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The widespread occurrence of Microplastics (MPs) has aroused increasing concerns. However, the fate of MPs in remote areas remains poorly understood. Here, the spatial distribution, potential sources, and environmental risks of MPs were analyzed in the headstream of the Yellow River on the eastern Tibetan Plateau. The average MP abundances are (464.3 ± 200.9) items /m3 and (63.6 ± 34.7) items /kg in the water and sediment, respectively, with both majority polymer is polypropylene (PP) (water: 28.7 %; sediment: 25.2 %). The structural equation modeling and conditional fragmentation model were used in this study to analyze the source and impact factors of riverine MPs. According to the models, MPs were influenced by water quality parameters and anthropogenic activities. Furthermore, the source analysis through MP characteristics and statistical analysis showed that the main sources of MPs include domestic sewage, plastic waste disposal, and the use of agricultural plastic film. Moreover, the differences in MP sources along the river were distinguished by the conditional fragmentation model. The potential ecological risks of MPs were evaluated, resulting in relatively medium-to-low levels. Our findings will serve as important references for improving the understanding of the plateau environmental impacts of MP distribution in the headwaters of large rivers.
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The APOE 4 allele remains the primary genetic risk factor for sporadic Alzheimer's disease, whereas the APOE 2 allele emerges as a protective factor. Therapeutic approaches in murine models with human APOE alleles, such as modulating APOE levels and converting isoforms, show efficacy. However, there is a lack of in vitro APOE2-mutant human neuronal models. Hence, in this study, we generated human induced pluripotent stem cells (hiPSCs) from the peripheral blood mononuclear blood cells (PMBC) of a 42-year-old female donor carrying the APOE-ε2/ε2 allele. The newly generated hiPSC displayed normal karyotype and could differentiate into three germ layers. Besides, they retained their original genotype and expressed pluripotency markers.
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BACKGROUND: Liver injury post allogeneic hematopoietic stem cell transplantation (Allo-HSCT), particularly first-time occurrences, is a prevalent and severe complication. METHODS: Clinical data from 262 patients treated at 3 medical centers in Shenzhen, China, between January 2018 and December 2021 were retrospectively collected. Risk factors and outcomes of initial liver injury post allo-HSCT were analyzed. RESULTS: Liver injury occurred in 70.8% of patients, with drug-induced liver injury (DILI) being the most common cause. Other causes included graft-versus-host disease (GVHD) and veno-occlusive disease (VOD). Pre-transplant HBsAg positivity was a significant risk factor. Differences in the timing and survival outcomes were observed among patients with different causes and types of liver injury. Patients with VOD or hepatic aGVHD had lower overall survival compared to those with DILI or hepatic cGVHD. Patients with isolated enzyme elevation had a more favorable prognosis than those with isolated bilirubin elevation or simultaneous enzyme and bilirubin elevation. CONCLUSION: Findings of our study serve as a crucial resource for clinicians, assisting in the challenging task of diagnosing and managing liver injuries after allo-HSCT, especially when it occurs for the first time, which may ultimately help to reduce early treatment-related mortality and enhance the long-term survival of transplant recipients.
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Per- and polyfluoroalkyl substances (PFASs), especially as emerging compounds, have been widely detected in coastal seawater. However, the awareness of the interaction between PFASs at environmental concentrations and marine diatoms is still limited. In this study, Skeletonema costatum was exposed to three co-existing PFASs, namely hexafluoropropylene oxide dimer acid (HFPO-DA), 6 : 2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES), and perfluoroethylcyclohexane sulfonate (PFECHS) (15-300 ng L-1 in total), for 14 days. In the 300 ng L-1 test group, the significant down-regulation of chlorophyllide a in porphyrin metabolism, light-harvesting capacity and carbon fixation were the main inhibitory mechanisms of photosynthesis by emerging PFASs at the 14th day compared to the 8th day, which indicated that they may have a shading effect on S. costatum. Additionally, mixed PFASs could also activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by up-regulating gene gp91 and down-regulating genes CaM4 and NDPK2 to generate excessive ROS. This resulted in a decrease in the algal biomass, which would further weaken the primary productivity of S. costatum. Our findings illustrated that mixed emerging PFASs at environmental concentrations may interfere with the carbon balance of marine diatoms.
