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1.
Water Res ; 178: 115842, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32361350

RESUMO

Due to complex composition of carbohydrates, lipid, protein, cellulose, hemicellulose and lignin, wastewater (WW) and organic fraction municipal solid waste (OFMSW) represent nutrient and carbon rich resources. Conventionally, value chains in the waste sector have considered OFMSW and WW as unwanted by-products as opposed to potential valuable resources. Full exploitation of these resources calls for a value chain transformation towards proactive resource recovery. This study focuses on the waste supply chain optimisation to recover value added products from OFMSW. The research leads to a systems-modelling approach, which integrates spatial data analyses, mathematical mixed integer linear programming (MILP) optimisation and technology performance evaluation to inform the design of waste-to-resource value chains. A UK based study on OFMSW is presented to demonstrate the efficacy of the approach. The study captures variation in OFMSW quantity and composition, incorporating over 600 existing anaerobic digestion (AD) operational plants in the UK, while potential sites for new waste-recovery facilities are identified, accounting for transportation and logistics, using a GIS-based analysis. Key outcomes are analysed (technology type, size, location, logistical connections), placing emphasis on the need to consider the value of the resource recovery potential over the lifetime of an AD or thermochemical treatment facility in the design process. Such an approach offers a promising pathway for tackling the open challenges currently hindering the waste-to-resource transformation.

2.
Sci Total Environ ; 713: 136359, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32019007

RESUMO

Consumer demand has increased for pastured poultry products as the drive for sustainable farming practices and ethical treatments of livestock have become popular in the press. It is necessary to identify the important meteorological factors associated with the prevalence of Salmonella in the pastured poultry settings since the presence of Salmonella in the environment could lead to contamination of the final product. The objective of this study was to develop a model to describe the relationship between meteorological factors and the presence of Salmonella on the pastured poultry farms. The random forest method was used to develop a model where 83 meteorological factors were included as the predicting variables. The soil model identified humidity as the most important variable associated with Salmonella prevalence, while high wind gust speed and average temperature were identified as important meteorological variables in the feces model. The developed models were robust in predicting the prevalence of Salmonella in pastured poultry farms with the area under receiver operating characteristic (ROC) curve values of 0.884 and 0.872 for the soil model and feces model, respectively. The predictive models developed in this study can provide users with practical and effective tools to make informed decisions with scientific evidence regarding the meteorological parameters that are important to monitor for increased on-farm Salmonella prevalence.


Assuntos
Salmonelose Animal , Salmonella , Animais , Fazendas , Conceitos Meteorológicos , Aves Domésticas , Prevalência , Sudeste dos Estados Unidos
3.
Rev Sci Instrum ; 91(1): 014103, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32012638

RESUMO

PC software-based portable cyclic voltammetry (PCV) systems have the advantages of portability, high performance, and real-time detection. In this paper, the PCV system used cyclic voltammetry (CV) as the main detection and analysis method and contained the following components: a three-electrode unit, a portable potentiostat, and PC software. The PC software was used as the system control and display, and a dynamic peak position adjustment (DPPA) algorithm for E. coli measurements based on thick biofilm modification on electrodes was designed especially for this system to realize the real-time correspondence between the measured results and the modified electrodes. The performance test results obtained by setting different detection parameters in the PCV system were compared with those of commercial electrochemical workstations. The difference was less than 4.99%, with a relative standard deviation less than 0.20%. An electrochemical biosensor based on a Prussian blue-multiwalled carbon nanotube-gold nanoparticle composite was developed for E. coli detection. After constructing an antibody-BSA-E. coli electrode modification on the sensor, experimental data processed by the DPPA algorithm showed that the logarithm (lg DfE.coli) of the E. coli dilution factor and the peak current response had a linear relationship. The PCV system could quickly and accurately detect E. coli concentrations with dynamic adjustment algorithms for biofilm-modified electrodes. Furthermore, the system could detect the electrochemical activities of various high-sensitivity biomolecules, showing great detection potential for on-site monitoring and meeting the requirements of real-time and portable detection in various food safety fields.

