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Cellulose, as the most abundant natural polymer on Earth, has long captured researchers' attention due to its high strength and modulus. Nevertheless, transferring its exceptional mechanical properties to macroscopic 2D and 3D materials poses numerous challenges. This review provides an overview of the research progress in the development of strong cellulose-based materials using both the "bottom-up" and "top-down" approaches. In the "bottom-up" strategy, various forms of regenerated cellulose-based materials and nanocellulose-based high-strength materials assembled by different methods are discussed. Under the "top-down" approach, the focus is on the development of reinforced cellulose-based materials derived from wood, bamboo, rattan and straw. Furthermore, a brief overview of the potential applications fordifferent types of strong cellulose-based materials is given, followed by a concise discussion on future directions.
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Esophageal squamous cell carcinoma stands as a notably aggressive malignancy within the digestive system. In cases of early esophageal cancer without lymph node metastasis, endoscopic surgical resection offers a viable alternative, often resulting in improved patient quality of life. However, the paucity of methods to preoperatively ascertain lymph node involvement complicates surgical planning. SOX4 gene was previously found to be highly associated with invasive metastasis in our work through single-cell RNA sequencing on 5 paired tumor/peritumor tissues. This research included the collection of 124 tissue samples from 106 patients (106 tumor and 18 lymph node specimens). Samples were methodically arranged into a tissue microarray and treated with immunohistochemical staining. Statistical analysis was conducted to assess the relationship between them. In the univariate analysis, 3 factors were identified as statistically significant in relation to lymph node metastasis: T category (P = .014), vascular invasion (P < .001), and SOX4 intensity (P = .001). Additionally, when evaluating SOX4 intensity alongside other clinical indicators, SOX4 was shown to independently influence lymph node metastasis. Further, the multivariate analysis revealed that vascular invasion (P < .001) and SOX4 intensity (P = .003) were significantly associated with lymph node metastasis, exhibiting hazard ratios of 10.174 and 7.142, respectively. The results of our study indicate that both SOX4 expression and vascular invasion serve as predictors of lymph node metastasis in patients diagnosed with category T1 esophageal squamous cell carcinoma, underscoring the potential utility of SOX4 in prognostic evaluations.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Metástase Linfática , Fatores de Transcrição SOXC , Feminino , Humanos , Masculino , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/secundário , Carcinoma de Células Escamosas do Esôfago/cirurgia , Linfonodos/patologia , Linfonodos/metabolismo , Prognóstico , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição SOXC/genéticaRESUMO
BACKGROUND: To analyze the expression of interleukin-33 (IL-33), growth-stimulated expression gene 2 (ST2), nuclear factor-kappaB (NF-κB) and immune cell infiltration in prostate cancer, this study aims to provide an experimental basis for the clinical prevention and treatment of prostate cancer. METHODS: The expression of IL-33 in PCa tissues was analyzed using TCGA, TIMER and HPA databases. Using the UALCAN database, the systematic exploration of the relationship between IL-33 and various clinicopathological parameters was conducted. The correlation between IL-33 expression and immune cell infiltration was investigated using TIMER, CIBERSORT and GEPIA databases. To verify these analyses, 22 cases of normal prostate (NP), 76 cases of benign prostatic hyperplasia (BPH), and 100 cases of PCa were recruited. Immunohistochemical staining was performed to examine the expression of IL-33, ST2, NF-κB, and the infiltration of immune cells. Correlations between these factors were then determined. RESULTS: The expression of IL-33, ST2 and NF-κB was significantly lower in PCa tissues compared with NP (p < 0.05). IL-33 was not associated with age in PCa but showed associations with race, molecular characteristics, lymph node metastatic status, TP53 mutation and tumor grade. Furthermore, IL-33 was associated with immune cell infiltration. Positive correlations were observed between IL-33 and ST2 expressions, as well as between IL-33 and CD68+ macrophages in BPH and PCa. CONCLUSIONS: IL-33, ST2 and NF-κB are lowly expressed in PCa tissues, their expression decreases with the increasing malignancy of cancer. IL-33, ST2 and NF-κB are factors associated with PCa immune infiltration. IL-33 has an inhibitory effect on prostate cancer through the IL-33/ST2/NF-κB signalling pathway.
