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The past 4 decades have witnessed tremendous efforts in deciphering the role of O-GlcNAcylation in a plethora of biological processes. Chemists and biologists have joined hand in hand in the sweet adventure to unravel this unique and universal yet uncharted post-translational modification, and the recent advent of cutting-edge chemical biology and mass spectrometry tools has greatly facilitated the process. Compared with O-GlcNAc, DNA damage response (DDR) is a relatively intensively studied area that could be traced to before the elucidation of the structure of DNA. Unexpectedly, yet somewhat expectedly, O-GlcNAc has been found to regulate various DDR pathways: homologous recombination, nonhomologous end joining, base excision repair, and translesion DNA synthesis. In this review, we first cover the recent structural studies of the O-GlcNAc transferase and O-GlcNAcase, the elegant duo that "writes" and "erases" O-GlcNAc modification. Then we delineate the intricate roles of O-GlcNAc transferase and O-GlcNAcase in DDR. We envision that this is only the beginning of our full appreciation of how O-GlcNAc regulates the blueprint of life-DNA.
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N-Acetilglucosaminiltransferases , Animais , Humanos , beta-N-Acetil-Hexosaminidases/metabolismo , beta-N-Acetil-Hexosaminidases/genética , DNA/metabolismo , DNA/química , Dano ao DNA , Reparo do DNA , N-Acetilglucosaminiltransferases/metabolismo , N-Acetilglucosaminiltransferases/genética , Processamento de Proteína Pós-Traducional , GenomaRESUMO
Podocytes are essential to maintaining the integrity of the glomerular filtration barrier, but they are frequently affected in lupus nephritis (LN). Here, we show that the significant upregulation of Drp1S616 phosphorylation in podocytes promotes mitochondrial fission, leading to mitochondrial dysfunction and podocyte injury in LN. Inhibition or knockdown of Drp1 promotes mitochondrial fusion and protects podocytes from injury induced by LN serum. In vivo, pharmacological inhibition of Drp1 reduces the phosphorylation of Drp1S616 in podocytes in lupus-prone mice. Podocyte injury is reversed when Drp1 is inhibited, resulting in the alleviation of proteinuria. Mechanistically, complement component C5a (C5a) upregulates the phosphorylation of Drp1S616 and promotes mitochondrial fission in podocytes. Moreover, the expression of C5a receptor 1 (C5aR1) is notably upregulated in podocytes in LN. C5a-C5aR1 axis-controlled phosphorylation of Drp1S616 and mitochondrial fission are substantially suppressed when C5aR1 is knocked down by siRNA. Moreover, lupus-prone mice treated with C5aR inhibitor show reduced phosphorylation of Drp1S616 in podocytes, resulting in significantly less podocyte damage. Together, this study uncovers a novel mechanism by which the C5a-C5aR1 axis promotes podocyte injury by enhancing Drp1-mediated mitochondrial fission, which could have significant implications for the treatment of LN.
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Complemento C5a , Dinaminas , Nefrite Lúpica , Dinâmica Mitocondrial , Podócitos , Receptor da Anafilatoxina C5a , Podócitos/metabolismo , Podócitos/patologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Nefrite Lúpica/etiologia , Animais , Receptor da Anafilatoxina C5a/metabolismo , Receptor da Anafilatoxina C5a/genética , Camundongos , Dinaminas/metabolismo , Dinaminas/genética , Complemento C5a/metabolismo , Humanos , Fosforilação , Modelos Animais de Doenças , Mitocôndrias/metabolismo , Transdução de Sinais , FemininoRESUMO
The aim of this study was to explore the molecular mechanisms through which different levels of GAA affect chicken muscle development by influencing miRNA expression, to lay a theoretical foundation for the identification of key functional small RNAs related to poultry muscle development, and to provide new insights into the regulatory mechanisms of GAA on muscle development and meat quality in broilers. It provides a new theoretical basis for using GAA as a feed additive to improve feed performance. Small RNA sequencing technology was utilized to obtain the expression profiles of miRNA in the broiler pectoral muscle fed with different levels of GAA (0 g/kg, 1.2 g/kg and 3.6 g/kg). An analysis of differentially expressed miRNAs revealed 90 such miRNAs in the three combination comparisons, with gga-miR-130b-5p exhibiting significant differences across all three combinations. Furthermore, three of the differentially expressed miRNAs were performed by RT-qPCR verification, yielding results consistent with those obtained from small RNA sequencing. Target gene prediction, as well as the GO and KEGG enrichment analysis of differentially expressed miRNAs, indicated their involvement in muscle cell differentiation and other processes, particularly those associated with the MAPK signaling pathway. This study has, thus, provided valuable insights and resources for the further exploration of the miRNA molecular mechanism underlying the influence of guanidine acetic acid on broiler muscle development. Combined with previous studies and small RNA sequencing, adding 1.2 g/kg GAA to the diet can better promote the muscle development of broilers.