4.
Anim Reprod Sci ; 214: 106287, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32087914

RESUMO

Estrogen receptor alpha (ERα) is a ligand-activated transcription factor that regulates cellular responses to estrogens and transcription processes of target genes. In this study, changes in DNA methylation and histone modifications in the promoter region and Exon 1 of the ERα gene were analyzed to ascertain epigenetic changes associated with increased ERα mRNA abundance during reproductive maturation from 90 (egg production not yet initiated) to 160 (after egg production was initiated) d of age (d post-hatching) in chicken ovaries. The results indicate there was no difference in CpG methylation at the promoter and Exon 1 except at the region analyzed with primer pairs F2 and R2, where percentage of methylated CpG of Sites 2 and 8 after reproductive maturation was greater compared with before reproductive maturation. By using the chromatin immunuoprecipitation (ChIP) assay combined with SYBR green quantitative PCR, effects of histone modifications were evaluated, including histone H3K4 di + tri methylation, H3K9 phosphorylation and trimethylation, H3K36 methylation and H3K27 acetylation on chicken ERα mRNA transcript abundance. The results indicated that there was a greater histone H3K27 acetylation and lesser H3K36 trimethylation associated with increased abundance of ERα mRNA transcript in chicken ovaries after reproductive maturation (90 compared with 160 d of age). In consistent with this finding, the relative abundance of transcriptional coactivator p300 mRNA transcript and protein in the ovaries was markedly greater in reproductively mature than immature chickens. Findings provide insights into the epigenetic regulations of the chicken ERα gene expression that is required for chicken ovarian development.

5.
Nanotechnology ; 31(16): 165403, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-31891915

RESUMO

Flexible all-solid-state supercapacitors (ASSSs) have caught the scientific attention to meet the explosive demand for portable and wearable electronic devices. However, it is difficult for flexible electrode materials to obtain a high areal capacitance at a high mass loading, which limits their commercial applications. In this study, vanadium oxide (V2O5) nanoparticles are introduced into Ti3C2 flakes with the aid of cetyltrimethylammonium bromide (CTAB). The intercalation of V2O5 particles in the interlayer of Ti3C2 establishes a hierarchical structure and facilitates the electrolyte penetration. As a result, the prepared CT-Ti3C2@V2O5 composite electrode achieves a high areal capacitance of 2065 mF cm-2 at 3 mA cm-2 and superior active mass loading (15 mg cm-2). Meanwhile, over 93% capacitance is maintained after 6000 cycles at 18 mA cm-2. The ASSS based on CT-Ti3C2@V2O5 delivers a high areal capacitance of 477 mF cm-2 at 1 mV s-1 and exhibits stable performance at different bending states, which reaches to the advanced level for the ASSSs based on MXenes.

6.
Int J Mol Med ; 45(2): 623-633, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894313

RESUMO

The objective of the present study was to investigate the molecular mechanism underlying the role of metformin (Met) in reducing the risk of endometrial hyperplasia (EH). Reverse transcription­quantitative polymerase chain reaction, western blot and immunohistochemistry (IHC) assays were used to study the effects of Met and tamoxifen on the expression levels of urothelial cancer associated 1 (UCA1), microRNA­144 (miR­144) and other factors along the transforming growth factor­ß1 (TGF­ß1)/protein kinase B (AKT) signaling pathway. In addition, MTT and flow cytometry assays were performed to detect the effect of Met on cell proliferation and apoptosis. Tamoxifen treatment increased the weight of the uterus and the level of UCA1, while decreasing the expression of miR­144. In addition, treatment with tamoxifen (2.0 and 3.5 µg) upregulated the protein expression levels of TGF­ß and p­AKT, while downregulating the protein expression of active Caspase­3 in a dose­dependent manner. By contrast, Met reduced cell viability, promoted cell apoptosis, and reduced the expression levels of UCA1, TGF­ß and p­AKT, while upregulating the expression of miR­144 and active Caspase­3 in a dose­dependent manner. Furthermore, Met also reduced the weight of uterus. However, tamoxifen and Met did not exert any effect on the protein levels of total AKT and total Caspase­3. The levels of TGF­ß and p­AKT proteins in the EH group were much higher when compared with those in the sham group, while Met treatment reduced these protein levels to a certain extent. In addition, the expression of active Caspase­3 in the EH group was much lower than that in the sham group, while Met treatment increased its level to a certain extent. In conclusion, the current study suggested that Met reduces the risk of EH by reducing the expression levels of UCA1, TGF­ß and p­AKT, while increasing the levels of miR­144 and active Caspase­3 in a dose­dependent manner.

