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1.
Artigo em Inglês | MEDLINE | ID: mdl-38648756

RESUMO

OBJECTIVES: The efficacy of artificial intelligence (AI)-driven chatbots like ChatGPT4 in specialized medical consultations, particularly in rheumatology, remains underexplored. This study compares the proficiency of ChatGPT4' responses with practicing rheumatologists to inquiries from patients with systemic lupus erythematosus (SLE). METHODS: In this cross-sectional study, we curated 95 frequently asked questions (FAQs), including 55 in Chinese and 40 in English. Responses for FAQs from ChatGPT4 and 5 rheumatologists were scored separately by a panel of rheumatologists and a group of patients with SLE across 6 domains (scientific validity, logical consistency, comprehensibility, completeness, satisfaction level, and empathy) on a 0-10 scale (a score of 0 indicates entirely incorrect responses, while 10 indicates accurate and comprehensive answers). RESULTS: Rheumatologists' scoring revealed that ChatGPT4-generated responses outperformed those from rheumatologists in satisfaction level and empathy, with mean differences of 0.537 (95% CI, 0.252-0.823; p < 0.01) and 0.460 (95% CI, 0.227-0.693 p < 0.01), respectively. From the SLE patients' perspective, ChatGPT4-generated responses were comparable to the rheumatologist-provided answers in all 6 domains. Subgroup analysis revealed ChatGPT4 responses were more logically consistent and complete regardless of language, and exhibited greater comprehensibility, satisfaction, and empathy in Chinese. However, ChatGPT4 responses were inferior in comprehensibility for English FAQs. CONCLUSION: ChatGPT4 demonstrated comparable, possibly better in certain domains, to address FAQs from patients with SLE, when compared with the answers provided by specialists. This study showed the potential of applying ChatGPT4 to improve consultation in SLE patients.

2.
An Bras Dermatol ; 99(3): 342-349, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38522973

RESUMO

BACKGROUND: Dermatomyositis (DM) is an infrequent disease subgroup of idiopathic inflammatory myopathies characterized by distinct skin lesions. However, high heterogeneity makes clinical diagnosis and treatment of DM very challenging. OBJECTIVES: Unsupervised classification in DM patients and analysis of key factors related to clinical outcomes. METHODS: This retrospective study was conducted between 2017 and 2022 at the Department of Rheumatology, Xiangya Hospital, Central South University. 162 DM patients were enrolled for unsupervised hierarchical cluster analysis. In addition, we divided the clinical outcomes of DM patients into four subgroups: withdrawal, stabilization, aggravation, and death, and compared the clinical profiles amongst the subgroups. RESULTS: Out of 162 DM patients, three clusters were defined. Cluster 1 (n = 40) was mainly grouped by patients with prominent muscular involvement and mild Interstitial Lung Disease (ILD). Cluster 2 (n = 72) grouped patients with skin rash, anti-Melanoma Differentiation Associated protein 5 positive (anti-MDA5+), and Rapid Progressive Interstitial Lung Disease (RP-ILD). Cluster 3 (n = 50) grouped patients with the mildest symptoms. The proportion of death increased across the three clusters (cluster 3 < cluster 1 < cluster 2). STUDY LIMITATIONS: The number of cases was limited for the subsequent construction and validation of predictive models. We did not review all skin symptoms or pathological changes in detail. CONCLUSIONS: We reclassified DM into three clusters with different risks for poor outcome based on diverse clinical profiles. Clinical serological testing and cluster analysis are necessary to help clinicians evaluate patients during follow-up and conduct phenotype-based personalized care in DM.


