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1.
Eur J Hosp Pharm ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839267

RESUMO

BACKGROUND: Medication dispensing errors cause wastage of medicines and increase healthcare costs, with serious consequences for patients. However, few studies have systematically and completely reviewed dispensing errors, with inadequate attention to the objective regularity and risk factors for dispensing errors. OBJECTIVES: To explore the potential causes and risk factors influencing the prevalence of medication dispensing errors. METHODS: We collected patient-reported medication dispensing errors from a large tertiary care hospital in South China over 11 years. We assessed the characteristics of dispensing errors, labelled the causes, compared them with more than 25 million prescriptions from 2012 to 2022, identified the susceptibility factors for the occurrence of dispensing errors, and analysed the characteristics and patterns of the errors. RESULTS: A total of 376 patient-reported dispensing errors were recorded. It took an average of 5.2 days for a patient to find an error. Only 37.5% of errors were reviewed by the patient within 24 hours. These errors directly contributed to a medication loss of US$188 406. Of the 160 recorded pharmacists, 112 (70%) committed dispensing errors. Dispensing errors were affected by the pharmacists' use of the machine, workload and the length of monthly vacation. Of the dispensing errors, 47.9% (n=180) were caused by medication packaging or names that were similar. Antibiotics (n=32, 8.5%) were the most common types of drugs dispensed incorrectly, and traditional Chinese medicines (n=31, 8.2%) and immunosuppressants (n=21, 5.6%) were the most likely to be dispensed in inaccurate quantities. CONCLUSIONS: Organising adequate staff and using machines to prepare medicines may be necessary to reduce dispensing errors. When pharmacists have been away from work for more than 72 hours they should find their rhythm in other positions before dispensing medicines. It is more important to prioritise the differentiation of medicines with similar packaging over those with similar names when arranging drug shelving.

2.
Technol Health Care ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38875057

RESUMO

BACKGROUND: Dysfunctions in metabolism and endocrine systems are outcomes of disruptions in human physiological processes, often leading to disease onset. External factors can hinder the human body's innate capacity for self-regulation and healing, particularly when immune responses are compromised, allowing these factors to interfere with normal bodily functions directly. OBJECTIVE: To explore the effect of uric acid expression water in blood on the occurrence of atrial fibrillation in patients with hyperthyroidism, the expression level of uric acid in the blood and other physiological indexes were compared between patients with no symptoms of atrial fibrillation and patients with hyperthyroidism with symptoms of atrial fibrillation, to find the correlation between them. METHODS: A group of 112 hyperthyroidism patients who were admitted to our hospital from September 2019 to March 2020 were chosen and split into two groups. The control group consisted of 56 individuals (21 men and 35 women) aged between 16 and 86 years old, with an average age of 46.23 years (± 7.63). The observation group consisted of 56 individuals (24 males and 32 females) between 15 and 79 years, with an average age of 53.44 years (± 8.91). RESULTS: In the patients who were not treated with drugs before hospitalization the disease course and symptoms varied. The patients' clinical medical and demographic data were recorded and the patients' physiological indexes were obtained through blood tests and analysis. The differences between the two groups were analyzed by renal function, blood lipid index, thyroid function, and cardiac ultrasound, and these influencing factors were analyzed by regression analysis. The research adhered to ethical norms and ensured clear data presentation by using a rigorous technique to compare uric acid levels and physiological indicators among various patient groups. CONCLUSION: The study concentrated on the validation, repeatability, and contextual interpretation of data to provide a robust and rigorously scientific comparison. The most common is the increase of uric acid in the blood, which can induce other diseases, and atrial fibrillation is one of the most common diseases of cardiovascular diseases.