7.
Neurol Res ; 42(1): 47-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31900069

RESUMO

Objective: Long non-coding RNAs (lncRNAs) are theorized to serve a critical role in cerebral ischemia/reperfusion injury. The purpose of this study was to determine whether knockdown of lncRNA SNHG1 protected against oxygen-glucose deprivation/reperfusion (OGD/R)-induced cell death in vitro and to investigate the underlying mechanisms. Methods: The expression levels of SNHG1 and miR-424 were detected by RT-qPCR analysis. The expression levels of apoptosis-related proteins were detected by western blot analysis. Cell viability and apoptosis were detected by MTT assay and flow cytometric analysis, respectively. Bioinformatic prediction and dual-luciferase reporter assay were performed to study the interaction between SNHG1 and miR-424. Results: The results showed that SNHG1 expression level was increased in OGD/R-treated SH-SY5Y cells, and knockdown of SNHG1 alleviates OGD/R-induced apoptosis and mitochondrial dysfunction in SH-SY5Y cells. Moreover, we found that SNHG1 might serve as a ceRNA for miR-424 in SH-SY5Y cells, and rescue experiments further confirmed that miR-424 inhibitor blocked the beneficial role of SNHG1 knockdown in OGD/R-treated SH-SY5Y cells. Conclusion: Taken together, this research supported the first evidence that lncRNA SNHG1 regulates OGD/R-induced cell death through serving as a ceRNA for miR-424 in SH-SY5Y cells.

8.
Clin Neurophysiol ; 131(1): 54-62, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31751840

RESUMO

OBJECTIVE: There is increasing evidence of cognitive impairment (CI) frequently occurring in patients with multiple system atrophy (MSA); however, the neurobiological mechanisms underlying CI in patients with MSA remain unclear. METHODS: We enrolled 61 patients with probable MSA and 33 healthy controls (HC). We used degree centrality (DC) analysis to assess changes in the centrality level of MSA-CI related brain nodes. We conducted a secondary seed-based functional connectivity (FC) analysis to investigate dysfunctions in cognitive networks related to MSA. Further, we analysed the correlation between clinical symptoms and acquired connectivity measures. RESULTS: Compared with HC, patients with MSA-CI and those with MSA with normal cognition (MSA-NCI) exhibited lower DC values in the left calcarine and right postcentral regions and higher DC values in the bilateral caudate and left precuneus. There were significant differences in the DC values in the right middle prefrontal gyrus between the MSA-CI and MSA-NCI groups. The mean DC values in the right middle prefrontal gyrus (RMPFG) were correlated with clinical cognitive severity. Consequently, we used this brain region as a seed in secondary seed-based FC analysis and observed FC changes within the right precuneus, inferior parietal lobe, and right insula. CONCLUSIONS: Decreased middle prefrontal cortex activity and its altered functional connectivity with the precuneus, inferior parietal lobe, and insula are possible biomarkers of cognitive dysfunction in patients with MSA-CI. SIGNIFICANCE: Cognitive impairment in MSA is associated with alterations in the dorsolateral prefrontal cortex network.

