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1.
J Am Chem Soc ; 146(19): 12976-12983, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38567925

RESUMO

Electrocatalytic reduction of nitrate to ammonia (NRA) has emerged as an alternative strategy for sewage treatment and ammonia generation. Despite excellent performances having been achieved over cobalt-based electrocatalysts, the reaction mechanism as well as veritable active species across a wide potential range are still full of controversy. Here, we adopt CoP, Co, and Co3O4 as model materials to solve these issues. CoP evolves into a core@shell structured CoP@Co before NRA. For CoP@Co and Co catalysts, a three-step relay mechanism is carried out over superficial dynamical Coδ+ active species under low overpotential, while a continuous hydrogenation mechanism from nitrate to ammonia is unveiled over superficial Co species under high overpotential. In comparison, Co3O4 species are stable and steadily catalyze nitrate hydrogenation to ammonia across a wide potential range. As a result, CoP@Co and Co exhibit much higher NRA activity than Co3O4 especially under a low overpotential. Moreover, the NRA performance of CoP@Co is higher than Co although they experience the same reaction mechanism. A series of characterizations clarify the reason for performance enhancement highlighting that CoP core donates abundant electrons to superficial active species, leading to the generation of more active hydrogen for the reduction of nitrogen-containing intermediates.

2.
Oral Dis ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38251222

RESUMO

OBJECTIVE: Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential treatment clue is still insufficient. MATERIALS AND METHODS: We conducted the high-resolution mass spectrometry (MS) of synovial fluid collected from 60 patients with normal disk position to ADD and ADD with osteoarthritis (OA). The proteins with significant changes among the 3 groups were analyzed by biological information and further validated by in primary rat condyle chondrocytes and OA animal model. RESULTS: FGL2, THBS4, TNC, FN1, OMD etc. were significantly increased in ADD without OA (p < 0.05), which reflected the active extracellular matrix and collagen metabolism. FGFR1, FBLN2, GRB2 etc. were significantly increased in ADD with OA group (p < 0.05), which revealed an association with apoptosis and ferroptosis. Proteins such as P4HB, CBLN4, FHL1, VIM continuously increase in the whole disease progress (p < 0.05). Both the in vitro and in vivo results are consistent with protein changes detected in MS profile. CONCLUSION: This study firstly provides the expression changes of proteins from normal disc condyle relationship toward ADD with OA, which can be selected and studied further as disease progress marker and potential treatment targets.

3.
Angew Chem Int Ed Engl ; 63(27): e202406750, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38651747

RESUMO

Electrocatalytic reduction of nitrate to ammonia provides a green alternate to the Haber-Bosch method, yet it suffers from sluggish kinetics and a low yield rate. The nitrate reduction follows a tandem reaction of nitrate reduction to nitrite and subsequent nitrite hydrogenation to generate ammonia, and the ammonia Faraday efficiency (FE) is limited by the competitive hydrogen evolution reaction. Herein, we design a heterostructure catalyst to remedy the above issues, which consists of Ni nanosphere core and Ni(OH)2 nanosheet shell (Ni/Ni(OH)2). In situ Raman spectroscopy reveals Ni and Ni(OH)2 are interconvertible according to the applied potential, facilitating the cascade nitrate reduction synergistically. Consequently, it attains superior electrocatalytic nitrate reduction performance with an ammonia FE of 98.50 % and a current density of 0.934 A cm-2 at -0.476 V versus reversible hydrogen electrode, and exhibits an average ammonia yield rate of 84.74 mg h-1 cm-2 during the 102-hour stability test, which is highly superior to the reported catalysts tested under similar conditions. Density functional theory calculations corroborate the synergistic effect of Ni and Ni(OH)2 in the tandem reaction of nitrate reduction. Moreover, the Ni/Ni(OH)2 catalyst also possesses good capability for methanol oxidation and thus is used to establish a system coupling with nitrate reduction.