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Patients suffering from hepatic ischemia-reperfusion injury (HIRI) frequently exhibit postoperative cognitive deficits. Our previous observations have emphasized the diurnal variation in hepatic ischemia-reperfusion injury-induced cognitive impairment, in which gut microbiota-associated hippocampal lipid metabolism plays an important role. Herein, we further investigated the molecular mechanisms involved in the process. Hepatic ischemia-reperfusion surgery was performed under morning (ZT0, 08:00) and evening (ZT12, 20:00). Fecal microbiota transplantation was used to associate HIRI model with pseudo-germ-free mice. The novel object recognition test and Y-maze test were used to assess cognitive function. 16S rRNA gene sequencing and analysis were used for microbial analysis. Western blotting was used for hippocampal protein analysis. Compared with the ZT0-HIRI group, ZT12-HIRI mice showed learning and short term memory impairment, accompanied by down-regulated expression of hippocampal CB1R, but not CB2R. Both gut microbiota composition and microbiota metabolites were significantly different in ZT12-HIRI mice compared with ZT0-HIRI. Fecal microbiota transplantation from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior and down-regulated hippocampal CB1R and ß-arrestin1. Intraperitoneal administration of CB1R inhibitor AM251 (1 mg/kg) down-regulated hippocampal CB1R and caused cognitive impairment in ZT0-HIRI mice. And intraperitoneal administration of CB1R agonist WIN 55,212-2 (1 mg/kg) up-regulated hippocampal CB1R and improved cognitive impairment in ZT12-HIRI mice. In summary, the results suggest that gut microbiota may regulate the diurnal variation of HIRI-induced cognitive function by interfering with hippocampal CB1R.
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Disfunção Cognitiva , Microbioma Gastrointestinal , Hipocampo , Receptor CB1 de Canabinoide , Traumatismo por Reperfusão , Animais , Masculino , Camundongos , Ritmo Circadiano/fisiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Hipocampo/metabolismo , Fígado/metabolismo , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , Receptor CB1 de Canabinoide/metabolismo , Traumatismo por Reperfusão/metabolismoRESUMO
Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
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Córnea , Neovascularização da Córnea , Nanopartículas , Soluções Oftálmicas , Neovascularização da Córnea/tratamento farmacológico , Animais , Nanopartículas/química , Soluções Oftálmicas/química , Córnea/metabolismo , Córnea/efeitos dos fármacos , Camundongos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/farmacologia , Tamanho da Partícula , Humanos , Masculino , Camundongos Endogâmicos C57BL , CoelhosRESUMO
BACKGROUND: Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive symptoms in older adults, but the optimal dose for different exercise types remains unclear. As such, the aim of this meta-analysis was to examine the dose-response relationship between overall and specific types of exercise with depression symptoms in older adults. METHODS: This systematic review and network meta-analysis included a search of PubMed, Medline, Embase, PsycINFO, Cochrane library, and Web of Science for randomized controlled trials of exercise in older adults with depression symptoms from inception to 15 July 2023. Comprehensive data extraction covered dose, treatment regimen, demographics and study duration. Dosage metrics, encompassing METs-min/week, were scrutinized in correlation with the Minimal Clinically Importance Difference (MCID). RESULTS: A total of 47 studies involving 2895 participants and 7 kinds of exercise were included in the review. Without considering the dose, the results of our network meta-analysis indicated that Walking was the most effective in alleviating depression in older adults, in addition to Aerobic exercise (AE), Yoga, Qigong, Resistance training (RT), and Tai Chi (TC), which were equally effective. However, the results of the dose-response analysis found that Aerobic exercise was most effective at a dose of 1000 METs-min/week. It is noteworthy that Walking is significantly effective in alleviating depressive symptoms in older adults at very low doses. In terms of clinical benefits, we found that overall exercise doses in the range of 600 ~ 970 METs-min/week were clinically effective. Considering the specific types of exercise, Aerobic exercise, Resistance training, Walking, and Yoga were found to be effective at doses ranging from 820 ~ 1000 METs-min/week, 520 ~ 1000 METs-min/week, 650 ~ 1000 METs-min/week, 680 ~ 1000 METs-min/week, respectively. At the same time, we found that when the age exceeded 81 years, even when participating in exercise, it did not achieve the effect of alleviating depressive symptoms in older adults. CONCLUSIONS: In conclusion, including Walking, AE, Yoga, Qigong, RT, and TC, effectively alleviate depressive symptoms in older adults. Furthermore, we established statistically and clinically significant threshold doses for various exercise types. Early initiation of exercise is beneficial, but its efficacy diminishes from the age of 80, and beyond 81, exercise no longer significantly alleviates depressive symptoms.