Assuntos
Dermatomiosite , Fenótipo , Humanos , Dermatomiosite/classificação , Dermatomiosite/patologia , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Feminino , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Adulto , Análise por Conglomerados , Idoso , Doenças Pulmonares Intersticiais/classificação , Doenças Pulmonares Intersticiais/diagnóstico , Testes Sorológicos , Avaliação de Resultados em Cuidados de Saúde , Autoanticorpos/sangue , Helicase IFIH1 Induzida por Interferon/imunologia , Índice de Gravidade de Doença
3.
Ann Rheum Dis ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302260

RESUMO

OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous autoimmune diseases. Intron retention (IR) serves as an important post-transcriptional and translational regulatory mechanism. This study aims to identify changes in IR profiles in IIM subtypes, investigating their influence on proteins and their correlations with clinical features. METHODS: RNA sequencing and liquid chromatography-tandem mass spectrometry were performed on muscle tissues obtained from 174 patients with IIM and 19 controls, following QC procedures. GTFtools and iREAD software were used for IR identification. An analysis of differentially expressed IRs (DEIs), exons and proteins was carried out using edgeR or DEP. Functional analysis was performed with clusterProfiler, and SPIRON was used to assess splicing factors. RESULTS: A total of 6783 IRs located in 3111 unique genes were identified in all IIM subtypes compared with controls. IIM subtype-specific DEIs were associated with the pathogenesis of respective IIM subtypes. Splicing factors YBX1 and HSPA2 exhibited the most changes in dermatomyositis and immune-mediated necrotising myopathy. Increased IR was associated with reduced protein expression. Some of the IIM-specific DEIs were correlated with clinical parameters (skin rash, MMT-8 scores and muscle enzymes) and muscle histopathological features (myofiber necrosis, regeneration and inflammation). IRs in IFIH1 and TRIM21 were strongly correlated with anti-MDA5+ antibody, while IRs in SRP14 were associated with anti-SRP+ antibody. CONCLUSION: This study revealed distinct IRs and specific splicing factors associated with IIM subtypes, which might be contributing to the pathogenesis of IIM. We also emphasised the potential impact of IR on protein expression in IIM muscles.

4.
Angew Chem Int Ed Engl ; 63(4): e202316481, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38063138

RESUMO

Boronate rearrangements, such as the Matteson and Petasis reactions, are valuable metal-free reactions for the transfer of the carbo group on boron to intramolecular electrophilic sites. However, only highly reactive electrophiles are suitable, and ketones are too inactive for those boronate rearrangements due to the high energy barriers. We disclose here the 1,3-boronate rearrangement to ketones, for which a high energy barrier (44.9 kcal/mol) is prohibitory for thermal reactions in the ground state. The reaction is enabled by the key keto-enol-boronate bidentate complex formation in situ, which absorbs visible light to reach the excited state for the chemoselective 1,3-boronate rearrangement to ketones. Experimental and computational investigations exclude free radical intermediates from organoboronates. The aryl, alkenyl, and alkyl boronic acids react with various 1,3-diketones driven by visible light irradiation to construct structurally diverse ß-keto tertiary alcohols under metal-free conditions. The reaction demonstrates substrate diversity with 58 examples, yields up to 98 %, and it is suitable for gram-scale synthesis.

