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An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Astragaloside IV is a significant chemical component derived from the medicinal plant Astragalus membranaceus. Despite the characterization of several glycosyltransferases from A. membranaceus, the complete biosynthetic pathway of astragaloside IV has not been fully elucidated. In this study, we propose a biosynthetic pathway for astragaloside IV that involves a sequence of oxidation-reduction reactions. The biosynthesis pathway from cycloastragenol to astragaloside IV encompasses four key steps: C-3 oxidation, 6-O-glucosylation, C-3 reduction, and 3-O-xylosylation. We identified a hydroxysteroid dehydrogenase AmHSD1 from A. membranaceus. AmHSD1 catalyzes the C-3 oxidation of cycloastragenol, yielding cycloastragenol-3-one, and the C-3 reduction of cycloastragenol-3-one-6-O-glucoside, resulting in cycloastragenol-6-O-glucoside. Additionally, the glycosyltransferases AmGT8 and AmGT1, previously reported by our groups, were identified as catalyzing the 6-O-glucosylation and 3-O-xylosylation steps, respectively. Astragaloside IV was successfully synthesized in transient expression in Nicotiana benthamiana using the combination of AmHSD1, AmGT8 and AmGT1. These results support the proposed four-step biosynthetic pathway and suggest that AmHSD1 probably plays a crucial role in the biosynthesis of astragaloside IV within A. membranaceus.
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Shape-morphing systems, which can perform complex tasks through morphological transformations, are of great interest for future applications in minimally invasive medicine1,2, soft robotics3-6, active metamaterials7 and smart surfaces8. With current fabrication methods, shape-morphing configurations have been embedded into structural design by, for example, spatial distribution of heterogeneous materials9-14, which cannot be altered once fabricated. The systems are therefore restricted to a single type of transformation that is predetermined by their geometry. Here we develop a strategy to encode multiple shape-morphing instructions into a micromachine by programming the magnetic configurations of arrays of single-domain nanomagnets on connected panels. This programming is achieved by applying a specific sequence of magnetic fields to nanomagnets with suitably tailored switching fields, and results in specific shape transformations of the customized micromachines under an applied magnetic field. Using this concept, we have built an assembly of modular units that can be programmed to morph into letters of the alphabet, and we have constructed a microscale 'bird' capable of complex behaviours, including 'flapping', 'hovering', 'turning' and 'side-slipping'. This establishes a route for the creation of future intelligent microsystems that are reconfigurable and reprogrammable in situ, and that can therefore adapt to complex situations.
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Osteoarthritis (OA) is a prevalent debilitating whole-joint disorder. Currently, a growing number of proteomic studies have been performed to evaluate molecular biomarkers in several tissues from OA patients; however, little is known about the protein profiles in subchondral bone of OA. In this study, proteomic analysis was performed on subchondral bone from patients with OA to identify differentially expressed proteins (DEPs). Bioinformatics tools were used to further investigate these DEPs. Thereafter, DEPs were validated in the samples from patients with OA, as well as in bilateral ovariectomy-induced OA (OVX-OA) rats using immunohistochemistry. A comprehensive subchondral bone proteome profile of patients with OA was constructed. Additionally, biological information analysis showed that a majority of DEPs participated in the dysregulation of the complement and coagulation cascades. The validation experiments suggested that SerpinA5, the protein involved in the complement and coagulation cascades, was significantly increased in severely damaged subchondral bone of patients with OA compared to the control group. Furthermore, the increase of SerpinA5 in OVX-OA rats compared to control rats was also confirmed. Our results indicated that the dysregulation of coagulation and complement pathways plays a role in the progression of OA, and it provides a promising therapeutic target of OA.
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Cartilagem Articular , Osteoartrite do Joelho , Osteoartrite , Humanos , Feminino , Ratos , Animais , Proteômica , Osteoartrite/genética , Osso e Ossos/metabolismo , Biomarcadores , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/metabolismo , Cartilagem Articular/metabolismoRESUMO
Scarce and expensive iridium oxide is still the cornerstone catalyst of polymer-electrolyte membrane electrolyzers for green hydrogen production because of its exceptional stability under industrially relevant oxygen evolution reaction (OER) conditions. Earth-abundant transition metal oxides used for this task, however, show poor long-term stability. We demonstrate here the use of nitrogen-doped cobalt oxide as an effective iridium substitute. The catalyst exhibits a low overpotential of 240 mV at 10 mA cm-2 and negligible activity decay after 1000 h of operation in an alkaline electrolyte. Incorporation of nitrogen dopants not only triggers the OER mechanism switched from the traditional adsorbate evolution route to the lattice oxygen oxidation route but also achieves oxygen nonbonding (ONB) states as electron donors, thereby preventing structural destabilization. In a practical anion-exchange membrane water electrolyzer, this catalyst at anode delivers a current density of 1000 mA cm-2 at 1.78 V and an electrical efficiency of 47.8 kW-hours per kilogram hydrogen.
