflow might solve this problem. PURPOSE: The purpose of this clinical study was to develop a completely digital workflow aided by a cone beam computed tomography (CBCT) scan for the fabrication of IFCDs and to evaluate the accuracy of this workflow with regard to the maintenance of jaw relationships. MATERIAL AND METHODS: All participants received a preoperative CBCT scan while wearing radiographic diagnosis dentures and occluding in the maximum intercuspal position. After the implant surgery, CBCT scanning, intraoral scanning, and stereophotogrammetry were performed to identify jaw anatomy, soft tissue, and the 3-dimensional (3D) locations of the implants, respectively. Then, all data were merged to transfer jaw relationships and generate digital casts to fabricate interim prostheses. A posttreatment CBCT scan was performed while the participants were wearing the interim prostheses and occluding in the maximum intercuspal position. The preoperative and postoperative jaw relationships were compared by CBCT cephalometric analysis. A meaningful and unacceptable difference was defined as 0.8 degrees and 2.4 degrees, respectively. RESULTS: Six participants (6 jaw relationships, 9 arches, and 58 implants) were included. All interim prostheses were stable and achieved symmetric occlusion after only minimal adjustment. A total of 18 angles were measured. Three angles revealed a meaningful minimal difference, and 1 angle revealed an unacceptable minimal difference. No prosthodontic complications were reported during the study. CONCLUSIONS: A completely digital workflow for fabricating IFCDs achieved sufficient accuracy for the maintenance of jaw relationships throughout the treatment.
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Desenho Assistido por Computador , Implantes Dentários , Humanos , Fluxo de Trabalho , Tomografia Computadorizada de Feixe Cônico , Prótese Total , Implantação Dentária Endóssea/métodosRESUMO
STATEMENT OF PROBLEM: Conventional impression techniques for complete arch implant-supported prostheses are technique-sensitive. Stereophotogrammetry (SPG) and intraoral scanning (IOS) may offer an alternative to conventional impression making. PURPOSE: The purpose of this prospective study was to compare the accuracy of IOS and SPG for complete arch implant scans and to evaluate the passive fit of frameworks fabricated with SPG. MATERIAL AND METHODS: Laboratory scanning of gypsum casts, SPG, and IOS were performed for all participants. The data regarding the abutment platform were superimposed to calculate the 3D deviation of SPG and IOS compared with that of laboratory scanning as an evaluation of accuracy. The effect of implant position and number on accuracy was analyzed. The more accurate technique between SPG and IOS was used to fabricate the titanium frameworks, as was laboratory scanning. The passive fit of the frameworks was assessed by clinical examination, the Sheffield test, and panoramic radiography. RESULTS: Seventeen participants (21 arches, 120 implants) were included. The accuracy of SPG ranged from 2.70 µm to 92.80 µm, with a median (Q1, Q3) of 17.00 (11.68, 22.50) µm, which was significantly more accurate than that of IOS, ranging from 21.30 µm to 815.60 µm, with a median (Q1, Q3) of 48.95 (34.78, 75.88) µm. No significant correlation was found between position or number of implants and 3D deviation in the SPG group. A weak positive correlation was found between implant number and 3D deviation in the IOS group. SPG and laboratory scanning were used to fabricate titanium frameworks. The passive fit between the frameworks and abutment platforms was confirmed. CONCLUSIONS: SPG, which was not affected by position or number of implants, was more accurate than IOS and comparable with laboratory scanning. The frameworks fabricated based on SPG and laboratory scanning were comparable in their passive fit. The SPG technique may be an alternative to laboratory scanning for complete arch implant scans.