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Depressão , Metanálise em Rede , Humanos , Idoso , Depressão/terapia , Depressão/psicologia , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Exercício Físico/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
OBJECTIVES: Peri-implant diseases, being the most common implant-related complications, significantly impact the normal functioning and longevity of implants. Experimental models play a crucial role in discovering potential therapeutic approaches and elucidating the mechanisms of disease progression in peri-implant diseases. This narrative review comprehensively examines animal models and common modeling methods employed in peri-implant disease research and innovatively summarizes the in vitro models of peri-implant diseases. MATERIALS AND METHODS: Articles published between 2015 and 2023 were retrieved from PubMed/Medline, Web of Science, and Embase. All studies focusing on experimental models of peri-implant diseases were included and carefully evaluated. RESULTS: Various experimental models of peri-implantitis have different applications and advantages. The dog model is currently the most widely utilized animal model in peri-implant disease research, while rodent models have unique advantages in gene knockout and systemic disease induction. In vitro models of peri-implant diseases are also continuously evolving to meet different experimental purposes. CONCLUSIONS: The utilization of experimental models helps simplify experiments, save time and resources, and promote advances in peri-implant disease research. Animal models have been proven valuable in the early stages of drug development, while technological advancements have brought about more predictive and relevant in vitro models. CLINICAL RELEVANCE: This review provides clear and comprehensive model selection strategies for researchers in the field of peri-implant diseases, thereby enhancing understanding of disease pathogenesis and providing possibilities for developing new treatment strategies.
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Implantes Dentários , Modelos Animais de Doenças , Peri-Implantite , Animais , Humanos , CãesRESUMO
A bioinspired semisynthesis of human-interleukin-6 bearing N-glycan at Asn143 (143glycosyl-IL-6) was performed by intentional glycosylation effects and protein folding chemistry for regioselective peptide-backbone activation. 143Glycosyl-IL-6 is a genetically coded cytokine, but isolation was difficult owing to a tiny amount. IL6-polypeptide (1-141-position) with an intentionally inserted cysteine at 142-position was expressed in E. coli. The expressed polypeptide was treated with a chemical folding process to make a specific helices bundle conformation through native two-disulfide bonds (43-49 and 72-82). Utilizing the successfully formed free-142-cysteine, sequential conversions using cyanation of 142-cysteine, hydrazinolysis, and thioesterification created a long polypeptide (1-141)-thioester. However, the resultant polypeptide-thioester caused considerable aggregation owing to a highly hydrophobic peptide sequence. After the reduction of two-disulfide bonds of polypeptide (1-141)-thioester, an unprecedented hydrophilic N-glycan tag was inserted at the resultant cysteine thiols. The N-glycan tags greatly stabilized polypeptide-thioester. The subsequent native chemical ligation and desulfurization successfully gave a whole 143glycosyl-IL-6 polypeptide (183-amino acids). Removal of four N-glycan tags and immediate one-pot in vitro folding protocol efficiently produced the folded 143glycosyl-IL-6. The folded 143glycosyl-IL-6 exhibited potent cell proliferation activity. The combined studies with molecular dynamics simulation, semisynthesis, and bioassays predict the bioactive conformation of latent 143glycosyl-IL-6.