4.
Ecol Lett ; 26(6): 942-954, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37078102

RESUMO

Release from enemies can lead to rapid evolution in invasive plants, including reduced metabolic investment in defence. Conversely, reassociation with enemies leads to renewed evolution of defence, but the potential costs of this evolution are poorly documented. We report increased resistance of the invader Ambrosia artemisiifolia after reassociation with a coevolved specialist herbivore, and that this increase corresponds with reduced abiotic stress tolerance. Herbivore resistance was higher, but drought tolerance was lower in plants from populations with a longer reassociation history, and this corresponded with changes in phenylpropanoids involved in insect resistance and abiotic stress tolerance. These changes were corroborated by shifts in the expression of underlying biosynthetic genes and plant anti-oxidants. Together, our findings suggest rapid evolution of plant traits after reassociation with coevolved enemies, resulting in genetically based shifts in investment between abiotic and biotic stress responses, providing insights into co-evolution, plant invasion and biological control.


Assuntos
Evolução Biológica , Herbivoria , Animais , Herbivoria/fisiologia , Plantas , Insetos , Estresse Fisiológico
5.
Angew Chem Int Ed Engl ; 61(44): e202213009, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36106683

RESUMO

The scalable and durable electrosynthesis of high-valued organonitrogen compounds from carbon- and nitrogen-containing small molecules, especially operating at a high current density, is highly desirable. Here, a one-pot electrooxidation method to synthesize formamide (HCONH2 ) from methanol and ammonia over a commercial boron-doped diamond (BDD) catalyst is reported. The formamide selectivity from methanol and formamide Faradaic efficiency (FE HCONH 2 ${{_{{\rm HCONH}{_{2}}}}}$ ) achieve 73.2 % and 41.2 % at the current density of 120 mA cm-2 with high durability. The C-N bond originates from the nucleophilic attack of ammonia on an aldehyde-like intermediate. Impressively, an 8 L electrolyzer is employed for the pilot plant test over a 2200 cm2 BDD electrode, which exhibits 33.5 % FE HCONH 2 ${{_{{\rm HCONH}{_{2}}}}}$ at 120 mA cm-2 (current: 264 A) with a yield rate of 36.9 g h-1 , demonstrating the potential of this technique for large-scale electrosynthesis of formamide.

6.
J Prosthet Dent ; 126(1): 14-18, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33323177

RESUMO

The application of a virtual dental patient with dynamic occlusion during esthetic restoration in a digital workflow is described. An intraoral scanner, a facial scanner, a jaw motion analyzer, and cone beam computed tomography were used to transfer patient data and construct the virtual dental patient. With the aid of the virtual dental patient, predictability and accuracy can increase throughout treatment, simplifying the clinical evaluation and prosthesis adjustment with improved esthetic outcomes.


Assuntos
Desenho Assistido por Computador , Estética Dentária , Tomografia Computadorizada de Feixe Cônico , Humanos , Imageamento Tridimensional , Fluxo de Trabalho
7.
Genomics ; 111(6): 1760-1770, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30529702

RESUMO

Meiotic recombination plays an important role in the process of genetic evolution. Previous researches have shown that the recombination rates provide important information about the mechanism of recombination study. However, at present, most methods ignore the hidden correlation and spatial autocorrelation of the DNA sequence. In this study, we proposed a predictor called iRSpot-DTS to identify hot/cold spots based on the benchmark datasets. We proposed a feature extraction method called dinucleotide-based spatial autocorrelation(DSA) which can incorporate the original DNA properties and spatial information of DNA sequence. Then it used t-SNE method to remove the noise which outperformed PCA. Finally, we used SAE softmax classifier to do classification which is based on networks and can get more hidden information of DNA sequence, our iRSpot-DTS achieved remarkable performance. Jackknife cross validation tests were done on two benchmark datasets. We achieved state-of-the-art results with 96.61% overall accuracy(OA), 93.16% Matthews correlation coefficient (MCC) and over 95% in Sn and Sp which are the best in this state.