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BACKGROUND: Talent transfer (TT) program is an appropriate approach to address the talent gap evident in specific sports activities, while little is known about the injury characteristics of snowboarding athletes involved in the TT program. OBJECTIVE: To determine the epidemiology of injuries among snowboarders involved in the TT program. METHODS: A total of 244 athletes who were not previously engaged in winter sports were selected for training in snowboarding that lasted for 109 days. The injuries and at-risk exposures (A-Es) data were recorded by physicians. Injury rates (IRs), incidence rate ratios (IRRs), and injury proportion ratios (IPRs) were calculated and compared by sex and age groups. RESULTS: The overall and time loss (TL) IR were 32.4/1000 A-Es and 12.2/1000 A-Es respectively. The overall and non-time loss (NTL) IRR were higher for female athletes than for male athletes. Additionally, the overall IRR and TL-IRR for female athletes were higher in those athletes who aged ≤15 years old. Over 93% of TL injuries resulted in participation restriction time of ≤7 days (male athletes, 93.94%; female athletes, 94.10%). Trunk (28.43%), knee joints (21.33%), and hand/wrist (16.53%) were found as the common sites of injury in both female and male athletes. The most frequent type of injury was contusion (male athletes: 53.00%, female athletes: 59.10%) resulted from ground/apparatus contact (male athletes: 75.10%, female athletes: 75.20%). CONCLUSION: The risk injury among snowboarding athletes involved in the TT program during the first snow season training was found noticeable, especially for younger female athletes. The high incidence of ground/apparatus contact-related injuries suggested the necessity of specifically designed training programs and braces for snowboarding athletes involved in the TT program.
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Atletas , Traumatismos em Atletas , Esqui , Humanos , Feminino , Masculino , Estudos Prospectivos , Traumatismos em Atletas/epidemiologia , Adolescente , Adulto , Esqui/lesões , Adulto Jovem , Incidência , Fatores de RiscoRESUMO
Plant-mediated interactions between herbivores play an important role in regulating the composition of herbivore community. The fall armyworm (FAW), Spodoptera frugiperda, which has become one of the most serious pests on corn in China since it invaded in 2018, has been found feeding rice in the field. However, how FAW interacts with native rice insect pests remains largely unknown. Here, we investigated the interaction between FAW and a resident herbivore, striped stem borer (SSB, Chilo suppressalis) on rice. The infestation of rice leaf sheaths (LSs) by SSB larvae systemically enhanced the level of jasmonic acid (JA), abscisic acid (ABA), and trypsin proteinase inhibitors (TPIs), reduced relative water content (RWC) in leaf blades (LBs), and suppressed the growth of FAW larvae. In contrast, because FAW larvae infested LBs and did not affect defence responses in LSs, they did not influence the performance of SSB larvae. Using different mutants, together with bioassays and chemical analysis, we revealed that SSB-induced suppression of FAW larvae growth depended on both the SSB-activated JA pathway and RWC in LBs, whereas the ABA pathway activated by SSB larvae promoted the growth of FAW larvae by impeding water loss. These results provide new insights into mechanisms underlying plant-mediated interactions between herbivores.
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INTRODUCTION: Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease of the intestine. The intestinal microbiota is essential in the occurrence and development of UC. Gut gases are produced via bacterial fermentation or chemical interactions, which can reveal altered intestinal microbiota, abnormal cellular metabolism, and inflammation responses. Recent studies have demonstrated that UC patients have an altered gut gas metabolism. AREAS COVERED: In this review, we integrate gut gas metabolism advances in UC and discuss intestinal gases' clinical values as new biomarkers or therapeutic targets for UC, providing the foundation for further research. Literature regarding gut gas metabolism and its significance in UC from inception to October 2023 was searched on the MEDLINE database and references from relevant articles were investigated. EXPERT OPINION: Depending on their type, concentration, and volume, gut gases can induce or alleviate clinical symptoms and regulate intestinal motility, inflammatory responses, immune function, and oxidative stress, significantly impacting UC. Gut gases may function as new biomarkers and provide potential diagnostic or therapeutic targets for UC.
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Amaranthus roxburghianus H.W. Kung 1935, belonging to the Amaranthaceae family, is recognized for its significant medicinal properties. However, molecular research on this species has been limited. This study represents the inaugural documentation of the sequencing and assembly of the complete plastome of A. roxburghianus. The genome spans a total length of 149,969 base pairs (bp), exhibiting a conventional quadripartite structure. This structure comprises a large single-copy (LSC) region of 83,917 bp, a small single-copy (SSC) region of 18,124 bp, and two inverted repeat (IR) regions, each extending to 23,964 bp. In its entirety, the A. roxburghianus plastome encompasses 128 genes, of which 107 are unique, encompassing 77 individual protein-coding genes, 26 unique tRNA genes, and four unique rRNA genes. Phylogenetic analysis has shown a close resemblance between A. roxburghianus and A. polygonoides, both part of the subgenus Albersia. Although the genus Amaranthus is roughly divided into three subgenera, additional plastid genomic data are required for a more accurate assignment of A. albus and A. blitoides. The sequencing of this plastome is a significant step forward, likely to expedite the development of molecular markers and significantly contribute to genetic assays involving this distinctive species.