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Semisynthesis using recombinant polypeptides is a powerful approach for the synthesis of proteins having a variety of modifications. Peptide thioesters, of which the peptide C-terminus is activated by a thioester, are utilized for coupling peptide building blocks. Biological methods employing intein have been a center for the C-terminal thioesterification of recombinant polypeptides. Chemical activation has emerged as an alternative methodology for synthesizing peptide thioesters from recombinant polypeptides. Chemical reactions are compatible with various solutions containing organic solvents, chaotropic reagents, or detergents that are generally incompatible with biomolecules such as intein. Despite the potential utility of chemical activation, available methods remain limited. This article introduces the methods for the chemical activation of a peptide C-terminus applied to the chemical synthesis of proteins. By showcasing these methodologies, we aim to accelerate the advancement of new chemical reactions and methodologies and broaden the frontiers for the chemical synthesis of proteins.
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This work demonstrates the synthesis of a variety of perfluoroalkyl heterocycles via a visible-light-driven radical-polar crossover cyclization strategy. In this process, single-electron reduction/SNV-type/cyclization sequences follow the radical addition reaction of a diazoester, which differs from the current role of diazoesters as radical precursors/acceptors. This transformation demonstrates excellent functional group compatibility and allows for the modification of many bioactive molecules with diazoesters. Such a reaction could represent a novel approach to the photochemical transformation of diazo compounds.
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Coking wastewater (CWW) treatment is difficult due to its complex composition and high biological toxicity. Iron-carbon mediators was used to enhance the treatment of CWW through iron-carbon microelectrolysis (ICME). The results indicated that the removal rate of COD and phenolic compounds were enhanced by 24.1 % and 23.5 %, while biogas production and methane content were promoted by 50 % and 7 %. Microbial community analysis indicated that iron-carbon mediators had a transformative impact on the reactor's performance and dependability by enriching microorganisms involved in direct and indirect electron transfer, such as Anaerolineae and Methanothrix. The mediator also produced noteworthy gains in LB-EPS and TB-EPS, increasing by roughly 109.3 % and 211.6 %, respectively. PICRISt analysis demonstrated that iron-carbon mediators effectively augment the abundance of functional genes associated with metabolism, Citrate cycle, and EET pathway. This study provides a new approach for CWW treatment.
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Reatores Biológicos , Carbono , Coque , Ferro , Águas Residuárias , Águas Residuárias/química , Ferro/metabolismo , Ferro/química , Carbono/química , Carbono/metabolismo , Metano/metabolismo , Eliminação de Resíduos Líquidos/métodos , Biocombustíveis , Análise da Demanda Biológica de Oxigênio , Resíduos Industriais , Poluentes Químicos da Água/metabolismo , Fenóis/metabolismo , Bactérias/metabolismo , Bactérias/genéticaRESUMO
The traditional Chinese Baijiu brewing process utilizes natural inoculation and open fermentation. The microbial composition and abundance in the microecology of Baijiu brewing often exhibit unstable characteristics, which directly results in fluctuations in Baijiu quality. The microbiota plays a crucial role in determining the quality of Baijiu. Analyzing the driving effect of technology and raw materials on microorganisms. Elucidating the source of core microorganisms and interactions between microorganisms, and finally utilizing single or multiple microorganisms to regulate and intensify the Baijiu fermentation process is an important way to achieve high efficiency and stability in the production of Baijiu. This paper provides a systematic review of the composition and sources of microbiota at different brewing stages. It also analyzes the relationship between raw materials, brewing processes, and brewing microbiota, as well as the steps involved in the implementation of brewing microbiota regulation strategies. In addition, this paper considers the feasibility of using Baijiu flavor as a guide for Baijiu brewing regulation by synthesizing the microbiota, and the challenges involved. This paper is a guide for flavor regulation and quality assurance of Baijiu and also suggests new research directions for regulatory strategies for other fermented foods.