3.
Int J Biol Macromol ; : 133150, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878930

RESUMO

The extraction of Li+ from liquid lithium resources is a pivotal focus of current research endeavors. Attapulgite (ATP), characterized by its distinctive layered structure and inherent ion exchange properties, emerges as an exceptional material for fabricating lithium-ion sieve. Ion-imprinted chitosan/ATP composite materials are successfully synthesized, demonstrating efficacy in selectively absorbing Li+. The results emphasize the rich functional groups present in H-CTP-2, enhancing its absorbability and selectivity, with an adsorption capacity of 37.56 mg•g-1. The adsorption conforms to the Langmuir and pseudo-second-order kinetic model. Li+ coordination involves amino and hydroxyl group, indicating a chemisorption process. Furthermore, the substantial pore structure and significant specific surface area of ATP significantly promote Li+ adsorption, suggesting its participation not only in chemisorption but also in physical adsorption. The fabricated ion-imprinted materials boast substantial adsorption capacity, exceptional selectivity, and rapid kinetics, highlighting their potential for effectively separating Li+ from aqueous solution.

4.
Environ Monit Assess ; 196(7): 596, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839676

RESUMO

The issue of soil acidification in tea plantations has become a critical concern due to its potential impact on tea quality and plant health. Understanding the factors contributing to soil acidification is essential for implementing effective soil management strategies in tea-growing regions. In this study, a field study was conducted to investigate the effects of tea plantations on soil acidification and the associated acid-base buffering capacity (pHBC). We assessed acidification, pHBC, nutrient concentrations, and cation contents in the top 0-20 cm layer of soil across forty tea gardens of varying stand ages (0-5, 5-10, 10-20, and 20-40 years old) in Anji County, Zhejiang Province, China. The results revealed evident soil acidification due to tea plantation activities, with the lowest soil pH observed in tea gardens aged 10-20 and 20-40 years. Higher levels of soil organic matter (SOM), total nitrogen (TN), Olsen phosphorus (Olsen-P), available iron (Fe), and exchangeable hydrogen (H+) were notably recorded in 10-20 and 20-40 years old tea garden soils, suggesting an increased risk of soil acidification with prolonged tea cultivation. Furthermore, prolonged tea cultivation correlated with increased pHBC, which amplified with tea stand ages. The investigation of the relationship between soil pHBC and various parameters highlighted significant influences from soil pH, SOM, cation exchange capacity, TN, available potassium, Olsen-P, exchangeable acids (including H+ and aluminum), available Fe, and available zinc. Consequently, these findings underscore a substantial risk of soil acidification in tea gardens within the monitored region, with SOM and TN content being key driving factors influencing pHBC.


Assuntos
Camellia sinensis , Monitoramento Ambiental , Nitrogênio , Solo , Solo/química , Camellia sinensis/química , Nitrogênio/análise , China , Concentração de Íons de Hidrogênio , Ecossistema , Fósforo/análise , Chá/química , Agricultura
5.
J Affect Disord ; 360: 249-258, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38795782

RESUMO

BACKGROUND: LGBTQ+ populations have been reported to have higher rates of depression compared with their heterosexual peers. Such data provided us the impetus to conduct a meta-analysis on the worldwide prevalence of major depressive disorder (MDD) in LGBTQ+ populations and moderating factors that contributed to differences in prevalence estimates between studies. METHODS: A systematic literature search was performed in major international (PubMed, PsycINFO, Web of Science, EMBASE) and Chinese (Chinese Nation Knowledge Infrastructure (CNKI) and WANFANG) databases from dates of inception to 10 December 2021. RESULTS: 48 articles comprising 4,616,903 individuals were included in the meta-analysis. The overall prevalence of MDD was 32.2 % (95%CI: 30.8-33.6 %, I2 = 99.6 %, τ2 = 0.284). MDD prevalence was higher in the LGBTQ+ samples from the United States than other countries, though the difference was not significant in moderator analyses. Moderator analyses indicated point and lifetime prevalence of MDD were significantly higher than estimates based on the past year (Q = 6.270, p = 0.043). Furthermore, studies that relied on convenience sampling had a higher prevalence of MDD than those based on other sampling methods (Q = 8.159, p = 0.017). In meta-regression analyses, mean age (B = 0.03, z = 9.54, p < 0.001) and study quality assessment score (B = 0.24, z = 67.64, p < 0.001) were positively associated with pooled prevalence of MDD while mediation data of year of study (B = -0.08, z = -72.55, p < 0.001) and sample size (B = -1.46, z = -37.83, p < 0.001) were negatively associated with pooled prevalence of MDD in LGBTQ+ samples. CONCLUSIONS: MDD is common among in LGBTQ+ individuals. Considering the negative consequences MDD has on daily life and well-being, appropriate prevention and treatment measures should be provided to vulnerable members of these populations. The findings of this meta-analysis could facilitate identifying at-risk subgroups, developing relevant health policy for LGBTQ+ individuals and allocating health resources from an intersectionality perspective.