5.
Int Immunopharmacol ; 124(Pt A): 110803, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37625367

RESUMO

OBJECTIVE: Dermatomyositis (DM) is the best known subtype of idiopathic inflammatory myopathies. The hallmarks of DM muscle pathology including microangiopathy, inflammatory infiltration, and perifascicular atrophy. Recent findings have revealed pathogenetic effects of myeloperoxidase (MPO) by causing oxidative damage and regulating abnormal immunity in multiple disease conditions. In this study, we aimed to explore the role of MPO in the pathogenesis of DM. METHODS: The peripheral blood mononuclear cell (PBMC) mRNA expression and DNA methylation of MPO were verified using real-time qPCR and bisulfite pyrosequencing, respectively. Plasma MPO levels were measured with enzyme-linked immunosorbent assay, and their relationships with clinical characteristics were analyzed. The expression and distribution of MPO in muscle were tested by immunofluorescence. Purified human native MPO protein was used to stimulate human dermal microvascular endothelial cells (HDMECs) and skeletal muscle myotubes. The cell viability, tube forming capacity, permeability, adhesion molecule expressions in HDMECs, and atrophy and programmed cell death pathways in myotubes were then observed. RESULTS: MPO gene methylation was decreased, while mRNA expression and plasma levels were increased in DM. Plasma MPO of DM patients was positively correlated with serum creatine kinase (CK). MPO mainly distributed around endomysia capillaries and perifascicular atrophy in DM muscle biopsies, and was co-localized with CD4+, CD8+ T cells and CD19+ B cells. MPO not only could influence the cell viability, tube forming capacity, permeability and expression of adhesion molecules (including ICAM 1, VCAM 1 and E-selectin) of HDMECs, but also could cause atrophy of myotubes. CONCLUSIONS: Our study disclosed, for the first time, that MPO plays an important role in promoting inflammatory infiltration and inducing muscle damage in DM patients. MPO may be a potential biomarker for DM muscle involvement and MPO targeted drugs may be promising in DM treatment.

6.
JMIR Mhealth Uhealth ; 11: e45531, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37261895

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a global health burden. However, the efficacy of different modes of eHealth care in facilitating self-management for patients with CKD is unclear. OBJECTIVE: The aim of this study was to evaluate the effectiveness of a mobile app-based intelligent care system in improving the kidney outcomes of patients with CKD. METHODS: Our study was a retrospective analysis based on the KidneyOnline intelligent system developed in China. Patients with CKD but not dependent on dialysis who registered on the KidneyOnline app between January 2017 and January 2021 were screened. Patients in the the KidneyOnline intelligent system group and those in the conventional care group were 1:1 matched according to their baseline characteristics. The intervention group received center-based follow-up combined with the KidneyOnline intelligent patient care system, which was a nurse-led, patient-oriented collaborative management system. Health-related data uploaded by the patients were integrated using deep learning optical character recognition (OCR). Artificial intelligence (AI)-generated personalized recipes, lifestyle intervention suggestions, early warnings, real-time questions and answers, and personalized follow-up plans were also provided. Patients in the conventional group could get professional suggestions from the nephrologists through regular clinical visits, but they did not have access to the service provided by AI and the health coach team. Patients were followed for at least 3 months after recruitment or until death or start of renal replacement therapy. RESULTS: A total of 2060 eligible patients who registered on the KidneyOnline app from 2017 to 2021 were enrolled for the analysis. Of those, 902 (43.8%) patients were assessed for survival analysis after propensity score matching, with 451(50%) patients in the KidneyOnline intelligent patient care system group and 451(50%) patients in the conventional care group. After a mean follow-up period of 15.8 (SD 9.5) months, the primary composite kidney outcome occurred in 28 (6%) participants in the KidneyOnline intelligent patient care system group and 32 (7%) in the conventional care group, with a hazard ratio of 0.391 (95% CI 0.231-0.660; P<.001). Subgroup survival analysis demonstrated that the KidneyOnline care system significantly reduced the risk of composite kidney outcome, irrespective of age, sex, baseline estimated glomerular filtration rate (eGFR), and proteinuria. In addition, the mean arterial pressure (MAP) significantly decreased from 88.9 (SD 10.5) mmHg at baseline to 85.6 (SD 7.9) mmHg at 6 months (P<.001) in the KidneyOnline intelligent patient care system group and from 89.3 (SD 11.1) mmHg to 87.5 (SD 8.2) mmHg (P=.002) in the conventional CKD care group. CONCLUSIONS: The utilization of the KidneyOnline intelligent care system was associated with reduced risk of unfavorable kidney outcomes in nondiabetic patients with CKD.


