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The selective hydrogenation of biomass derivatives presents a promising pathway for the production of high-value chemicals and fuels, thereby reducing reliance on traditional petrochemical industries. Recent strides in catalyst nanostructure engineering, achieved through tailored support properties, have significantly enhanced the hydrogenation performance in biomass upgrading. A comprehensive understanding of biomass selective upgrading reactions and the current advancement in supported catalysts is crucial for guiding future processes in renewable biomass. This review aims to summarize the development of supported nanocatalysts for the selective hydrogenation of the US DOE's biomass platform compounds derivatives into valuable upgraded molecules. The discussion includes an exploration of the reaction mechanisms and conditions in catalytic transfer hydrogenation (CTH) and high-pressure hydrogenation. By thoroughly examining the tailoring of supports, such as metal oxide catalysts and porous materials, in nano-supported catalysts, we elucidate the promoting role of nanostructure engineering in biomass hydrogenation. This endeavor seeks to establish a robust theoretical foundation for the fabrication of highly efficient catalysts. Furthermore, the review proposes prospects in the field of biomass utilization and address application bottlenecks and industrial challenges associated with the large-scale utilization of biomass.
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Heterojunctions play a crucial role in improving the absorption of visible light and performance of photocatalysts for organic contaminants degradation in water. In this work, a novel type-II-II Ag2CO3/Bi2WO6 (AB) heterojunction was synthesized by hydrothermal reaction and in situ-precipitation methods. The mechanisms of charge transfer and carrier separation at the interface of heterojunctions and the influence on the photocatalytic activity were investigated. The degradation of levofloxacin (LEV) under visible light irradiation was employed to evaluate the photocatalytic performance of AB. The results showed that 85.4% LEV was degraded by AB, which was 1.38 and 1.39 times higher than that of Bi2WO6 and Ag2CO3, respectively. The work functions of the different crystal planes in the AB heterojunction, which was calculated by density functional theory, are a significant difference. The Fermi energy (Ef) of Ag2CO3 (- 6.005 eV) is lower than Bi2WO6 (- 3.659 eV), but the conduction band (CB) is higher. Therefore, using AB heterojunctions as an example, the research explored the mechanism of type-II-II which CB and Ef of one semiconductor cannot simultaneously surpass those of another material, based on the built-in electric field theory. Through this analysis, a deeper understanding of type-II heterojunctions was achieved, and providing valuable insights into the behavior of this specific heterojunction system.
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To explore the effect of periodontal disease on the progression of diabetic kidney disease (DKD), to observe the effects of artesunate (ART) intervention on periodontal and kidney tissues in type 1 diabetic rats with periodontitis, and to explore the possibility of ART for the treatment of DKD. Rat models of diabetes mellitus, periodontitis, and diabetes mellitus with periodontitis were established through streptozotocin (STZ) intraperitoneal injection, maxillary first molar ligation, and P. gingivalis ligation applied sequentially. Ten weeks after modeling, ART gavage treatment was given for 4 weeks. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were used to investigate the inflammatory factors, fibrogenisis, autophagy-related factors, and proteins in periodontal and kidney tissues, and 16S rDNA sequencing was used to detect the changes in dental plaque fluid and kidney tissue flora. Compared to the control group, the protein expression levels of transforming growth factor ß1 (TGF-ß1) and COL-IV in the periodontal disease (PD) group were increased. The protein expression of TGF-ß1, Smad3, and COL-IV increased in the DM group and the DM + PD group, and the expression of TGF-ß1, Smad3, and COL-IV was upregulated in the DM + PD group. These results suggest that periodontal disease enhances renal fibrosis and that this process is related to the TGF-ß1/Smad/COL-IV signaling pathway. Among the top five dominant bacteria in the kidney of the DM + PD group, the abundance of