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The shortage of decades-long continuous measurements of ecosystem processes limits our understanding of how changing climate impacts forest ecosystems. We used continuous eddy-covariance and hydrometeorological data over 2002-2022 from a young Douglas-fir stand on Vancouver Island, Canada to assess the long-term trend and interannual variability in evapotranspiration (ET) and transpiration (T). Collectively, annual T displayed a decreasing trend over the 21 years with a rate of 1% yr-1, which is attributed to the stomatal downregulation induced by rising atmospheric CO2 concentration. Similarly, annual ET also showed a decreasing trend since evaporation stayed relatively constant. Variability in detrended annual ET was mostly controlled by the average soil water storage during the growing season (May-October). Though the duration and intensity of the drought did not increase, the drought-induced decreases in T and ET showed an increasing trend. This pattern may reflect the changes in forest structure, related to the decline in the deciduous understory cover during the stand development. These results suggest that the water-saving effect of stomatal regulation and water-related factors mostly determined the trend and variability in ET, respectively. This may also imply an increase in the limitation of water availability on ET in young forests, associated with the structural and compositional changes related to forest growth.
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BACKGROUND AND PURPOSE: The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN. METHODS: A total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat-primed PCR and GC-rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno-associated virus (AAV)-mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection. RESULTS: Four PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p-value = 0.29). Skin biopsy showed P62-positive intranuclear NOTCH2NLC-polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa-NOTCH2NLC-(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN. CONCLUSIONS: Overall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons.
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Doença de Parkinson , Animais , Humanos , Camundongos , Neurônios Dopaminérgicos/patologia , Corpos de Inclusão Intranuclear/genética , Corpos de Inclusão Intranuclear/patologia , Camundongos Transgênicos , Degeneração Neural/patologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Substância Negra/patologia , Expansão das Repetições de TrinucleotídeosRESUMO
BACKGROUND: Natural medicines present a considerable analytical challenge due to their diverse botanical origins and complex multi-species composition. This inherent complexity complicates their rapid identification and analysis. Tangerine peel, a product of the Citrus species from the Rutaceae family, is widely used both as a culinary ingredient and in traditional Chinese medicine. It is classified into two primary types in China: Citri Reticulatae Pericarpium (CP) and Citri Reticulatae Pericarpium Viride (QP), differentiated by harvest time. A notable price disparity exists between CP and another variety, Citri reticulatae "Chachi" (GCP), with differences being based on the original variety. METHODS: This study introduces an innovative method using portable miniature mass spectrometry for swift on-site analysis of QP, CP, and GCP, requiring less than a minute per sample. And combined with machine learning to differentiate the three types on site, the method was used to try to distinguish GCP from different storage years. RESULTS: This novel method using portable miniature mass spectrometry for swift on-site analysis of tangerine peels enabled the characterization of 22 compounds in less than one minute per sample. The method simplifies sample processing and integrates machine learning to distinguish between the CP, QP, and GCP varieties. Moreover, a multiple-perceptron neural network model is further employed to specifically differentiate between CP and GCP, addressing the significant price gap between them. CONCLUSIONS: The entire analytical time of the method is about 1 minute, and samples can be analyzed on site, greatly reducing the cost of testing. Besides, this approach is versatile, operates independently of location and environmental conditions, and offers a valuable tool for assessing the quality of natural medicines.
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Citrus , Aprendizado de Máquina , Espectrometria de Massas , Citrus/química , Citrus/classificação , Espectrometria de Massas/métodosRESUMO
The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.