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Extracellular enzymes are not only strongly correlated with disease development but also play critical roles in modulating immune responses. Therefore, real-time monitoring of extracellular enzymatic activity can afford straightforward insights into their spatiotemporal dynamics upon drug stimulus, and provide promising tools to unravel their key roles in modulating the cell signaling. Although DNA-based sensing probes have been frequently developed for the detection of a variety of biomolecules, there still lacks a modular design strategy for amplified imaging of extracellular enzymatic activity associated with live cells. Herein, we developed an enzymatically triggerable signal amplification strategy for real-time dynamic imaging of extracellular enzyme activity through a cell membrane-confined hybrid chain reaction (HCR). We demonstrated that, by modifying the initiator DNA with enzyme-specific incision sites and cholesterol tail, extracellular enzyme-trigged HCR could be fulfilled on the surface of the cellular membrane, facilitating amplified detection of extracellular enzymatic activity. Dynamic monitoring of enzyme secretion of cancer cells upon stimulus or macrophage cells upon inflammation challenge has also been achieved. We envision that the design strategy could provide valuable information for dissecting the role of extracellular enzymes in modulating cell responses to drug treatment.
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Membrana Celular , Humanos , Membrana Celular/metabolismo , Animais , Camundongos , Células RAW 264.7 , DNA/metabolismo , DNA/química , Colesterol/metabolismo , Colesterol/análise , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacosRESUMO
Based on our previous findings that salicylic acid and jasmonic acid increased Nostoc flagelliforme polysaccharide yield by regulating intracellular nitric oxide (NO) levels, the mechanism through which NO affects polysaccharide biosynthesis in Nostoc flagelliforme was explored from the perspective of S-nitrosylation (SNO). The addition of NO donor and scavenger showed that intracellular NO had a significant positive effect on the polysaccharide yield of N. flagelliforme. To explore the mechanism, we investigated the relationship between NO levels and the activity of several key enzymes involved in polysaccharide biosynthesis, including fructose 1,6-bisphosphate aldolase (FBA), glucokinase (GK), glucose 6-phosphate dehydrogenase (G6PDH), mitochondrial isocitrate dehydrogenase (ICDH), and UDP-glucose dehydrogenase (UGDH). The enzymatic activities of G6PDH, ICDH, and UGDH were shown to be significantly correlated with the shifts in intracellular NO levels. For further validation, G6PDH, ICDH, and UGDH were heterologously expressed in Escherichia coli and purified via Ni+-NAT affinity chromatography, and subjected to a biotin switch assay and western blot analysis, which revealed that UGDH and G6PDH were susceptible to SNO. Furthermore, mass spectrometry analysis of proteins treated with S-nitrosoglutathione (GSNO) identified the SNO modification sites for UGDH and G6PDH as cysteine 423 and cysteine 249, respectively. These findings suggest that NO modulates polysaccharide biosynthesis in N. flagelliforme through SNO of UGDH and G6PDH. This reveals a potential mechanism through which NO promotes polysaccharide synthesis in N. flagelliforme, while also providing a new strategy for improving the industrial production of polysaccharides.