Assuntos
Tutoria , Aplicativos Móveis , Insuficiência Renal Crônica , Humanos , Estudos Retrospectivos , Inteligência Artificial , Insuficiência Renal Crônica/terapia , Rim
7.
Sci Adv ; 9(19): eadg2583, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37163595

RESUMO

An obstacle to conducting diverse bioorthogonal reactions in living systems is the sensitivity of artificial metal catalysts. It has been reported that artificial metallocatalysts can be assembled in "cleaner" environments in cells for stabilized performance, which is powerful but is limited by the prerequisite of using specific cells. We report here a strategy to establish membrane-anchored catalysts with precise spatial control via liposome fusion-based transport (MAC-LiFT), loading bioorthogonal catalytic complexes onto either or both sides of the membrane leaflets. We show that the inner face of the cytoplasmic membrane serves as a reliable shelter for metal centers, protecting the complexes from deactivation thus substantially lowering the amount of catalyst needed for effective intracellular catalysis. This MAC-LiFT approach makes it possible to establish catalyst-protective systems with exclusively exogenous agents in a wide array of mammalian cells, allowing convenient and wider use of diverse bioorthogonal reactions in live cellular systems.


Assuntos
Lipossomos , Metais , Animais , Membrana Celular , Catálise , Mamíferos
8.
Angew Chem Int Ed Engl ; 62(34): e202303280, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37040089

RESUMO

Dispersing metal-organic framework (MOF) solids in stable colloids is crucial for their availability and processibility. Herein, we report a crown ether surface coordination approach for functionalizing the surface-exposed metal sites of MOF particles with amphiphilic carboxylated crown ether (CEC ). The surface-bound crown ethers significantly improve MOF solvation without compromising the accessible voids. We demonstrate that CEC -coated MOFs exhibit exceptional colloidal dispersibility and stability in 11 distinct solvents and six polymer matrices with a wide range of polarities. The MOF-CEC can be instantaneously suspended in immiscible two-phase solvents as an effective phase-transfer catalyst and can form various uniform membranes with enhanced adsorption and separation performance, which highlights the effectiveness of crown ether coating.

9.
Front Pharmacol ; 13: 852055, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517781

RESUMO

Background: Cytokines play a vital role in the pathogenesis of idiopathic inflammatory myopathies (IIMs). Here, we investigated the expression of serum cytokine profiles in untreated IIMs and their correlations with clinical indicators, and further studied the expression of related cytokines receptors in IIMs. Methods: The Human 48-Plex Luminex assay for cytokines was performed in the serum of IIMs, including 93 untreated and 18 follow-up (39 samples) patients, and 32 healthy controls (HC). Mann-Whitney U test with bonferroni adjusted was used to identify the differentially expressed cytokines among groups. Celltalker software was used to identify the receptors of differentially expressed cytokines. The expression of receptors was further validated by published GEO datasets (muscle, blood and skin), RT-qPCR, western blot and flow cytometry. Results: The serum levels of Eotaxin, IL7, IL18, IP10, MCP1, MCSF, MIG and SCGFß were elevated in the 93 untreated patients. Except for IL7, all other cytokines were decreased after treatment and their levels were positively correlated with clinical indices such as LDH, ESR, CRP, ALT, IgA, AST and IgG while negatively correlated with albumin and MMT8. According to the serum myositis-specific antibodies (MSAs), patients were classified into three groups: anti-ARS (Jo-1, OJ, EJ, PL7, PL12), anti-MDA5 positive, and anti-TIF1γ positive. Compared with HC, the levels of IP10 and MIG were increased in three groups. Moreover, IL18 and MSCF were increased in anti-ARS patients, and CTACK, Eotaxin, IL1Rα, IL7, IL18, MCP1, MCP3, MCSF and SCGFß were elevated in anti-MDA5 patients. Twenty receptors of the 8 differentially expressed cytokines were matched by celltalker software, among them, IL18R1 and CCR1 were up-regulated in blood, muscle and skin of IIMs from the analysis of GEO published datasets. RT-qPCR and western blot further validated IL18R1 was upregulated in the muscle tissues of dermatomyositis. The number of IL18R1+CD4+ cells was increased while IL18R1+CD8+ cells was decreased in peripheral blood of anti-MDA5 patients. Conclusion: This study showed that cytokine profiles were significantly changed in IIMs, and different MSA groups had unique cytokine expression patterns. The levels of some cytokine were correlated with clinical indices. The IL18 receptor IL18R1 might play important roles in IIMs.