Proteobacteria increased most significantly, followed by Actinobacteria and Firmicutes with mild increases. The relative abundance of Proteobacteria, Actinobacteria, and Firmicutes in the kidney tissues of DM and PD groups also showed an increasing trend compared with the CON group. Proteobacteria and Firmicutes in the kidney of the PD group and DM + PD group showed an increasing trend, which may mediate the increase of oxidative stress in the kidney and promote the occurrence and development of DN. Periodontal disease may lead to an imbalance of renal flora, aggravate renal damage in T1DM, cause glomerular inflammation and renal tubulointerstitial fibrosis, and reduce the level of autophagy. ART delays the process of renal fibrosis by inhibiting the TGF-ß-Smad signaling pathway.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) causes severe bone loss after tooth extraction as a hyperglycemic environment causes aberrant bone homeostasis. Artesunate (ART) is known to possess anti-inflammation and osteogenic properties. However, its osteogenesis property in alveolar bone remains unclear. This study aimed to explore the osteogenic and immunoregulatory effects of artesunate-loaded thermosensitive chitosan hydrogel (ART-loaded TCH) on maxilla tooth extraction in T2DM rats. METHODS: T2DM rats were induced by a high-fat diet and streptozotocin. Different concentrations of ART-loaded TCH were applied in tooth extraction sockets. Bone loss and the expression of osteogenic regulatory factors (OPG, ALP, RANK) were evaluated. The immunoregulatory effects of ART-loaded TCH were observed through detecting the infiltration of T lymphocytes and their cytokines. The underlying mechanisms were explored. RESULTS: Results showed that the 150 mg/ml ART-loaded TCH group significantly ameliorated maxilla bone height and bone mineral density when compared with the T2DM group (p < 0.05). It also improved the expression of OPG, ALP, and RANK. Although the alteration of CD4+ T, CD8+ T, and CD4+:CD8+ T ratio has no significant difference among groups, the release of Th1 and Th2 in the 150 mg/ml ART-loaded TCH group has been significantly regulated than in the T2DM group (p < 0.05). Besides, ART-loaded TCH treatment inhibited the expression of p38 MAPK and ERK1 in T2DM maxilla. CONCLUSIONS: Therefore, the results indicated that 150 mg/ml ART-loaded TCH could be an effective method to prevent bone loss in T2DM tooth extraction rats by modulating the immunoregulation of Th1 and Th2 and the MAPK signaling pathway.
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Quitosana , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratos , Animais , Osteogênese , Hidrogéis/farmacologia , Quitosana/uso terapêutico , Quitosana/farmacologia , Artesunato/uso terapêutico , Artesunato/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Maxila , Linfócitos T/metabolismo , Extração Dentária/métodosRESUMO
Selective oxidations are important reactions in organic synthesis for fine chemical industry and conventional methods are expensive and produce a lot of toxic wastes. Herein, we demonstrate a facile and environmentally benign technique for liquid phase selective oxidation based on graphene-supported Mn single-atom-catalyst (SAMn-G) for efficient peroxymonosulfate (PMS) activation. The active Mn component in the developed SAMn-G catalyst reached single-atomic dispersion on graphene substrate via the coordination of individual Mn atoms with the doped N from the graphene framework. SAMn-G activated PMS via a nonradical-dominated pathway, which could convert aromatic alcohols into aldehydes or ketones at a mild temperature. The SAMn-G catalyst exhibited superior conversion and aldehyde selectivity in alcohol oxidation in comparison with their counterpart catalysts possessing either homogeneous Mn ions or oxide particles. The high activation efficiency of SAMn-G is due to the synergistic effect between Mn atoms and graphene substrate, as well as the dominated reaction pathway from nonradical oxidation, which is more selective than these free radicals to oxidize the alcohols. Concerted experimental evidence indicates that the non-radical oxidation process was highly possible to follow the electron transfer mechanism by PMS/organic adsorption on the surface of the catalyst. This study provides a fundamental understanding of PMS activation mediated by single atom catalyst for organic synthesis and the achieved insights can also help the catalyst design for other liquid phase selective oxidation processes.