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Antineoplásicos , Proliferação de Células , Neoplasias Colorretais , Depsipeptídeos , Compostos Macrocíclicos , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Depsipeptídeos/farmacologia , Depsipeptídeos/uso terapêutico , Depsipeptídeos/química , Depsipeptídeos/síntese química , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Normal sleepers may be at risk for insomnia during COVID-19. Identifying psychological factors and neural markers that predict their insomnia risk, as well as investigating possible courses of insomnia development, could lead to more precise targeted interventions for insomnia during similar public health emergencies. Insomnia severity index of 306 participants before and during COVID-19 were employed to determine the development of insomnia, while pre-COVID-19 psychometric and resting-state fMRI data were used to explore corresponding psychological and neural markers of insomnia development. Normal sleepers as a group reported a significant increase in insomnia symptoms after COVID-19 outbreak (F = 4.618, P = 0.0102, df = 2, 609.9). Depression was found to significantly contribute to worse insomnia (ß = 0.066, P = 0.024). Subsequent analysis found that functional connectivity between the precentral gyrus and middle/inferior temporal gyrus mediated the association between pre-COVID-19 depression and insomnia symptoms during COVID-19. Cluster analysis identified that postoutbreak insomnia symptoms followed 3 courses (lessened, slightly worsened, and developed into mild insomnia), and pre-COVID-19 depression symptoms and functional connectivities predicted these courses. Timely identification and treatment of at-risk individuals may help avoid the development of insomnia in the face of future health-care emergencies, such as those arising from COVID-19 variants.
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COVID-19 , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Distúrbios do Início e da Manutenção do Sono/epidemiologia , COVID-19/complicações , Depressão/diagnóstico por imagem , Emergências , SARS-CoV-2 , Encéfalo/diagnóstico por imagemRESUMO
Lewis acids of solid catalysts have been featured for a pivotal role in promoting various reactions. Regarding the oxidation protocol to remove formaldehyde, the inherent drawback of the best-studied MnO2 materials in acidic sites has eventually caused deficiency of active hydroxyls to sustain low-temperature activity. Herein, the cryptomelane-type MnO2 was targeted and it was tuned via incorporation of Zr metal, exhibiting great advances in not only the complete HCHO-to-CO2 degradation but also cycling performance. Zr species were existent in doping state in the MnO2 lattice, rendering lower crystallinity and breaking the regular growth of MnO2 crystallites, which thereby tripled surface area and created larger volume of smaller mesopores. Meantime, the local electronic properties of Mn atoms were also changed by Zr doping, i.e., more low-valence Mn species were formed due to the electron transfer from Zr to Mn. The results of infrared studies demonstrate the higher possession of Lewis acid sites on ZrMn, and this high degree of electrophilic agents favored the production of hydroxyl species. Furthermore, the reactivity of surface hydroxyls, as investigated by CO temperature programmed reduction and temperature programmed desorption of adsorbed O2, was obviously improved as well after Zr modification. It is speculated jointly with the characterizations of the post-reaction catalysts that the accelerated production of active hydroxyls helped rapidly convert formaldehyde into key intermediate-formate, which was then degraded into CO2, avoiding the side reaction path with undesired intermediate-hydrocarbonate-over the pristine MnO2, where active sites were blocked and formaldehyde oxidation was inhibited. Additionally, Zr decoration could stabilize Lewis acidity to be more resistant to heat degeneration, and this merit brought about advantageous thermal recyclability for cycled application.
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Ácidos de Lewis , Óxidos , Óxidos/química , Compostos de Manganês/química , Dióxido de Carbono , Formaldeído/química , CatáliseRESUMO
Mammalian cell lines are frequently used as the preferred host cells for producing recombinant therapeutic proteins (RTPs) having post-translational modified modification similar to those observed in proteins produced by human cells. Nowadays, most RTPs approved for marketing are produced in Chinese hamster ovary (CHO) cells. Recombinant therapeutic antibodies are among the most important and promising RTPs for biomedical applications. One of the issues that occurs during development of RTPs is their degradation, which caused by a variety of factors and reducing quality of RTPs. RTP degradation is especially concerning as they could result in reduced biological functions (antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity) and generate potentially immunogenic species. Therefore, the mechanisms underlying RTP degradation and strategies for avoiding degradation have regained an interest from academia and industry. In this review, we outline recent progress in this field, with a focus on factors that cause degradation during RTP production and the development of strategies for overcoming RTP degradation. KEY POINTS: ⢠The recombinant therapeutic protein degradation in CHO cell systems is reviewed. ⢠Enzymatic factors and non-enzymatic methods influence recombinant therapeutic protein degradation. ⢠Reducing the degradation can improve the quality of recombinant therapeutic proteins.