Assuntos
Algoritmos , Sequência de Bases , DNA/genética , Recombinação Genética , Análise de Sequência de DNA , Software , Biologia Computacional
8.
J Hazard Mater ; 469: 133908, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38428297

RESUMO

Uranium, as the most essential resource for nuclear power production, provides 13% of global electricity demand, has attracted considerable attention. However, it is still a great challenge for uranium extraction from natural water like salt lakes as the background of high salinity and low concentration (3.3 ∼ 330 ppb). Meanwhile, current uranium extraction strategies are generally focus on extraction capacity or selectivity but neglect to enhance extraction rate. In this work, we designed a novel kind of NIR-driven intelligent nanorobots catchers (MSSA-AO) with amidoxime as claws for uranium capture, which showed almost 100% extraction rate and an ultrafast extraction rate. Importantly, high extraction capacity (221.5 mg g-1) and selectivity were taken into consideration as well as good regeneration performance. Furthermore, amidoxime NRCs boosted in extraction amount about 16.7% during the first 5 min with self-driving performance. Overall, this work suggests a new strategy for ultrafast extraction of uranium from natural water with low abundance selectively by self-propelled NRCs, showing great possibility in outdoor application and promising for meeting huge energy needs globally.

9.
BMC Med Genomics ; 17(1): 137, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778403

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with a poor survival rate due to anatomical limitations of the head and a lack of reliable biomarkers. Cuproptosis represents a novel cellular regulated death pathway, and N6-methyladenosine (m6A) is the most common internal RNA modification in mRNA. They are intricately connected to tumor formation, progression, and prognosis. This study aimed to construct a risk model for HNSCC using a set of mRNAs associated with m6A regulators and cuproptosis genes (mcrmRNA). METHODS: RNA-seq and clinical data of HNSCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to develop a risk model through the least absolute shrinkage and selection operator (LASSO) analysis. Survival analysis and receiver operating characteristic (ROC) analysis were performed for the high- and low-risk groups. Additionally, the model was validated using the GSE41613 dataset from the Gene Expression Omnibus (GEO) database. GSEA and CIBERSORT were applied to investigate the immune microenvironment of HNSCC. RESULTS: A risk model consisting of 32 mcrmRNA was developed using the LASSO analysis. The risk score of patients was confirmed to be an independent prognostic indicator by multivariate Cox analysis. The high-risk group exhibited a higher tumor mutation burden. Additionally, CIBERSORT analysis indicated varying levels of immune cell infiltration between the two groups. Significant disparities in drug sensitivity to common medications were also observed. Enrichment analysis further unveiled significant differences in metabolic pathways and RNA processing between the two groups. CONCLUSIONS: Our risk model can predict outcomes for HNSCC patients and offers valuable insights for personalized therapeutic approaches.


Assuntos
Adenosina , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Adenosina/análogos & derivados , Adenosina/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Prognóstico , Feminino , Biomarcadores Tumorais/genética , Medição de Risco , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Microambiente Tumoral
10.
Sci Bull (Beijing) ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38942698

RESUMO

Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses; however, highly transmissible and mutated variants, such as the Omicron variant, weaken the neutralization potential of the vaccines, thus, raising serious concerns about their efficacy. Additionally, while neutralizing antibodies (nAbs) tend to wane more rapidly than cell-mediated immunity, long-lasting T cells typically prevent severe viral illness by directly killing infected cells or aiding other immune cells. Importantly, T cells are more cross-reactive than antibodies, thus, highly mutated variants are less likely to escape lasting broadly cross-reactive T cell immunity. Therefore, T cell antigen-based human coronavirus (HCoV) vaccines with the potential to serve as a supplementary weapon to combat emerging SARS-CoV-2 variants with resistance to nAbs are urgently needed. Alternatively, T cell antigens could also be included in B cell antigen-based vaccines to strengthen vaccine efficacy. This review summarizes recent advancements in research and development of vaccines containing T cell antigens or both T and B cell antigens derived from proteins of SARS-CoV-2 variants and/or other HCoVs based on different vaccine platforms.

11.
Theranostics ; 14(1): 220-248, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164142

RESUMO

Red blood cells (RBCs) are the most abundant cell type in the blood, and play a critical role in oxygen transport. With the development of nanobiotechnology and synthetic biology, scientists have found multiple ways to take advantage of the characteristics of RBCs, such as their long circulation time, to construct universal RBCs, develop drug delivery systems, and transform cell therapies for cancer and other diseases. This article reviews the component and aging mystery of RBCs, the methods for the applied universal RBCs, and the application prospects of RBCs, such as the engineering modification of RBCs used in cytopharmaceuticals for drug delivery and immunotherapy. Finally, we summarize some perspectives on the biological features of RBCs and provide further insights into translational medicine.