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Background: The occurrence, progression, and prognosis of colorectal cancer (CRC) are regulated by EGFR-mediated signaling pathways. However, the relationship between the core genes (KRAS/NRAS/BRAF/PIK3CA) status in the signaling pathways and clinicopathological characteristics of CRC patients in Hakka population remains controversial. Methods: Patients were genotyped for KRAS (codons 12, 13, 61, 117, and 146), NRAS (codons 12, 61, 117, and 146), BRAF (codons 600), and PIK3CA (codons 542, 545 and 1047) mutations. Clinical records were collected, and clinicopathological characteristic associations were analyzed together with mutations of studied genes. Results: Four hundred and eight patients (256 men and 152 women) were included in the analysis. At least one mutation in the four genes was detected in 216 (52.9%) patients, while none was detected in 192 (47.1%) patients. KRAS, NRAS, BRAF, and PIK3CA mutation status were detected in 190 (46.6%), 11 (2.7%), 10 (2.5%), 34 (8.3%) samples, respectively. KRAS exon 2 had the highest proportion (62.5%). Age, tumor site, tumor size, lymphovascular invasion, and perineural invasion were not associated with gene mutations. KRAS mutations (adjusted OR 1.675, 95% CI 1.017-2.760, P=0.043) and NRAS mutations (adjusted OR 5.183, 95% CI 1.239-21.687, P=0.024) appeared more frequently in patients with distant metastasis. BRAF mutations (adjusted OR 7.224, 95% CI 1.356-38.488, P=0.021) and PIK3CA mutations (adjusted OR 3.811, 95% CI 1.268-11.455, P=0.017) associated with poorly differentiated tumor. Conclusion: KRAS/NRAS mutations are associated with distant metastasis and BRAF/PIK3CA mutations are associated with poor tumor differentiation in CRC. And the results provided a better understanding between clinicopathological characteristics and gene mutations in CRC patients.
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Multi-component pharmaceutical systems such as cocrystal and salt have gained popularity in academia and industry due to their ability to regulate the poor physicochemical properties of active pharmaceutical ingredients (APIs). However, different crystal states, namely polymorphs are becoming a key factor influencing future clinical drug safety. It remains an under explored field, particularly how to hit the polymorphs of multi-components system quickly and effectively. For the first time, a novel drug-drug salt of lamotrigine (LAM)-tolfenamic acid (TOL) with two polymorphs and two solvates were discovered in this study. Forms I and II exist in rhombohedral and block crystal morphologies, whereas methanol and ethanol solvates are crystallized as rods and flakes, respectively. Further physicochemical properties were characterized and compared between parent compounds and the four crystal forms. The apparent solubilities of the new four crystal forms were higher than TOL but lower than LAM. The intrinsic dissolution rates of all crystal forms at 37.0 °C followed a similar trend, and all crystal forms were non-hygroscopic (<1.0%). Two stable polymorphs provide a new choice for the further formulation development.
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Cristalização , Lamotrigina , Solubilidade , Preparações FarmacêuticasRESUMO
The assessment of population genetic structure is the basis for understanding the genetic information of indigenous breeds and is important for the protection and management of indigenous breeds. However, the population genetic differentiation of many local breeds still remains unclear. Here, we performed a genome-wide comparative analysis of Jinding, Liancheng white, Putian black, and Shanma ducks based on the genomic sequences using RAD sequencing to understand their population structure and genetic diversity. The population parameters showed that there were obvious genetic differences among the four indigenous breeds, which were separated groups. Among them, Liancheng white and Shanma ducks may come from the same ancestor because the phylogenetic tree forms three tree trunks. In addition, during the runs of homozygosity (ROH), we found that the average inbreeding coefficient of Liancheng white and Putian black ducks was the lowest and the highest, respectively. Five genomic regions were considered to be the hotspots of autozygosity among these indigenous duck breeds, and the candidate genes involved a variety of potential variations, such as muscle growth, pigmentation, and neuroregulation. These findings provide insights into the further improvement and conservation of Fujian duck breeds.
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BACKGROUND: The link between glutathione S-transferase P1 (GSTP1) c.313A > G polymorphism and chemotherapy-related adverse events remains controversial. The goal of this study was to assess how this variant affected the toxicity of anthracycline-/paclitaxel-based chemotherapy in patients with breast cancer. METHODS: This study retrospectively investigated pharmacogenetic associations of GSTP1 c.313A > G with chemotherapy-related adverse events in 142 breast cancer patients who received anthracycline and/or paclitaxel chemotherapy. RESULTS: There were 61 (43.0%), 81 (57.0%), 43 (30.3%), and 99 (69.7%) patients in the T0-T2, T3-T4, N0-N1, and N2-N3 stages, respectively. There were 108 (76.1%) patients in clinical stages I-III and 34 (23.9%) patients in clinical stage IV. The numbers of patients with luminal A, luminal B, HER2 + , and triple-negative breast cancer (TNBC) were 10 (7.0%), 77 (54.2%), 33 (23.2%), and 22 (15.5%), respectively. The numbers of patients who carried GSTP1 c.313A > G A/A, A/G, and G/G genotypes were 94 (66.2%), 45 (31.7%), and 3 (2.1%), respectively. There were no statistically significant differences in the proportion of certain toxicities in patients with A/G, G/G, and A/G + G/G genotypes, except for neutropenia, in which the proportion of patients with A/G + G/G (χ2 = 6.586, P = 0.035) genotypes was significantly higher than that with the AA genotype. The logistic regression analysis indicated that GSTP1 c.313A > G mutation (A/G + G/G vs. A/A genotype) (adjusted OR 4.273, 95% CI 1.141-16.000, P = 0.031) was an independent variable associated with neutropenia. CONCLUSIONS: The findings of this study indicate that the GSTP1 c.313A > G mutation is an independent risk factor for neutropenia hematotoxicity in breast cancer patients induced by anthracycline-/paclitaxel-based chemotherapy.