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Apoptose , Indústrias , Animais , Cricetinae , Humanos , Células CHO , Cricetulus , ProteóliseRESUMO
A directed vat set (DVS) starter was proposed to improve the drawbacks of liquid starters in fermented production and enhance the survival rates of B. animalis subsp. lactis BZ11, S. thermophilus Q-1, and Lactiplantibacillus plantarum LB12. The protective agent formula was optimized using the response surface method (RSM), with the survival rate as the benchmark. The best combination of cryoprotectants was determined to be BZ11: 10 % skimmed milk powder, 3 % sodium glutamate, and 15 % trehalose; LB12: 10 % skim milk powder, 5 % glutamate sodium, and 10 % trehalose; Q-1: 10 % skimmed milk powder, 3 % sodium glutamate, and 10 % trehalose. The survival rate of BZ11 significantly increased to 92.87 ± 1.25 %. The DVS fermented milk did not differ significantly from the control group regarding cholesterol removal, live cell counts and pH (p > 0.05). All DVS can be stored for at least 2500 d at -20 °C-this DVS starter for fermented milk benefits from its large-scale and automated commercial production.
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Leite , Glutamato de Sódio , Animais , Fermentação , Taxa de Sobrevida , Trealose/farmacologia , Pós , Criopreservação/métodos , Crioprotetores/farmacologiaRESUMO
BACKGROUND: The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture. METHODS: A retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death. RESULTS: Among the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin < 100 g/l (OR = 2.732, P = 0.002), ASA score ≥ 3 (OR = 2.551, P = 0.005), CCI ≥ 3 (OR = 18.412, P = 0.018) and time to surgery > 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days. CONCLUSIONS: Patients over 80 years old with haemoglobin < 100 g/l, ASA score ≥ 3, CCI ≥ 3, and multiple comorbidities, especially myocardial infarction and chronic pulmonary disease before surgery, are at a higher risk of 1-year mortality. Doctors should pay more attention to these vulnerable patients, and a surgical delay greater than 14 days should be avoided.
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Fraturas do Quadril , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Fraturas do Quadril/mortalidade , Fraturas do Quadril/cirurgia , China/epidemiologia , Idoso de 80 Anos ou mais , Fatores de Risco , Centros de Atenção Terciária/tendências , Medição de Risco/métodosRESUMO
BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis is a common clinical fracture type. There are many surgical treatment options for OVCF, but there is a lack of comparison among different options. Therefore, we counted a total of 104 cases of OVCF operations with different surgical plans, followed up the patients, and compared the surgical outcome indications before, after and during the follow-up. METHOD: 104 patients who underwent posterior osteotomy (Modified PSO, SPO, PSO, VCR) and kyphosis correction surgery at our hospital between April 2006 and August 2021 with a minimum follow-up period of 24 months were included. All cases were injuries induced by a fall incurred while standing or lifting heavy objects without high-energy trauma. The mean CT value was 71 HU, which was below 110 HU, indicating severe osteoporosis. The indications for surgery included gait disturbance due to severe pain with pseudarthrosis, increased kyphotic angle, and progressive neurological symptoms. Pre- and postoperative CL, TLK, TK, PrTK, TKmax, GK, LL, PI, SS, PT, SVA, TPA, were investigated radiologically. Additionally, We evaluated estimated blood loss, surgical time and perioperative symptom. RESULT: The results show, after operation, TLK (37.32 ± 10.61° vs. 11.01 ± 8.06°, P < 0.001), TK (35.42 ± 17.64° vs. 25.62 ± 12.24°, P < 0.001), TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001), SVA (44.91 ± 48.67 vs. 23.52 ± 30.21, P = 0.013), CL (20.23 ± 13.21° vs. 11.45 ± 9.85°, P = 0.024) and TPA (27.44 ± 12.76° vs. 13.91 ± 9.24°, P = 0.009) were improved significantly in modified Pedicle subtraction osteotomy (mPSO) after operation. During follow-up, TLK (37.32 ± 10.61° vs. 13.88 ± 10.02°, P < 0.001) and TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001) were improved significantly in Modified PSO group. In additon, estimated blood loss (790.0 ± 552.2 ml vs. 987.0 ± 638.5 ml, P = 0.038), time of operation (244.1 ± 63.0 min vs. 292.4 ± 87.6 min, P = 0.025) were favorable in Modified PSO group compared to control group. CONCLUSION: To conclude, mPSO could acquire a favorable degree of kyphosis correction as well as fewer follow-up complications. Compared with other surgical methods, it also has the advantages of less surgical trauma and shorter operation time. It can be an effective solution for the treatment of OVCF.