Assuntos
Eritrócitos , Ciência Translacional Biomédica , Eritrócitos/metabolismo , Sistemas de Liberação de Medicamentos , Terapia Baseada em Transplante de Células e Tecidos , Biologia
12.
Langmuir ; 29(44): 13568-75, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24093805

RESUMO

A new phenylboronic acid based gelator was developed to prepare low-molecular-weight organogel (LMOG), which could interact with several solvents to assemble into a three-dimensional nanofiber network. (1)H NMR spectroscopy study suggests that the driving force for the gelation includes hydrogen bonding and π-π stacking. Evaluated by UV-spectroscopy, the gel showed a prompt initial response to glucose at low concentration of 0.012 mmol/mL, which is a critical concentration of venous plasma glucose for diabetes. Significantly, this organogel exhibits excellent sensitivity to glucose among seven sugars tested (i.e., mannitol, galactose, lactose, maltose, sucrose, and fructose). The proposed formation of hydrogen-bonded complexes during the glucose sensing was supported by our energy calculation. Meanwhile, this organogel exhibits pH-response. Importantly, this LMOG could be conveniently recycled and thus be reused.


Assuntos
Ácidos Borônicos/química , Técnicas de Química Analítica/instrumentação , Glucose/análise , Géis , Glucose/química , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Peso Molecular
13.
Int J Biol Macromol ; 245: 125515, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37353117

RESUMO

Since May 2022, the mpox virus (MPXV) has spread worldwide and become a potential threat to global public health. Vaccines are important tools for preventing MPXV transmission and infection in the population. However, there are still no available potent and applicable vaccines specifically for MPXV. Herein, we highlight several potential vaccine targets for MPVX and emphasize potent immunogens, such as M1R, E8L, H3L, A29L, A35R, and B6R proteins. These proteins can be integrated into diverse vaccine platforms to elicit powerful B-cell and T-cell responses, thereby providing protective immunity against MPXV infection. Overall, research on the MPXV vaccine targets would provide valuable information for developing timely effective MPXV-specific vaccines.


Assuntos
Vacinas Virais , Monkeypox virus , Linfócitos B
14.
J Orthop Surg Res ; 18(1): 108, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36793047

RESUMO

OBJECTIVE: We aimed to investigate the adoption of treatment patterns for hip fractures combined with minimally invasive surgical treatment of fragility fractures of the pelvis in older individuals and reviewed and analysed the treatment efficacy and feasibility. METHODS AND DATA: From September 2017 to February 2021, 135 older individuals with fragility fractures of the pelvis were admitted to our hospital. We retrospectively analysed patients who received surgical or conservative treatments. The general preoperative data, including sex, age, disease duration, cause of injury, AO/OTA type, BMI, bone mineral density, time from injury to admission, time from injury to surgery, ASA classification, number of underlying diseases, mean bed rest, clinical fracture healing, VAS score and Majeed functional score, were recorded. RESULTS: The mean follow-up time for all 135 patients was 10.5 ± 3.6 months. Among 135 patients, 95 survived, and 11 and 29 patients passed after the surgical (mortality rate = 17.74%) and conservative (mortality rate = 39.73%) treatments, respectively. The average follow-up time for the 95 surviving patients was 14.5 ± 1.8 months. The Majeed and VAS scores for the operation group were significantly better than those of the conservative group. The bed rest and fracture healing times were also shorter in the surgical treatment group than in the conservative group. CONCLUSION: The use of a minimally invasive surgical treatment combined with the geriatric hip fracture treatment model to treat fragility fractures of the pelvis improved the quality of life in older patients.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Ossos Pélvicos , Humanos , Idoso , Estudos Retrospectivos , Tratamento Conservador , Qualidade de Vida , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Ossos Pélvicos/cirurgia , Ossos Pélvicos/lesões , Fraturas do Quadril/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
15.
Environ Sci Pollut Res Int ; 30(23): 63323-63334, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36988799