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Neoplasias da Mama , Neutropenia , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Glutationa Transferase/uso terapêutico , Humanos , Mutação , Neutropenia/induzido quimicamente , Neutropenia/genética , Paclitaxel/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Periodontitis is an inflammatory disease of the gums. Periodontitis in diabetic patients can aggravate insulin resistance; however, its molecular and biological mechanism remains unclear. This study aimed to explore the effects of diabetic periodontitis on liver function and determine the mechanism by which artesunate improves liver function. Rats with streptozotocin-induced diabetes were divided into five groups: normal control (NC), diabetic periodontitis (DM + PD), artesunate intervention (ART), insulin intervention (INS), and combined medication intervention (ART + INS) groups. Drug interventions were then administered to the rats in each group as follows: 50 mg/kg artesunate to the ART group, 6 U/kg insulin to the INS group, and 50 mg/kg artesunate + 6 U/kg insulin to the ART + INS group. Blood samples, liver tissues, and the maxillary alveolar bone were collected postsacrifice. ART was found to significantly ameliorate hyperglycemia, blood lipid concentrations, and liver function. The levels of inflammatory factors reduced; the effect was more pronounced in the ART + INS group. Artesunate presumably inhibits the TLR4/NF-κB signaling pathway and expression of downstream inflammatory factors, thereby exerting a protective effect on diabetes-related liver function. This offers a fresh approach to treat diabetes mellitus.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Periodontite , Animais , Artesunato/efeitos adversos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Insulina , Fígado , NF-kappa B/metabolismo , Periodontite/complicações , Periodontite/tratamento farmacológico , Periodontite/metabolismo , RatosRESUMO
Inflammation triggers pulmonary vascular remodelling. Ferroptosis, a nonapoptotic form of cell death that is triggered by iron-dependent lipid peroxidation and contributes to the pathogenesis of several inflammation-related diseases, but its role in pulmonary hypertension (PH) has not been studied. We examined endothelial cell ferroptosis in PH and the potential mechanisms. Pulmonary artery endothelial cells (PAECs) and lung tissues from monocrotaline (MCT)-induced PH rats were analysed for ferroptosis markers, including lipid peroxidation, the labile iron pool (LIP) and the protein expression of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and NADPH oxidase-4 (NOX4). The effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on endothelial cell ferroptosis and pulmonary vascular remodelling in MCT-induced rats were studied in vitro and in vivo. Ferroptosis was observed in PAECs from MCT-induced PH rats in vitro and in vivo and was characterized by a decline in cell viability accompanied by increases in the LIP and lipid peroxidation, the downregulation of GPX4 and FTH1 expression and the upregulation of NOX4 expression. High-mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signalling was measured by western blotting. These changes were significantly blocked by Fer-1 administration in vitro and in vivo. These results suggest that Fer-1 plays a role in inhibiting ferroptosis-mediated PAEC loss during the progression of PH. The ferroptosis-induced inflammatory response depended on the activation of HMGB1/TLR4 signalling, which activated the NLRP3 inflammasome in vivo. We are the first to suggest that pulmonary artery endothelial ferroptosis triggers inflammatory responses via the HMGB1/TLR4/NLRP3 inflammasome signalling pathway in MCT-induced rats. Treating PH with a ferroptosis inhibitor and exploring new treatments based on ferroptosis regulation might be promising therapeutic strategies for PH.