Assuntos
Transtorno Depressivo Maior , Minorias Sexuais e de Gênero , Humanos , Transtorno Depressivo Maior/epidemiologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Prevalência , Saúde Global/estatística & dados numéricos , Masculino , Feminino , Adulto
6.
J Endod ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38821263

RESUMO

Understanding the intricate anatomical morphology of fused-rooted mandibular second molars (MSMs) is essential for root canal treatment. The present study utilized a deep learning approach to identify the three-dimensional root canal morphology of MSMs from two-dimensional X-ray images. METHODS: A total of 271 fused-rooted MSMs were included in the study. Micro-computed tomography (micro-CT) reconstruction images and two-dimensional X-ray projection images were obtained. The ground truth of three-dimensional root canal morphology was determined through micro-CT images, which were classified into merging, symmetrical, and asymmetrical types. To amplify the X-ray image dataset, traditional augmentation techniques from the python package Augmentor and a multi-angle projection method were employed. Identification of root canal morphology was conducted using the pre-trained VGG19, ResNet18, ResNet50, and EfficientNet-b5 on X-ray images. The classification results from convolutional neural networks (CNNs) were then compared with those performed by endodontic residents. RESULTS: The multi-angle projection augmentation method outperformed the traditional approach in all CNNs except for EfficientNet-b5. ResNet18 combined with the multi-angle projection method outperformed all other combinations, with an overall accuracy of 79.25%. In specific classifications, accuracies of 81.13%, 86.79%, and 90.57% were achieved for merging, symmetrical, and asymmetrical types, respectively. Notably, CNNs surpassed endodontic residents in classification performance; the average accuracy for endodontic residents were only 60.38% (P< 0.05). CONCLUSIONS: CNNs were more effective than endodontic residents in identifying the three-dimensional root canal morphology of MSMs. The result indicates that CNNs possess the capacity to employ two-dimensional images effectively in aiding three-dimensional diagnoses.

7.
J Am Chem Soc ; 146(22): 14927-14934, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38767459

RESUMO

Bicyclo[1.1.0]butane-containing compounds feature a unique chemical reactivity, trigger "strain-release" reaction cascades, and provide novel scaffolds with considerable utility in the drug discovery field. We report the synthesis of new bicyclo[1.1.0]butane-linked heterocycles by a nucleophilic addition of bicyclo[1.1.0]butyl anions to 8-isocyanatoquinoline, or, alternatively, iminium cations derived from quinolines and pyridines. The resulting bicyclo[1.1.0]butanes are converted with high regioselectivity to unprecedented bridged heterocycles in a rhodium(I)-catalyzed annulative rearrangement. The addition/rearrangement process tolerates a surprisingly large range of functional groups. Subsequent chemo- and stereoselective synthetic transformations of urea, alkene, cyclopropane, and aniline moieties of the 1-methylene-5-azacyclopropa[cd]indene scaffolds provide several additional new heterocyclic building blocks. X-ray structure-validated quantum mechanical DFT calculations of the reaction pathway indicate the intermediacy of rhodium carbenoid and metallocyclobutane species.

8.
Mol Cancer ; 23(1): 108, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762484

RESUMO

Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.


Assuntos
Antígeno B7-H1 , Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Neoplasias/metabolismo , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/etiologia , Neoplasias/genética , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/metabolismo , Animais , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica
9.
Transl Psychiatry ; 14(1): 227, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816419