RESUMO

The novel coronavirus SARS-CoV-2 has spread at an unprecedented rate since late 2019, leading to the global COVID-19 pandemic. During the pandemic, being able to detect SARS-CoV-2 in human populations with high coverage quickly is a huge challenge. As SARS-CoV-2 is excreted in human excreta and thus exposed to the aqueous environment through sewers, the goal is to develop an ideal, non-invasive, cost-effective epidemiological method for detecting SARS-CoV-2. Wastewater surveillance has gained widespread interest and is increasingly being investigated as an effective early warning tool for monitoring the spread and evolution of the virus. This review emphasizes important findings on SARS-CoV-2 wastewater-based epidemiology (WBE) in different continents and techniques used to detect SARS-CoV-2 in wastewater during the period 2020-2022. The results show that WBE is a valuable population-level method for monitoring SARS-CoV-2 and is a valuable early warning alert. It can assist policymakers in formulating relevant policies to avoid the negative impacts of early or delayed action. Such strategy can also help avoid unnecessary wastage of medical resources, rationalize vaccine distribution, assist early detection, and contain large-scale outbreaks.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Águas Residuárias , Pandemias , Vigilância Epidemiológica Baseada em Águas Residuárias
16.
Med Sci Sports Exerc ; 55(8): 1434-1444, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36989530

RESUMO

PURPOSE: A key determinant of long jump performance is the ability to increase the vertical velocity of the center of mass (COM) while minimizing the loss in forward velocity (running speed) during the take-off phase, but exactly how this occurs is not fully understood. We combined a three-dimensional musculoskeletal model of the body with dynamic optimization theory to simulate the biomechanics of the long jump take-off and determine the contributions of the individual leg muscles to jump performance. METHODS: The body was modeled as a 29-degree-of-freedom skeleton actuated by a combination of muscles and net joint torques. A dynamic optimization problem was solved to reproduce full-body motion and ground-force data recorded from experienced subelite jumpers. The optimization solution then was analyzed to determine each muscle's contribution to the ground-force impulse and hence the change in velocity of the COM during the take-off phase. RESULTS: The hip, knee, and ankle extensors dominated the change in velocity of the COM during take-off. Vasti (VAS) generated the highest support impulse and contributed one-third (33%) of the increase in vertical COM velocity generated by all the muscles. Soleus (SOL) and gluteus maximus (GMAX) also developed substantial support impulses and contributed 24% and 16% of the increase in vertical COM velocity, respectively. VAS also generated the highest braking impulse and contributed approximately one-half (55%) of the loss in forward COM velocity generated by all the muscles, whereas SOL and GMAX made much smaller contributions (12% and 7%, respectively). CONCLUSIONS: VAS, SOL, and GMAX contributed nearly three-quarters (73%) of the increase in vertical COM velocity at take-off, suggesting that these muscles ought to be prioritized in strength training programs aimed at improving long jump performance.


Assuntos
Músculo Esquelético , Corrida , Humanos , Músculo Esquelético/fisiologia , Perna (Membro)/fisiologia , Extremidade Inferior/fisiologia , Articulação do Joelho/fisiologia , Fenômenos Biomecânicos
17.
Biomed Pharmacother ; 169: 115907, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37984308

RESUMO

The lack of a functional vascular supply has been identified as a major challenge limiting the clinical introduction of stem cell-based bone tissue engineering (BTE) for the repair of large-volume bone defects (LVBD). Various approaches have been explored to improve the vascular supply in tissue-engineered constructs, and the development of strategies that could effectively induce the establishment of a functional vascular supply has become a major goal of BTE research. One of the state-of-the-art methods is to incorporate both angiogenic and osteogenic cells in co-culture systems. This review clarifies the key concepts involved, summarises the cell types and models used to date, and systematically evaluates their performance. We also discuss the cell-to-cell communication between these two cell types and the strategies explored in BTE constructs with angiogenic and osteogenic cells to optimise their functions. In addition, we outline unresolved issues and remaining obstacles that need to be overcome for further development in this field and eventual successful repair of LVBD.