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Magnetite (Fe3O4) is extensively applied to enhance efficacy of anaerobic biological treatment systems designed for refractory wastewater. However, the interaction between magnetite, organic pollutants and microorganisms in digestion solution is constrained by magnetic attraction. To overcome this limitation and prevent magnetite aggregation, the core-shell composite materials with carbon outer layer enveloping magnetite core particles (Fe3O4@C) were developed. The impact of Fe3O4@C with varying Fe3O4 mass ratios on the anaerobic methanogenesis capability in the treatment of chloramphenicol (CAP) wastewater was investigated. Experimental results demonstrated that Fe3O4@C not only enhanced chemical oxygen demand (COD) removal efficiency and biogas production by 2.42-13.18% and by 7.53%-23.25%, respectively, but also reduced the inhibition of microbial activity caused by toxic substances and the secretion of extracellular polymeric substances (EPS) by microorganisms responding to adverse environments. The reinforcing capability of Fe3O4@C increased with the rise in Fe3O4 content. Furthermore, High-throughput pyrosequencing illustrated that Fe3O4@C enhanced the relative abundance of Methanobacterium, a hydrogen-utilizing methanogen capable of participating in direct interspecies electron transfer (DIET), by 5%. Metagenomic analysis indicated that Fe3O4@C improved the decomposition of complex organics into simpler compounds by elevating functional genes encoding key enzymes associated with organic matter metabolism, acetogenesis, and hydrogenophilic methanogenesis pathways. These findings suggest that Fe3O4@C have the potential to strengthen both the hydrogenophilic methanogenesis and DIET processes. This insight offers a novel perspective on the anaerobic bioaugmentation of high-concentration refractory organic wastewater.
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Electrospinning is an effective method to prepare nanofibers at present. Aiming at problems such as low spinnable viscosity and the low productivity of the traditional multi-needle, a radial nozzle was proposed in this paper. In order to solve the problem of end effects in multi-nozzle electrospinning, COMSOL Multiphysics 6.0 software was used to simulate the electric field in electrospinning with seven radial nozzles. And the influence on the electric field intensity and distribution of the structural parameters of the radial nozzle, including the number, length, tip-shape, and tip-pointing direction of the vanes, were studied. Then, the electric field intensity of any point on the central axis of a radial nozzle was obtained based on the principle of electric field superposition, and then the rotation angle of the vanes corresponding to the minimum Coulomb repulsion force on the target point was deduced. At last, the method of electric field homogenization of a rotating vane arrangement was obtained. In the simulation, the strength and homogenization of the electric field were taken as the research objective, and the optimum structure parameters of the radial nozzle were obtained; the uniform theory of the electric field based on the orientation of the vanes was verified. Then, electrospinning with seven radial nozzles was performed, and it was found that each radial nozzle can produce multiple jets during electrospinning, and the prepared electrospun membranes have even thickness and high porosity. What is more, the fibers are relatively finer and more uniform.
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Spherical agglomeration (SA) is a processing technique that enhances the physical properties of particles, reduces the number of unit operations in pharmaceutical manufacturing, and improves process efficiency. However, one of the limitations of SA is its high nonlinearity, which makes scalability a challenge. This prospective study was designed to realize the optimization of SA process parameters of aspirin, the world's first and most widely used nonsteroidal anti-inflammatory drug, by developing a green SA model through response surface methodology. First, Plackett-Burman experiments were conducted to identify the key operating variables affecting SA, and Sustainability Index (STI) was defined to evaluate the effects of these operating variables on the SA and the energy input to the environment during the post-processing process. Furthermore, the effects of three independent variables on mean size, yield, and STI were investigated based on Box-Behnken design. A second-order regression equation with response values was developed to optimize the above three objectives. As a result, the spherical products were obtained with excellent powder properties, including anti-caking property, filtration property, and tableting performance compared to the raw materials. This work provides an experimental and modelling basis for the further application of this environmentally-friendly SA technology.