RESUMO

Psychiatric syndromes are common following recovery from Coronavirus Disease 2019 (COVID-19) infection. This study investigated the prevalence and the network structure of depression, insomnia, and suicidality among mental health professionals (MHPs) who recovered from COVID-19. Depression and insomnia were assessed with the Patient Health Questionnaire (PHQ-9) and Insomnia Severity Index questionnaire (ISI7) respectively. Suicidality items comprising suicidal ideation, suicidal plan and suicidal attempt were evaluated with binary response (no/yes) items. Network analyses with Ising model were conducted to identify the central symptoms of the network and their links to suicidality. A total of 9858 COVID-19 survivors were enrolled in a survey of MHPs. The prevalence of depression and insomnia were 47.10% (95% confidence interval (CI) = 46.09-48.06%) and 36.2% (95%CI = 35.35-37.21%), respectively, while the overall prevalence of suicidality was 7.8% (95%CI = 7.31-8.37%). The key central nodes included "Distress caused by the sleep difficulties" (ISI7) (EI = 1.34), "Interference with daytime functioning" (ISI5) (EI = 1.08), and "Sleep dissatisfaction" (ISI4) (EI = 0.74). "Fatigue" (PHQ4) (Bridge EI = 1.98), "Distress caused by sleep difficulties" (ISI7) (Bridge EI = 1.71), and "Motor Disturbances" (PHQ8) (Bridge EI = 1.67) were important bridge symptoms. The flow network indicated that the edge between the nodes of "Suicidality" (SU) and "Guilt" (PHQ6) showed the strongest connection (Edge Weight= 1.17, followed by "Suicidality" (SU) - "Sad mood" (PHQ2) (Edge Weight = 0.68)). The network analysis results suggest that insomnia symptoms play a critical role in the activation of the insomnia-depression-suicidality network model of COVID-19 survivors, while suicidality is more susceptible to the influence of depressive symptoms. These findings may have implications for developing prevention and intervention strategies for mental health conditions following recovery from COVID-19.


Assuntos
COVID-19 , Depressão , Pessoal de Saúde , Distúrbios do Início e da Manutenção do Sono , Ideação Suicida , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Feminino , Masculino , China/epidemiologia , Adulto , Prevalência , Depressão/epidemiologia , Depressão/psicologia , Pessoa de Meia-Idade , Pessoal de Saúde/psicologia , Inquéritos e Questionários , SARS-CoV-2 , Tentativa de Suicídio/estatística & dados numéricos , Tentativa de Suicídio/psicologia
10.
Med Oncol ; 41(6): 159, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761335

RESUMO

RNA modification has garnered increasing attention in recent years due to its pivotal role in tumorigenesis and immune surveillance. N6-methyladenosine (m6A) modification is the most prevalent RNA modification, which can affect the expression of RNA by methylating adenylate at the sixth N position to regulate the occurrence and development of tumors. Dysregulation of m6A affects the activation of cancer-promoting pathways, destroys immune cell function, maintains immunosuppressive microenvironment, and promotes tumor cell growth. In this review, we delve into the latest insights into how abnormalities in m6A modification in both tumor and immune cells orchestrate immune evasion through the activation of signaling pathways. Furthermore, we explore how dysregulated m6A modification in tumor cells influences immune cells, thereby regulating tumor immune evasion via interactions within the tumor microenvironment (TME). Lastly, we highlight recent discoveries regarding specific inhibitors of m6A modulators and the encapsulation of m6A-targeting nanomaterials for cancer therapy, discussing their potential applications in immunotherapy.


Assuntos
Adenosina , Imunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/patologia , Evasão Tumoral/imunologia , Animais , Evasão da Resposta Imune/imunologia , Transdução de Sinais/imunologia
11.
Folia Parasitol (Praha) ; 712024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38813809

RESUMO

Coccidiosis is a protozoan intestinal disease that reduces the production of the sheep industry and causes large economic losses for sheep. Although chemically synthesised drugs are routinely employed to treat coccidiosis in sheep, the anticoccidial drug resistance and drug residues in edible meat have prompted an urgent search for alternatives. Herein, the anticoccidial properties of diclazuril, a conventional anticoccidial drug, and Allium sativum, Houttuynia cordata and Portulaca oleracea were assessed. Forty 45-day-old lambs naturally infected with Eimeria spp. were selected and randomly divided into five groups. The results showed that the sheep treated for coccidiosis had considerably decreased average daily gain (ADG) during both administration and withdrawal of the drug compared to the control group. Furthermore, at days 14, 21, 28 and 35, respectively, the three herbs and diclazuril had similar anticoccidial effects, with lower oocysts per gram (OPG) than the control group. On day 78, OPG in the three herbal groups was significantly lower than in the diclazuril group. In addition, the abundance and composition of the gut microbiota were changed in sheep treated with the three herbs and diclazuril compared to the untreated sheep. Moreover, some intestinal microorganisms have a correlation with OPG and ADG when using Spearman correlation analysis. In summary, our results suggest that all three herbs produce anticoccidial effects similar to diclazuril and modulate the balance of gut microbiota in growing lambs.