9.
Environ Sci Pollut Res Int ; 27(1): 587-596, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31808084

RESUMO

There have been many studies on the model of volatile organic compound (VOC) emissions from individual dry building material and have been validated in the chamber. Actually, VOC emitted from multiple dry building materials simultaneously indoor. The concentration of VOC indoor increases and will inhibit the VOC emission of dry building materials indoor. This paper developed a new model predicting indoor VOC concentrations caused by simultaneous emissions from multiple dry building materials, with a consideration of impact from dynamic VOC concentrations on the emission rate. The model has been used to predict the VOC emissions from a combination of medium-density fiberboard (MDF) and consolidated compound floor (CCF) simultaneously. The study demonstrated a good prediction performance of the newly proposed model, against field experimental data. The study also showed that when multiple dry building materials emit pollutants in a common space, a mutual inhibition effect could be observed. Furthermore, when multiple dry building materials emit VOC simultaneously, the change of VOC concentrations in the air followed the trends of VOC emissions from building materials with higher initial concentration (C0), diffusion coefficient (Dm), and the partition coefficient (Kma).

10.
Med Sci Monit ; 25: 9138-9158, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786580

RESUMO

BACKGROUND Acute rejection (AR) is a common complication of kidney transplantation. The transforming growth factor beta (TGF-ß) signaling pathway has been observed to be involved in several cellular functions. Our study aimed to investigate the correlations between single-nucleotide polymorphisms (SNPs) in TGF-ß-related genes and the risk of AR in renal transplant recipients. MATERIAL AND METHODS This retrospective, single-center study included 200 Chinese renal transplant recipients. All exons, exon/intron boundaries, and flanking regions of the TGF-ß signaling pathway were detected by targeting sequencing (TS) based on next-generation sequencing technology. Tagger SNPs and haplotypes were identified after adjustment. A general linear model (GLM) was used to explore the confounding effect of clinical variables. Five adjusted inheritance models were utilized to investigate the influence of SNPs on AR, and Banff score was applied to evaluate the effect of related SNPs on pathological changes. RESULTS A total of 188 SNPs on TGF-ß genes were detected. Analysis of adjustment led to identification of 31 tagger SNPs and 10 haplotype blocks. After the analysis of a general linear model and 5 sirolimus-adjusted multiple inheritance models, 1 of the SNPs - rs1131243 on the TGF-ßR3 gene - was observed to be significantly associated with the occurrence of AR. Based on Banff score, no significant association was observed between SNPs and pathological changes. CONCLUSIONS In this study, we observed that the SNP rs1131243 on the TGF-ßR3 gene was significantly associated with the occurrence of AR in Chinese renal transplant recipients.

11.
Ann Transplant ; 24: 553-568, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31582715

RESUMO

BACKGROUND Interstitial fibrosis and tubular atrophy (IF/TA) have been recognized as crucial factors contributing to graft loss resulting from chronic renal allograft injuries. Recent studies have indicated a significant association between the progression of organ fibrosis and single nucleotide polymorphisms (SNPs) found on certain genes. Our research sought to understand these potential associations and detect the potential impact of SNPs on ubiquitin-related genes related to allograft fibrosis in kidney transplant recipients. MATERIAL AND METHODS There were 200 patients enrolled in this study, from which samples were extracted for total DNA. Targeted next-generation sequencing was used to detect SNPs on 9 genes (FBXL21, PIAS1/2, SUMO1/2/3/4, UBE2D1, and UBE2I). Minor allele frequency (MAF) and Hardy-Weinberg equilibrium (HWE) tests were used and followed by linkage disequilibrium analysis. General linear models (GLM) were used to identify significant confounding factors. Finally, multiple inheritance models and haplotype analyses were conducted to explore associations between SNPs and the degree of the severity of renal allograft fibrosis. RESULTS In total, 144 SNPs were identified in targeted sequencing. After filtering based on results from MAF and HWE tests, 15 tagger SNPs were selected for further analyses of associations. GLMs indicated that the administration of sirolimus significantly contributed to the degree of severity of allograft fibrosis (P=0.011). After adjusting for confounding factors and applying a Bonferroni correction, multiple inheritance model analyses indicated that the recessive model of rs644731 of the PIAS2 gene was significantly correlated with the occurrence of IF/TA (P=0.01). Furthermore, single-locus based analysis of rs644731 did not indicate that it had a positive influence on IF/TA in a degree-dependent manner. Finally, linkage disequilibrium analysis revealed 3 haplotypes all lacking significant correlation with respect to the IF/TA experimental cohort. CONCLUSIONS We are the first to reveal that mutations of rs644731 in the PIAS2 gene were significantly correlated with the progression of IF/TA in kidney transplant recipients.