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Fraturas por Compressão , Fraturas por Osteoporose , Osteotomia , Fraturas da Coluna Vertebral , Humanos , Fraturas por Compressão/cirurgia , Feminino , Masculino , Osteotomia/métodos , Idoso , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Resultado do Tratamento , Cifose/cirurgia , Cifose/etiologiaRESUMO
Four undescribed sesquiterpenoids, lemneolemnanes A-D (1-4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1-4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer's disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.
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Antozoários , Caenorhabditis elegans , Sesquiterpenos , Animais , Antozoários/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Caenorhabditis elegans/efeitos dos fármacos , Cristalografia por Raios X , Doença de Alzheimer/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Estrutura MolecularRESUMO
BACKGROUND: The treatment of infected bone defects remains a clinical challenge. With the development of three-dimensional printing technology, three-dimensional printed implants have been used for defect reconstruction. The aim of this study was to investigate the clinical outcomes of three-dimensional printed porous prosthesis in the treatment of femoral defects caused by osteomyelitis. METHODS: Eleven patients with femoral bone defects following osteomyelitis who were treated with 3D-printed porous prosthesis at our institution between May 2017 and July 2021, were included. Eight patients were diagnosed with critical-sized defects, and the other three patients were diagnosed with shape-structural defects. A two-stage procedure was performed for all patients, and the infection was eradicated and bone defects were occupied by polymethylmethacrylate spacer during the first stage. The 3D-printed prosthesis was designed and used for the reconstruction of femoral defects in the second stage. Position of the reconstructed prostheses and bone growth were measured using radiography. The union rate, complications, and functional outcomes at the final follow-up were assessed. RESULTS: The mean length of the bone defect was 14.0 cm, union was achieved in 10 (91%) patients. All patients showed good functional performance at the most recent follow-up. In the critical-sized defect group, one patient developed a deep infection that required additional procedures. Two patients had prosthetic dislocations. Radiography demonstrated good osseous integration of the implant-bone interface in 10 patients. CONCLUSION: The 3D printed prostheses enable rapid anatomical and mechanically stable reconstruction of extreme femur bone defects, effectively shortens treatment time, and achieves satisfactory clinical outcomes.
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Fêmur , Osteomielite , Impressão Tridimensional , Desenho de Prótese , Titânio , Humanos , Osteomielite/cirurgia , Osteomielite/etiologia , Osteomielite/diagnóstico por imagem , Masculino , Feminino , Fêmur/cirurgia , Fêmur/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto , Porosidade , Resultado do Tratamento , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos , Implantação de Prótese/efeitos adversos , Estudos Retrospectivos , Idoso , Adulto Jovem , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/instrumentaçãoRESUMO
It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.
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Água Potável , Insuficiência Renal Crônica , Animais , Água Potável/análise , Peixe-Zebra , Sri Lanka , Insuficiência Renal Crônica/etiologia , MetabolomaRESUMO
Multifunctional N, Fe-doped carbon dots (N, Fe-CDs) were synthesized by the one-step hydrothermal method using ferric ammonium citrate and dicyandiamide as raw materials. The N, Fe-CDs exhibited peroxidase-like (POD) activity by catalyzing the oxidization of 3,3',5,5'-tetramethylbenzidine (TMB) to the green oxidation state ox-TMB in the presence of hydrogen peroxide (H2O2). Subsequently, based on the POD activity of N, Fe-CDs, an efficient and sensitive colorimetric method for the detection of H2O2 and ascorbic acid (AA) was established with a limit of detection of 0.40 µM and 2.05 µM. The proposed detection method has been successfully applied to detect AA in fruit juice, vitamin C tablets, and human serum samples and has exhibited excellent application prospects in biotechnology and food fields. Furthermore, N, Fe-CDs also showed a protective effect on the cell damage caused by H2O2 and could be used as an antioxidant agent.
Assuntos
Ácido Ascórbico , Carbono , Sucos de Frutas e Vegetais , Peróxido de Hidrogênio , Oxirredução , Pontos Quânticos , Peróxido de Hidrogênio/química , Ácido Ascórbico/química , Humanos , Carbono/química , Pontos Quânticos/química , Sucos de Frutas e Vegetais/análise , Benzidinas/química , Colorimetria/métodos , Limite de Detecção , Ferro/química , Nitrogênio/química , Peroxidase/química , Peroxidase/metabolismo , Antioxidantes/química , Antioxidantes/farmacologiaRESUMO
Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 (HhUGT74AG11) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28-O-glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C-28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C-7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6, CaUGT74AG2, and PgUGT74AE2, further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11, was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.