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Óxido Nítrico , Nostoc , Nostoc/metabolismo , Nostoc/enzimologia , Nostoc/genética , Óxido Nítrico/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Glucosefosfato Desidrogenase/genética , Polissacarídeos Bacterianos/metabolismo , Polissacarídeos Bacterianos/biossíntese , Polissacarídeos/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Escherichia coli/genética , Escherichia coli/metabolismoRESUMO
Hybrid genotypes can provide significant yield gains over conventional inbred varieties due to heterosis or hybrid vigor. However, hybrids can also display unintended negative attributes or phenotypes such as extreme pathogen susceptibility. The necrotrophic pathogen Pyrenophora teres f. maculata (Ptm) causes spot form net blotch, which has caused significant yield losses to barley worldwide. Here, we report on a non-transgressive hybrid susceptibility locus in barley identified between the three parental lines CI5791, Tifang and Golden Promise that are resistant to Ptm isolate 13IM.3. However, F2 progeny from CI5791 × Tifang and CI5791 × Golden Promise crosses exhibited extreme susceptibility. The susceptible phenotype segregated in a ratio of 1 resistant:1 susceptible representing a genetic segregation ratio of 1 parental (res):2 heterozygous (sus):1 parental (res) suggesting a single hybrid susceptibility locus. Genetic mapping using a total of 715 CI5791 × Tifang F2 individuals (1430 recombinant gametes) and 149 targeted SNPs delimited the hybrid susceptibility locus designated Susceptibility to Pyrenophora teres 2 (Spt2) to an ~ 198 kb region on chromosome 5H of the Morex V3 reference assembly. This single locus was independently mapped with 83 CI5791 × Golden Promise F2 individuals (166 recombinant gametes) and 180 genome wide SNPs that colocalized to the same Spt2 locus. The CI5791 genome was sequenced using PacBio Continuous Long Read technology and comparative analysis between CI5791 and the publicly available Golden Promise genome assembly determined that the delimited region contained a single high confidence Spt2 candidate gene predicted to encode a pentatricopeptide repeat-containing protein.
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Ascomicetos , Mapeamento Cromossômico , Hordeum , Doenças das Plantas , Hordeum/genética , Hordeum/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Ascomicetos/fisiologia , Resistência à Doença/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Hibridização Genética , Vigor Híbrido/genética , GenótipoRESUMO
BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death around the world. Most CVDs-related death can be prevented by the optimal management of risk factors such as unhealthy diet and physical inactivity. Clinical practice guidelines (CPGs) for CVDs, provide some evidence-based recommendations which help healthcare professionals to achieve the best care for patients with CVDs. This systematic review aims to appraise the methodological quality of CPGs systematically and summarize the recommendations of self-managed non-pharmacological interventions for the prevention and management of CVDs provided by the selected guidelines. METHODS: A comprehensive electronic literature search was conducted via six databases (PubMed, Medline, The Cochrane Library, Embase, CINAHL, and Web of Science), seven professional heart association websites, and nine guideline repositories. The Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument was adopted to critically appraise the methodological quality of the selected guidelines. Content analysis was used to summarise recommended self-managed non-pharmacological interventions for CVDs. RESULTS: Twenty-three CPGs regarding different CVDs were included, in which four guidelines of CVDs, three for coronary heart diseases, seven for heart failure, two for atrial fibrillation, three for stroke, three for peripheral arterial disease, and one for hypertrophic cardiomyopathy. Twenty CPGs were appraised as high quality, and three CPGs as moderate quality. All twenty-three CPGs were recommended for use with or without modification. The domain of "Editorial Independence" had the highest standardized percentage (93.47%), whereas the domain of "Applicability" had the lowest mean domain score of 75.41%. The content analysis findings summarised some common self-managed non-pharmacological interventions, which include healthy diet, physical activity, smoking cessation, alcohol control, and weight management. Healthy diet and physical acidity are the most common and agreed on self-managed interventions for patients with CVDs. There are some inconsistencies identified in the details of recommended interventions, the intervention itself, the grade of recommendation, and the supported level of evidence. CONCLUSION: The majority of the summarized non-pharmacological interventions were strongly recommended with moderate to high-quality levels of evidence. Healthcare professionals and researchers can adopt the results of this review to design self-managed non-pharmacological interventions for patients with CVDs.