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Depression is a common non-motor symptom of Parkinson's disease. Previous studies demonstrated that hydroxysafflor yellow A had properties of improving motor symptoms of Parkinson's disease. The effect of hydroxysafflor yellow A on depression in Parkinson's disease mice is investigated in this study. To induce Parkinson's disease model, male Swiss mice were exposed to rotenone (30 mg/kg) for 6 weeks. The chronic unpredictable mild stress was employed to induce depression from week 3 to week 6. Sucrose preference, tail suspension, and forced swimming tests were conducted. Golgi and Nissl staining of hippocampus were carried out. The levels of dopamine, 5-hydroxytryptamine and the expression of postsynaptic density protein 95, brain-derived neurotrophic factor in hippocampus were assayed. It showed that HSYA improved the depression-like behaviors of Parkinson's disease mice. Hydroxysafflor yellow A attenuated the injury of nerve and elevated contents of dopamine, 5-hydroxytryptamine in hippocampus. Treatment with hydroxysafflor yellow A also augmented the expression of postsynaptic density protein 95 and brain-derived neurotrophic factor. These findings suggest that hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice through regulating the contents of postsynaptic density protein 95 and brain-derived neurotrophic factor, therefore protecting neurons and neuronal dendrites of the hippocampus.
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Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo , Chalcona , Depressão , Hipocampo , Quinonas , Serotonina , Animais , Quinonas/farmacologia , Quinonas/uso terapêutico , Chalcona/análogos & derivados , Chalcona/farmacologia , Chalcona/uso terapêutico , Masculino , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Comportamento Animal/efeitos dos fármacos , Serotonina/metabolismo , Dopamina/metabolismo , Rotenona/farmacologia , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/psicologiaRESUMO
BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness. METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy. RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness. CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.
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Colite Ulcerativa , Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , Sideróforos , Humanos , Colite Ulcerativa/terapia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/genética , Masculino , Feminino , Fezes/microbiologia , Adulto , Pessoa de Meia-Idade , Microbioma Gastrointestinal/genética , Sideróforos/metabolismo , Resultado do Tratamento , Bactérias/genética , Genes Bacterianos , Dosagem de Genes , Curva ROCRESUMO
The epigenetic target CREB (cyclic-AMP responsive element binding protein) binding protein (CBP) and its homologue p300 were promising therapeutic targets for the treatment of acute myeloid leukemia (AML). Herein, we report the design, synthesis, and evaluation of a class of CBP/p300 PROTAC degraders based on our previously reported highly potent and selective CBP/p300 inhibitor 5. Among the compounds synthesized, 11c (XYD129) demonstrated high potency and formed a ternary complex between CBP/p300 and CRBN (AlphaScreen). The compound effectively degraded CBP/p300 proteins and exhibited greater inhibition of growth in acute leukemia cell lines compared to its parent compound 5. Furthermore, 11c demonstrated significant inhibition of tumor growth in a MOLM-16 xenograft model (TGI = 60%) at tolerated dose schedules. Our findings suggest that 11c is a promising lead compound for the treatment of AML.
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Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Camundongos , Proteína p300 Associada a E1A/antagonistas & inibidores , Proteína p300 Associada a E1A/metabolismo , Relação Estrutura-Atividade , Descoberta de Drogas , Proteína de Ligação a CREB/antagonistas & inibidores , Proteína de Ligação a CREB/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Fatores de Transcrição de p300-CBP/metabolismo , Proteólise/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, ß-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of ß-caryophyllene against T. castaneum eggs and pupae are LD50 (median lethal dose, 50%) = 0.156 mg/cm2 and ED50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of ß-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of ß-caryophyllene and limonene was 7:1, the LD50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm2, displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of ß-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, ß-caryophyllene, and limonene.