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During the ultrasound multi-layer focused scanning inspection process, the sequential images characterizing the defect morphology suffer from inter-layer contour information loss, which causes a reduction in the accuracy of defect 3D reconstruction, subsequently leading to errors in the characterization of the defect size and morphology. In order to address the above issues, a new method based on the Attention-based Residual Completion Network (ARC) is proposed for ultrasonic point cloud completion to characterize metal defects. Firstly, the ARC network extracts global contour morphological features and local edge detail features from the ultrasonic point cloud through consecutive residual convolutions. Subsequently, the two sets of features are concatenated and finally fed into a decoder based on self-attention, realizing the reconstruction of lost contour information and enhancing the 3D reconstruction accuracy of defects. In the experiment, an ultrasonic microscope was used to inspect actual steel plates. The internal defects were then completed using the ARC network, and the completion results were compared with the metallographic images of the defects. The experiment results indicated that, after completion, the characterization accuracy of defect morphology and sizes is enhanced by an average of 10.31 %. The ARC network provides a novel method for high-precision 3D characterization of internal defects in metal materials.
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Background: Numerous studies have already identified an association between excessive consumption of red meat and colorectal cancer (CRC). However, there has been a lack of detailed understanding regarding the disease burden linked to diet high in red meat and CRC. Objective: We aim to offer evidence-based guidance for developing effective strategies that can mitigate the elevated CRC burden in certain countries. Methods: We used the data from the Global Burden of Disease (GBD) Study 2019 to evaluate global, regional, and national mortality rates and disability-adjusted Life years (DALYs) related to diet high in red meat. We also considered factors such as sex, age, the socio-demographic index (SDI), and evaluated the cross-national inequalities. Furthermore, we utilized DALYs data from 204 countries and regions to measure cross-country inequalities of CRC by calculating the slope index of inequality and concentration index as standard indicators of absolute and relative inequalities. Discussion: The results show that globally, the age-standardized mortality rate (ASMR) and age-standardized disability adjusted life year rate (ASDR) related to CRC due to diet high in red meat have decreased, with estimated annual percent change (EAPCs) of -0.32% (95% CI -0.37 to -0.28) and-0.18% (95% CI -0.25 to -0.11). Notably, the burden was higher among males and the elderly. The slope index of inequality rose from 22.0 (95% CI 18.1 to 25.9) in 1990 to 32.9 (95% CI 28.3 to 37.5) in 2019 and the concentration index fell from 59.5 (95% CI 46.4 to 72.6) in 1990 to 48.9 (95% CI 34.6 to 63.1) in 2019. Also, according to our projections, global ASDR and ASMR might tend to increase up to 2030. Conclusion: ASMR and ASDR for CRC associated with high red meat diets declined globally from 1990 to 2019, but the absolute number of cases is still rising, with men and the elderly being more affected. CRC associated with diets high in red meat exhibits significant income inequality, placing a disproportionate burden on wealthier countries. Moreover, according to our projections, ASMR and ASDR are likely to increase globally by 2030. In order to address this intractable disease problem, understanding changes in global and regional epidemiologic trends is critical for policy makers and others.