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Doenças Cardiovasculares , Insuficiência Cardíaca , Doença Arterial Periférica , Autogestão , Humanos , Doenças Cardiovasculares/terapia , Guias de Prática Clínica como AssuntoRESUMO
Bacterial outer membrane vesicles (OMVs) can package and deliver virulence factors into host cells, which is an important mechanism mediating host-pathogen interactions. It has been reported that small RNAs (sRNAs) can be packed into OMVs with varying relative abundance, which might affect the function and/or stability of host mRNAs. In this study, we used OptiPrep density gradient ultra-high-speed centrifugation to purify OMVs from Pseudomonas aeruginosa. Next, the sequences and abundance of sRNAs were detected by using Small RNA-Seq. In particular, sRNA4518698, sRNA2316613 and sRNA809738 were the three most abundant sRNAs in OMVs, which are all fragments of P. aeruginosa non-coding RNAs. sRNAs were shielded within the interior of OMVs and remained resistant to external RNase cleavage. The miRanda and RNAhybrid analysis demonstrated that those sRNAs could target a large number of host mRNAs, which were enriched in host immune responses by the functions of GO and KEGG enrichment. Experimentally, we demonstrated that the transfection of synthetic sRNA4518698, sRNA2316613, or sRNA809738 could reduce the expression of innate immune response genes in RAW264.7 cells. Together, we demonstrated that P. aeruginosa OMVs sRNAs can regulate innate immune responses. This study uncovered a mechanism in which the OMVs regulate host responses by transferring bacterial sRNAs.
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Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/fisiologia , Infecções por Pseudomonas/microbiologia , Imunidade Inata , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , Interações Hospedeiro-Patógeno , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Aroma or fragrance in rice is a genetically controlled trait; Its high appreciation by consumers increases the rice market price. Previous studies have revealed that the rice aroma is controlled by a specific gene called BETAINE ALDEHYDE DEHYDROGENASE (OsBADH2), and mutation of this gene leads to the accumulation of an aromatic substance 2-acetyl-1-pyrroline (2-AP). The use of genetic engineering to produce aroma in commercial and cultivated hybrids is a contemporary need for molecular breeding. The current study reports the generation of aroma in the three-line hybrid restorer line Shu-Hui-313 (SH313). We created knock-out (KO) lines of OsBADH2 through the CRISPR/Cas9. The analysis of KO lines revealed a significantly increased content of 2AP in the grains compared with the control. However, other phenotypic traits (plant height, seed setting rate, and 1000-grain weight) were significantly decreased. These KO lines were crossed with a non-aromatic three-line hybrid rice male sterile line (Rong-7-A) to produce Rong-7-You-626 (R7Y626), R7Y627 and R7Y628. The measurement of 2-AP revealed significantly increased contents in these cross combinations. We compared the content of 2-AP in tissues at the booting stage. Data revealed that young spike stalk base contained the highest content of 2-AP and can be used for identification (by simple chewing) of aromatic lines under field conditions. In conclusion, our dataset offers a genetic source and illustrates the generation of aroma in non-aromatic hybrids, and outlines a straightforward identification under field conditions.