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Inseticidas , Lamiaceae , Óleos Voláteis , Pupa , Tribolium , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Tribolium/efeitos dos fármacos , Lamiaceae/química , Inseticidas/farmacologia , Inseticidas/química , Pupa/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Limoneno/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/químicaRESUMO
The electronic structure of the molecule is significantly influenced by the number of conjugated C=C bonds. In this work, the influence of the conjugated C=C bonds of the SNCN derivatives on the excited state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) properties are studied by density functional theory (DFT) and time-dependent density functional theory (TDDFT). The calculation level is proved to be reasonable by calculating electronic spectra. The hydrogen bond parameters, infrared vibrational frequency (IR), reduction density gradient (RDG) isosurface, topological analysis and potential energy curves of SNCN derivatives in ground state (S0) and the first excited state (S1) are analyzed. According to theoretical research results, ESIPT reaction has a higher likelihood of occurring in the S1 state. Moreover, the ESIPT reaction becomes more challenging to occur with the number of conjugated C=C bonds rising. Finally, the analyses of the frontier molecular orbitals (FMOs), dipole moment and charge transfer transition confirm that the ICT effect is aided by the increased number of conjugated C=C bonds. This work indicates that the number of conjugated C=C bonds can regulate the ESIPT and ICT processes, which provides guidance for the study of fluorescent groups with similar characteristics.
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Microplastics (MPs) have been found in remote high-altitude areas, but the main source and migration process remained unclear. This work explored the characteristics and potential sources of MPs in the Yarlung Tsangpo River Basin. The average abundances of MPs in water, sediment, and soil samples were 728.26 ± 100.53 items/m3, 43.16 ± 5.82 items/kg, and 61.92 ± 4.29 items/kg, respectively, with polypropylene and polyethylene as the main polymers. The conditional fragmentation model revealed that the major source of MPs lower than 4000 m was human activities, while that of higher than 4500 m was atmospheric deposition. Community analysis was further conducted to explore the migration process and key points of MPs among different compartments in the basin. It was found that Lhasa (3600 m) and Shigatse (4100 m) were vital sources of MPs inputs in the midstream and downstream, respectively. This work would provide new insights into the fate of MPs in high-altitude areas.
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Altitude , Monitoramento Ambiental , Microplásticos , Rios , Rios/química , Microplásticos/análise , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Sedimentos Geológicos/análiseRESUMO
AKT, also known as protein kinase B (PKB), serves as a crucial regulator of numerous biological functions, including cell growth, metabolism, and tumorigenesis. Increasing evidence suggests that the kinase activity of AKT is regulated via ubiquitination by various E3 ligase enzymes in response to different stimuli. However, the molecular mechanisms underlying insulin-induced AKT ubiquitination are not yet fully understood. Here, we show that activation of the insulin receptor (IR) leads to enhanced ubiquitination of AKT1 at K8 and K14 residues, facilitated by the cytosolic E3 ubiquitin ligase enzyme, TRAF6. Further investigation using AKT1 mutants with modified nucleocytoplasmic shuttling properties reveals that TRAF6-mediated AKT1 ubiquitination occurs within the nucleus in a ß-Arr2-dependent manner. The nuclear entry of TRAF6 depends on importin ß1, while ß-Arr2 regulates this process by facilitating the interaction between TRAF6 and importin ß1. Additionally, the ubiquitination of AKT1 is essential for its translocation to the activated IR on the plasma membrane, where it plays a functional role in recruiting Glut4 and facilitating glucose uptake. This study uncovers the cellular components and processes involved in insulin-induced ubiquitination and activation of AKT1, providing insights and detailed strategies for manipulating AKT1.
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Núcleo Celular , Insulina , Proteínas Proto-Oncogênicas c-akt , Fator 6 Associado a Receptor de TNF , Ubiquitinação , beta-Arrestina 2 , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ubiquitinação/fisiologia , Ubiquitinação/efeitos dos fármacos , Insulina/metabolismo , Insulina/farmacologia , Animais , Fator 6 Associado a Receptor de TNF/metabolismo , Núcleo Celular/metabolismo , Camundongos , Humanos , beta-Arrestina 2/metabolismo , beta-Arrestina 2/genética , Células HEK293RESUMO
The coexistence of amyloid-ß (Aß) and human islet amyloid polypeptide (hIAPP) in the brain and pancreas is associated with an increased risk of Alzheimer's disease (AD) and type 2 diabetes (T2D) due to their coaggregation and cross-seeding. Despite this, the molecular mechanisms underlying their interaction remain elusive. Here, we systematically investigated the cross-talk between Aß and hIAPP using atomistic discrete molecular dynamics (DMD) simulations. Our results revealed that the amyloidogenic core regions of both Aß (Aß10-21 and Aß30-41) and hIAPP (hIAPP8-20 and hIAPP22-29), driving their self-aggregation, also exhibited a strong tendency for cross-interaction. This propensity led to the formation of ß-sheet-rich heterocomplexes, including potentially toxic ß-barrel oligomers. The formation of Aß and hIAPP heteroaggregates did not impede the recruitment of additional peptides to grow into larger aggregates. Our cross-seeding simulations demonstrated that both Aß and hIAPP fibrils could mutually act as seeds, assisting each other's monomers in converting into ß-sheets at the exposed fibril elongation ends. The amyloidogenic core regions of Aß and hIAPP, in both oligomeric and fibrillar states, exhibited the ability to recruit isolated peptides, thereby extending the ß-sheet edges, with limited sensitivity to the amino acid sequence. These findings suggest that targeting these regions by capping them with amyloid-resistant peptide drugs may hold potential as a therapeutic approach for addressing AD, T2D, and their copathologies.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Diabetes Mellitus Tipo 2 , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Simulação de Dinâmica Molecular , Doença de Alzheimer/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Humanos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Agregados ProteicosRESUMO
To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose.Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula.In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -8.73%, 1.37%, and -0.48%, respectively. The corresponding value was -11.15%, 1.99%, and -0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -12.63%, -6.47%, and -0.54% when the sampling time shifted.The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic.