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Punch sticking during tablet manufacturing is a prevalent issue for many active pharmaceutical ingredients (APIs) encountered by the pharmaceutical industry. Tenofovir amibufenamide fumarate (TMF), a heavyweight drug for the treatment of hepatitis B, was selected as a model drug due to its tendency to punch sticking during tablet compression. In this study, the cause of sticking was explored by investigating crystal habits, excipients and structure characteristics. The difference in sticking of three crystal habits can be visually represented through direct compression experiments on powdered samples and analysis of crystal surfaces. The excipients play a direct role in decreasing the probability of sticking, and the extent of sticking can be assessed by measuring the tensile strength of the tablet. Additionally, the plasticity index was utilized to theoretically analyze the potential enhancements of four excipients. These experimental results indicate that the block-shaped crystals have superior ability of anti-sticking and that suitable excipients can significantly improve the sticking situation of TMF. Ultimately, the phenomenon of punch sticking was additionally examined through computational calculations, focusing on the mechanical characteristics of TMF molecules and intermolecular interactions. The strategy of combining experiments and simulation calculations has broader significance for the study of drug production.
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Excipientes , Excipientes/química , Comprimidos/química , Pressão , Resistência à Tração , Tenofovir , Composição de Medicamentos/métodosRESUMO
Background: Daqu is an essential starter for baijiu brewing in China. However, the microbial enrichment and metabolic characteristics of Daqu formed at different fermentation temperatures are still unclear. Methods: High-throughput sequencing technology and the non-targeted metabolomics were used to compare the microbial communities and metabolites of Taorong-type high-temperature Daqu and middle-temperature Daqu. In this study, the relationship between microorganisms and metabolites was established. Results: The study found that the composition and metabolites of the microbial community differed due to the difference in Daqu-making temperature. The bacterial diversity of Taorong-type high-temperature Daqu was higher than that of middle-temperature Daqu, while the fungal community diversity of Taorong-type middle-temperature Daqu was higher than that of high temperature Daqu. A total of 1,034 differential metabolites were screened from the two types of Daqu, and 76 metabolites with significant differences were detected (P < 0.001 and variable importance in projection (VIP) > 1.15). Tetraacetylethylenediamine is the metabolite with the largest differential fold among the 76 differential metabolites, which can be used as a potential marker metabolite of high-temperature Daqu. Conclusion: This study helps elucidate the microbial assembly mechanisms and functional expression under different processing conditions through a further understanding of the composition and metabolic profile differences of different types of Daqu microflora in Taorong-type baijiu.
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Microbiota , Micobioma , Temperatura , Metabolômica , ChinaRESUMO
BACKGROUND: Environmental factors like air pollution and temperature can trigger acute myocardial infarction (AMI). However, the link between large-scale weather patterns (synoptic types) and AMI admissions has not been extensively studied. This research aimed to identify the different synoptic air types in Beijing and investigate their association with AMI occurrences. METHODS: We analyzed data from Beijing between 2013 and 2019, encompassing 2556 days and 149,632 AMI cases. Using principal component analysis and hierarchical clustering, classification into distinct synoptic types was conducted based on weather and pollution measurements. To assess the impact of each type on AMI risk over 14 days, we employed a distributed lag non-linear model (DLNM), with the reference being the lowest risk type (Type 2). RESULTS: Four synoptic types were identified: Type 1 with warm, humid weather; Type 2 with warm temperatures, low humidity, and long sunshine duration; Type 3 with cold weather and heavy air pollution; and Type 4 with cold temperatures, dryness, and high wind speed. Type 4 exhibited the greatest cumulative relative risk (CRR) of 1.241 (95%CI: 1.150, 1.339) over 14 days. Significant effects of Types 1, 3, and 4 on AMI events were observed at varying lags: 4-12 days for Type 1, 1-6 days for Type 3, and 1-11 days for Type 4. Females were more susceptible to Types 1 and 3, while individuals younger than 65 years old showed increased vulnerability to Types 3 and 4. CONCLUSION: Among the four synoptic types identified in Beijing from 2013 to 2019, Type 4 (cold, dry, and windy) presented the highest risk for AMI hospitalizations. This risk was particularly pronounced for males and people under 65. Our findings collectively highlight the need for improved methods to identify synoptic types. Additionally, developing a warning system based on these synoptic conditions could be crucial for prevention.