10.
J Healthc Eng ; 2022: 8349851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281524

RESUMO

Objective: To explore the clinical intervention effect of transumbilical single-port laparoscopic-assisted Duhamel operation on children with Hirschsprung's disease (HD) and to analyze the effect of treatment on children with serum C-reactive protein (CRP) and interleukin-6 (IL-6) effects. Methods: Retrospectively select 80 children with HD who underwent surgery in our hospital from May 2017 to May 2020 as the research subjects and they are classified as group A according to the difference of the children's surgical procedures (receiving transumbilical single-port laparoscopic-assisted Duhamel surgery, 40 cases) and group B (receiving conventional laparoscopic surgery, 40 cases), compare the perioperative period (operating time, intraoperative blood loss, surgical posthospitalization, and postoperative gastrointestinal function recovery time), early postoperative complications (perianal dermatitis, urinary retention, enterocolitis, and anastomotic leakage), and late postoperative complications (anastomotic stenosis, dirty stool, recurrence of constipation, and enterocolitis), compare the differences in the levels of CRP and IL-6 between the two groups of children before and after the operation, and conduct a 1-year follow-up of the two groups of children to compare the long-term defecation status. Results: The surgical time of children in group A, postoperative hospitalization time, and postoperative gastrointestinal function recovery time were significantly shorter than those of group B, and the differences between groups were statistically significant (P < 0.05). A group of patients: the total incidence of postearly complications was 5.00% lower than 22.50% (P < 0.05) in group B (P < 0.05), and the total incidence of previous complications after group A of patients was 10.00% lower than 27.50% of group B (P < 0.05). The two groups of serum CRP and IL-6 in two groups were not statistically significant (P > 0.05), and the serum CRP and IL-6 levels of children in group A after surgery were 3 days. It is obviously lower than those in group B, and the differences between groups have statistical significance (P < 0.05). At 1 month after surgery, the average bowel movement time in group A is significantly lower than those of group B (P < 0.05); during the 1-12 months, the difference between the defecation frequency group of the group A and group B did not have statistically significance (P > 0.05). Conclusion: Transumbilical single-port laparoscopic assistant Duhamel operation of HD has a good intervention effect, compared to traditional laparoscopic surgery, the operation time, postoperative hospitalization time, and postoperative gastrointestinal function recovery time, and also help to reduce postoperative near-long complications The incidence improves the stress reactions and long-term defecation functions in children.


Assuntos
Enterocolite , Doença de Hirschsprung , Laparoscopia , Proteína C-Reativa , Criança , Enterocolite/epidemiologia , Enterocolite/etiologia , Enterocolite/cirurgia , Doença de Hirschsprung/complicações , Doença de Hirschsprung/cirurgia , Humanos , Interleucina-6 , Laparoscopia/métodos , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
11.
Wien Klin Wochenschr ; 134(5-6): 202-207, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35038004

RESUMO

OBJECTIVE: To identify and reclassify the patients in the lupus nephritis (LN) cohort, and to further analyze the prominent clinical features and clinical significance of each cluster. METHODS: In this retrospective cross-sectional study, we used a two-step clustering method to classify 635 patients with LN into different clusters, then we observed the main differences and analyzed relevant clinical significance between the clusters. RESULTS: Cluster 1 (20.5%) presented with the highest disease severity, patients in this group had the disease for a longer duration and higher systemic lupus erythematosus disease activity index (SLEDAI) score, with multiple positive auto-antibodies and lower complement level. Patients of cluster 2 (20.8%) had lower levels of IgG, IgA and IgM, with renal function being relatively worse in this cluster than in clusters 1 and 3. Cluster 3 was the largest group (58.7%), and the patients in this group showed mild disease severity. CONCLUSION: This study reclassified LN patients in a large cohort into three clusters. Our classification might be helpful to implement targeted therapy at various stages of systemic lupus erythematosus.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Estudos Transversais , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
12.
Contrast Media Mol Imaging ; 2021: 8139200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34908914