Assuntos
Coccidiose , Microbioma Gastrointestinal , Doenças dos Ovinos , Animais , Coccidiose/veterinária , Coccidiose/tratamento farmacológico , Coccidiose/parasitologia , Microbioma Gastrointestinal/efeitos dos fármacos , Ovinos , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Oocistos/efeitos dos fármacos , Coccidiostáticos/farmacologia , Coccidiostáticos/administração & dosagem , Eimeria/efeitos dos fármacos , Eimeria/fisiologia , Triazinas/farmacologia , Triazinas/administração & dosagem
12.
Eur J Med Chem ; 272: 116487, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38759452

RESUMO

Acute lung injury (ALI) and inflammatory bowel disease (IBD) are common inflammatory illnesses that seriously affect people's health. Herein, a series of 4-hydroxylcoumarin (4-HC) derivatives were designed and synthesized. The inhibitory effects of these compounds on LPS-induced interleukin-6 (IL-6) release from J774A.1 cells were then screened via ELISA assay, compound B8 showed 3 times more active than the lead compound 4-HC. The most active compound B8 had the IC50 values of 4.57 µM and 6.51 µM for IL-6 release on mouse cells J774A.1 and human cells THP-1, respectively. Furthermore, we also found that B8 could act on the MAPK pathway. Based on the target prediction results of computer virtual docking, kinase inhibitory assay was carried out, and it revealed that targeting IRAK1 was a key mechanism for B8 to exert anti-inflammatory activity. Moreover, B8 exerted a good therapeutic effect on the dextran sulfate sodium (DSS)-induced colitis model and liposaccharide (LPS)-induced ALI mouse models. The acute toxicity experiments indicated that high-dose B8 caused no adverse reactions in mice, confirming its safety in vivo. Additionally, the preliminary pharmacokinetic (PK) parameters of B8 in SD rats were also examined, revealing a bioavailability (F) of 28.72 %. In conclusion, B8 is a potential candidate of drug for the treatment of ALI and colitis.


Assuntos
4-Hidroxicumarinas , Lesão Pulmonar Aguda , Colite , Desenho de Fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Colite/tratamento farmacológico , Colite/induzido quimicamente , Camundongos , Humanos , Relação Estrutura-Atividade , 4-Hidroxicumarinas/farmacologia , 4-Hidroxicumarinas/química , 4-Hidroxicumarinas/síntese química , Estrutura Molecular , Sulfato de Dextrana , Masculino , Relação Dose-Resposta a Droga , Ratos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Interleucina-6/metabolismo , Interleucina-6/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Simulação de Acoplamento Molecular , Camundongos Endogâmicos C57BL , Linhagem Celular
13.
Microbiol Resour Announc ; 13(6): e0083223, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38717174

RESUMO

Here, we report the complete genome sequences of three Porphyromonas gingivalis, one from patient with esophageal cancer (LyEC01), and the other two from periodontally healthy individuals (LyG-1 and LyG-2) in 2021 and 2023. The genome sizes of LyEC01, LyG-1, and LyG-2 were 2,408,275, 2,411,440, and 2,411,481 bp, respectively.