12.
Proteomics ; 19(20): e1900158, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31487437

RESUMO

Increasing evidence shows that the succinylation of lysine residues mainly regulates enzymes involved in the carbon metabolism pathway, in both prokaryotic and eukaryotic cells. Deinococcus radiodurans is one of the most radioresistant organisms on earth and is famous for its robust resistance. A major goal in the current study of protein succinylation is to explore its function in D. radiodurans. High-resolution LC-MS/MS is used for qualitative proteomics to perform a global succinylation analysis of D. radiodurans and 492 succinylation sites in 270 proteins are identified. These proteins are involved in a variety of biological processes and pathways. It is found that the enzymes involved in nucleic acid binding/processing are enriched in D. radiodurans compared with their previously reported levels in other bacteria. The mutagenesis studies confirm that succinylation regulates the enzymatic activities of species-specific proteins PprI and DdrB, which belong to the radiation-desiccation response regulon. Together, these results provide insight into the role of lysine succinylation in the extreme resistance of D. radiodurans.

13.
ChemistryOpen ; 8(8): 1109-1120, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31417841

RESUMO

To enable a more sustainable wastewater treatment processes, a transition towards resource recovery methods that have minimal environmental impact while being financially viable is imperative. Phosphorus (P) is a finite resource that is being discharged into the aqueous environment in excessive quantities. As such, understanding the financial and environmental effectiveness of different approaches for removing and recovering P from wastewater streams is important to reduce the overall impact of wastewater treatment. In this study, a process-systems modelling framework for comprehensively evaluating these approaches in terms of both economic and environmental impacts is developed. Applying this framework, treatment pathways are designed, simulated and analysed to determine the most suitable approaches for P removal and recovery. The purpose of this methodology is not only to assist with plant design, but also to identify the principal economic and environmental factors acting as barriers to implementing a given technology, incorporating the impact of waste recovery. The results suggest that the chemical and ion-exchange approaches studied deliver sustainable advantages over biological pathways, both economically and environmentally, with each possessing different strengths. The assessment methodology developed enables a more rational and environmentally sound wastewater plant design approach to be taken.

14.
Angew Chem Int Ed Engl ; 58(41): 14483-14488, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31350802

RESUMO

It is a challenging task to promote the activity and selectivity of a catalyst via precisely engineering the microenvironment, an important factor related with the catalytic performance of natural catalysts. Motivated by the water effect in promoting the catalytic activity explored in this work, a nanoreactor modified with phosphine ligand enabled the efficient hydrogenation of benzoic acid (BA) over Ru nanoparticles (NPs) in organic solvent under mild conditions, which cannot be achieved in unmodified nanoreactors. Both density functional theory (DFT) calculations and catalytic performance tests showed that the phosphine ligands can manipulate the adsorption strength of BA on Ru NPs by tuning the surface properties as well as preferentially interacting with the carboxyl of BA. The insights obtained in the present study provide a novel concept of nanoreactor design by anchoring ligands near catalytically active centers.

15.
Environ Sci Pollut Res Int ; 26(25): 25445-25451, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31264150

RESUMO

The effect of polystyrene (PS) particles on the toxicity of triphenyltin (TPT) to the marine diatom Skeletonema costatum was investigated. The 0.1-µm PS particles attached to the cell walls of S. costatum but did not cause adverse effects on the growth of the diatom. The adsorption of TPT to PS particles was negligible in seawater systems, but the presence of 0.1-µm PS significantly reduced the bioavailable concentrations of TPT in f/2-Si medium, indicating a potential three-way interaction between TPT, PS particles, and components of f/2-Si medium. The adsorption of TPT to PS of smaller size (i.e., 0.1 µm) was stronger than that of PS of larger size (i.e., 5 µm), which was probably attributed to larger surface areas of smaller PS particles. The presence of PS could reduce the toxicity of TPT. IC50 values of TPT increased from 0.56 to 0.85 and 0.71 µg/L at the presence of 20 mg/L 0.1-µm PS and 5-µm PS, respectively. The overall results of this study profiled the combined toxic effects of PS and TPT on marine phytoplankton species and highlighted the difference in adsorption of organic pollutants by microplastics in different ambient mediums.