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Implantes Dentários , Humanos , Estudos Prospectivos , Titânio , Desenho Assistido por Computador , Prótese Dentária Fixada por Implante , Técnica de Moldagem Odontológica , Imageamento TridimensionalRESUMO
OBJECTIVE: Altered metabolites are important for the tumourigenicity of hepatocellular carcinoma (HCC). We performed integrative metabolomics analysis of the metabolites changes in portal venous blood and in comparison with the metabolites changes in liver tissues and stool samples of HCC patients and healthy liver donors. DESIGN: Serum (portal and central vein), liver tissue (HCC tumour and adjacent non-tumour, normal liver) and stool samples were collected from 102 subjects (52 HCC patients and 50 healthy controls) in the discovery cohort; and 100 subjects (50 HCC patients and 50 healthy controls) in an independent validation cohort. Untargeted metabolomic profiling was performed using high-performance liquid chromatography-mass spectrometry. The function of candidate metabolites was validated in hepatocyte cell lines. RESULTS: Detailed metabolomic evaluation showed distinct clusters of metabolites in serum, liver tissue and stool samples from patients with HCC and control individuals (p<0.001). HCC patients had significantly higher levels of portal vein serum and HCC tissue metabolites of DL-3-phenyllactic acid, L-tryptophan, glycocholic acid and 1-methylnicotinamide than healthy controls, which were associated with impaired liver function and poor survival. On the other hand, HCC patients had lower levels of linoleic acid and phenol in portal vein and stool samples than healthy controls. Linoleic acid and phenol significantly inhibited HCC proliferation, inferring their anti-HCC function as protective metabolites. CONCLUSIONS: The integrative metabolome analysis of serum, tissue and stool metabolites revealed unreported metabolic alterations in HCC patients. In portal vein, we identified elevated and depleted metabolites signifying that they might play a role in HCC development.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/metabolismo , Humanos , Ácido Linoleico , Neoplasias Hepáticas/metabolismo , Metaboloma , Metabolômica/métodos , Fenóis , Veia PortaRESUMO
BACKGROUND: Deep-sea mussels living in the cold seeps with enormous biomass act as the primary consumers. They are well adapted to the extreme environment where light is absent, and hydrogen sulfide, methane, and other hydrocarbon-rich fluid seepage occur. Despite previous studies on diversity, role, evolution, and symbiosis, the changing adaptation patterns during different developmental stages of the deep-sea mussels remain largely unknown. RESULTS: The deep-sea mussels (Bathymodiolus platifrons) of two developmental stages were collected from the cold seep during the ocean voyage. The gills, mantles, and adductor muscles of these mussels were used for the Illumina sequencing. A total of 135 Gb data were obtained, and subsequently, 46,376 unigenes were generated using de-novo assembly strategy. According to the gene expression analysis, amounts of genes were most actively expressed in the gills, especially genes involved in environmental information processing. Genes encoding Toll-like receptors and sulfate transporters were up-regulated in gills, indicating that the gill acts as both intermedium and protective screen in the deep-sea mussel. Lysosomal enzymes and solute carrier responsible for nutrients absorption were up-regulated in the older mussel, while genes related to toxin resistance and autophagy were up-regulated in the younger one, suggesting that the older mussel might be in a vigorous stage while the younger mussel was still paying efforts in survival and adaptation. CONCLUSIONS: In general, our study suggested that the adaptation capacity might be formed gradually during the development of deep-sea mussels, in which the gill and the symbionts play essential roles.
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Mytilidae , Transcriptoma , Animais , Brânquias/metabolismo , Metano/metabolismo , SimbioseRESUMO
Aims: To investigate the prognostic value of hemoglobin combined with geriatric nutritional risk index (GNRI) scores in patients undergoing postoperative radiotherapy for esophageal squamous cell carcinoma (ESCC). Patients & methods: Patients who underwent esophagectomy and postoperative radiotherapy were included in this retrospective study. Their preoperative hemoglobin and GNRI were collected to establish hemoglobin-GNRI (H-GNRI) scores, and their association with OS was evaluated. Results: Patients with high H-GNRI scores had better prognosis than those with low scores (p < 0.001). Differentiation (p = 0.001), T classification (p = 0.010), N classification (p = 0.001) and H-GNRI score (p = 0.018) were independent prognostic factors for all patients. Conclusion: H-GNRI score is an independent prognostic factor for the survival of patients with ESCC managed by surgery and postoperative radiotherapy.
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Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Hemoglobinas/análise , Desnutrição/epidemiologia , Avaliação Nutricional , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/sangue , Carcinoma de Células Escamosas do Esôfago/complicações , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia , Feminino , Seguimentos , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Desnutrição/sangue , Desnutrição/diagnóstico , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: This study aimed to explore the effects of metformin on osteogenic differentiation of alveolar bone marrow mesenchymal stem cells (BMSCs) from type-2 diabetes mellitus (T2DM) patients (DM-BMSCs) and implant osseointegration in rats, screen the optimal concentration, and investigate whether metformin could protect against the adverse impact of T2DM on BMSC osteogenic capacity. SUBJECTS AND METHODS: Different concentrations of metformin were administered to human-derived BMSCs and Wistar rats receiving implants. ALP detection, alizarin red staining, real-time RT-PCR and Western blotting were performed to detect osteogenesis and investigate the mechanism. Toluidine blue staining was performed to analyse bone-implant contact in rats. RESULTS: Metformin increased implant osseointegration in a rat model and promoted the osteogenic capacity of DM-BMSCs via the AMPK/BMP/Smad signalling pathway, and 125 µM was the optimal concentration; however, concentrations over 200 µM, metformin showed an inhibitory effect on DM-BMSCs. Additionally, metformin at the optimal concentration (125 µM) identified in this study could compensate for the negative impacts of T2DM on the osteogenic differentiation of BMSCs. CONCLUSIONS: Metformin can promote the osteogenesis of BMSCs from T2DM patients and osseointegration in rats, and it might be an effective drug for increasing the success rate of T2DM-associated implants.