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The construction of aerobic denitrification (AD) systems in an antibiotic-stressed environment is a serious challenge. This study investigated strategy of cyclic stress with concentration gradient (5-30 mg/L) of sulfamethoxazole (SMX) in a sequencing batch reactor (SBR), to achieve operation of AD. Total nitrogen removal efficiency of system increased from about 10 % to 95 %. Original response of abundant-rare genera to antibiotics was changed by SMX stress, particularly conditionally rare or abundant taxa (CRAT). AD process depends on synergistic effect of heterotrophic nitrifying aerobic denitrification bacteria (Paracoccus, Thauera, Hypomicrobium, etc). AmoABC, napA, and nirK were functionally co-expressed with multiple antibiotic resistance genes (ARGs) (acrR, ereAB, and mdtO), facilitating AD process. ARGs and TCA cycling synergistically enhance the antioxidant and electron transport capacities of AD process. Antibiotic efflux pump mechanism played an important role in operation of AD. The study provides strong support for regulating activated sludge to achieve in situ AD function.
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Reatores Biológicos , Desnitrificação , Sulfametoxazol , Sulfametoxazol/farmacologia , Aerobiose , Esgotos/microbiologia , Antibacterianos/farmacologia , Nitrogênio/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacosRESUMO
Immunoglobulin A nephropathy (IgAN) is a complex autoimmune disease with various underlying causes and significant clinical heterogeneity. There are large individual differences in its development, and the etiology and pathogenesis are still poorly understood. While it is known that immunobiological factors play a significant role in the pathophysiology of IgAN, the specific nature of these factors has yet to be fully elucidated. Numerous investigations have verified that cluster of differentiation 4+ (CD4+) and CD8+ T lymphocytes are involved in the immunopathogenesis of IgAN. Furthermore, certain data also point to γδT cells' involvement in the pathophysiology of IgAN. By thoroughly examining the mechanisms of action of these T cells in the context of IgAN, this review sheds light on the immunopathogenesis of the disease and its associated factors. The review is intended to provide reference value for the future research in this field and promising treatment clues for clinical patients.
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Porcine epidemic diarrhea virus (PEDV) has become a challenging problem in pig industry worldwide, causing significant profit losses. Lactobacillus rhamnosus GG (LGG) has been regarded as a safe probiotic strain and has been shown to exert protective effects on the intestinal dysfunction caused by PEDV. This study evaluated the effect of LGG on the gut health of lactating piglets challenged with PEDV. Fifteen piglets at 7 days of age were equally assigned into 3 groups (5 piglets per group): 1) control group (basal diet); 2) PEDV group: (basal diet + PEDV challenged); 3) LGG + PEDV group (basal diet + 3×109 CFU/pig/day LGG + PEDV). The trial lasted 11 days including 3 days of adaptation. The treatment with LGG was from D4 to D10. PEDV challenge was carried out on D8. PEDV infection disrupted the cell structure, undermined the integrity of the intestinal tract, and induced oxidative stress, and intestinal damage of piglets. Supplementation of LGG improved intestinal morphology, enhanced intestinal antioxidant capacity, and alleviated jejunal mucosal inflammation and lipid metabolism disorders in PEDV-infected piglets, which may be regulated by LGG by altering the expression of TNF signaling pathway, PPAR signaling pathway, and fat digestion and absorption pathway.