14.
Cancer Lett ; 593: 216970, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38763475

RESUMO

Venetoclax is a BCL2-targeted drug employed in treating various cancers, particularly hematologic malignancies. Venetoclax combination therapies are increasingly recognized as promising treatment strategies for acute myeloid leukemia (AML). In this study, we conducted an unbiased drug screen and identified anlotinib, a promising multi-targeted receptor tyrosine kinase inhibitor with oral activity currently utilized in the treatment of solid tumor, as a potent enhancer of venetoclax's anticancer activity in AML. Our investigation encompassed AML cell lines, primary cells, and mouse models, demonstrating effective low-dose combination therapy of anlotinib and venetoclax with minimal cytopenia or organ damage. Proteomic analysis revealed abnormal mitotic signals induced by this combination in AML cells. Mechanistically, anlotinib synergized with venetoclax by suppressing ARPP19 protein, leading to sustained activation of PP2A-B55δ. This inhibited AML cells from entering the mitotic phase, culminating in mitotic catastrophe and apoptosis. Additionally, we identified a specific synthetic lethal vulnerability in AML involving an ARPP19 mutation at S62 phosphorylation. These findings underscore the therapeutic potential of anlotinib and venetoclax combination therapy in AML, warranting further clinical investigation.


Assuntos
Apoptose , Compostos Bicíclicos Heterocíclicos com Pontes , Sinergismo Farmacológico , Indóis , Leucemia Mieloide Aguda , Mitose , Quinolinas , Sulfonamidas , Ensaios Antitumorais Modelo de Xenoenxerto , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Humanos , Sulfonamidas/farmacologia , Sulfonamidas/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Animais , Quinolinas/farmacologia , Quinolinas/administração & dosagem , Mitose/efeitos dos fármacos , Camundongos , Indóis/farmacologia , Indóis/administração & dosagem , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
15.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1848-1864, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812197

RESUMO

Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 µmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas , Ressonância de Plasmônio de Superfície , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas/métodos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Controle de Qualidade , Humanos , Espectrometria de Massa com Cromatografia Líquida
16.
Eur J Clin Pharmacol ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691139

RESUMO

OBJECTIVES: To describe the pharmacokinetic (PK) characteristics of nirmatrelvir/ritonavir in renal transplant recipients and explore the potential factors that related to the PK variance of nirmatrelvir/ritonavir and its interaction with calcineurin inhibitor (CNI). METHODS: Renal transplant recipients treated with CNI and nirmatrelvir/ritonavir were prospectively enrolled. Steady-state plasma concentrations of nirmatrelvir/ritonavir were determined by high-performance liquid chromatography-tandem mass spectrometry, and the PK parameters were calculated using non-compartmental analysis. Spearman correlation analysis was used for exploring influencing factors. RESULTS: A total of eight recipients were enrolled; for nirmatrelvir and ritonavir, AUC/dose was 0.24179 ± 0.14495 and 0.06196 ± 0.03767 µg·h·mL-1·mg-1. Red blood cell (RBC), hematocrit (Ht), hemoglobins (Hb), and creatinine clearance (Ccr) were negatively correlated with AUC/dose of nirmatrelvir, while Ccr, CYP3A5 genotype, and CYP3A4 genotype were related to the AUC/dose of ritonavir. Ccr was negatively correlated with the C0/dose of tacrolimus (TAC) after termination of nirmatrelvir/ritonavir (rs = -0.943, p = 0.008). CONCLUSIONS: The PK characteristics of nirmatrelvir/ritonavir vary greatly among renal transplant recipients. Factors including Ccr and CYP3A5 genotype were related to the in vivo exposure of nirmatrelvir/ritonavir. During the whole process before and after nirmatrelvir/ritonavir therapy, it is recommended to adjust the CNI basing on renal function to avoid CNI toxicity exposure.

17.
Sci Data ; 11(1): 453, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704376

RESUMO

Water body (WB) extraction is the basic work of water resources management. Tibetan Plateau is one of the largest alpine lake systems in the world. However, research on the characteristics of water bodies (WBs) is mainly focused on large and medium WBs due to spatial resolution. This research presents a dataset containing a 2-m resolution map of WBs in 2020 based on Gaofen-1 data, and morphometric and landscape indices of WBs across the Tibetan Plateau. The Swin-UNet model is well performed with overall accuracy at 98%. The total area of WBs is 56354.6 km2 across Tibetan Plateau in 2020. The abundance compared with that from size-abundance relationship indicate WBs in the Tibetan Plateau conformed to the classic power scaling law. We evaluate the influence of spatial-resolution in WB extraction, which shows the dataset could be valuable to fill the gap of existing WBs map, especially for small waters. The dataset is valuable for revealing the spatial patterns of WBs, and understanding the impacts of climate change on water resources in Plateau.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38730553