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Betaína/análogos & derivados , Oryza , Oryza/genética , Sistemas CRISPR-Cas/genética , Odorantes , Genes de PlantasRESUMO
Fused porphyrinoids have received increasing interest in light of their extended conjugation and unique coordination behavior. On the basis of our previously reported multiply fused pentaphyrin isomers 1 and 2, a novel isomer 3 has been synthesized in this work. 3 possesses a hexacyclic fused moiety with a nearly coplanar CCNN cavity involving an inverted pyrrole, which is slightly different from the CNNN ones of 1 and 2 involving an N-confused pyrrole. 1-3 possess cavities with three depronatable protons and thus they all can generate Cu(III) complexes. However, only 3Cu is stable under ambient conditions. On the other hand, 3 remains intact upon treatment with Pd(II) ions, while 1 and 2 could undergo structural rearrangement to accommodate Pd(II), affording 1Pd and 2Pd accompanied by the formation of a lactone ring and the addition of a methoxy group, respectively. Compared with the free bases, the complexes show distinct aromaticity and more intense near-infrared (NIR) absorption up to ca. 1600, 1170, and 1500 nm, respectively. The results indicate that the subtle modification of the linking modes between the pyrrolic units in the fused pentaphyrinoids is effective in modulating the coordination behavior for synthesizing complexes with tunable aromaticity and NIR absorption.
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The first amidation of carbazoles at the N9 position via palladium-catalyzed hydroamination of isocyanates is demonstrated. This simple, general and efficient method could deliver a wide range of carbazole-N-carboxamides in up to 99% yield. The salient features of this transformation include simple conditions with no need for a strong base, high chemo- and regio-selectivities and good functional group tolerance. In particular, this work-up-free and chromatography-free protocol is time-saving, cost-effective and user-friendly.
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Reactivating p53 activity to restore its anticancer function is an attractive cancer treatment strategy. In this study, we designed and synthesized a series of novel PROTACs to reactivate p53 via the co-degradation of CK1α and CDK7/9 proteins. Bioactivity studies showed that the selected PROTAC 13i exhibited potency antiproliferative activity in MV4-11 (IC50 = 0.096 ± 0.012 µM) and MOLM-13 (IC50 = 0.072 ± 0.014 µM) cells, and induced apoptosis of MV4-11 cells. Western-blot analysis showed that PROTAC 13i triple CK1α and CDK7/9 protein degradation resulted in the significantly increased expression of p53. At the same time, the transcriptional repression due to the degradation significantly reduced downstream gene expression of MYC, MDM2, BCL-2 and MCL-1, and reduced the inflammatory cytokine levels of TNF-α, IL-1ß and IL-6 in PMBCs. These results indicate the beneficial impact of simultaneous CK1α and CDK7/9 degradation for acute myeloid leukemia therapy.
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Antineoplásicos , Caseína Quinase Ialfa , Proliferação de Células , Quinase 9 Dependente de Ciclina , Quinases Ciclina-Dependentes , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia Mieloide Aguda , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Caseína Quinase Ialfa/metabolismo , Caseína Quinase Ialfa/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/metabolismo , Relação Dose-Resposta a Droga , Apoptose/efeitos dos fármacos , Descoberta de Drogas , Linhagem Celular Tumoral , Proteólise/efeitos dos fármacos , Células Tumorais Cultivadas , Quimera de Direcionamento de Proteólise , Quinase Ativadora de Quinase Dependente de CiclinaRESUMO
BACKGROUND AND AIMS: It has been reported that maresin 1 (MaR1) is able to protect against the development of atherogenesis in cellular and animal models. This study was performed to investigate whether plasma MaR1 is associated with the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level. METHODS AND RESULTS: The study included 2822 non-ASCVD participants from a community-based cohort who were followed for about 8 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for ASCVD events according to baseline MaR1 quartiles were calculated using the Cox proportional hazards model. During follow-up, a total of 290 new ASCVD cases were identified. The restricted cubic spline analysis indicated a linear dose-response association between plasma MaR1 and incident ASCVD. In addition, the adjusted-HR (95% CI) for ASCVD events associated with one standard deviation increase in MaR1 was 0.79 (0.68-0.91). Moreover, the adjusted-HRs (95% CIs) for ASCVD events associated with the second, third and fourth quartiles versus the first quartile of plasma MaR1 were 1.00, 1.04 (0.76, 1.42), 0.88 (0.64, 1.22) and 0.58 (0.41, 0.84), respectively. Mediation analyses showed that the association between MaR1 and incident ASCVD was partially mediated by small dense low-density lipoprotein cholesterol, with a mediation proportion of 9.23%. Further, the net reclassification improvement and integrated discrimination improvement of ASCVD risk were significantly improved when MaR1 was added to basic model established by conventional risk factors (all p < 0.01). CONCLUSIONS: Elevated plasma MaR1 concentrations are associated with a lower risk of ASCVD development.