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Células Endoteliais/metabolismo , Ferroptose/efeitos dos fármacos , Hipertensão Pulmonar/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Toxinas Bacterianas/metabolismo , Células Cultivadas , Cicloexilaminas/farmacologia , Regulação para Baixo/efeitos dos fármacos , Ferroptose/genética , Proteína HMGB1/metabolismo , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Inflamação/metabolismo , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Monocrotalina/toxicidade , Fenilenodiaminas/farmacologia , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Piezocatalysis, a newly emerging catalysis technology that relies on the piezopotential and piezoelectric properties of the catalysts, is attracting unprecedented research enthusiasm for applications in energy conversion, organic synthesis, and environmental remediation. Despite the rapid development in the past three years, the mechanism of piezocatalysis is still under debate. A fundamental understanding of the working principles of this technology should enable the future design and optimization of piezocatalysts. Herein, we provide an overview of the two popular theories used to explain the observed piezocatalysis: energy band theory and screening charge effect. A comprehensive discussion and clarification of the differences, relevance, evidence, and contradiction of the two mechanisms are provided. Finally, challenges and perspectives for future mechanistic studies are highlighted. Hopefully, this Review can help readers gain a better understanding of piezocatalysis and enable its application in their own research.
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BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) acts as the key enzyme catabolizing pyrimidines, and may affect the tumor progression. DPYD gene mutations affect DPD activity. The relationship between DPYD IVS14+1G>A, c.1627A>G, c.85T>C and lymph node metastasis (LNM) and distant metastasis (DM) of colorectal cancer (CRC) was investigated. METHODS: A total of 537 CRC patients were enrolled in this study. DPYD polymorphisms were analyzed by polymerase chain reaction (PCR)-Sanger sequencing. The relationship between DPYD genotypes and clinical features of patients, metastasis of CRC was analyzed. RESULTS: About DPYD c.1627A>G, A/A (57.7%) was the most common genotype, followed by A/G (35.6%), G/G (6.7%) genotypes. In c.85T>C, T/T, T/C, and C/C genotypes are accounted for 83.6%, 16.0%, and 0.4%, respectively. Logistic regression analysis revealed that DPYD c.1627A>G A/G and G/G genotypes in the dominant model (A/G + G/G vs. A/A) were significant risk factors for the LNM (p = 0.029, OR 1.506, 95% CI = 1.048-2.165) and DM (p = 0.039, OR 1.588, 95% CI = 1.041-2.423) of CRC. In addition, DPYD c.1627A>G polymorphism was more common in patients with abnormal serum carcinoembryonic antigen (CEA) (>5 ng/ml) (p = 0.003) or carbohydrate antigen 24-2 (CA24-2) (>20 U/ml) level (p = 0.015). CONCLUSIONS: The results suggested that DPYD c.1627A>G A/G, G/G genotypes are associated with increased risk of LNM and DM of CRC.
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Neoplasias Colorretais , Di-Hidrouracila Desidrogenase (NADP)/genética , Predisposição Genética para Doença/genética , Metástase Linfática/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The selective oxidations of alcohols into corresponding aldehydes or ketones are essential reactions for organic synthesis. The development of facile, green and cost-effective protocols to accomplish selective oxidation is highly attractive. Here, we present the selective oxidation of alcohols using peroxymonosulfate (PMS) oxidants with N-doped graphene-like carbon (NG) synthesized via a metal-free approach without producing a large amount of hazardous wastes. In the tested selective oxidation reaction, over 96% of benzyl alcohol (BzOH) was converted into benzaldehyde (BzH) with high selectivity under mild conditions. The synthesized NG catalyst contains abundant electrophilic oxygen species, serving as the major active sites for the generation of reactive radicals from PMS to enable the selective oxidation of BzOH in the radical pathway. Besides, non-radical oxidation of BzOH occurs via the electron transfer through the surface coordinated complex, dominantly upon the N species. Particularly, the configuration of integrated pyridinic N is possible to create active domains for BzOH oxidation with activated PMS. This work opens a new avenue to convert metal-free raw materials into effectively functionalized carbon materials, coupled with their potential applications in the selective oxidation of alcohols.