RESUMO

OBJECTIVES: Mycophenolic acid (MPA) is recommended for lupus nephritis (LN) treatment, but with large inter-individual variability in pharmacokinetics (PK). The aim of this study is to reveal the relationship between MPA exposure and disease response and adverse drug reactions in pediatric LN patients. METHOD: This was a population-based observational cohort study. A total of 86 pediatric LN patients treated with mycophenolate mofetil (MMF) for induction therapy were enrolled. The area-under the concentration-time curve (AUC) was calculated using MPA concentrations according to a limited sampling strategy. Receiver operating characteristic analysis was performed to assess the MPA-AUC threshold values. The cumulative incidence of renal remission and inactive SLE over time was evaluated by Kaplan-Meier's analysis. RESULTS: MPA-AUC was identified as an independent factor associated with renal remission and lupus activity at 6 and 12 months after MMF treatment, and the improved renal remission rates was correlated with higher MPA-AUC, with thresholds of 29.81 and 30.63 µg·h·mL - 1 at 6 and 12 months, respectively. Furthermore, the thresholds for maintaining the hypoactive state of LN were 30.96 and 31.19 µg·h·mL - 1at 6 months and 12 months, respectively. Patients reaching target thresholds for MPA-AUC achieved renal response or stable disease earlier. In addition, the MPA-AUC threshold for decreasing MMF-related adverse reactions was 50.80 µg·h·mL - 1. CONCLUSION: The initial and long-term treatments of pediatric LN patients with MMF should be individualized according to the MPA-AUC, and the recommended MPA exposure is 31.19-50.80 µg·h·mL - 1.

19.
J Phys Chem Lett ; 15(19): 5103-5111, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38708945

RESUMO

The vast compositional space available in high-entropy oxide semiconductors offers unique opportunities for electronic band structure engineering in an unprecedented large room. In this work, with wide band gap semiconductor lithium niobate (LiNbO3) as a model system, we show that the substitutional addition of high-entropy metal cation mixtures within the Nb sublattice can lead to the formation of a single-phase solid solution featuring a substantially narrowed band gap and intense broadband visible light absorption. The resulting high-entropy LiNbO3 [denoted as Li(HE)O3] crystallizes as well-faceted nanocubes; atomic-resolution imaging and elemental mapping via transmission electron microscopy unveil a distinct local chemical complexity and lattice distortion, characteristics of high-entropy stabilized solid solution phases. Because of the presence of high-entropy stabilized Co2+ dopants that serve as active catalytic sites, Li(HE)O3 nanocubes can accomplish the visible light-driven photocatalytic water splitting in an aqueous solution containing methanol as a sacrificial electron donor without the need of any additional co-catalysts.

20.
Sci Rep ; 14(1): 11011, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744937

RESUMO

Spider silk is a promising material with great potential in biomedical applications due to its incredible mechanical properties and resistance to degradation of commercially available bacterial strains. However, little is known about the bacterial communities that may inhabit spider webs and how these microorganisms interact with spider silk. In this study, we exposed two exopolysaccharide-secreting bacteria, isolated from webs of an orb spider, to major ampullate (MA) silk from host spiders. The naturally occurring lipid and glycoprotein surface layers of MA silk were experimentally removed to further probe the interaction between bacteria and silk. Extensibility of major ampullate silk produced by Triconephila clavata that was exposed to either Microbacterium sp. or Novosphigobium sp. was significantly higher than that of silk that was not exposed to bacteria (differed by 58.7%). This strain-enhancing effect was not observed when the lipid and glycoprotein surface layers of MA silks were removed. The presence of exopolysaccharides was detected through NMR from MA silks exposed to these two bacteria but not from those without exposure. Here we report for the first time that exopolysaccharide-secreting bacteria inhabiting spider webs can enhance extensibility of host MA silks and silk surface layers play a vital role in mediating such effects.


Assuntos
Seda , Aranhas , Animais , Aranhas/microbiologia , Aranhas/metabolismo , Seda/metabolismo , Bactérias/metabolismo , Polissacarídeos Bacterianos/metabolismo
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