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Aterosclerose , Biomarcadores , Ácidos Docosa-Hexaenoicos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Aterosclerose/epidemiologia , Aterosclerose/sangue , Aterosclerose/diagnóstico , Medição de Risco , Incidência , China/epidemiologia , Biomarcadores/sangue , Idoso , Fatores de Tempo , Ácidos Docosa-Hexaenoicos/sangue , Adulto , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Proteção , População do Leste AsiáticoRESUMO
Herein, we aimed to develop an easily available and efficient screening method for diabetic peripheral neuropathy (DPN) suitable for primary care settings, emphasizing simplicity, speed, and accuracy. Nerve conduction studies were conducted on 214 patients with diabetes, encompassing the outcomes of five distinct assessments: diabetic neuropathy symptom (DNS), vibration perception threshold (VPT), and nerve screening. The diagnostic accuracy of the VPT and nerve screening was evaluated by comparing them with that of the nerve conduction study. To assess diagnostic efficacy, various combinations were examined, including DNS combined with VPT, pain, temperature, touch, and ankle reflex. The diagnostic performance of DNS was superior to that of the five neurological screening items and VPT, with sensitivity, specificity, and accuracy of 0.68, 0.81, and 0.73, respectively. Among the two combined methods, "DNS + ankle reflex" was identified as having the highest diagnostic value, with an area under the curve, a sensitivity, a specificity, and an accuracy of 0.81, 0.89, 0.70, and 0.80, respectively. Furthermore, a combination of "DNS + ankle reflex + touch + pain + VPT" achieved the best performance among the five combinations, with an area under the curve, sensitivity, specificity, and accuracy of 0.85, 0.93, 0.68, and 0.81, respectively. The combination of DNS, ankle reflex, touch, pain, and VPT methods showed the highest diagnostic value for DPN. However, considering factors including accuracy, time, and economic cost, we recommend using a simpler combination of DNS and ankle reflex for large-scale screening of patients with DPN.
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Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Neuropatias Diabéticas/diagnóstico , Tornozelo , Percepção , Reflexo , Dor/diagnóstico , Dor/etiologiaRESUMO
PURPOSE: To evaluate the availability, cost, affordability of anti-cancer medicines in Nanjing, Jiangsu. METHODS: A longitudinal tracking investigation study was performed to collect information about 24 essential anti-cancer medicines (EAMs) and 17 innovative anti-cancer medicines (IAMs) in 26 healthcare institutions in Nanjing from 2016 to 2020. The availability, cost, drug utilization and affordability of EAMs and IAMs were investigated. RESULTS: The availability of EAMs showed no significant changes in Nanjing, but the availability of IAMs showed a significant increase in 2018 and 2019 and tended to stabilize in 2020. For EAMs, the DDDc(Defined Daily Dose cost) of LPGs (Lowest-Priced Generics) showed no significant changes, and the DDDc of OBs (Originator Brands) and IAMs significantly decreased. The DDDs(Defined Daily Doses) of EAMs (LPGs) showed a decreasing trend since 2016 and rose again in 2019. Overall, the DDDs of EAMs (LPGs) decreased by 25.18% between 2016 and 2020, but the proportion selected for clinical treatment remained at 67.35% in 2020. The DDDs of EAMs (OBs) and IAMs both showed an increasing trend year by year, with a proportional increase of 207.72% and 652.68%, respectively; but the proportion selected for clinical treatment was only 16.09% and 16.56% respectively in 2020. EAMs (LPGs) had good affordability for urban residents but poor affordability for rural residents; the affordability of EAMs (OBs) and IAMs was poor for both urban and rural residents. CONCLUSIONS: There were no significant changes in the availability and cost of EAMs (LPGs), whose lower prices showed better affordability. Although their relative change in drug utilization showed a decreasing trend, they still dominated clinical treatment. Driven by the national drug price negotiation (NDPN) policy, the availability of IAMs was on the rise. It is necessary to further develop and strengthen policies for essential medicines procurement assessment to improve the accessibility of EAMs.