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BACKGROUND: The concentration levels of major and trace elements are significantly correlated with human health. However, studies profiling major and trace elements among female using methamphetamine are rare. This study aims to investigate the major and trace elements changes and discover elemental biomarkers in plasma of female methamphetamine (METH) addicts in six months' compulsory treatment. METHODS: A total of 60 female METH addicts selected from drug rehabilitation center were randomly divided into three equal groups: (1) Detoxification for one month; (2) Detoxification for three months; (3) Detoxification for six months. Twenty healthy women, without drug abuse history were selected as control group. Four major elements including Na, Mg, K, Ca and twelve trace elements including V, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Sn, Pb were determined using inductively coupled plasma mass spectrometry (ICP-MS). The results were analyzed using One-way Analysis of Variance (ANOVA) and Student-Newman-Keuls (SNK test). Elemental biomarkers were discovered based on orthogonal partial least squares discriminant analysis (OPLS-DA). RESULTS: The four groups used in the study were divided into four significant sections according to scatter plots. The total elemental concentrations of three METH withdrawal groups were increased compared to the control group. Over six months, element contents of the withdrawal groups gradually equaled element contents of the control group in compulsory treatment. The variable importance in the projection values (VIP > 1) of OPLS-DA model and SNK test (p < 0.05) revealed Fe, Cu, Cr and Se as elemental biomarkers. CONCLUSION: Major and trace elements demonstrated significant differences between control group and three METH withdrawal groups. Fe, Cu, Cr and Se are potential elemental biomarkers among METH-abused female groups. Metabolic disorders of major and trace elements exist in the female methamphetamine addicts.
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Transtornos Relacionados ao Uso de Anfetaminas/reabilitação , Oligoelementos/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Espectrometria de Massas/métodos , Metanfetamina/efeitos adversos , Centros de Tratamento de Abuso de SubstânciasRESUMO
OBJECTIVE: Colorectal cancer (CRC) is one of the most common and lethal malignancies. The identification of precise and noninvasive biomarkers is urgently needed to aid the early diagnosis and clinical management of CRC. METHODS: A total of 112 patients with CRC and 115 healthy control subjects were included in this study. Serum levels of matrix metalloproteinase (MMP)-7, MMP-9, MMP-11, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were analyzed by enzyme-linked immunosorbent assay, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 levels were measured using an automatic immunoassay analyzer. RESULTS: MMP-7, MMP-9, MMP-11, TIMP-1, TIMP-2, CEA, and CA19-9 levels were all significantly higher in CRC patients compared with healthy controls. MMP-7, TIMP-1, and CEA levels were also closely related to clinicopathologic features in patients with CRC. The combination of serum CEA, MMP-7, and TIMP-1 significantly improved the diagnostic value compared with any single marker (area under the curve 0.858-0.890). Furthermore, a combined detection model including MMP-7, TIMP-1, and CEA improved both the specificity and sensitivity for detecting CRC. CONCLUSIONS: The results showed that combined detection of CEA, MMP-7, and TIMP-1 in serum could provide a specific and sensitive biomarker for the diagnosis of CRC.
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Antígeno Carcinoembrionário , Neoplasias Colorretais , Biomarcadores Tumorais , Antígeno CA-19-9 , Neoplasias Colorretais/diagnóstico , Humanos , Metaloproteinase 11 da Matriz , Metaloproteinase 7 da Matriz , Metaloproteinase 9 da Matriz , Prognóstico , Inibidor Tecidual de Metaloproteinase-1 , Inibidor Tecidual de Metaloproteinase-2RESUMO
The development of novel single atom catalyst (SAC) is highly desirable in organic synthesis to achieve the maximized atomic efficiency. Here, a Co-based SAC on nitrogen-doped graphene (SACo@NG) with high Co content of 4.1 wt% is reported. Various characterization results suggest that the monodispersed Co atoms are coordinated with N atoms to form robust and highly effective catalytic centers to activate peroxymonosulfate (PMS) for organic selective oxidation. The catalytic performance of the SACo@NG/PMS system is conducted on the selective oxidation of benzyl alcohol (BzOH) showing high efficiency with over 90% conversion and benzaldehyde selectivity within 180 min under mild conditions. Both radical and non-radical processes occurred in the selective oxidation of BzOH, but the non-radical oxidation plays the dominant role which is accomplished by the adsorption of BzOH/PMS on the surface of SACo@NG and the subsequent electron transfer through the carbon matrix. This work provides new insights to the preparation of efficient transition metal-based single atom catalysts and their potential applications in PMS mediated selective oxidation of alcohols.
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BACKGROUND: The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway. METHODS: A total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR. RESULTS: The results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05). CONCLUSIONS: ART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.
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Artesunato/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Hipoglicemiantes/uso terapêutico , Animais , Aorta Torácica/patologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/patologia , Cardiomiopatias Diabéticas/patologia , Lipídeos/sangue , Masculino , Miocárdio/patologia , NF-kappa B/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren's syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague-Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.