Assuntos
Diatomáceas/efeitos dos fármacos , Compostos Orgânicos de Estanho/química , Fitoplâncton/crescimento & desenvolvimento , Plásticos/metabolismo , Poliestirenos/metabolismo , Adsorção , Tamanho da Partícula , Poliestirenos/química , Água do Mar
16.
Front Genet ; 10: 430, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156697

RESUMO

In hens, follicle selection is an important process affecting egg laying traits. This study investigated the role of parathyroid hormone-like hormone (PTHLH) in chicken follicle selection, its transcriptional regulation and genetic effects on egg laying traits. PTHLH and its receptor PTH1R were mainly expressed in follicles of 6-8 mm in diameter, exhibits differential expression pattern in the theca and granulosa cells of pre- and hierarchal follicles. PTHLH stimulates the proliferation of follicular granulosa and theca cells, the expression of StAR and CYP11A1 mRNA and the production of progesterone (P4) in pre-hierarchal follicles. Treatment with FSH increased PTHLH mRNA expression in pre-hierarchal follicular theca cells and hierarchal follicular granulosa cells. Two critical regions regulating chicken PTHLH transcription were revealed, each of which harbored a SNP: C>T (chr1: 72530014) for AP-1 and a SNP: A>G (chr1: 72531676). Hens with diplotype AC/GT were younger at first laying and laid more eggs at 32 weeks. The haplotype (G-1827T-165) with double mutations had the greatest promoter activity of chicken PTHLH transcription. Collectively, PTHLH plays an important role in chicken follicle selection by stimulating cell proliferation and steroidogenesis. Polymorphisms in chicken PTHLH promoter region are associated with egg laying traits by affecting the binding of transcription factor AP-1.

17.
ChemistryOpen ; 8(6): 659, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31172002

RESUMO

Invited for this month's cover picture is the group of Dr Miao Guo from Department of Chemical Engineering at the Imperial College London (UK). The cover picture shows modelling research on the co-polymerisation of waste-sourced limonene oxide with CO2 to produce poly(limonene carbonate), which offers a sustainable pathway to achieve carbon capture and utilisation. A computational approach to process design was integrated with sustainability evaluation to model this synthetic pathway and identify the environmental-damaging and performance-limiting steps for further improvement. Our research highlights the potential of closed-loop manufacturing systems with waste recovery, which is instrumental in building a sustainable circular economy. Read the full text of their Full Paper at 10.1002/open.201900015.

18.
ChemistryOpen ; 8(6): 668-688, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31172004

RESUMO

Poly(limonene carbonate) (PLC) has been highlighted as an attractive substitute to petroleum derived plastics, due to its utilisation of CO2 and bio-based limonene as feedstocks, offering an effective carbon capture and utilisation pathway. Our study investigates the techno-economic viability and environmental sustainability of a novel process to produce PLC from citrus waste derived limonene, coupled with an anaerobic digestion process to enable energy cogeneration and waste recovery maximisation. Computational process design was integrated with a life cycle assessment to identify the sustainability improvement opportunities. PLC production was found to be economically viable, assuming sufficient citrus waste is supplied to the process, and environmentally preferable to polystyrene (PS) in various impact categories including climate change. However, it exhibited greater environmental burdens than PS across other impact categories, although the environmental performance could be improved with a waste recovery system, at the cost of a process design shift towards energy generation. Finally, our study quantified the potential contribution of PLC to mitigating the escape of atmospheric CO2 concentration from the planetary boundary. We emphasise the importance of a holistic approach to process design and highlight the potential impacts of biopolymers, which is instrumental in solving environmental problems facing the plastic industry and building a sustainable circular economy.