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Antineoplásicos , Custos de Medicamentos , Medicamentos Essenciais , Acessibilidade aos Serviços de Saúde , Estudos Longitudinais , Humanos , China , Antineoplásicos/uso terapêutico , Antineoplásicos/economia , Antineoplásicos/provisão & distribuição , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Medicamentos Essenciais/provisão & distribuição , Medicamentos Essenciais/economia , Custos de Medicamentos/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Drogas em Investigação/economiaRESUMO
BACKGROUND: An isokinetic moment curve (IMC) pattern-damaged structure prediction model may be of considerable value in assisting the diagnosis of knee injuries in clinical scenarios. This study aimed to explore the association between irregular IMC patterns and specific structural damages in the knee, including anterior cruciate ligament (ACL) rupture, meniscus (MS) injury, and patellofemoral joint (PFJ) lesions, and to develop an IMC pattern-damaged structure prediction model. METHODS: A total of 94 subjects were enrolled in this study and underwent isokinetic testing of the knee joint (5 consecutive flexion-extension movements within the range of motion of 90°-10°, 60°/s). Qualitative analysis of the IMCs for all subjects was completed by two blinded examiners. A multinomial logistic regression analysis was used to investigate whether a specific abnormal curve pattern was associated with specific knee structural injuries and to test the predictive effectiveness of IMC patterns for specific structural damage in the knee. RESULTS: The results of the multinomial logistic regression revealed a significant association between the irregular IMC patterns of the knee extensors and specific structural damages ("Valley" - ACL, PFJ, and ACL + MS, "Drop" - ACL, and ACL + MS, "Shaking" - ACL, MS, PFJ, and ACL + MS). The accuracy and Macro-averaged F1 score of the predicting model were 56.1% and 0.426, respectively. CONCLUSION: The associations between irregular IMC patterns and specific knee structural injuries were identified. However, the accuracy and Macro-averaged F1 score of the established predictive model indicated its relatively low predictive efficacy. For the development of a more accurate predictive model, it may be essential to incorporate angle-specific and/or speed-specific analyses of qualitative and quantitative data in isokinetic testing. Furthermore, the utilization of artificial intelligence image recognition technology may prove beneficial for analyzing large datasets in the future.
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Lesões do Ligamento Cruzado Anterior , Articulação do Joelho , Amplitude de Movimento Articular , Humanos , Masculino , Feminino , Adulto , Amplitude de Movimento Articular/fisiologia , Articulação do Joelho/fisiopatologia , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Adulto Jovem , Fenômenos Biomecânicos/fisiologia , Traumatismos do Joelho/fisiopatologia , Valor Preditivo dos Testes , Lesões do Menisco Tibial/fisiopatologia , Articulação Patelofemoral/fisiopatologia , Articulação Patelofemoral/lesões , Pessoa de Meia-IdadeRESUMO
The continuous and rapid increase of chemical pollution in surface waters has become a pressing and widely recognized global concern. As emerging contaminants (ECs) in surface waters, pharmaceutical and personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have attracted considerable attention due to their wide occurrence and potential threat to human health. Therefore, a comprehensive understanding of the occurrence and risks of ECs in Chinese surface waters is urgently required. This study summarizes and assesses the environmental occurrence concentrations and ecological risks of 42 pharmaceuticals, 15 personal care products (PCPs), and 20 EDCs frequently detected in Chinese surface waters. The ECs were primarily detected in China's densely populated and highly industrialized regions. Most detected PPCPs and EDCs had concentrations between ng/L to µg/L, whereas norfloxacin, caffeine, and erythromycin had relatively high contamination levels, even exceeding 2000 ng/L. Risk evaluation based on the risk quotient method revealed that 34 PPCPs and EDCs in Chinese surface waters did not pose a significant risk, whereas 4-nonylphenol, 4-tert-octylphenol, 17α-ethinyl estradiol, 17ß-estradiol, and triclocarban did. This review provides a comprehensive summary of the occurrence and associated hazards of typical PPCPs and EDCs in Chinese surface waters over the past decade, and will aid in the regulation and control of these ECs in Chinese surface waters.