Assuntos
Neovascularização Fisiológica , Engenharia Tecidual , Engenharia Tecidual/métodos , Técnicas de Cocultura , Osso e Ossos , Osteogênese , Alicerces Teciduais , Regeneração Óssea
18.
J Neurosurg Sci ; 67(2): 241-247, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35301841

RESUMO

INTRODUCTION: The aim of this meta-analysis was to evaluate the effects of acellular nerve grafts (ANGs) with bone marrow mesenchymal stem cells (BMSCs) or Schwann cells (SCs) on the treatment of sciatic nerve defect in rats. EVIDENCE ACQUISITION: Electronic databases were accessed to identify eligible targets. ANGs data were extracted for meta-analysis using Review Manager 5.3. EVIDENCE SYNTHESIS: The rats subjected to ANGs+BMSCs or ANGs+SCs are characterized by different sciatic nerve function index, nerve conduction, latency, amplitude, myelin sheath thickness, myelinated nerve fibers and gastrocnemius wet weight. accompanied with evidently superior recovery of limb function. These differences are of statistical significance (P<0.05) when compared to that of control group with ANGs only. CONCLUSIONS: ANGs with BMSCs or SCs can promote nerve regeneration and functional recovery in peripheral nerve defects.


Assuntos
Células-Tronco Mesenquimais , Células de Schwann , Ratos , Animais , Ratos Sprague-Dawley , Células de Schwann/transplante , Regeneração Nervosa/fisiologia , Nervo Isquiático
19.
PLoS One ; 18(2): e0278466, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36812214

RESUMO

There have been over 621 million cases of COVID-19 worldwide with over 6.5 million deaths. Despite the high secondary attack rate of COVID-19 in shared households, some exposed individuals do not contract the virus. In addition, little is known about whether the occurrence of COVID-19 resistance differs among people by health characteristics as stored in the electronic health records (EHR). In this retrospective analysis, we develop a statistical model to predict COVID-19 resistance in 8,536 individuals with prior COVID-19 exposure using demographics, diagnostic codes, outpatient medication orders, and count of Elixhauser comorbidities in EHR data from the COVID-19 Precision Medicine Platform Registry. Cluster analyses identified 5 patterns of diagnostic codes that distinguished resistant from non-resistant patients in our study population. In addition, our models showed modest performance in predicting COVID-19 resistance (best performing model AUROC = 0.61). Monte Carlo simulations conducted indicated that the AUROC results are statistically significant (p < 0.001) for the testing set. We hope to validate the features found to be associated with resistance/non-resistance through more advanced association studies.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Aprendizado de Máquina , Registros Eletrônicos de Saúde
20.
ACS Nano ; 17(3): 2537-2553, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36730125

RESUMO

As mesenchymal stem-cell-derived small extracellular vesicles (MSC-sEVs) have been widely applied in treatment of degenerative diseases, it is essential to improve their cargo delivery efficiency in specific microenvironments of lesions. However, the interaction between the microenvironment of recipient cells and MSC-sEVs remains poorly understood. Herein, we find that the cargo delivery efficiency of MSC-sEVs was significantly reduced under hypoxia in inflammaging nucleus pulposus cells due to activated endocytic recycling of MSC-sEVs. Hypoxia-inducible factor-1 (HIF-1)-induced upregulated RCP (also known as RAB11FIP1) is shown to promote the Rab11a-dependent recycling of internalized MSC-sEVs under hypoxia via enhancing the interaction between Rab11a and MSC-sEV. Based on this finding, si-RCP is loaded into MSC-sEVs using electroporation to overcome the hypoxic microenvironment of intervertebral disks. The engineered MSC-sEVs significantly inhibit the endocytic recycling process and exhibit higher delivery efficiency under hypoxia. In a rat model of intervertebral disk degeneration (IDD), the si-RCP-loaded MSC-sEVs successfully treat IDD with improved regenerative capacity compared with natural MSC-sEV. Collectively, the findings illustrate the intracellular traffic mechanism of MSC-sEVs under hypoxia and demonstrate that the therapeutic capacity of MSC-sEVs can be improved via inhibiting endocytic recycling. This modifying strategy may further facilitate the application of extracellular vesicles in hypoxic tissues.


Assuntos
Vesículas Extracelulares , Ratos , Animais , Hipóxia
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