RESUMO

In order to analyze multi-index monitoring and the effect of reducing cesarean section, this paper selects March 2018 and March 2019 in two obstetrics and gynecology hospitals, referred to as hospital A and hospital B. As research objects, 313 pregnant women were divided into multi-index group and conventional group, while analyzing various indicators of each group of cesarean collection. The results show that the total CNAXE rate was 48.10% and 39.29%, respectively, for 2018 and 2019, respectively, and the cesarean section of the conventional group was 65.75% and 63.64%. By contrasting data of multi-index group and conventional group, hospital B differences were significant (P < 0.05), and hospital A difference was extremely significant (P < 0.01). In Cesarean section, obstetric sectors can help maternal treatment strategies by monitoring a series of related indicators for maternal to reduce Cesarean section and improve prognosis.


Assuntos
Cesárea , Resultado da Gravidez , Feminino , Humanos , Gravidez
13.
Math Biosci Eng ; 18(5): 5347-5363, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34517491

RESUMO

With the development of online medical service platform, patients can find more medical information resources and obtain better medical treatment. However, it is difficult for patients to discover the most suitable doctors from the complex information resources. Therefore, the analysis and mining of Electronic Health Record(EHR) is very important for patients' timely and accurate treatment. Discovering the most suitable doctor is actually predicting the exact performance of the doctor for a specific disease. We believe that "a curative/bad treatment is likely to be caused by a good/bad doctor, and a good/bad doctor has a higher/lower evaluation by the patient(s)". In this paper, we propose a novel approach named SeekDoc, which is to seek the most effective doctor for a specific disease. Specifically, we build a doctor-disease heterogeneous information network and collect patients reviews and rating records for doctors. Then, we embed the comprehensive comment data for doctors and the constructed heterogeneous information network. Next, we use the autoencoder mechanism to learn the embedded features, which is an effective learning algorithm for constructing the latent feature representation in an unsupervised manner. After this learning, the latent features are input into the extreme gradient boosting (XGBoost) algorithm to improve their detection capabilities. Finally, extensive experiments show that our method can effectively and efficiently predict the doctor's experience score for specific diseases and has good performance compared with other algorithms.


Assuntos
Registros Eletrônicos de Saúde , Médicos , Algoritmos , Humanos , Projetos de Pesquisa
14.
Am J Transl Res ; 13(4): 3238-3245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017494

RESUMO

OBJECTIVE: To systematically explore the risk factors that influence cesarean section rate, and establish a prediction model to investigate a system effectively reducing cesarean section rates. METHODS: This retrospective study was carried out in the medical institutions in Xingtai city, where cesarean section could be conducted. The data of parturients who gave birth to children in the past five years were collected using the hospital information system. Based on the Robson's ten group classification system, parturients were grouped. The difference of cesarean section rate in each group and its main influencing factors were then analyzed. The above factors and factors such as age, education background, and knowledge on childbirth were independent variables, while cesarean section was the dependent variable. A logistic regression model was constructed to determine the correlation between relevant influencing factors and cesarean section. RESULTS: In the past 5 years, cesarean section rate in Xingtai city had been maintained at a relatively high level. Cesarean section rates in the R2 and R5 groups were the highest. Parity, fetal position, number of fetuses, and gestational weeks were all factors affecting cesarean section rate (all P < 0.01). After screening the above factors using logistic regression analysis, a regression equation was established: logistic (p) = -1.061 + 1.107 * parity + 0.196 * fetal position + 2.245 * number of fetuses - 0.070 * gestational week + 0.234 * age - 0.278 * education background + 0.623 * knowledge on childbirth. CONCLUSION: The Robson classification system plays an important role in evaluating and supervising parturients' conditions. Based on the Robson classification system, we find that parity, fetal position, number of fetuses, and gestational weeks are the main factors influencing cesarean section rate. Using logistic regression analysis, a prediction model, with guiding significance on the control of cesarean section rate, is established.