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Cosméticos , Disruptores Endócrinos , Monitoramento Ambiental , Poluentes Químicos da Água , China , Cosméticos/análise , Disruptores Endócrinos/análise , Preparações Farmacêuticas/análise , Medição de Risco , Poluentes Químicos da Água/análiseRESUMO
DNAzymes exhibit tremendous application potentials in the field of biosensing and gene regulation due to its unique catalytic function. However, spatiotemporally controlled regulation of DNAzyme activity remains a daunting challenge, which may cause nonspecific signal leakage or gene silencing of the catalytic systems. Here, we report a photochemical approach via modular weaving active DNAzyme into the skeleton of tetrahedral DNA nanocages (TDN) for light-triggered on-demand liberation of DNAzyme and thus conditional control of gene regulation activity. We demonstrate that the direct encoding of DNAzyme in TDN could improve the biostability of DNAzyme and ensure the delivery efficiency, comparing with the conventional surface anchoring strategy. Furthermore, the molecular weaving of the DNA nanostructures allows remote control of DNAzyme-mediated gene regulation with high spatiotemporal precision of light. In addition, we demonstrate that the approach is applicable for controlled regulation of the gene editing functions of other functional nucleic acids.
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Técnicas Biossensoriais , DNA Catalítico , DNA Catalítico/metabolismo , DNA/química , Regulação da Expressão Gênica , Esqueleto/metabolismoRESUMO
Achieving the complete mineralization of persistent pollutants in wastewater is still a big challenge. Here, we propose an efficient photo-self-Fenton reaction for the degradation of different pollutants using the high-density (Ag: 22â wt %) of atomically dispersed AgCo dual sites embedded in graphic carbon nitride (AgCo-CN). Comprehensive experimental measurements and density functional theory (DFT) calculations demonstrate that the Ag and Co dual sites in AgCo-CN play a critical role in accelerating the photoinduced charge separation and forming the self-Fenton redox centers, respectively. The bimetallic AgCo-CN exhibited excellent photocatalytic performance toward the phenol even under extreme conditions due to an efficient degradation pathway and in situ generation of the hydrogen peroxide producing the main active oxygen species (â OH and 1 O2 ) and showed long-term activity in a self-design photo-Filter reactor for the purification of the phenol. Our discoveries pave the way for the design of efficient single-atoms photocatalysts-based photo-self-Fenton reaction for recalcitrant pollutant treatment.
RESUMO
Dispersion of single atoms (SAs) in the host is important for optimizing catalytic activity. Herein, we propose a novel strategy to tune oxygen vacancies in CeO2-X directionally anchoring the single atom platinum (PtSA), which is uniformly dispersed on the rGO. The catalyst's performance for the hydrogen evolution reaction (HER) can be enhanced by controlling different densities of CeO2-X in rGO. The PtSA performs best optimally densified and loaded on homogeneous and moderately densified CeO2-X/rGO (PtSA-M-CeO2-X/rGO). It exhibited higher activity in HER with an overpotential of 25â mV at 0.5â M H2SO4 and 33â mV at 1 KOH than that of almost reported electrocatalysts. Furthermore, it exhibited stability for 90â hours at -100â mA cm-2 in 1 KOH and -150â mA cm-2 in 0.5â M H2SO4 conditions, respectively. Through comprehensive experiments and theoretical calculations, the suitable dispersion density of PtSA on the defects of CeO2-X with more active sites gives the potential for practical applications. This research paves the way for developing single-atom catalysts with exceptional catalytic activity and stability, holding promise in advanced green energy conversion through defects engineering.