19.
Clin Lymphoma Myeloma Leuk ; 19(8): e470-e477, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31171473

RESUMO

BACKGROUND: The Revised International Staging System (R-ISS) has been widely adopted to prognosticate multiple myeloma. As a result, the continued utility of conventional metaphase karyotyping has been called into question. PATIENTS AND METHODS: A multi-center study for newly diagnosed patients with multiple myeloma who received novel agent(s) at induction was conducted. Conventional metaphase karyotype information was categorized based on ploidy. We evaluated the impact of ploidy on overall survival (OS) including multivariate analysis, taking into account the R-ISS stages, transplant status, age, and novel agent(s) used at induction. We also evaluated if it is possible to identify high-risk (HR) patients with conventional karyotyping when a fluorescence in situ hybridization analysis is not available. Results were validated in an independent cohort. RESULTS: There were 308 patients evaluable. Ploidy significantly affected the OS of patients with R-ISS stage II, with non-hyperdiploid patients doing the worst. In the multivariate analysis, ploidy was significantly associated with OS. R-ISS stage II patients with or without non-hyperdiploid karyotype had significantly different survival. We replaced HR fluorescence in situ hybridization abnormalities with HR metaphase karyotypic abnormalities (non-hyperdiploid karyotype). When compared with R-ISS, there was a high level of concordance in HR patients identified using HR karyotypic abnormalities. These results were validated with an independent cohort of 375 patients. CONCLUSION: Conventional metaphase karyotyping is an independent prognostic factor even in the setting of R-ISS.

20.
Front Pharmacol ; 10: 586, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214029

RESUMO

Type 2 diabetes mellitus (T2DM) is prevalent, with a dramatic increase in recent years. Moreover, its microvascular and macrovascular complications cause significant societal issues. The demand for new and effective antidiabetic therapies grows with each passing day and motivates organizations and individuals to pay more attention to such products. In this article, we focused on oral antihyperglycemic drugs patented in China and introduced them according to their antihyperglycemic mechanisms. By searching the website of State Intellectual Property Office of the People's Republic of China (http://www.sipo.gov.cn), 2,500 antihyperglycemic patents for T2DM were identified and analyzed. These consisted of 4 patents for derivatives of herbal extracts (0.2%), 162 patents for herbal extracts (6.5%), 61 compositions for traditional Chinese medicine (TCM) (2.4%), 2,263 patents for synthetic compounds (90.5%), and 10 (0.4%) patents of the combination of synthetic compounds and TCM. As the most common drugs for diabetes mellitus, synthetic compounds can also be classified into several categories according to their working mechanisms, such as insulin secretion promotor agents, insulin sensitizer agents, α-glucosidase inhibitors, and so forth. This article discussed the chemical structure, potential antihyperglycemic mechanism of these antihyperglycemic drugs in patents in China. Expert opinion: Insulin sensitivity and ß-cell function could be improved by weight loss to prevent prediabetes into T2DM. However, 40-50% patients with impaired glucose tolerance (IGT) still progress to T2DM, even after successful long-term weight loss. Antihyperglycemic remedies provide a treatment option to improve insulin sensitivity and maintain ß-cell function. Combination therapy is the best treatment for diabetes. Combination therapy can reduce the dosage of each single drug option, and avoid the side effects. Drugs with different mechanisms are complementary, and are better adapted to patients with changing conditions. Classical combination therapies include combinations such as sulfonylureas plus biguanides or glucosidase inhibitors, biguanide plus glucosidase inhibitors or insulin sensitizers, insulin treatment plus biguanides or glucosidase inhibitors. The general principle of combination therapy is that two drugs with different mechanisms are selected jointly, and the combination of three types of hypoglycemic drugs is not recommended. After reading a large amount of literature, we have rarely found a case of three oral hypoglycemic agents, which may mean that the combination of three oral hypoglycemic agents is unnecessary and has unpredictable risks. There is no objection to the idea of multi-drug therapy. But multiple drugs can only be used when it shows a significant benefit to the patients. Combined use of multiple antidiabetic drugs poses a risk to patients due to drug interactions and overtreatment.

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