15.
J Am Chem Soc ; 141(41): 16237-16242, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31573801

RESUMO

The intermolecular radical addition to the carbonyl group is difficult due to the facile fragmentation of the resulting alkoxyl radical. To date, the intermolecular radical addition to ketones, a valuable approach to construct quaternary carbon centers, remains a formidable synthetic challenge. Here, we report the first visible-light-induced intermolecular alkyl boronic acid addition to α-ketoacids enabled by the Lewis acid activation. The in situ boron complex formation is confirmed by various spectroscopic measurements and mechanistic probing experiments, which facilitates various alkyl boronic acid addition to the carbonyl group and prevents the cleavage of the newly formed C-C bond. Diversely substituted lactates can be synthesized from readily available alkyl boronic acids and ketoacids at room temperature merely under visible light irradiation, without any additional reagent. This boron activation approach can be extended to alkyl dihydropyridines as radical precursors with external boron reagents for primary, secondary, and tertiary alkyl radical additions. The pharmaceutically useful anticholinergic precursors are easily scaled up in multigrams under metal-free conditions in flow reactors.

16.
ACS Appl Mater Interfaces ; 9(46): 41043-41054, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29077388

RESUMO

Herein, we studied the adsorption behaviors of organic micropollutants, such as anticonvulsant carbamazepine (CBZ) and antibiotic tetracycline hydrochloride (TC), on zirconium metal-organic framework UiO-66 in water. The maximum adsorption capacities of CBZ and TC on the UiO-66 were 37.2 and 23.1 mg·g-1 at 25 °C, respectively. The adsorption isotherms and kinetics of CBZ and TC were well described by using the Langmuir model and pseudo-second-order model, respectively, and the adsorptions on UiO-66 are endothermic reactions. The adsorption capacities of CBZ and TC on UiO-66 were decreased with the increase of solution pH. The presence of humic acid could improve the adsorption of CBZ and TC on UiO-66, but K+ ion inhibited their adsorption obviously. In addition, Ca2+ and Al3+ ions also suppressed the adsorption of TC on UiO-66. The competitive adsorption suggested that the adsorption sites for CBZ on UiO-66 were different from those for TC. The surface interactions between UiO-66 and the two micropollutants were demonstrated by powder X-ray diffraction, Fourier transform infrared (FT-IR) spectra, scanning electron microscopy, nitrogen adsorption/desorption isotherms, and X-ray photoelectron (XPS) spectra. The characterizations showed that the adsorption of CBZ on UiO-66 is mainly a physisorption, and the hydrophobic effect played a crucial role during the adsorption of CBZ; meanwhile weak π-π electron donor-acceptor interaction and electrostatic attraction also existed. However, the adsorption of TC on UiO-66 is mainly a chemisorption; in addition to the strong electrostatic attraction and π-π electron donor-acceptor interaction forces, the nitrogenous groups of TC played an important role, which can replace the carboxylic groups coordinated with Zr-O clusters. The obtained results will aid us to comprehend the surface interaction between organic micropollutants and UiO-66 and expand the application of UiO-66 as sorbent for removal of pollutants from water.

17.
J Ovarian Res ; 10(1): 5, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-28095884

RESUMO

BACKGROUD: Ovarian transplantation is a useful method for preserving the fertility of young women with cancer who undergo radiotherapy and chemotherapy. Follicle-stimulating hormone (FSH) is use to protect transplanted ovarian tissues from ischemia injury through promoting revascularization after transplantation, but the side effect of high level FSH is ovarian overstimulation leading to substantial follicular loss. In this study, we investigated the optimal usage of FSH on revascularization in the in vitro cultured ovarian tissues before and after transplantation. RESULTS: FSH mainly exhibited an additive response in the gene and protein expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and follicle stimulating hormone receptor (FSHR) with its raised concentrations (0.15 IU/ml, 0.30 IU/ml and 0.60 IU/ml) and prolonged treatment (3 h, 6 h, 12 h, 24 h). The concentrations with 0.60 IU/ml FSH could obviously promoted the expression of VEGF, bFGF and FSHR, but under this concentration FSH could also overstimulated the ovarian tissue leading to follicular loss. With the increase of culture time, the gene and protein expression of VEGF and bFGF both were up-regulated in all of the FSH added groups, but FSHR expression decreased when culture time exceeded 12 h. So we chose 0.30 IU/ml FSH added concentration and 6 h culture time as the FSH usage condition in functional revascularization verification experiment, and found that under this condition FSH promoted 2.5 times increase of vascular density in treated group than in control group after ovarian tissues transplantation. CONCLUSION: Ovarian intervention with 0.30 IU/ml FSH for 6 h is an optimal FSH usage condition which could accelerate the revascularization in the allotransplanted ovarian tissue and can not produce ovarian overstimulation.


Assuntos
Hormônio Foliculoestimulante/farmacologia , Neovascularização Fisiológica , Transplante de Órgãos , Ovário/irrigação sanguínea , Ovário/transplante , Animais , Biomarcadores , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Expressão Gênica , Imuno-Histoquímica , Camundongos , Ovário/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Transplante Homólogo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Biomed Mater ; 7(3): 035012, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22475630

RESUMO

In this study, calcium-alginate microgels coated with a polyelectrolyte multilayer (PEM) were fabricated as a controlled-release system. This system was constructed via an electrostatic droplet generation technique followed by a layer-by-layer (LbL) self-assembly technique. The electrostatic droplet generation technique was reported as an easy method of preparing microgels, due to their mild preparation conditions and ability to preserve the biological activity of the encapsulated drugs. With the LbL self-assembly technique, the PEM could be fabricated on the microgels attributed to the electrostatic attraction between positive-charged chitosan (Chi) and negative-charged dextran sulfate (Dex). The properties of the prepared microgels were investigated using dynamic laser scattering (DLS), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectrum and zeta potential analyzer. In vitro release study indicated that the initial burst release of the bovine serum albumin (BSA) from PEM-coated microgels was less compared to the uncoated microgels (19% versus 31% in 24 h). In addition, the sustained release of BSA from the PEM-coated microgels was recorded up to 1 month without any damage to BSA integrity. Thus, our results demonstrated that the PEM-coated microgels not only prolonged the release time, but also relieved the initial burst problem to some degree and preserved the biological activity of the encapsulated drugs. Moreover, the release rate of BSA could be regulated by controlling the number of deposited layers. In conclusion, this study presented an easy yet effective method for the controlled, sustained release of biological macromolecules.


Assuntos
Alginatos/química , Materiais Revestidos Biocompatíveis/síntese química , Preparações de Ação Retardada/química , Eletrólitos/química , Géis/química , Soroalbumina Bovina/química , Animais , Bovinos , Difusão , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Teste de Materiais
19.
Recent Pat Drug Deliv Formul ; 5(3): 265-74, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21834779

RESUMO

Intelligent hydrogel, also known as smart hydrogels, are materials with great potential for development in drug delivery system. Intelligent hydrogel also has the ability to perceive as a signal structure change and stimulation. The review introduces the temperature-, pH-, electric signal-, biochemical molecule-, light- and pressure- sensitive hydrogels. Finally, we described the application of intelligent hydrogel in drug delivery system and the recent patents involved for hydrogel in drug delivery.


Assuntos
Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Animais , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Composição de Medicamentos/tendências , Sistemas de Liberação de Medicamentos/tendências , Técnicas Eletroquímicas , Humanos , Hidrogéis , Concentração de Íons de Hidrogênio , Luz , Patentes como Assunto , Transição de Fase , Pressão , Temperatura
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